Xanomeline combinations for treating neurological disorders

Abstract

The present invention relates to new compositions containing xanomeline and a CYP2D6 inhibitor. The present invention also relate to the use of xanomeline and a CYP2D6 inhibitor to increase a subject's xanomeline plasma concentrations. The present invention also relate to the use of xanomeline and a CYP2D6 inhibitor for treating disease including neurological disorders, such as psychosis and schizophrenia.

Description

XANOMELINE COMBINATIONS FOR TREATING NEUROLOGICAL DISORDERSCROSS-REFERENCE TO RELATED APPLICATIONSThis application claims the benefits of U.S. Provisional Application Serial No. 63 / 733,023, filed on December 12, 2024 the disclosure of which is incorporated herein by reference in its entirety.

[0001] The present disclosure relates to new compositions, and their application as pharmaceuticals for treating disease. Methods of treating neurological disorders, such as psychosis and schizophrenia, in a human or animal subject are also provided.

[0002] Xanomeline is a mixed muscarinic partial agonist across all five muscarinic receptor subtypes. Activating the muscarinic system through muscarinic agonists may treat several diseases, including schizophrenia, Alzheimer’s disease, Parkinson’s disease, depression, movement disorders, drug addiction, pain, and neurodegeneration, such as tauopathies or synucleinopathies. Schizophrenia is characterized by a set of symptoms divided into positive symptoms (e.g., hallucinations, delusional thoughts, etc.), negative symptoms (e.g., social isolation, anhedonia, etc.), and cognitive symptoms (e.g., inability to process information, poor working memory, etc. However, the lack of muscarinic receptor subtype selectivity has been problematic for the development of this drug and it failed in Phase III studies as a single agent drug. To reduce the peripheral side effects, xanomeline was recently reformulated and approved by the FDA for the treatment of schizophrenia, in combination with the peripherally restricted antagonist, trospium, which blocks peripheral muscarinic effects.

[0003] Xanomeline is metabolized by multiple cytochrome P450s in the gut and liver. In vitro metabolism studies indicate likely contributions from CYPs 2D6, 2B6, 1A2, 2C9, and 2C19, and flavin monooxygenases (FMO1 and FMO3). There are no active metabolites contributing to the drug’s efficacy.

[0004] At one stage, development of the xanomeline-trospium combination product was placed on clinical hold due to concerns over preclinical findings of biliary hyperplasia. Although these concerns were ultimately addressed and the program allowed to proceed to the clinic, aminotransferase elevations were found in patients in these studies and the approved product is contraindicated in patients with moderate to severe hepatic impairment and not recommended for use in patients with mild impairment. The FDA has also suggested that reactive metabolites formed following extensive first-pass metabolism of xanomeline after oral administration contribute to the histopathology changes seen.

[0005] Preclinically, xanomeline has also been identified as raising both animals’ blood pressure and heart rate. Clinically, the approved product’s FDA label carries a warning of risk of increases in subject’s heart rate following the combination’s administration and the FDA has speculatedthat xanomeline’ s main metabolite, S5_l, might contribute to these cardiovascular effects by inhibiting the norepinephrine reuptake transporter in vivo.

[0006] No formal drug-drug interaction study for xanomeline in human subjects has yet been published. However, the FDA, in reviewing the clinical data available for the approval of its combination product with trospium, found that, in comparison to normal metabolizers, the median Cmaxand median AUCo-iih of xanomeline were estimated to increase by 234% and 215% respectively, in CYP2D6 poor metabolizers, 28% and 15%, respectively, in CYP2D6 intermediate metabolizers, while both parameters decreased by 43% in ultrarapid metabolizers. In light of this profile, the approved product’s label does not contain a warning for either specific CYP2D6 metabolizer populations or for the co-administration of any known CYP2D6 inhibitor.

[0007] There remains a need for improved compositions of xanomeline which maintain its clinical efficacy with reduced hepatic and cardiovascular side-effects.SUMMARY OF THE INVENTION

[0008] The present invention relates to new compositions containing xanomeline and a CYP2D6 inhibitor.

[0009] The present invention also relates to the use of xanomeline and a C YP2D6 inhibitor for treating diseases including neurological disorders, such as psychosis and schizophrenia.DETAILED DESCRIPTION

[0010] The present inventions may be understood more readily by reference to the following detailed description taken in connection with any accompanying figures and examples, which form a part of this disclosure. It is to be understood that these inventions are not limited to the specific products, methods, conditions or parameters described and / or shown herein, and that the terminology used herein is for the purpose of describing particular embodiments by way of example only and is not intended to be limiting of the claimed inventions.

[0011] The entire disclosures of each patent, patent application, and publication cited or described in this document are hereby incorporated herein by reference.

[0012] As employed above and throughout the disclosure, the following terms and abbreviations, unless otherwise indicated, shall be understood to have the following meanings.

[0013] In the present disclosure the singular forms “a”, “an”, and “the” include the plural reference, and reference to a particular numerical value includes at least that particular value, unless the context clearly indicates otherwise. Thus, for example, a reference to “a particle” is a reference to one or more of such particles and equivalents thereof known to those skilled in the art, andso forth. Furthermore, when indicating that a certain element “may be” X, Y, or Z, it is not intended by such usage to exclude in all instances other choices for the element.

[0014] When values are expressed as approximations, by use of the antecedent “about”, it will be understood that the particular value forms another embodiment. As used herein, “about X” (where X is a numerical value) preferably refers to ±10% of the recited value, inclusive. For example, the phrase “about 8” preferably refers to a value of 7.2 to 8.8, inclusive; as another example, the phrase “about 8%” preferably refers to a value of 7.2% to 8.8%, inclusive. Where present, all ranges are inclusive and combinable. For example, when a range of “1 to 5” is recited, the recited range should be construed as optionally including ranges “1 to 4”, “1 to 3”, “1-2”, “1-2 & 4-5”, “1-3 & 5”, and the like. In addition, when a list of alternatives is positively provided, such a listing can also include embodiments where any of the alternatives may be excluded. For example, when a range of “1 to 5” is described, such a description can support situations whereby any of 1, 2, 3, 4, or 5 are excluded; thus, a recitation of “1 to 5” may support “1 and 3-5, but not 2”, or simply “wherein 2 is not included”. The phrase “at least about x” is intended to embrace both “about x” and “at least x”. It is also understood that where a parameter range is provided, all integers within that range, and tenths thereof, are also provided by the invention. For example, “2 - 5 hours” includes 2 hours, 2.1 hours, 2.2 hours, 2.3 hours etc... up to 5 hours.

[0015] As used herein, the term "combination therapy" means the administration of two or more therapeutic agents to treat a therapeutic condition or disorder described in the present disclosure. Such administration encompasses co-administration of these therapeutic agents in a substantially simultaneous manner, such as in a single dosage form having a fixed ratio of active ingredients or in multiple dosage forms, such as separate capsules for each active ingredient. In addition, such administration also encompasses use of each type of therapeutic agent in a sequential manner. In either case, the treatment regimen will provide beneficial effects of the drug combination in treating the conditions or disorders described herein.

[0016] As used herein, the phrase "therapeutically effective" is intended to qualify the amount of active ingredients used in the treating a disease or disorder or on the effecting of a clinical endpoint.

[0017] As used herein, the term “therapeutically acceptable” refers to those compounds (or salts, prodrugs, tautomers, zwitterionic forms, etc.) suitable for use in contact with the tissues of patients without undue toxicity, irritation, and allergic response, are commensurate with a reasonable benefit / risk ratio, and are effective for their intended use.

[0018] As used herein, reference to "treatment" of a patient is intended to include prophylaxis. Treatment may also be pre-emptive in nature, i.e., it may include prevention of disease. Prevention of a disease may involve complete protection from disease, for example as in the case of prevention of infection with a pathogen or may involve prevention of disease progression. For example, prevention of a disease may not mean complete foreclosure of anyeffect related to the diseases at any level, but instead may mean prevention of the symptoms of a disease to a clinically significant or detectable level. Prevention of diseases may also mean prevention of progression of a disease to a later stage of the disease. Treatment also includes the reduction or amelioration of one or more symptoms of a disease or condition.

[0019] As used herein, the term “patient” is generally synonymous with the term “subject” and includes all mammals including humans. Examples of patients include humans, livestock such as cows, goats, sheep, pigs, and rabbits, and companion animals such as dogs, cats, rabbits, and horses. Preferably, the patient is a human.

[0020] As used herein, the term "prodrug" refers to a compound that is made more active in vivo. Certain compounds disclosed herein may also exist as prodrugs. Prodrugs of the compounds described herein are structurally modified forms of the compound that readily undergo chemical changes under physiological conditions to provide the compound. Additionally, prodrugs can be converted to the compound by chemical or biochemical methods in an ex-vivo environment. For example, prodrugs can be slowly converted to a compound when placed in a transdermal patch reservoir with a suitable enzyme or chemical reagent. Prodrugs are often useful because, in some situations, they may be easier to administer than the compound, or parent drug. They may, for instance, be bioavailable by oral administration whereas the parent drug is not. The prodrug may also have improved solubility in pharmaceutical compositions over the parent drug. A wide variety of prodrug derivatives are known in the art, such as those that rely on hydrolytic cleavage or oxidative activation of the prodrug. An example, without limitation, of a prodrug would be a compound which is administered as an ester (the "prodrug"), but then is metabolically hydrolyzed to the carboxylic acid, the active entity. Additional examples include peptidyl derivatives of a compound.

[0021] As used herein, the term “xanomeline” refers to the chemical compound pyridine, 3-[4- (hexyloxy)-l,2,5-thiadiazol-3-yl]-l,2,5,6-tetrahydro-l-methyl-, or a pharmaceutically acceptable salt thereof. Suitable salts include those formed with both organic and inorganic acids. Such acid addition salts will normally be pharmaceutically acceptable. However, salts of non-pharmaceutically acceptable salts may be of utility in the preparation and purification of the compound in question. Basic addition salts may also be formed and be pharmaceutically acceptable.

[0022] The chemical compounds described herein according to the invention are also intended to include such compounds wherein the molecular structures include isotopes of carbon, hydrogen and nitrogen atoms occurring on those structures. Isotopes include those atoms having the same atomic number but different mass numbers. For example, isotopes of hydrogen include deuterium. Isotopes of carbon include13C. Isotopes of nitrogen include15N. Accordingly, within the chemical structure of any chemical compound taught in this application as suitable for the formulations disclosed herein:• any hydrogen atom or group of hydrogen atoms, could suitably be replaced by an isotope of hydrogen, e.g., deuterium;• any carbon atom or group of carbon atoms, could suitably be replaced by an isotope of carbon, e.g.,13C; and• any nitrogen atom or group of nitrogen atoms, could suitably be replaced by an isotope of nitrogen, e.g.,15N.

[0023] As used herein, the term “pharmaceutically acceptable salt” refers to salts or zwitterionic forms of the compounds disclosed herein which are water or oil- soluble or dispersible and pharmaceutically acceptable. The salts can be prepared during the final isolation and purification of the compounds or separately by reacting the appropriate compound in the form of the free base with a suitable acid. Representative acid addition salts include acetate, adipate, alginate, L-ascorbate, aspartate, benzoate, benzenesulfonate (besylate), bisulfate, butyrate, camphorate, camphorsulfonate, citrate, digluconate, formate, fumarate, gentisate, glutarate, glycerophosphate, glycolate, hemisulfate, heptanoate, hexanoate, hippurate, hydrochloride, hydrobromide, hydroiodide, 2-hydroxyethansulfonate (isethionate), lactate, maleate, malonate, DL-mandelate, mesitylenesulfonate, methanesulfonate, naphthylenesulfonate, nicotinate, 2- naphthalenesulfonate, oxalate, pamoate, pectinate, persulfate, 3-phenylproprionate, phosphonate, picrate, pivalate, propionate, pyroglutamate, succinate, sulfonate, tartrate, L- tartrate, trichloroacetate, trifluoroacetate, phosphate, glutamate, bicarbonate, paratoluenesulfonate (p-tosylate), and undecanoate. Basic addition salts can be prepared during the final isolation and purification of the compounds by reacting a carboxy group with a suitable base such as the hydroxide, carbonate, or bicarbonate of a metal cation or with ammonia or an organic primary, secondary, or tertiary amine. The cations of pharmaceutically acceptable salts include lithium, sodium, potassium, calcium, magnesium, and aluminum, as well as nontoxic quaternary amine cations such as ammonium, tetramethylammonium, tetraethylammonium, methylamine, dimethylamine, trimethylamine, triethylamine, diethylamine, ethylamine, tributylamine, pyridine, N,N-dimethylaniline, N-methylpiperidine, N-methylmorpholine, dicyclohexylamine, procaine, dibenzylamine, N,N-dibenzylphenethylamine, 1 -ephenamine, and N,N'-dibenzylethylenediamine. Other representative organic amines useful for the formation of base addition salts include ethylenediamine, ethanolamine, diethanolamine, piperidine, and piperazine. In one embodiment of the invention, the pharmaceutically acceptable salt of xanomeline is the tartrate salt. In one embodiment of the invention, the tartrate salt of xanomeline is the (2R, 3R) tartrate.

[0024] Xanomeline is a functionally selective M1 / M4 agonist that has shown a promising therapeutic profile in preclinical and clinical trials. The carbon-hydrogen bonds of xanomeline contain a naturally occurring distribution of hydrogen isotopes, namely 1H or protium (about 99.9844%),2H or deuterium (about 0.0156%), and3H or tritium (in the range between about 0.5 and 67 tritium atoms per 1018 protium atoms). Increased levels of deuterium incorporation may produce a detectable Kinetic Isotope Effect (KIE) that could affect the pharmacokinetic, pharmacologic and / or toxicologic profiles of such muscarinic agonists in comparison with the compound having naturally occurring levels of deuterium.

[0025] To eliminate foreign substances, such as therapeutic agents, from its circulation system, the animal body expresses various enzymes, such as the cytochrome P450 enzymes or CYPs, esterases, proteases, reductases, dehydrogenases, and monoamine oxidases, to react with and convert these foreign substances to more polar intermediates or metabolites for renal excretion. Some of the most common metabolic reactions of pharmaceutical compounds involve the oxidation of a carbon-hydrogen (C-H) bond to either a carbon-oxygen (C-O) or carbon-carbon (C-C) pi-bond. The resultant metabolites may be stable or unstable under physiological conditions, and can have substantially different pharmacokinetic, pharmacodynamic, and acute and long-term toxicity profiles relative to the parent compounds. For most drugs, such oxidations are generally rapid and ultimately lead to administration of multiple or high daily doses.

[0026] Xanomeline is likely metabolized in humans by liver enzymes. Other sites on the molecule may also undergo transformations leading to metabolites with as-yet-unknown pharmacology / toxicology. Limiting the production of these metabolites has the potential to decrease the danger of the administration of the drug and may even allow decreased dosages with yet comparable efficacy and improved safety profiles, both locally and systemically. All these transformations can occur through polymorphically-expressed enzymes, which exacerbate the interpatient variability. For the foregoing reasons, there is a strong likelihood that a longer half-life medicine will diminish these problems with greater safety and cost savings.

[0027] The present invention relates to combinations of xanomeline and a CYP2D6 inhibitor and to pharmaceutical compositions suitable for oral administration thereof.

[0028] As used herein, the term “CYP2D6 inhibitor” refers to a drug and compound which inhibits or antagonizes the biosynthesis or actions of cytochrome P-450 CYP2D6 such that, when administered together with orally administered xanomeline, increases xanomeline’s AUC to a level at least 3 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor. As used herein, the term “CYP2D6 inhibitor” shall not include the molecules darifenacin and / or rolapitant. In one embodiment of the invention, the CYP2D6 inhibitor does not substantially cross the blood-brain-barrier (BBB). In another embodiment of the invention, the CYP2D6 does cross the blood-brain-barrier (BBB). In one embodiment of the invention, the CYP2D6 does cross the blood-brain-barrier (BBB) but is not pharmacologically active centrally and, beyond raising central xanomeline exposure levels,neither impacts nor interferes with xanomeline’s central pharmacological activity. In another embodiment of the invention, the CYP2D6 does cross the blood-brain-barrier (BBB) and provides complementary central pharmacological activity to xanomeline.

[0029] Examples of drugs described as potentially inhibiting CYP2D6 include fluoxetine, paroxetine, mirabegron, quinidine, buproprion, amiodarone, fluvoxamine, venlafaxine, duloxetine, ritonavir, thioridazine, cinacalcet, clomipramine, diphenhydramine, clozapine, celecoxib, delavirdine, tranylcypromine, terbinafine, sertraline, methotrimeprazine, clemastine, cocaine, methadone, ticlopidine, chloroquine, tipranavir, dronedarone, isoniazid, lumefantrine, nilotinib, cholecalciferol, indinavir, ziprasidone, abiraterone, cobicistat, clobazam, panobinostat, rucaparib, midostaurin, midodrine, manidipine, pitolisant, curcumin, risperidone, ranitidine, pindolol, loratadine, nortriptyline, propafenone, propranolol, imatinib, amlodipine, felodipine, omeprazole, oxybutynin, primaquine, selegiline, methimazole, thiothixene, verapamil, vinblastine, vinorelbine, temsirolimus, rabeprazole, vilazodone, deramciclane, peginterferon alfa-2b, entacapone, ospemifene, phenylbutyric acid, sulconazole, glycerol, phenylbutyrate, rhein, escitalopram, buprenorphine, asunaprevir, amitriptyline, impramine, dosulepine, desipramine, verumafenib, ritanserin, fusidic acid, lercanidipine, perhexiline, everolimus, citalopram, cimetidine, metoprolol, clotrimazole, quinine, ketoconazole, nevirapine, lidocaine, hydroxyzine, fenfluramine, moclobemide, reboxetine, lansoprazole, doxepin, fluphenazine, dextropropoxyphene, tamoxifen, perphenazine, chlorpheniramine, acebutolol, terfenadine, amodiaquine, azelastine, miconazole, proguanil, nefazodone, dexfenfluramine, halofantrine, rotigotine, atorvastatin, cerivastatin, tripelennamine, sparteine, mibefradil, pipotiazine, etoricoxib, biperiden, cyclosporine, cisapride, dimethyl sulfoxide, efavirenz, epinastine, hydroxyurea, hydroxychloroquine, labetalol, mepyramine, mifepristone, nicotinamide, niacin, oxamniquine, oxprenolol, rosiglitazone, saquinavir, sulfaphenazole, tegaserod, sorafenib, bicalutamide, asenapine, dexmedetomidine, indisulam, naloxegol, oxymetholone, stiripentol, vernakalant, enasidenib, artenimol, melprerone, levomepromazine, isavuconazole, phenelzine, safinamide, iproniazid, levnatinib, rilpivirine, gefitinib, lomustine, diacerein, darunavir, abemaciclib, acomitinib, St. John’s Wort, rifamycin, triclabendazole, orphenadrine, dosorubicin, dexchlorpheniramine, mizolastine, trazodone, clinafloxacin, desvenlafaxine, haloperidol, amoxapine, nifendipine, pimozide, nelfinavir, bepridil, oritavancin, cannabidiol, curcumin sulfate, nabiximols, ranolazine, nicardipine, lorcaserin, eliglustat, pazopanib, flecainide, lasmiditan, elexacaftor, ubrogepant, osilodrostat, fedratinib, methylene blue, clofazimine, clascoterone, berotralstat, tirbanibulin, zafirlukast, menadione, ethambutol, ropeginteferon alfa-2b, viloxazine, brincidofovir, belumosudil, fexinidazole, sotagliflozin, quercetin, cannabinol, cariprazine, pirfenidone, telotristat ethyl, cobimetinib, resveratrol, adagrasib, pirtobrutinib, bardenafil, rizatriptan, tezacaftor, encorafenib, isavuconazonium, mavorixafor and sofpironium.

[0030] As used herein, the term “does not substantially cross the blood-brain-barrier” can be used interchangeably with the term “non-CNS penetrant” and means that most, almost all, or all of the amount of the CYP2D6 inhibitor administered to the subject does not cross the blood brain barrier. For example, less than 25 percent, less than 20 percent, less than 15 percent, less than 10 percent, less than 5, less than 3 percent, or less than 1 percent of the amount of the CYP2D6 inhibitor administered does not cross the blood brain barrier. Methods of determining whether a molecule crosses the blood brain barrier are known in the art.

[0031] As used herein, the term “does cross the blood-brain-barrier” can be used interchangeably with the term “CNS penetrant” and means that most, almost all, or all of the amount of the CYP2D6 inhibitor administered to the subject does cross the blood brain barrier. For example, more than 25 percent, more than 30 percent, more than 40 percent, more than 50 percent, more than 60 percent, more than 70 percent, more than 80 percent, more than 90 percent, more than 95 percent, more than 97 percent or more than 99 percent of the amount of the CYP2D6 inhibitor administered does cross the blood brain barrier.

[0032] As used herein, the term “AUC” shall refer to the area under the plasma concentration / time curve. In one embodiment of the invention, the AUC can refer to the area under the plasma concentration / time curve from time 0 to the last quantifiable concentration. In another embodiment of the invention, the AUC can refer to the area under the plasma concentration / time curve from time 0 until the extrapolated concentration at infinity. In another embodiment of the invention, the AUC can refer to the area under the plasma concentration / time curve over the steady state dosing interval. In another embodiment of the invention, the AUC can refer to the area under the plasma concentration / time curve from time 0 until 2 hours, until 3 hours, until 4 hours, until 5 hours, until 6 hours, until 7 hours, until 8 hours, until 9 hours, until 10 hours, until 11 hours, until 12 hours, until 13 hours, until 14 hours, until 15 hours, until 16 hours, until 17 hours, until 18 hours, until 19 hours, until 20 hours, until 21 hours, until 22 hours, until 23 hours, until 24 hours, until 30 hours or until 36 hours.

[0033] In one embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 3 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 3 -fold, at least 4-fold, at least 5-fold, at least 6-fold, at least 7-fold, at least 8-fold, at least 9-fold, at least 10-fold, at least 11- fold, at least 12-fold, at least 13-fold, at least 14-fold, at least 15-fold, at least 16-fold, at least 17-fold, at least 18-fold, at least 19-fold, at least 20-fold, at least 21-fold, at least 22-fold, at least 23-fold, at least 24-fold or at least 25-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor or any range within the aforementioned values.

[0034] In one embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 300% more than the level which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 300% more than the level, at least 400% more than the level, at least 500% more than the level, 600% more than the level, 700% more than the level, 800% more than the level, 900% more than the level, 1000% more than the level, 1100% more than the level, 1200% more than the level, 1300% more than the level, 1400% more than the level, 1500% more than the level, 1600% more than the level, 1700% more than the level, 1800% more than the level, 1900% more than the level, 2000% more than the level, 2100% more than the level, 2200% more than the level, 2300% more than the level, 2400% more than the level or 2500% more than the level which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor or any range within the aforementioned values.

[0035] In one embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 3 -fold that which would be achieved by orally administering the same amount of xanomeline without the CYP2D6 inhibitor. In one embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 3-fold that which would be achieved by orally administering the same amount of xanomeline without the CYP2D6 inhibitor following a single concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 3 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 1 day’s concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 2 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 3 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 3 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 3 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 4 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 5 days’ concomitant administration of theCYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’ s AUC to a level at least 3 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 6 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’ s AUC to a level at least 3 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 7 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 8 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 3 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 9 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 3 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 10 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 11 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 3 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 12 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 3 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 13 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 14 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 3 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 15 days’ concomitant administration of the CYP2D6 inhibitor together withxanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 3 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 16 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 17 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 3 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 18 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 3 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 19 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 20 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 3 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 21 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline.

[0036] In one embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 4-fold that which would be achieved by orally administering the same amount of xanomeline without the CYP2D6 inhibitor. In one embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 4-fold that which would be achieved by orally administering the same amount of xanomeline without the CYP2D6 inhibitor following a single concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 1 day’s concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 2 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, theCYP2D6 inhibitor increases xanomeline’s AUC to a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 3 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 4 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 5 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 6 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 7 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 8 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 9 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 10 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 11 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 12 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increasesxanomeline’s AUC to a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 13 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 14 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 15 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 16 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 17 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 18 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 19 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 20 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 21 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline.

[0037] In one embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 5 -fold that which would be achieved by orally administering the same amount of xanomeline without the CYP2D6 inhibitor. In one embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 5-fold that which would be achievedby orally administering the same amount of xanomeline without the CYP2D6 inhibitor following a single concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’ s AUC to a level at least 5 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 1 day’s concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 2 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 5 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 3 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 5 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 4 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 5 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 5 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 6 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 5 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 7 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 8 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 5 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 9 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 5 -fold that which would be achieved by administering thesame amount of xanomeline without the CYP2D6 inhibitor following at least 10 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 11 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 5 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 12 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 5 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 13 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 14 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 5 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 15 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 5 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 16 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 17 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 5 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 18 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 5 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 19 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 5-fold that which would be achieved by administering the same amount of xanomelinewithout the CYP2D6 inhibitor following at least 20 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’ s AUC to a level at least 5 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 21 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline.

[0038] In one embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 3 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following the oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 1 day’s concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 3 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 2 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 3 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 3 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 4 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 3 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 5 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 6 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 3 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 7 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 3 -fold that which would be achieved by administering thesame amount of xanomeline without the CYP2D6 inhibitor following at least 8 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 9 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 3 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 10 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 3 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 11 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 12 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 3 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 13 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 3 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 14 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 15 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 3 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 16 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 3 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 17 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 3-fold that which would be achieved by administering the same amount of xanomelinewithout the CYP2D6 inhibitor following at least 18 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’ s AUC to a level at least 3 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 19 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’ s AUC to a level at least 3 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 20 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 21 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline.

[0039] In one embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following the oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 1 day’s concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 2 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 3 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 4 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 5 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 4-fold that which would be achieved by administering the same amount of xanomelinewithout the CYP2D6 inhibitor following at least 6 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’ s AUC to a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 7 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’ s AUC to a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 8 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 9 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 10 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 11 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 12 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 13 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 14 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 15 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitorfollowing at least 16 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 17 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 18 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 19 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 20 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 21 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline.

[0040] In one embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 5 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following the oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 1 day’s concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 5 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 2 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 3 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 5 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitorfollowing at least 4 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 5 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 5 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 6 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 5 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 7 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 5 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 8 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 9 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 5 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 10 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 5 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 11 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 12 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 5 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 13 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 5 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 14 days’concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 15 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 5 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 16 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 5 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 17 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 18 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 5 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 19 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 5 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 20 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s AUC to a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 21 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline.

[0041] In one embodiment of the invention, the CYP2D6 inhibitor decreases the AUC of one or more xanomeline metabolites at least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor. In one embodiment of the invention, the CYP2D6 inhibitor decreases the AUC of one or more xanomeline metabolites to a level at least 10%, at least 20%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95% or at least 100% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor or any range within the aforementioned values. In one embodiment of the invention, the AUC of one or more xanomeline metabolitesfollowing administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor.

[0042] As used herein, the term “xanomeline metabolites” shall refer to any know metabolite including but not limited to the metabolites identified in the U.S. Food and Drug Administration's ("U.S. FDA") Integrated Review document for New Drug Application No. 216158 - COBENFY® (xanomeline tartrate and trospium chloride) dated September 26, 2024 and particularly the metabolites identified in Figure 11, p. 154 of the Integrated Review document, the contents of which are incorporated herein by reference.

[0043] In one embodiment of the invention, xanomeline metabolites comprises the main metabolites formed following oral xanomeline administration to a human subject. In one embodiment of the invention, xanomeline metabolites comprises the S5_l metabolite of xanomeline. In another embodiment of the invention, xanomeline metabolites comprises the S5_3 metabolite of xanomeline. In another embodiment of the invention, xanomeline metabolites comprises the S5_20 metabolite of xanomeline. In another embodiment of the invention, xanomeline metabolites comprises the S5_26 metabolite of xanomeline.

[0044] In one embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC at least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor. In one embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC at least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following a single concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC at least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 1 day’s concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC at least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 2 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC at least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 3 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC at least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 4 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In anotherembodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC at least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 5 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC at least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 6 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC at least 10% which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 7 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC at least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 8 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC at least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 9 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC at least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 10 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC at least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 11 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC at least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 12 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC at least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 13 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC at least 10% that which would be achieved by administering the same amount ofxanomeline without the CYP2D6 inhibitor following at least 14 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC at least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 15 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC at least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 16 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC at least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 17 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC at least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 18 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC at least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 19 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC at least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 20 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC at least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 21 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline.

[0045] In one embodiment of the invention, the AUC of one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6. In one embodiment of the invention, the AUC of one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following a single concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the AUCof one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 1 day’s concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the AUC of one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 2 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the AUC of one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 3 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the AUC of one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 4 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the AUC of one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 5 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the AUC of one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 6 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the AUC of one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 7 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the AUC of one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 8 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the AUC of one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 9 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the AUC of one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6following at least 10 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the AUC of one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 11 days’ concomitant administration of the C YP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the AUC of one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 12 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the AUC of one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 13 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the AUC of one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 14 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the AUC of one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 15 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the AUC of one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 16 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the AUC of one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 17 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the AUC of one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 18 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the AUC of one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 19 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the AUC of one or more of the xanomeline metabolites followingadministration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 20 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the AUC of one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 21 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline.

[0046] In one embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC at least 10% that which would be achieved by orally administering the same amount of xanomeline without the CYP2D6 inhibitor. In one embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC at least 10% that which would be achieved by orally administering the same amount of xanomeline without the CYP2D6 inhibitor following a single concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC at least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 1 day’s concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC at least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 2 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC at least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 3 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC at least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 4 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC at least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 5 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC at least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 6 days’ concomitant oraladministration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC at least 10% which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 7 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC at least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 8 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC at least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 9 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC at least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 10 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC at least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 11 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC at least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 12 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC at least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 13 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC at least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 14 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC at least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 15 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’AUC at least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 16 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC at least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 17 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC at least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 18 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC at least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 19 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC at least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 20 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC at least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 21 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline.

[0047] In one embodiment of the invention, the AUC of one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by orally administering the same amount of xanomeline without the CYP2D6. In one embodiment of the invention, the AUC of one or more xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following a single concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the AUC of one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 1 day’s concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the AUC of one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 2 days’ concomitant oral administration of the CYP2D6 inhibitortogether with xanomeline. In another embodiment of the invention, the AUC of one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 3 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the AUC of one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 4 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the AUC of one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 5 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the AUC of one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 6 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the AUC of one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 7 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the AUC of one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 8 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the AUC of one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 9 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the AUC of one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 10 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the AUC of one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 11 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the AUC of one or more of thexanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 12 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the AUC of one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 13 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the AUC of one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 14 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the AUC of one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 15 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the AUC of one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 16 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the AUC of one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 17 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the AUC of one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 18 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the AUC of one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 19 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the AUC of one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 20 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the AUC of one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same asthat achieved by administering the same amount of xanomeline without the CYP2D6 following at least 21 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline.

[0048] As used herein, the term “Cmax” shall refer to the mean (average) observed maximum plasma concentration assayed. In one embodiment of the invention, the Cmaxshall be assayed following any single administration. In one embodiment of the invention, the Cmaxshall be assayed at steady-state. In some embodiments, the method disclosed herein further comprises measuring plasma levels in the patient.

[0049] In one embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’ s Cmaxto a level at least 3 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 3-fold, at least 4-fold, at least 5-fold, at least 6-fold, at least 7-fold, at least 8-fold, at least 9-fold, at least 10-fold, at least 11- fold, at least 12-fold, at least 13-fold, at least 14-fold, at least 15-fold, at least 16-fold, at least 17-fold, at least 18-fold, at least 19-fold, at least 20-fold, at least 21-fold, at least 22-fold, at least 23-fold, at least 24-fold or at least 25-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor or any range within the aforementioned values.

[0050] In one embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 300% more than the level which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 300% more than the level, at least 400% more than the level, at least 500% more than the level, 600% more than the level, 700% more than the level, 800% more than the level, 900% more than the level, 1000% more than the level, 1100% more than the level, 1200% more than the level, 1300% more than the level, 1400% more than the level, 1500% more than the level, 1600% more than the level, 1700% more than the level, 1800% more than the level, 1900% more than the level, 2000% more than the level, 2100% more than the level, 2200% more than the level, 2300% more than the level, 2400% more than the level or 2500% more than the level which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor or any range within the aforementioned values.

[0051] In one embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 3 -fold that which would be achieved by orally administering the same amount of xanomeline without the CYP2D6 inhibitor. In one embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 3-fold that which would be achieved by orally administering the same amount of xanomeline without the CYP2D6 inhibitor following a single concomitant administration of the CYP2D6 inhibitor together with xanomeline. Inanother embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 3 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 1 day’s concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 2 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 3 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 3 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 4 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 5 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 6 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 3 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 7 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 8 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 9 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 3 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 10 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment ofthe invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 11 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 12 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 3 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 13 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 14 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 15 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 3 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 16 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 17 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 18 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 3 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 19 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 20 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6inhibitor increases xanomeline’s Cmaxto a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 21 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline.

[0052] In one embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 4-fold that which would be achieved by orally administering the same amount of xanomeline without the CYP2D6 inhibitor. In one embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 4-fold that which would be achieved by orally administering the same amount of xanomeline without the CYP2D6 inhibitor following a single concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 1 day’s concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 2 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 3 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 4 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 5 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 6 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 7 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without theCYP2D6 inhibitor following at least 8 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 9 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 10 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 11 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 12 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 13 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 14 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 15 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 16 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 17 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least18 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 19 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 20 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 21 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline.

[0053] In one embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 5 -fold that which would be achieved by orally administering the same amount of xanomeline without the CYP2D6 inhibitor. In one embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 5-fold that which would be achieved by orally administering the same amount of xanomeline without the CYP2D6 inhibitor following a single concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 5 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 1 day’s concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 2 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 3 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 5 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 4 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 5 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6inhibitor increases xanomeline’s Cmaxto a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 6 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 5 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 7 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 8 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 9 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 5 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 10 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 11 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 12 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 5 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 13 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 14 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 15 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto alevel at least 5 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 16 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 17 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 18 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 5 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 19 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 20 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 21 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline.

[0054] In one embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 3 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following the oral administration of the CYP2D6 inhibitor together with xanomeline. In one embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 3 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following a single concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 1 day’s concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 2 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 3 -fold that which would be achieved by administering thesame amount of xanomeline without the CYP2D6 inhibitor following at least 3 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmax to a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 4 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmax to a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 5 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 3 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 6 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmax to a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 7 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmax to a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 8 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 3 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 9 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmax to a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 10 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmax to a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 11 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 3 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 12 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmax to a level at least 3-fold that which would be achieved by administering the same amount of xanomelinewithout the CYP2D6 inhibitor following at least 13 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 14 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 3 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 15 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 16 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 17 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 3 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 18 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 19 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 20 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 3 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 21 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline.

[0055] In one embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following the oral administration of the CYP2D6 inhibitor together with xanomeline. In one embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following a singleconcomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 1 day’s concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 2 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 3 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 4 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 5 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 6 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 7 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 8 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 9 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 10 days’ concomitant oral administration ofthe CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 11 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 12 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 13 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 14 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 15 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 16 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 17 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 18 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 19 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 20 days’ concomitant oral administration of the CYP2D6 inhibitor togetherwith xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 21 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline.

[0056] In one embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 5 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following the oral administration of the CYP2D6 inhibitor together with xanomeline. In one embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 5 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following a single concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 1 day’s concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 2 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 5 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 3 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 4 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 5 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 5 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 6 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 7 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, theCYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 8 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 5 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 9 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 10 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 11 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 5 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 12 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 13 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 14 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 5 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 15 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 16 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 17 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increasesxanomeline’s Cmaxto a level at least 5 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 18 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 19 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 20 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases xanomeline’s Cmaxto a level at least 5 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 21 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline.

[0057] In one embodiment of the invention, the CYP2D6 inhibitor decreases the Cmaxof one or more xanomeline metabolites at least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor. In one embodiment of the invention, the C YP2D6 inhibitor decreases the Cmaxof one or more xanomeline metabolites to a level at least 10%, at least 20%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95% or at least 100% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor or any range within the aforementioned values. In one embodiment of the invention, the Cmaxof one or more xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor.

[0058] In one embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ Cmaxat least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor. In one embodiment of the invention, the C YP2D6 inhibitor decreases one or more of the xanomeline metabolites’ Cmaxat least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following a single concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ Cmaxat least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 1 day’s concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ Cmaxat least 10% that which would beachieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 2 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ Cmaxat least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 3 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ Cmaxat least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 4 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ Cmaxat least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 5 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ Cmaxat least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 6 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ Cmaxat least 10% which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 7 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ Cmaxat least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 8 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ Cmaxat least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 9 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ Cmaxat least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 10 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ Cmaxat least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 11 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In anotherembodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ Cmaxat least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 12 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ Cmaxat least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 13 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ Cmaxat least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 14 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ Cmaxat least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 15 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ Cmaxat least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 16 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ Cmaxat least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 17 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ Cmaxat least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 18 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ Cmaxat least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 19 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ Cmaxat least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 20 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ Cmaxat least 10% that which would be achieved by administering the same amount of xanomeline without theCYP2D6 inhibitor following at least 21 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline.

[0059] In one embodiment of the invention, the Cmaxof one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6. In one embodiment of the invention, the Cmaxof one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following a single concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the Cmaxof one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 1 day’s concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the Cmaxof one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 2 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the Cmaxof one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 3 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the Cmaxof one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 4 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the Cmaxof one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 5 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the Cmaxof one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 6 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the Cmaxof one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 7 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the Cmaxof one or more of the xanomeline metabolites following administration of the CYP2D6inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 8 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the Cmax of one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 9 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the Cmax of one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 10 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the Cmaxof one or more of the xanomeline metabolites following administration of the C YP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 11 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the Cmax of one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 12 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the Cmax of one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 13 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the Cmax of one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 14 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the Cmax of one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 15 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the Cmax of one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 16 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the Cmax of one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 17 days’ concomitant administration of the CYP2D6 inhibitor together withxanomeline. In another embodiment of the invention, the Cmaxof one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 18 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the Cmaxof one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 19 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the Cmaxof one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 20 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the Cmaxof one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 21 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline.

[0060] In one embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ Cmaxat least 10% that which would be achieved by orally administering the same amount of xanomeline without the CYP2D6 inhibitor. In one embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ Cmaxat least 10% that which would be achieved by orally administering the same amount of xanomeline without the CYP2D6 inhibitor following a single concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ Cmaxat least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 1 day’s concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ Cmaxat least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 2 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ Cmaxat least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 3 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ Cmaxat least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitorfollowing at least 4 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ Cmax at least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 5 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ Cmax at least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 6 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ Cmax at least 10% which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 7 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ Cmax at least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 8 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ Cmaxat least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 9 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ Cmax at least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 10 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ Cmax at least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 11 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ Cmax at least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 12 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ Cmax at least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 13 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomelinemetabolites’ Cmaxat least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 14 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ Cmaxat least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 15 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ Cmaxat least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 16 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ Cmaxat least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 17 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ Cmaxat least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 18 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ Cmaxat least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 19 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ Cmaxat least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 20 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ Cmaxat least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 21 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline.

[0061] In one embodiment of the invention, the Cmaxof one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by orally administering the same amount of xanomeline without the CYP2D6. In one embodiment of the invention, the Cmaxof one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following a single concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the Cmaxof one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 1 day’s concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the Cmaxof one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 2 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the Cmaxof one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 3 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the Cmaxof one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 4 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the Cmaxof one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 5 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the Cmaxof one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 6 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the Cmaxof one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 7 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the Cmaxof one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 8 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the Cmaxof one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 9 days’ concomitant oral administration of the C YP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the Cmaxof one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without theCYP2D6 following at least 10 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the Cmaxof one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 11 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the Cmaxof one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 12 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the Cmaxof one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 13 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the Cmaxof one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 14 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the Cmaxof one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 15 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the Cmaxof one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 16 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the Cmaxof one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 17 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the Cmaxof one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 18 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the Cmaxof one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 19 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the Cmaxof one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 20 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the Cmax of one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 21 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline.

[0062] In one embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmax to a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmax to a level at least 3-fold, at least 4-fold, at least 5-fold, at least 6-fold, at least 7-fold, at least 8-fold, at least 9-fold, at least 10-fold, at least 11-fold, at least 12-fold, at least 13-fold, at least 14-fold, at least 15-fold, at least 16-fold, at least 17-fold, at least 18-fold, at least 19-fold, at least 20-fold, at least 21-fold, at least 22-fold, at least 23-fold, at least 24-fold or at least 25-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor or any range within the aforementioned values.

[0063] In one embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmax to a level at least 300% more than the level which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmax to a level at least 300% more than the level, at least 400% more than the level, at least 500% more than the level, 600% more than the level, 700% more than the level, 800% more than the level, 900% more than the level, 1000% more than the level, 1100% more than the level, 1200% more than the level, 1300% more than the level, 1400% more than the level, 1500% more than the level, 1600% more than the level, 1700% more than the level, 1800% more than the level, 1900% more than the level, 2000% more than the level, 2100% more than the level, 2200% more than the level, 2300% more than the level, 2400% more than the level or 2500% more than the level which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor or any range within the aforementioned values.

[0064] In one embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmax to a level at least 3-fold that which would be achieved by orally administering the same amount of xanomeline without the CYP2D6 inhibitor. In one embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmax to a level at least 3-fold that which would be achieved by orally administering the same amount of xanomeline without the CYP2D6 inhibitor following a single concomitant administration of the CYP2D6inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmaxto a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 1 day’s concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmaxto a level at least 3 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 2 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmaxto a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 3 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmaxto a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 4 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmaxto a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 5 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmaxto a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 6 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmaxto a level at least 3 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 7 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmaxto a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 8 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmaxto a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 9 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmaxto a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without theCYP2D6 inhibitor following at least 10 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmax to a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 11 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmax to a level at least 3 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 12 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmaxto a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 13 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmax to a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 14 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmax to a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 15 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmax to a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 16 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmax to a level at least 3 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 17 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmax to a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 18 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmax to a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 19 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmax to a level at least 3-fold thatwhich would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 20 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmax to a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 21 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline.

[0065] In one embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmaxto a level at least 4-fold that which would be achieved by orally administering the same amount of xanomeline without the CYP2D6 inhibitor. In one embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmax to a level at least 4-fold that which would be achieved by orally administering the same amount of xanomeline without the CYP2D6 inhibitor following a single concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmax to a level at least 4- fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 1 day’s concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmax to a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 2 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmax to a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 3 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmax to a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 4 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmax to a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 5 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmax to a level at least 4- fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 6 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases bothxanomeline’s AUC and Cmax to a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 7 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmax to a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 8 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmax to a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 9 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmax to a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 10 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmax to a level at least 4- fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 11 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmax to a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 12 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmax to a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 13 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmax to a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 14 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmax to a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 15 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmax to a level at least 4- fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 16 days’ concomitant administration of the CYP2D6 inhibitor together withxanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’ s AUC and Cmax to a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 17 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmax to a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 18 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmax to a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 19 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmax to a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 20 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmax to a level at least 4- fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 21 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline.

[0066] In one embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmax to a level at least 5-fold that which would be achieved by orally administering the same amount of xanomeline without the CYP2D6 inhibitor. In one embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmax to a level at least 5-fold that which would be achieved by orally administering the same amount of xanomeline without the CYP2D6 inhibitor following a single concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmax to a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 1 day’s concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmax to a level at least 5 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 2 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmax to a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 3 days’ concomitantadministration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmaxto a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 4 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmaxto a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 5 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmaxto a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 6 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmaxto a level at least 5 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 7 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmaxto a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 8 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmaxto a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 9 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmaxto a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 10 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmaxto a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 11 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmaxto a level at least 5 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 12 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmaxto a level at least 5-fold that which would be achieved by administering the sameamount of xanomeline without the CYP2D6 inhibitor following at least 13 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmax to a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 14 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmax to a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 15 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmax to a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 16 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmax to a level at least 5 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 17 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmaxto a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 18 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmax to a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 19 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmax to a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 20 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmax to a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 21 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline.

[0067] In one embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmaxto a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following the oral administration of the CYP2D6 inhibitor together with xanomeline. In one embodiment of the invention, the CYP2D6inhibitor increases both xanomeline’s AUC and Cmaxto a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following a single concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmato a level at least 3 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 1 day’s concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmaxto a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 2 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmax to a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 3 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmax to a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 4 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmato a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 5 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmax to a level at least 3 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 6 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmaxto a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 7 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmax to a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 8 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmato a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 9 days’ concomitant oral administration of the CYP2D6inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmaxto a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 10 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmaxto a level at least 3 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 11 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmaxto a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 12 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmaxto a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 13 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmaxto a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 14 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmaxto a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 15 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmaxto a level at least 3 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 16 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmaxto a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 17 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmaxto a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 18 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmaxto a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without theCYP2D6 inhibitor following at least 19 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmax to a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 20 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmax to a level at least 3 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 21 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline.

[0068] In one embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmaxto a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following the oral administration of the CYP2D6 inhibitor together with xanomeline. In one embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmax to a level at least 4- fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following a single concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmax to a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 1 day’s concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmax to a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 2 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmax to a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 3 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmax to a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 4 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmax to a level at least 4- fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 5 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmax to a level at least 4-fold that which would be achieved byadministering the same amount of xanomeline without the CYP2D6 inhibitor following at least 6 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmax to a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 7 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmax to a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 8 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmax to a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 9 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmax to a level at least 4- fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 10 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmax to a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 11 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmax to a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 12 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmax to a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 13 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmax to a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 14 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmax to a level at least 4- fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 15 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases bothxanomeline’s AUC and Cmaxto a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 16 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmaxto a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 17 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmaxto a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 18 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmaxto a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 19 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmaxto a level at least 4- fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 20 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmaxto a level at least 4-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 21 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline.

[0069] In one embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmaxto a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following the oral administration of the CYP2D6 inhibitor together with xanomeline. In one embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmaxto a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following a single concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmaxto a level at least 5 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 1 day’s concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmaxto a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 2 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodimentof the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmaxto a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 3 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmaxto a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 4 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmaxto a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 5 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmaxto a level at least 5 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 6 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmaxto a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 7 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmaxto a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 8 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmaxto a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 9 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmaxto a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 10 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmaxto a level at least 5 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 11 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmaxto a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 12 days’ concomitantoral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmaxto a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 13 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmaxto a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 14 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmaxto a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 15 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmaxto a level at least 5 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 16 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmaxto a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 17 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmaxto a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 18 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmaxto a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 19 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmaxto a level at least 5-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 20 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor increases both xanomeline’s AUC and Cmaxto a level at least 5 -fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 21 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline.

[0070] In one embodiment of the invention, the CYP2D6 inhibitor decreases both the AUC and the Cmaxof one or more xanomeline metabolites at least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor. In one embodiment of the invention, the CYP2D6 inhibitor decreases both the AUC and the Cmax of one or more xanomeline metabolites to a level at least 10%, at least 20%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95% or at least 100% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor or any range within the aforementioned values. In one embodiment of the invention, both the AUC and the Cmax of one or more xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor.

[0071] In one embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC and Cmax at least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor. In one embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC and Cmax at least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following a single concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC and Cmax at least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 1 day’s concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC and Cmax at least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 2 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC and Cmax at least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 3 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC and Cmax at least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 4 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC and Cmax at least 10% that which would be achieved by administering the same amountof xanomeline without the CYP2D6 inhibitor following at least 5 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC and Cmaxat least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 6 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC and Cmaxat least 10% which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 7 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC and Cmaxat least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 8 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC and Cmaxat least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 9 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC and Cmaxat least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 10 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC and Cmaxat least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 11 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC and Cmaxat least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 12 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC and Cmaxat least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 13 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC and Cmaxat least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 14 days’ concomitantadministration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC and Cmax at least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 15 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC and Cmax at least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 16 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC and Cmax at least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 17 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC and Cmax at least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 18 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC and Cmax at least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 19 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC and Cmax at least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 20 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC and Cmax at least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 21 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline.

[0072] In one embodiment of the invention, both the AUC and the Cmax of one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6. In one embodiment of the invention, both the AUC and the Cmax of one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following a single concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, both the AUC and the Cmax of one or more of the xanomelinemetabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 1 day’s concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, both the AUC and the Cmaxof one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 2 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, both the AUC and the Cmaxof one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 3 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, both the AUC and the Cmaxof one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 4 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, both the AUC and the Cmaxof one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 5 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, both the AUC and the Cmaxof one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 6 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, both the AUC and the Cmaxof one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 7 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, both the AUC and the Cmaxof one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 8 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, both the AUC and the Cmaxof one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 9 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, both the AUC and the Cmaxof one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same asthat achieved by administering the same amount of xanomeline without the CYP2D6 following at least 10 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, both the AUC and the Cmax of one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 11 days’ concomitant administration of the C YP2D6 inhibitor together with xanomeline. In another embodiment of the invention, both the AUC and the Cmax of one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 12 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, both the AUC and the Cmax of one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 13 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, both the AUC and the Cmax of one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 14 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, both the AUC and the Cmax of one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 15 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, both the AUC and the Cmax of one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 16 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, both the AUC and the Cmax of one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 17 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, both the AUC and the Cmax of one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 18 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, both the AUC and the Cmax of one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 followingat least 19 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, both the AUC and the Cmaxof one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 20 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, both the AUC and the Cmaxof one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 21 days’ concomitant administration of the CYP2D6 inhibitor together with xanomeline.

[0073] In one embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC and Cmaxat least 10% that which would be achieved by orally administering the same amount of xanomeline without the CYP2D6 inhibitor. In one embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC and Cmaxat least 10% that which would be achieved by orally administering the same amount of xanomeline without the CYP2D6 inhibitor following a single concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC and Cmaxat least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 1 day’s concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC and Cmaxat least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 2 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC and Cmaxat least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 3 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC and Cmaxat least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 4 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC and Cmaxat least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 5 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’AUC and Cmaxat least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 6 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC and Cmaxat least 10% which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 7 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC and Cmaxat least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 8 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC and Cmaxat least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 9 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC and Cmaxat least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 10 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC and Cmaxat least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 11 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC and Cmaxat least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 12 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC and Cmaxat least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 13 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC and Cmaxat least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 14 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC and Cmaxat least 10% that which would be achieved by administering the same amountof xanomeline without the CYP2D6 inhibitor following at least 15 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC and Cmaxat least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 16 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC and Cmaxat least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 17 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC and Cmaxat least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 18 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC and Cmaxat least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 19 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC and Cmaxat least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 20 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor decreases one or more of the xanomeline metabolites’ AUC and Cmaxat least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor following at least 21 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline.

[0074] In one embodiment of the invention, both the AUC and the Cmaxof one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by orally administering the same amount of xanomeline without the CYP2D6. In one embodiment of the invention, both the AUC and the Cmaxof xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following a single concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, both the AUC and the Cmaxof one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 1 day’s concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. Inanother embodiment of the invention, both the AUC and the Cmaxof one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 2 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, both the AUC and the Cmaxof one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 3 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, both the AUC and the Cmaxof one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 4 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, both the AUC and the Cmaxof one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 5 days’ concomitant oral administration of the C YP2D6 inhibitor together with xanomeline. In another embodiment of the invention, both the AUC and the Cmaxof one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 6 days’ concomitant oral administration of the C YP2D6 inhibitor together with xanomeline. In another embodiment of the invention, both the AUC and the Cmaxof one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 7 days’ concomitant oral administration of the C YP2D6 inhibitor together with xanomeline. In another embodiment of the invention, both the AUC and the Cmaxof one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 8 days’ concomitant oral administration of the C YP2D6 inhibitor together with xanomeline. In another embodiment of the invention, both the AUC and the Cmaxof one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 9 days’ concomitant oral administration of the C YP2D6 inhibitor together with xanomeline. In another embodiment of the invention, both the AUC and the Cmaxof one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 10 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, both theAUC and the Cmaxof one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 11 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, both the AUC and the Cmaxof one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 12 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, both the AUC and the Cmaxof one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 13 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, both the AUC and the Cmaxof one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 14 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, both the AUC and the Cmaxof one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 15 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, both the AUC and the Cmaxof one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 16 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, both the AUC and the Cmaxof one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 17 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, both the AUC and the Cmaxof one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 18 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, both the AUC and the Cmaxof one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 19 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention,both the AUC and the Cmax of one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 20 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline. In another embodiment of the invention, both the AUC and the Cmax of one or more of the xanomeline metabolites following administration of the CYP2D6 inhibitor will be the same as that achieved by administering the same amount of xanomeline without the CYP2D6 following at least 21 days’ concomitant oral administration of the CYP2D6 inhibitor together with xanomeline.

[0075] In one embodiment of the invention, the CYP2D6 inhibitor is co-administered to a subject together with xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor is administered to a subject separately from the xanomeline.

[0076] In one embodiment of the invention, the CYP2D6 inhibitor is administered to a subject at the same dose frequency as xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor is administered to a subject at a different dose frequency to xanomeline. In one embodiment of the invention, the CYP2D6 inhibitor is administered to the subject more frequently than xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor is administered to the subject less frequently than xanomeline.

[0077] Before administering the claimed combinations, patients may have a lead-in period from one to fourteen days or longer, during which lead-in period the CYP2D6 inhibitor is given alone. In one embodiment, the CYP2D6 inhibitor is administered for one or more dose periods before administering xanomeline to accumulate the CYP2D6 inhibitor in the body, or for the CYP2D6 inhibitor to reach or approach steady-state exposure levels. This accumulation, or higher exposure levels of the CYP2D6 inhibitor, increases the blockade of cytochrome P-450 C YP2D6 and reduces the hepatobiliary metabolism of xanomeline potentially allowing for higher plasma exposures from the very first dose. In another embodiment of the invention, the CYP2D6 inhibitor is administered for one or more days before xanomeline.

[0078] In one embodiment of the invention, the CYP2D6 inhibitor is administered to a subject at least 12 hours prior to the first administration of xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor is administered to a subject at least 12 hours, at least 24 hours, at least 36 hours, at least 48 hours, at least 60 hours, at least 72 hours, at least 84 hours, at least 96 hours, at least 108 hours or at least 120 hours prior to the first administration of xanomeline. In another embodiment of the invention, the CYP2D6 inhibitor is first administered to a subject together with the first administration of xanomeline.

[0079] In one embodiment of the invention, the first administration of the CYP2D6 inhibitor is administered to a subject together with the first administration of xanomeline. In such an embodiment, levels of the CYP2D6 inhibitor can reach or approximate steady-state exposure levels over time while also increasing the blockade of cytochrome P-450 CYP2D6. This allowsfor the gradual increase over time in the plasma exposures of xanomeline as it reaches higher steady-state exposures while also increasing tolerability to the drug.

[0080] In one embodiment of the invention, following the first oral administration of xanomeline, the subject is administered the same dose of xanomeline every day. In another embodiment of the invention, following the first oral administration of xanomeline, the subject is administered an increasing dose for at least 3 days. In another embodiment of the invention, following the first oral administration of xanomeline, the subject is administered an increasing dose for at least 4 days. In another embodiment of the invention, following the first oral administration of xanomeline, the subject is administered an increasing dose for at least 5 days. In another embodiment of the invention, following the first oral administration of xanomeline, the subject is administered an increasing dose for at least 6 days. In another embodiment of the invention, following the first oral administration of xanomeline, the subject is administered an increasing dose for at least 7 days. In another embodiment of the invention, following the first oral administration of xanomeline, the subject is administered an increasing dose for at least 8 days. In another embodiment of the invention, following the first oral administration of xanomeline, the subject is administered an increasing dose for at least 9 days. In another embodiment of the invention, following the first oral administration of xanomeline, the subject is administered an increasing dose for at least 10 days. In another embodiment of the invention, following the first oral administration of xanomeline, the subject is administered an increasing dose for at least 11 days. In another embodiment of the invention, following the first oral administration of xanomeline, the subject is administered an increasing dose for at least 12 days. In another embodiment of the invention, following the first oral administration of xanomeline, the subject is administered an increasing dose for at least 13 days. In another embodiment of the invention, following the first oral administration of xanomeline, the subject is administered an increasing dose for at least 14 days. In another embodiment of the invention, following the first oral administration of xanomeline, the subject is administered an increasing dose for at least 15 days. In another embodiment of the invention, following the first oral administration of xanomeline, the subject is administered an increasing dose for at least 16 days. In another embodiment of the invention, following the first oral administration of xanomeline, the subject is administered an increasing dose for at least 17 days. In another embodiment of the invention, following the first oral administration of xanomeline, the subject is administered an increasing dose for at leasl8 days. In another embodiment of the invention, following the first oral administration of xanomeline, the subject is administered an increasing dose for at least 19 days. In another embodiment of the invention, following the first oral administration of xanomeline, the subject is administered an increasing dose for at least 20 days. In another embodiment of the invention, following the first oral administration of xanomeline, the subject is administered an increasing dose for at least 21 days.

[0081] In one embodiment of the invention, following the first oral administration of xanomeline, the dose of xanomeline administered to the subject increases over at least 3 days. In another embodiment of the invention, following the first oral administration of xanomeline, the dose of xanomeline administered to the subject increases over at least 4 days. In another embodiment of the invention, following the first oral administration of xanomeline, the dose of xanomeline administered to the subject increases over at least 5 days. In another embodiment of the invention, following the first oral administration of xanomeline, the dose of xanomeline administered to the subject increases over at least 6 days. In another embodiment of the invention, following the first oral administration of xanomeline, the dose of xanomeline administered to the subject increases over at least 7 days. In another embodiment of the invention, following the first oral administration of xanomeline, the dose of xanomeline administered to the subject increases over at least 8 days. In another embodiment of the invention, following the first oral administration of xanomeline, the dose of xanomeline administered to the subject increases over at least 9 days. In another embodiment of the invention, following the first oral administration of xanomeline, the dose of xanomeline administered to the subject increases over at least 10 days. In another embodiment of the invention, following the first oral administration of xanomeline, the dose of xanomeline administered to the subject increases over at least 11 days. In another embodiment of the invention, following the first oral administration of xanomeline, the dose of xanomeline administered to the subject increases over at least 12 days. In another embodiment of the invention, following the first oral administration of xanomeline, the dose of xanomeline administered to the subject increases over at least 13 days. In another embodiment of the invention, following the first oral administration of xanomeline, the dose of xanomeline administered to the subject increases over at least 14 days. In another embodiment of the invention, following the first oral administration of xanomeline, the dose of xanomeline administered to the subject increases over at least 15 days. In another embodiment of the invention, following the first oral administration of xanomeline, the dose of xanomeline administered to the subject increases over at least 16 days. In another embodiment of the invention, following the first oral administration of xanomeline, the dose of xanomeline administered to the subject increases over at least 17 days. In another embodiment of the invention, following the first oral administration of xanomeline, the dose of xanomeline administered to the subject increases over at least 18 days. In another embodiment of the invention, following the first oral administration of xanomeline, the dose of xanomeline administered to the subject increases over at least 19 days. In another embodiment of the invention, following the first oral administration of xanomeline, the dose of xanomeline administered to the subject increases over at least 20 days. In another embodiment of theinvention, following the first oral administration of xanomeline, the dose of xanomeline administered to the subject increases over at least 21 days.

[0082] In one embodiment of the invention, following the first oral administration of xanomeline, the increase in the xanomeline dose administered to the subject occurs on consecutive days. In another embodiment of the invention, following the first oral administration of xanomeline, the increase in xanomeline dose administered to the subject occurs on intermittent days. In one embodiment of the invention, the intermittent increase in xanomeline dose is after 2 days. In another embodiment of the invention, the intermittent increase in xanomeline dose is after 3 days. In another embodiment of the invention, the intermittent increase in xanomeline dose is after 4 days. In another embodiment of the invention, the intermittent increase in xanomeline dose is after 5 days. In another embodiment of the invention, the intermittent increase in xanomeline dose is after 6 days. In another embodiment of the invention, the intermittent increase in xanomeline dose is after 7 days. In another embodiment of the invention, the intermittent increase in xanomeline dose is after 2 days and after 3 days. In another embodiment of the invention, the intermittent increase in xanomeline dose is after 2 days and after 4 days. In another embodiment of the invention, the intermittent increase in xanomeline dose is after 2 days and after 5 days. In another embodiment of the invention, the intermittent increase in xanomeline dose is after 2 days and after 6 days. In another embodiment of the invention, the intermittent increase in xanomeline dose is after 2 days and after 7 days. In another embodiment of the invention, the intermittent increase in xanomeline dose is after 3 days and after 4 days. In another embodiment of the invention, the intermittent increase in xanomeline dose is after 3 days and after 5 days. In another embodiment of the invention, the intermittent increase in xanomeline dose is after 3 days and after 6 days. In another embodiment of the invention, the intermittent increase in xanomeline dose is after 3 days and after 7 days. In another embodiment of the invention, the intermittent increase in xanomeline dose is after 4 days and after 5 days. In another embodiment of the invention, the intermittent increase in xanomeline dose is after 4 days and after 6 days. In another embodiment of the invention, the intermittent increase in xanomeline dose is after 4 days and after 7 days. In another embodiment of the invention, the intermittent increase in xanomeline dose is after 5 days and after 6 days. In another embodiment of the invention, the intermittent increase in xanomeline dose is after 5 days and after 7 days. In another embodiment of the invention, the intermittent increase in xanomeline dose is after 6 days and after 7 days.

[0083] In one embodiment of the invention, following its first oral administration to a subject, xanomeline is administered the same dose frequency every day. In another embodiment of the invention, following its first oral administration to a subject, xanomeline is administered at an increasing dose frequency for at least 2 days. In another embodiment of the invention, following its first oral administration to a subject, xanomeline is administered every 12 hoursfor at least 3 additional doses. In another embodiment of the invention, following its first oral administration to a subject, xanomeline is administered every 12 hours for at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12 or at least 13 additional doses.

[0084] In one embodiment of the invention, following its first oral administration to a subject, xanomeline is administered every 12 hours for at least 3 additional doses following which it is administered every 24 hours. In another embodiment of the invention, following its first oral administration to a subject, xanomeline is administered every 12 hours for at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12 or at least 13 additional doses following which it is administered every 24 hours. In one embodiment of the invention, following its first oral administration to a subject, xanomeline is administered once every 24 hours, i.e. one daily. In one embodiment of the invention, following its first oral administration to a subject, xanomeline is administered every 12 hours, i.e., twice daily. In one embodiment of the invention, following its first oral administration to a subject, xanomeline is administered every 8 hours, i.e., three-times daily.

[0085] In one embodiment of the invention, the subject is an extensive, i.e., normal, metabolizer of xanomeline. In another embodiment of the invention, the subject is an ultra-rapid metabolizer of xanomeline. In another embodiment of the invention, the subject is an intermediate metabolizer of xanomeline. In another embodiment of the invention, the subject is a poor metabolizer of xanomeline. In another embodiment of the invention, the subject is selected from the group comprising extensive, ultra-rapid, intermediate and poor metabolizers of xanomeline. Methods of determining whether a subject is an extensive, ultra-rapid, intermediate or poor metabolizers of xanomeline are known in the art.

[0086] In one embodiment of the invention, the administration of a CYP2D6 inhibitor corrects a subject’s extensive metabolism of xanomeline so that after at least 3 days of combined administration, the subject metabolizes xanomeline as a poor metabolizer. In one embodiment of the invention, the administration of a CYP2D6 inhibitor corrects the subject’s extensive metabolism of xanomeline so that after at least 3 days, after at least 4 days, after at least 5 days, after at least 6 days, after at least 7 days, after at least 8 days, after at least 9 days or after at least 10 days of combined administration, the subject metabolizes xanomeline as a poor metabolizer.

[0087] In one embodiment of the invention, the administration of a CYP2D6 inhibitor corrects a subject’s ultra-rapid metabolism of xanomeline so that after at least 3 days of combined administration, the subject metabolizes xanomeline as a poor metabolizer. In one embodiment of the invention, the administration of a CYP2D6 inhibitor corrects the subject’s ultra-rapid metabolism of xanomeline so that after at least 3 days, after at least 4 days, after at least 5 days, after at least 6 days, after at least 7 days, after at least 8 days, after at least 9 days or after atleast 10 days of combined administration, the subject metabolizes xanomeline as a poor metabolizer.

[0088] In one embodiment of the invention, the administration of a CYP2D6 inhibitor corrects a subject’s intermediate metabolism of xanomeline so that after at least 3 days of combined administration, the subject metabolizes xanomeline as a poor metabolizer. In one embodiment of the invention, the administration of a CYP2D6 inhibitor corrects the subject’s intermediate metabolism of xanomeline so that after at least 3 days, after at least 4 days, after at least 5 days, after at least 6 days, after at least 7 days, after at least 8 days, after at least 9 days or after at least 10 days of combined administration, the subject metabolizes xanomeline as a poor metabolizer.

[0089] When given the same oral dose of xanomeline, plasma levels of xanomeline are significantly higher in poor metabolizers or intermediate metabolizers as compared to extensive metabolizers of xanomeline. The low plasma concentrations of xanomeline can limit its clinical utility as a single agent for ultra-rapid, extensive metabolizers, and possibly intermediate metabolizers, of xanomeline. A CYP2D6 inhibitor can inhibit the metabolism of xanomeline and can thus improve its therapeutic efficacy. Similarly, a CYP2D6 inhibitor may allow xanomeline to be given less often, such as once a day instead of twice a day, once a day instead of three times a day, once a day instead of four times a day, twice a day instead of three times a day, or twice a day instead of four times a day, without loss of therapeutic efficacy and can allow for lower doses of xanomeline to be administered which still provide the same circulating therapeutic plasma levels of the drug as administered without the inhibitor. This can allow for the reduction in local gastric adverse events, in addition to the reduction in hepatotoxicity.

[0090] In one embodiment of the invention, co-administration of the CYP2D6 inhibitor together with xanomeline can also provide a supplemental therapeutic mechanism of action to treat central nervous system disorders. In one embodiment of the invention, co-administration of the CYP2D6 inhibitor together with xanomeline can also provide symptomatic relief for peripheral muscarinic effects caused by xanomeline.

[0091] The present invention also relates to pharmaceutical compositions comprising combinations of xanomeline and a CYP2D6 inhibitor which are suitable for oral administration.

[0092] The compositions may conveniently be presented in unit dosage form and may be prepared by any of the methods well known in the art of pharmacy. Typically, these methods include the step of bringing into association xanomeline and a CYP2D6 inhibitor, or a pharmaceutically acceptable salt, ester, amide, prodrug or solvate thereof together with a carrier which constitutes one or more accessory ingredients. In general, the compositions are prepared by uniformly and intimately bringing into association the compounds with liquid carriers or finely divided solid carriers or both and then, if necessary, shaping the product into the desired formulation. In another embodiment a first composition comprising xanomeline and at least onepharmaceutically acceptable excipient and a second composition comprising CYP2D6 inhibitor and at least one pharmaceutically acceptable excipient are combined to form a unit dosage form with both the xanomeline and a CYP2D6 inhibitor.

[0093] Pharmaceutical compositions disclosed herein suitable for oral administration may be presented as discrete units such as capsules, cachets or tablets each containing a predetermined amount of the active ingredient; as a powder or granules; as a solution or a suspension in an aqueous liquid or a non-aqueous liquid; or as an oil-in-water liquid emulsion or a water-in-oil liquid emulsion. The compounds may also be presented as a bolus, electuary or paste.

[0094] Pharmaceutical compositions which can be used orally include tablets, push-fit capsules made of gelatin, as well as soft, sealed capsules made of gelatin and a plasticizer, such as glycerol or sorbitol. Tablets may be made by compression or molding, optionally with one or more accessory ingredients. Compressed tablets may be prepared by compressing in a suitable machine the active ingredient in a free-flowing form such as a powder or granules, optionally mixed with binders, inert diluents, or lubricating, surface active or dispersing agents. Molded tablets may be made by molding in a suitable machine a mixture of the powdered compound moistened with an inert liquid diluent. The tablets may optionally be coated or scored and may be formulated to provide slow or controlled release of the active ingredient therein. All formulations for oral administration should be in dosages suitable for such administration. The push-fit capsules can contain the active ingredients in admixture with filler such as lactose, binders such as starches, and / or lubricants such as talc or magnesium stearate and, optionally, stabilizers. In soft capsules, the active compounds may be dissolved or suspended in suitable liquids, such as fatty oils, liquid paraffin, or liquid polyethylene glycols. In addition, stabilizers may be added. Dragee cores are provided with suitable coatings. For this purpose, concentrated sugar solutions may be used, which may optionally contain gum arabic, talc, polyvinyl pyrrolidone, Carbopol gel, polyethylene glycol, and / or titanium dioxide, lacquer solutions, and suitable organic solvents or solvent mixtures. Dyestuffs or pigments may be added to the tablets or dragee coatings for identification or to characterize different combinations of active compound doses. In addition to the ingredients particularly mentioned above, the formulations described above may include other agents conventional in the art having regard to the type of formulation in question, for example those suitable for oral administration may include flavoring agents.

[0095] Preferred unit dosage forms are those containing an effective dose, as herein below recited, or an appropriate fraction thereof, of both xanomeline and the CYP2D6 inhibitor.

[0096] In one embodiment of the invention, the pharmaceutical composition is formulated as an oral dosage form comprising an immediate release formulation. In another embodiment of the invention, the pharmaceutical composition is formulated as an oral dosage form comprising a modified release formulation such as a delayed release formulation or a controlled releaseformulation. In one embodiment of the invention, the xanomeline is formulated as a controlled release formulation and the CYP2D6 inhibitor is formulated as an immediate release formulation. In another embodiment of the invention, the xanomeline is formulated as an immediate release formulation and the CYP2D6 inhibitor is formulated as a controlled release formulation. In one embodiment of the invention, the xanomeline is formulated as an enteric- coated delayed release formulation. In one embodiment of the invention, the xanomeline is coformulated as both an immediate release and enteric-coated delayed release formulation.

[0097] In some aspects, oral dosage forms of the disclosure include xanomeline, i.e., xanomeline as a free base. In other aspects, oral dosage forms of the disclosure include pharmaceutically acceptable salts of xanomeline. As used herein, amounts of xanomeline present in the oral dosage forms of the disclosure refer to amounts of xanomeline free base. For example, in those aspects wherein the oral dosage form comprises xanomeline free base, “50 mg of xanomeline” refers to 50 mg of the xanomeline free base in the oral dosage form. In aspects wherein the oral dosage form comprises a pharmaceutically acceptable salt of xanomeline, such as xanomeline tartrate, “50 mg of xanomeline” refers to 50 mg xanomeline free base, based on 76.7 mg of xanomeline tartrate in the oral dosage form.

[0098] In one embodiment of the invention, the oral dosage form comprises between 10 and 250mg of xanomeline, a CYP2D6 inhibitor and at least one pharmaceutically acceptable carrier. In one embodiment of the invention, the oral dosage form comprises lOmg, llmg, 12mg, 13mg, 14mg, 15mg, 16mg, 17mg, 18mg, 19mg, 20mg, 21mg, 22mg, 23mg, 24mg, 25mg, 26mg, 27mg,28mg, 29mg, 30mg, 31mg, 32mg, 33mg, 34mg, 35mg, 36mg, 37mg, 38mg, 39mg, 40mg,41mg, 42mg, 43mg, 44mg, 45mg, 46mg, 47mg, 48mg, 49mg, 50mg, 51mg, 52mg, 53mg,54mg, 55mg, 56mg, 57mg, 58mg, 59mg, 60mg, 61mg, 62mg, 63mg, 64mg, 65mg, 66mg,67mg, 68mg, 69mg, 70mg, 71mg, 72mg, 73mg, 74mg, 75mg, 76mg, 77mg, 78mg, 79mg,80mg, 81mg, 82mg, 83mg, 84mg, 85mg, 86mg, 87mg, 88mg, 89mg, 90mg, 91mg, 92mg,93mg, 94mg, 95mg, 96mg, 97mg, 98mg, 99mg, lOOmg, lOlmg, 102mg, 103mg, 104mg, 105mg, 106mg, 107mg, 108mg, 109mg, HOmg, lllmg, 112mg, 113mg, 114mg, 115mg,116mg, 117mg, 118mg, 119mg, 120mg, 121mg, 122mg, 123mg, 124mg, 125mg, 126mg,127mg, 128mg, 129mg, 130mg, 131mg, 132mg, 133mg, 134mg, 135mg, 136mg, 137mg,138mg, 139mg, 140mg, 141mg, 142mg, 143mg, 144mg, 145mg, 146mg, 147mg, 148mg,149mg, 150mg, 151mg, 152mg, 153mg, 154mg, 155mg, 156mg, 157mg, 158mg, 159mg,160mg, 161mg, 162mg, 163mg, 164mg, 165mg, 166mg, 167mg, 168mg, 169mg, 170mg,171mg, 172mg, 173mg, 174mg, 175mg, 176mg, 177mg, 178mg, 179mg, 180mg, 181mg,182mg, 183mg, 184mg, 185mg, 186mg, 187mg, 188mg, 189mg, 190mg, 191mg, 192mg,193mg, 194mg, 195mg, 196mg, 197mg, 198mg, 199mg, 200mg, 201mg, 202mg, 203mg,204mg, 205mg, 206mg, 207mg, 208mg, 209mg, 210mg, 211mg, 212mg, 213mg, 214mg,215mg, 216mg, 217mg, 218mg, 219mg, 220mg, 221mg, 222mg, 223mg, 224mg, 225mg,226mg, 227mg, 228mg, 229mg, 230mg, 231mg, 232mg, 233mg, 234mg, 235mg, 236mg, 237mg, 238mg, 239mg, 240mg, 241mg, 242mg, 243mg, 244mg, 245mg, 246mg, 247mg, 248mg, 249mg or 250mg of xanomeline, a CYP2D6 inhibitor and at least one pharmaceutically acceptable carrier. In one embodiment of the invention, the oral dosage form comprises 40mg of xanomeline, a CYP2D6 inhibitor and at least one pharmaceutically acceptable carrier. In another embodiment of the invention, the oral dosage form comprises 50mg of xanomeline, a CYP2D6 inhibitor and at least one pharmaceutically acceptable carrier. In another embodiment of the invention, the oral dosage form comprises 60mg of xanomeline, a CYP2D6 inhibitor and at least one pharmaceutically acceptable carrier. In another embodiment of the invention, the oral dosage form comprises 70mg of xanomeline, a CYP2D6 inhibitor and at least one pharmaceutically acceptable carrier. In another embodiment of the invention, the oral dosage form comprises 80mg of xanomeline, a CYP2D6 inhibitor and at least one pharmaceutically acceptable carrier. In another embodiment of the invention, the oral dosage form comprises 90mg of xanomeline, a CYP2D6 inhibitor and at least one pharmaceutically acceptable carrier. In another embodiment of the invention, the oral dosage form comprises lOOmg of xanomeline, a CYP2D6 inhibitor and at least one pharmaceutically acceptable carrier. In another embodiment of the invention, the oral dosage form comprises 125mg of xanomeline, a CYP2D6 inhibitor and at least one pharmaceutically acceptable carrier. In another embodiment of the invention, the oral dosage form comprises 150mg of xanomeline, a CYP2D6 inhibitor and at least one pharmaceutically acceptable carrier. In another embodiment of the invention, the oral dosage form comprises 175mg of xanomeline, a CYP2D6 inhibitor and at least one pharmaceutically acceptable carrier. In another embodiment of the invention, the oral dosage form comprises 200mg of xanomeline, a CYP2D6 inhibitor and at least one pharmaceutically acceptable carrier. In another embodiment of the invention, the oral dosage form comprises 225mg of xanomeline, a CYP2D6 inhibitor and at least one pharmaceutically acceptable carrier. In another embodiment of the invention, the oral dosage form comprises 250mg of xanomeline, a CYP2D6 inhibitor and at least one pharmaceutically acceptable carrier. In certain embodiments of the invention, the pharmaceutically acceptable carrier comprises cellulose or lactose.

[0099] In one embodiment of the invention, the oral dosage form comprises between 10 and 80mg of xanomeline, a CYP2D6 inhibitor and at least one pharmaceutically acceptable carrier and is suitable for twice or three- times daily administration to a subject. In one embodiment of the invention, the oral dosage form comprises between 65 and 250mg of xanomeline, a CYP2D6 inhibitor and at least one pharmaceutically acceptable carrier and is suitable for once-daily administration to a subject.

[0100] In one embodiment of the invention, the oral dosage form comprises between 10 and 250mg of xanomeline, deramciclane and at least one pharmaceutically acceptable carrier. In oneembodiment of the invention, the oral dosage form comprises lOmg, llmg, 12mg, 13mg, 14mg, 15mg, 16mg, 17mg, 18mg, 19mg, 20mg, 21mg, 22mg, 23mg, 24mg, 25mg, 26mg, 27mg,28mg, 29mg, 30mg, 31mg, 32mg, 33mg, 34mg, 35mg, 36mg, 37mg, 38mg, 39mg, 40mg,41mg, 42mg, 43mg, 44mg, 45mg, 46mg, 47mg, 48mg, 49mg, 50mg, 51mg, 52mg, 53mg,54mg, 55mg, 56mg, 57mg, 58mg, 59mg, 60mg, 61mg, 62mg, 63mg, 64mg, 65mg, 66mg,67mg, 68mg, 69mg, 70mg, 71mg, 72mg, 73mg, 74mg, 75mg, 76mg, 77mg, 78mg, 79mg,80mg, 81mg, 82mg, 83mg, 84mg, 85mg, 86mg, 87mg, 88mg, 89mg, 90mg, 91mg, 92mg, 93mg, 94mg, 95mg, 96mg, 97mg, 98mg, 99mg, lOOmg, lOlmg, 102mg, 103mg, 104mg, 105mg, 106mg, 107mg, 108mg, 109mg, HOmg, lllmg, 112mg, 113mg, 114mg, 115mg,116mg, 117mg, 118mg, 119mg, 120mg, 121mg, 122mg, 123mg, 124mg, 125mg, 126mg,127mg, 128mg, 129mg, 130mg, 131mg, 132mg, 133mg, 134mg, 135mg, 136mg, 137mg,138mg, 139mg, 140mg, 141mg, 142mg, 143mg, 144mg, 145mg, 146mg, 147mg, 148mg,149mg, 150mg, 151mg, 152mg, 153mg, 154mg, 155mg, 156mg, 157mg, 158mg, 159mg,160mg, 161mg, 162mg, 163mg, 164mg, 165mg, 166mg, 167mg, 168mg, 169mg, 170mg,171mg, 172mg, 173mg, 174mg, 175mg, 176mg, 177mg, 178mg, 179mg, 180mg, 181mg,182mg, 183mg, 184mg, 185mg, 186mg, 187mg, 188mg, 189mg, 190mg, 191mg, 192mg,193mg, 194mg, 195mg, 196mg, 197mg, 198mg, 199mg, 200mg, 201mg, 202mg, 203mg,204mg, 205mg, 206mg, 207mg, 208mg, 209mg, 210mg, 211mg, 212mg, 213mg, 214mg,215mg, 216mg, 217mg, 218mg, 219mg, 220mg, 221mg, 222mg, 223mg, 224mg, 225mg,226mg, 227mg, 228mg, 229mg, 230mg, 231mg, 232mg, 233mg, 234mg, 235mg, 236mg,237mg, 238mg, 239mg, 240mg, 241mg, 242mg, 243mg, 244mg, 245mg, 246mg, 247mg,248mg, 249mg or 250mg of xanomeline, deramciclane and at least one pharmaceutically acceptable carrier. In one embodiment of the invention, the oral dosage form comprises 40mg of xanomeline, deramciclane and at least one pharmaceutically acceptable carrier. In another embodiment of the invention, the oral dosage form comprises 50mg of xanomeline, deramciclane and at least one pharmaceutically acceptable carrier. In another embodiment of the invention, the oral dosage form comprises 60mg of xanomeline, deramciclane and at least one pharmaceutically acceptable carrier. In another embodiment of the invention, the oral dosage form comprises 70mg of xanomeline, deramciclane and at least one pharmaceutically acceptable carrier. In another embodiment of the invention, the oral dosage form comprises 80mg of xanomeline, deramciclane and at least one pharmaceutically acceptable carrier. In another embodiment of the invention, the oral dosage form comprises 90mg of xanomeline, deramciclane and at least one pharmaceutically acceptable carrier. In another embodiment of the invention, the oral dosage form comprises lOOmg of xanomeline, deramciclane and at least one pharmaceutically acceptable carrier. In another embodiment of the invention, the oral dosage form comprises 125mg of xanomeline, deramciclane and at least one pharmaceutically acceptable carrier. In another embodiment of the invention, the oral dosage form comprises150mg of xanomeline, deramciclane and at least one pharmaceutically acceptable carrier. In another embodiment of the invention, the oral dosage form comprises 175mg of xanomeline, deramciclane and at least one pharmaceutically acceptable carrier. In another embodiment of the invention, the oral dosage form comprises 200mg of xanomeline, deramciclane and at least one pharmaceutically acceptable carrier. In another embodiment of the invention, the oral dosage form comprises 225mg of xanomeline, deramciclane and at least one pharmaceutically acceptable carrier. In another embodiment of the invention, the oral dosage form comprises 250mg of xanomeline, deramciclane and at least one pharmaceutically acceptable carrier. In certain embodiments of the invention, the pharmaceutically acceptable carrier comprises cellulose or lactose.

[0101] In one embodiment of the invention, the oral dosage form comprises between 10 and 250mg of xanomeline, between 5 and 90mg of deramciclane and at least one pharmaceutically acceptable carrier. In one embodiment of the invention, the oral dosage form comprises lOmg, llmg, 12mg, 13mg, 14mg, 15mg, 16mg, 17mg, 18mg, 19mg, 20mg, 21mg, 22mg, 23mg, 24mg,25 mg, 26mg, 27mg, 28mg, 29mg, 30mg, 31mg, 32mg, 33mg, 34mg, 35mg, 36mg, 37mg,38mg, 39mg, 40mg, 41mg, 42mg, 43mg, 44mg, 45mg, 46mg, 47mg, 48mg, 49mg, 50mg,51mg, 52mg, 53mg, 54mg, 55mg, 56mg, 57mg, 58mg, 59mg, 60mg, 61mg, 62mg, 63mg,64mg, 65mg, 66mg, 67mg, 68mg, 69mg, 70mg, 71mg, 72mg, 73mg, 74mg, 75mg, 76mg, 77mg, 78mg, 79mg, 80mg, 81mg, 82mg, 83mg, 84mg, 85mg, 86mg, 87mg, 88mg, 89mg, 90mg, 91mg, 92mg, 93mg, 94mg, 95mg, 96mg, 97mg, 98mg, 99mg, lOOmg, lOlmg, 102mg, 103mg, 104mg, 105mg, 106mg, 107mg, 108mg, 109mg, HOmg, lllmg, 112mg, 113mg,114mg, 115mg, 116mg, 117mg, 118mg, 119mg, 120mg, 121mg, 122mg, 123mg, 124mg,125mg, 126mg, 127mg, 128mg, 129mg, 130mg, 131mg, 132mg, 133mg, 134mg, 135mg,136mg, 137mg, 138mg, 139mg, 140mg, 141mg, 142mg, 143mg, 144mg, 145mg, 146mg,147mg, 148mg, 149mg, 150mg, 151mg, 152mg, 153mg, 154mg, 155mg, 156mg, 157mg,158mg, 159mg, 160mg, 161mg, 162mg, 163mg, 164mg, 165mg, 166mg, 167mg, 168mg,169mg, 170mg, 171mg, 172mg, 173mg, 174mg, 175mg, 176mg, 177mg, 178mg, 179mg,180mg, 181mg, 182mg, 183mg, 184mg, 185mg, 186mg, 187mg, 188mg, 189mg, 190mg,191mg, 192mg, 193mg, 194mg, 195mg, 196mg, 197mg, 198mg, 199mg, 200mg, 201mg,202mg, 203mg, 204mg, 205mg, 206mg, 207mg, 208mg, 209mg, 210mg, 211mg, 212mg,213mg, 214mg, 215mg, 216mg, 217mg, 218mg, 219mg, 220mg, 221mg, 222mg, 223mg,224mg, 225mg, 226mg, 227mg, 228mg, 229mg, 230mg, 231mg, 232mg, 233mg, 234mg, 235mg, 236mg, 237mg, 238mg, 239mg, 240mg, 241mg, 242mg, 243mg, 244mg, 245mg, 246mg, 247mg, 248mg, 249mg or 250mg of xanomeline, between 5 and 90mg of deramciclane and at least one pharmaceutically acceptable carrier. In one embodiment of the invention, the oral dosage form comprises 40mg of xanomeline, between 5 and 90mg of deramciclane and at least one pharmaceutically acceptable carrier. In another embodiment of the invention, the oraldosage form comprises 50mg of xanomeline, between 5 and 90mg of deramciclane and at least one pharmaceutically acceptable carrier. In another embodiment of the invention, the oral dosage f...

Claims

1. CLAIMS1. The combination of xanomeline, or a pharmaceutically acceptable salt thereof, and a CYP2D6 inhibitor.

2. A pharmaceutical composition comprising xanomeline, or a pharmaceutically acceptable salt thereof, and a CYP2D6 inhibitor.

3. The pharmaceutical composition of claim 2, comprising between 10 and 250mg of xanomeline, or a pharmaceutically acceptable salt thereof.

4. The pharmaceutical composition of claim 3, comprising between 10 and 80mg of xanomeline, or a pharmaceutically acceptable salt thereof.

5. The pharmaceutical composition of claim 3, comprising between 65 and 250mg of xanomeline, or a pharmaceutically acceptable salt thereof.

6. The pharmaceutical composition of claim 2, wherein the CYP2D6 inhibitor is selected from the group consisting of fluoxetine, paroxetine, mirabegron, quinidine, buproprion, amiodarone, fluvoxamine, venlafaxine, duloxetine, ritonavir, thioridazine, cinacalcet, clomipramine, diphenhydramine, clozapine, celecoxib, delavirdine, tranylcypromine, terbinafine, sertraline, methotrimeprazine, clemastine, cocaine, methadone, ticlopidine, chloroquine, tipranavir, dronedarone, isoniazid, lumefantrine, nilotinib, cholecalciferol, indinavir, ziprasidone, abiraterone, cobicistat, clobazam, panobinostat, rucaparib, midostaurin, midodrine, manidipine, pitolisant, curcumin, risperidone, ranitidine, pindolol, loratadine, nortriptyline, propafenone, propranolol, imatinib, amlodipine, felodipine, omeprazole, oxybutynin, primaquine, selegiline, methimazole, thiothixene, verapamil, vinblastine, vinorelbine, temsirolimus, rabeprazole, vilazodone, deramciclane, peginterferon alfa-2b, entacapone, ospemifene, phenylbutyric acid, sulconazole, glycerol, phenylbutyrate, rhein, escitalopram, buprenorphine, asunaprevir, amitriptyline, impramine, dosulepine, desipramine, verumafenib, ritanserin, fusidic acid, lercanidipine, perhexiline, everolimus, citalopram, cimetidine, metoprolol, clotrimazole, quinine, ketoconazole, nevirapine, lidocaine, hydroxyzine, fenfluramine, moclobemide, reboxetine, lansoprazole, doxepin, fluphenazine, dextropropoxyphene, tamoxifen, perphenazine, chlorpheniramine, acebutolol, terfenadine, amodiaquine, azelastine, miconazole, proguanil, nefazodone, dexfenfluramine, halofantrine, rotigotine, atorvastatin, cerivastatin, tripelennamine, sparteine, mibefradil, pipotiazine, etoricoxib, biperiden, cyclosporine, cisapride, dimethyl sulfoxide, efavirenz, epinastine, hydroxyurea, hydroxychloroquine, labetalol, mepyramine, mifepristone, nicotinamide, niacin, oxamniquine, oxprenolol, rosiglitazone, saquinavir, sulfaphenazole, tegaserod, sorafenib, bicalutamide, asenapine, dexmedetomidine, indisulam, naloxegol, oxymetholone, stiripentol, vernakalant, enasidenib, artenimol, melprerone, levomepromazine, isavuconazole, phenelzine, safinamide, iproniazid, levnatinib, rilpivirine, gefitinib, lomustine, diacerein, darunavir, abemaciclib, acomitinib, St. John’s Wort,rifamycin, triclabendazole, orphenadrine, dosorubicin, dexchlorpheniramine, mizolastine, trazodone, clinafloxacin, desvenlafaxine, haloperidol, amoxapine, nifendipine, pimozide, nelfinavir, bepridil, oritavancin, cannabidiol, curcumin sulfate, nabiximols, ranolazine, nicardipine, lorcaserin, eliglustat, pazopanib, flecainide, lasmiditan, elexacaftor, ubrogepant, osilodrostat, fedratinib, methylene blue, clofazimine, clascoterone, berotralstat, tirbanibulin, zafirlukast, menadione, ethambutol, ropeginteferon alfa-2b, viloxazine, brincidofovir, belumosudil, fexinidazole, sotagliflozin, quercetin, cannabinol, cariprazine, pirfenidone, telotristat ethyl, cobimetinib, resveratrol, adagrasib, pirtobrutinib, bardenafil, rizatriptan, tezacaftor, encorafenib, isavuconazonium, mavorixafor, sofpironium, N- methylquinidinium, hydroxybupropion, R,R-hydroxybupropion, S,S-hydroxybupropion, threohydroxybupropion or R,R-threohydroxybupropion, and pharmaceutically acceptable salts thereof.

7. The pharmaceutical composition of claim 6, wherein the CYP2D6 inhibitor is selected from the group consisting of paroxetine, mirabegron, bupropion, deramciclane, cimetidine, A'-melhylquinidinium, hydroxybupropion, R,R-hydroxybupropion, S,S-hydroxybupropion, threohydroxybupropion, R,R- threohydroxybupropion, S,S-threohydroxybupropion, erythrohydroxybupropion, R,S- erythrohydroxybupropion or S,R-erythrohydroxybupropion, and pharmaceutically acceptable salts thereof.

8. The pharmaceutical composition of claim 1, wherein the composition is an oral dosage form.

9. A CYP2D6 inhibitor for use in a method of increasing xanomeline plasma levels in a subject in need of treatment with xanomeline, wherein the use comprises the co-administering the CYP2D6 inhibitor with xanomeline to the subject and wherein the co-administration increases xanomeline’s AUC to a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor.

10. A C YP2D6 inhibitor for use in a method of increasing xanomeline plasma levels in a subject in need of treatment with xanomeline, wherein the use comprises the co-administering the CYP2D6 inhibitor with xanomeline to the subject and wherein the co-administration decreases the AUC of one or more xanomeline metabolites at least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor.

11. A CYP2D6 inhibitor for use in a method of increasing xanomeline plasma levels in a subject in need of treatment with xanomeline, wherein the use comprises the co-administering the CYP2D6 inhibitor with xanomeline to the subject and wherein the co-administration increases xanomeline’s Cmaxto a level at least 3-fold that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor.

12. A C YP2D6 inhibitor for use in a method of increasing xanomeline plasma levels in a subject in need of treatment with xanomeline, wherein the use comprises the co-administering the CYP2D6 inhibitorwith xanomeline to the subject and wherein the co-administration decreases the Cmaxof one or more xanomeline metabolites at least 10% that which would be achieved by administering the same amount of xanomeline without the CYP2D6 inhibitor.

13. The CYP2D6 inhibitor for use according to any of claims 9 to 12, wherein the co-administration of the CYP2D6 inhibitor and xanomeline is once-daily.

14. The CYP2D6 inhibitor for use according to any of claims 9 to 12, wherein the co-administration of the CYP2D6 inhibitor and xanomeline is twice-daily.

15. The CYP2D6 inhibitor for use according to any of claims 9 to 12, wherein the subject in need of treatment of a central nervous system disorder selected from the group consisting of schizophrenia, Alzheimer’s disease, Huntington’s disease, Parkinson’s disease, Lewy Body dementia, psychosis, bipolar disorder and cognition deficit.

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