Oral formulation of cardiac sarcomere inhibitor

Abstract

Provided herein are formulations comprising the cardiac sarcomere inhibitor (R)—N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, methods for making such formulations, and methods for treating various cardiac diseases and conditions using such formulations. In one aspect, a formulation is provided that comprises: (i) (R)—N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharmaceutically acceptable salt thereof; (ii) a filler; (iii) a binder; (iv) a disintegrant; (v) a surfactant; and (vi) a lubricant.

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority benefit of U.S. Provisional Patent Application No. 62 / 875,358, filed July 17, 2019, the disclosure of which is incorporated herein by reference in its entirety.

[0002] Field Provided herein are formulations comprising the cardiac sarcomere inhibitor (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, methods of making such formulations, and methods of treating various cardiac diseases and conditions with such formulations. [Background technology]

[0003] background The cardiac sarcomere is the basic unit of muscular contraction in the heart. It is a highly ordered cytoskeletal structure composed of cardiac myosin, actin and a series of regulatory proteins. Cardiac myosin is the cytoskeletal motor protein in cardiac myocytes. Cardiac myosin is directly responsible for the conversion of chemical energy into mechanical force, resulting in myocardial contraction. The cardiac sarcomere is composed of a meshwork of contractile structural proteins that regulate myocardial function. The components of the cardiac sarcomere present targets for treating various cardiac diseases and conditions, for example, by increasing contractility or promoting complete relaxation, modulating contractile and diastolic function, respectively. The force and velocity of myocardial contraction are major determinants of organ function and are modulated by the cyclic interaction of actin and myosin. Regulation of actin-myosin binding is mediated by a meshwork of myofilament regulatory proteins and intracellular Ca. 2+The troponin complex and tropomyosin are thin filament proteins that govern the availability of actin-binding sites, while the essential and regulatory light chains, as well as myosin-binding protein C, modulate the positioning and mechanical properties of myosin.

[0004] Abnormalities in the cardiac sarcomere have been identified as a driving cause of various cardiac diseases and conditions, such as hypertrophic cardiomyopathy (HCM) and heart failure with preserved ejection fraction (HFpEF). Mutations in sarcomere proteins cause disease by rendering the myocardium either "high" or "low" contractile. Modulators of the cardiac sarcomere can be used to rebalance contractility and halt or reverse the disease process.

[0005] Current agents that target cardiac sarcomeres, such as inotropes (drugs that increase cardiac contractility), have poor selectivity for cardiac tissue and have recognized adverse effects that limit their use. These adverse effects include increased cytosolic Ca in inotropically stimulated myocardium. ++ These include increased rates of energy expenditure, exacerbated relaxation abnormalities, and cellular damage caused by potential arrhythmogenic side effects that may result from elevated cyclic AMP concentrations. Given the limitations of current agents, new approaches are needed to improve cardiac function in HCM and HFpEF.

[0006] There remains a great need for agents that can exploit new mechanisms of action and have better outcomes in terms of symptom relief, safety, and subject mortality over both the short and long term. New agents with improved therapeutic indexes over current agents provide a means to achieve these clinical outcomes. Agent selectivity to target cardiac sarcomeres (e.g., by targeting cardiac myosin) has been identified as a key means to achieve this improved therapeutic index.

[0007] A newly developed cardiac sarcomere inhibitor is described in International Application No. PCT / US2019 / 014344, published as International Publication No. WO 2019 / 144041, which is incorporated herein by reference. Specifically, International Application No. PCT / US2019 / 014344 describes a compound having the following structure: [ka] describes a family of compounds, including the compound (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide having the formula: The present disclosure provides formulations comprising the cardiac sarcomere inhibitor (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide. (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide is a selective allosteric inhibitor of cardiac myosin with little or no effect on smooth muscle myosin. Advantages of this compound include a wide therapeutic index, low effect on cardiac relaxation, and favorable pharmacokinetic and safety profiles. The present disclosure also provides methods of making formulations comprising the compound (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, as well as methods of treating various cardiac diseases and conditions with such formulations, such as methods of treating heart failure, including HCM and HFpEF. [Prior art documents] [Patent documents]

[0008] [Patent Document 1] International Publication No. 2019 / 144041 Summary of the Invention [Means for solving the problem]

[0009] overview In one aspect, a formulation is provided that includes: (i) (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (ii) a filler; (iii) a binder; (iv) a disintegrant; (v) a surfactant; and (vi) a lubricant.

[0010] In another aspect, a formulation is provided that includes: (i) (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide; (ii) a filler; (iii) a binder; (iv) a disintegrant; (v) a surfactant; and (vi) a lubricant.

[0011] In another aspect, there is provided a tablet comprising: (i) a core, the core having a total core weight including: (a)(ai) (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii) an intragranular filler; (a-iii) an intragranular binder; (a-iv) an intragranular disintegrant; and (av) an intragranular surfactant; and (b) an extragranular component including (bi) an extragranular filler; (b-ii) an extragranular disintegrant; and (b-iii) an extragranular lubricant; and optionally (ii) a coating layer comprising a coating agent.

[0012] In yet another aspect, there is provided a tablet comprising: (i) a core, the core having a total core weight including (a)(ai) intragranular components comprising (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide; (a-ii) intragranular filler; (a-iii) intragranular binder; (a-iv) intragranular disintegrant; and (av) intragranular surfactant; and (b) extragranular components comprising (bi) extragranular filler; (b-ii) extragranular disintegrant; and (b-iii) extragranular lubricant; and optionally (ii) a coating layer comprising a coating agent.

[0013] In yet another embodiment, (i) a core comprising: (a) (ai) (R)—N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii) an intragranular filler; (a-iii) an intragranular binder; (a-iv) an intragranular disintegrant; and (av) an intragranular surfactant. and (b) a core having a total core weight including extragranular components including (bi) an extragranular filler; (b-ii) an extragranular disintegrant; and (b-iii) an extragranular lubricant; and (ii) a coating layer including a coating agent, the method comprising: (1) adding (R)—N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazoline to a tablet having a total core weight including an extragranular component including (R)—N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazoline; (2) milling the granules comprising (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph or a pharma- ceutically acceptable salt thereof, an intragranular filler, an intragranular binder, an intragranular disintegrant and an intragranular surfactant to form an intragranular component; (3) blending the intragranular component with an extragranular filler, an extragranular disintegrant and an extragranular lubricant to form a final blended mixture; (4) compressing the final blended mixture to form a core; and (5) coating the core with a coating layer.

[0014] In yet another aspect, a method of making a tablet comprising: (i) a core, the core having a total core weight including (a)(ai) (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide; (a-ii) intragranular filler; (a-iii) intragranular binder; (a-iv) intragranular disintegrant; and (av) intragranular surfactant; and (b)(bi) extragranular filler; (b-ii) extragranular disintegrant; and (b-iii) extragranular lubricant; and (ii) a coating layer comprising a coating agent, the method comprising the steps of: (1) (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide; (a-ii) intragranular filler; (a-iii) intragranular binder; (a-iv) intragranular disintegrant; and (av) intragranular surfactant; and (b)(bi) extragranular filler; (b-ii) extragranular disintegrant; and (b-iii) extragranular lubricant; (2) milling the granules comprising (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, intragranular filler, intragranular binder, intragranular disintegrant and intragranular surfactant to form an intragranular component; (3) blending the intragranular component with an extragranular filler, an extragranular disintegrant and an extragranular lubricant to form a final blended mixture; (4) compressing the final blended mixture to form a core; and (5) coating the core with a coating layer.

[0015] In yet another aspect, a method of treating a cardiac disease in a subject in need thereof is provided, comprising administering to the subject a formulation described herein or a tablet described herein. In some embodiments, the cardiac disease is hypertrophic cardiomyopathy (HCM). In some embodiments, the HCM is obstructive or non-obstructive, or caused by sarcomeric and / or non-sarcomeric mutations. In some embodiments, the cardiac disease is heart failure with preserved ejection fraction (HFpEF). In some embodiments, the cardiac disease is selected from the group consisting of diastolic dysfunction, primary or secondary restrictive cardiomyopathy, myocardial infarction and angina pectoris, and left ventricular outflow tract obstruction. In some embodiments, the cardiac disease is hypertensive heart disease, congenital heart disease, cardiac ischemia, coronary heart disease, diabetic heart disease, congestive heart failure, right heart failure, cardiorenal syndrome, or infiltrative cardiomyopathy. In some embodiments, the cardiac disease is a condition that is or is related to cardiac aging and / or aging-induced diastolic dysfunction. In some embodiments, the cardiac disease is a condition that is, or is associated with, left ventricular hypertrophy and / or concentric left ventricular remodeling.

[0016] In another aspect, a method of treating a disease or condition associated with HCM in a subject in need thereof is provided, comprising administering to the subject a formulation described herein or a tablet described herein. In some embodiments, the disease or condition is selected from the group consisting of Fabry disease, Danon disease, mitochondrial cardiomyopathy, and Noonan syndrome.

[0017] In some aspects, a method of treating a disease or condition associated with secondary left ventricular wall thickening in a subject in need thereof is provided, comprising administering to the subject a formulation as described herein or a tablet as described herein. In some embodiments, the disease or condition is selected from the group consisting of hypertension, valvular heart disease (e.g., aortic stenosis and mitral regurgitation), metabolic syndrome (diabetes, obesity), end-stage renal disease, scleroderma, sleep apnea, amyloidosis, Fabry disease, Friedreich's ataxia, Danon disease, Noonan syndrome, and Pompe disease.

[0018] In another aspect, a method for treating a disease or condition associated with small left ventricular cavity and cavity obstruction, hyperkinetic left ventricular contraction, myocardial ischemia or cardiac fibrosis is provided, comprising administering to a subject a formulation as described herein or a tablet as described herein.Similarly, a method for treating muscular dystrophy (e.g., Duchenne muscular dystrophy) or glycogen storage disease is provided.

[0019] Similarly, provided is a method of inhibiting cardiac sarcomere in a subject in need thereof, comprising administering to the subject a formulation described herein or a tablet described herein. [Brief description of the drawings]

[0020] [Figure 1] FIG. 1 depicts a flow chart illustrating unit operations in the preparation of the formulations described herein.

[0021] [Diagram 2] FIG. 2 depicts a flow chart illustrating the unit operations in the preparation of the uncoated tablets described herein.

[0022] [Diagram 3]FIG. 3 depicts a flow chart illustrating the unit operations in the preparation of the coated tablets described herein. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0023] Detailed Description definition As used herein, the following words and phrases are generally intended to have the meanings set forth below, except to the extent that the context in which they are used indicates otherwise.

[0024] Use of the terms "a," "an," and the like, as used herein, refers to one or more, unless clearly indicated otherwise.

[0025] Reference herein to "about" a value or parameter includes (and describes) embodiments that are directed to that value or parameter itself. For example, a description stating "about X" includes a description of "X."

[0026] The term "pharmaceutical acceptable salt" refers to any salt of the compounds herein that is known to be non-toxic and is commonly used in pharmaceutical literature. In some embodiments, the pharmaceutical acceptable salt of the compound retains the biological effectiveness of the compounds described herein and is not biologically or otherwise undesirable. Examples of pharmaceutical acceptable salts can be found in Berge et al., Pharmaceutical Salts, J. Pharmaceutical Sciences, January 1977, 66(1), 1-19. Pharmaceutically acceptable acid addition salts can be formed with inorganic and organic acids. Inorganic acids from which salts can be derived include, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, and phosphoric acid. Organic acids from which salts can be derived include, for example, acetic acid, propionic acid, glycolic acid, pyruvic acid, lactic acid, oxalic acid, malic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, 2-hydroxyethylsulfonic acid, p-toluenesulfonic acid, stearic acid and salicylic acid. Pharmaceutically acceptable base addition salts can be formed with inorganic and organic bases. Inorganic bases from which salts can be derived include, for example, sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese and aluminum. Organic bases from which salts can be derived include, for example, primary, secondary and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines and basic ion exchange resins. Examples of organic bases include isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine and ethanolamine. In some embodiments, the pharma- ceutically acceptable base addition salt is selected from ammonium, potassium, sodium, calcium, and magnesium salts.

[0027] When the compound described herein is obtained as an acid addition salt, free base can be obtained by basifying the solution of the acid salt.On the contrary, when the compound is a free base, addition salt, particularly pharmaceutically acceptable addition salt, can be produced by dissolving the free base in a suitable organic solvent and treating the solution with acid according to the conventional procedure for preparing acid addition salt from a basic compound (see, for example, Berge et al., Pharmaceutical Salts, J. Pharmaceutical Sciences, January 1977, 66(1), 1-19).Those skilled in the art will recognize various synthetic methods that can be used to prepare pharmaceutically acceptable addition salt.

[0028] A "solvate" is formed by the interaction of a solvent with a compound. Suitable solvents include, for example, water and alcohol (e.g., ethanol). Solvates include hydrates having any ratio of compound to water, such as monohydrates, dihydrates, and hemihydrates.

[0029] The term "hydrate" refers to the chemical entity formed by the interaction of water and a compound, including, for example, a hemihydrate, monohydrate, dihydrate, trihydrate, etc.

[0030] As used herein, the term "polymorph" or "polymorphic form" refers to a crystalline form of a compound. Different polymorphs may have different physical properties, such as melting temperature, heat of fusion, solubility, dissolution rate and / or vibrational spectrum, as a result of, for example, the arrangement or conformation of molecules or ions in a crystal lattice. The difference in physical properties exhibited by polymorphs may affect pharmaceutical parameters, such as storage stability, compressibility, density (important in formulation and manufacturing of products) and dissolution rate (a key factor in bioavailability). Differences in stability may result from changes in chemical reactivity (e.g., differences in oxidation, such that a dosage form made of one polymorph changes color more quickly than one made of another polymorph), mechanical changes (e.g., tablets crumble during storage when a kinetically favored polymorph transforms into a thermodynamically more stable polymorph), or both (e.g., tablets of one polymorph are more susceptible to degradation at high humidity). In extreme cases, some polymorphic transitions may result in lack of efficacy or, in other extreme cases, toxicity as a result of differences in solubility / dissolution. Furthermore, the physical properties of the crystalline form may be important in processing; for example, one polymorph may be more likely to form solvates or may be difficult to filter and wash free of impurities (e.g., particle shape and size distribution may differ between polymorphs).

[0031] As used herein, the term "subject" refers to an animal, such as a mammal, bird or fish. In some embodiments, the subject is a mammal. Mammals include, for example, mice, rats, dogs, cats, pigs, sheep, horses, cows and humans. In some embodiments, the subject is a human, such as a human who is or will be the subject of treatment, observation or experiment. The formulations, tablets and methods described herein can be useful in both human therapy and veterinary applications.

[0032] As used herein, the term "therapeutic" refers to the ability to modulate cardiac sarcomere. As used herein, "modulation" refers to a change in activity as a direct or indirect response to the presence of a chemical entity as described herein, compared to the activity in the absence of the chemical entity. The change may be an increase in activity or a decrease in activity, and may be due to the direct interaction of the chemical entity with the target, or may be due to the interaction of the chemical entity with one or more other factors that then affect the activity of the target. For example, the presence of a chemical entity can increase or decrease the target activity, for example, by direct binding to the target, by causing another factor to increase or decrease (directly or indirectly) the target activity, or by increasing or decreasing (directly or indirectly) the amount of the target present in a cell or organism.

[0033] The term "therapeutically effective amount" or "effective amount" refers to an amount of a compound disclosed and / or described herein that is sufficient to perform treatment as defined herein when administered to a subject in need of such treatment. A therapeutically effective amount of a compound may be an amount sufficient to treat a disease responsive to modulation of cardiac sarcomere. A therapeutically effective amount will vary depending on, for example, the subject and disease state to be treated, the subject's weight and age, the severity of the disease state, the specific compound, the dosing regimen to be followed, the timing of administration, and the mode of administration, all of which can be easily determined by those skilled in the art. A therapeutically effective amount can be ascertained experimentally, for example, by assaying the blood concentration of a chemical entity, or theoretically, by calculating bioavailability.

[0034] "Treatment" (and related terms such as "treat", "treated", "treating") includes one or more of preventing a disease or disorder (i.e., preventing the clinical symptoms of a disease or disorder from developing), arresting a disease or disorder, slowing or arresting the development of clinical symptoms of a disease or disorder, and / or alleviating a disease or disorder (i.e., causing a remission or regression from clinical symptoms). The term encompasses situations where a disease or disorder is already experienced by a subject, and situations where a disease or disorder is not currently experienced, but is expected to develop. The term encompasses both complete and partial reduction or prevention of a condition or disorder, as well as complete or partial reduction of clinical symptoms of a disease or disorder. Thus, the compounds described and / or disclosed herein can prevent an existing disease or disorder from worsening, aid in the management of a disease or disorder, or reduce or eliminate a disease or disorder. When used prophylactically, the compounds disclosed and / or described herein can prevent a disease or disorder from developing, or reduce the extent of a disease or disorder that is likely to develop.

[0035] "ATPase" refers to an enzyme that hydrolyzes ATP. ATPases include proteins that include molecular motors such as myosin.

[0036] The compounds depicted herein may be represented as salts even if the salts are not depicted, and it is understood that the formulations, tablets and methods provided herein encompass all salts and solvates of the compounds depicted herein, as well as non-salt and non-solvated forms of the compounds, as would be well understood by one of skill in the art. In some embodiments, the salts of the compounds provided herein are pharma- ceutically acceptable salts. formulation

[0037] Provided herein is a formulation comprising: (i) (R)—N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (ii) a filler; (iii) a binder; (iv) a disintegrant; (v) a surfactant; and (vi) a lubricant.

[0038] In some embodiments, a formulation is provided that includes: (i) (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide; (ii) a filler; (iii) a binder; (iv) a disintegrant; (v) a surfactant; and (vi) a lubricant.

[0039] In some embodiments, the filler is selected from the group consisting of powdered cellulose, microcrystalline cellulose, silicified microcrystalline cellulose, kaolin, corn starch, maize starch, starch derivatives, pregelatinized starch, calcium phosphate, calcium hydrogen phosphate, dicalcium phosphate, tricalcium phosphate, compressible sugar, sugar alcohols, mannitol, sorbitol, maltitol, xylitol, lactitol, lactose, dextrose, maltose, sucrose, glucose, fructose, saccharose, raffinose, dextrates, trehalose, maltodextrin, and mixtures of any of the foregoing.

[0040] In some embodiments, the binder is selected from the group consisting of gum arabic, gum acacia, alginate, alginic acid, corn starch, copolyvidone, polyvinylpyrrolidone, gelatin, glyceryl behenate, hydroxyethylcellulose, hydroxypropylcellulose, carboxymethylcellulose, calcium carboxymethylcellulose, sodium carboxymethylcellulose, methylcellulose, hypromellose, lactose, polyvinyl alcohol, povidone, polyethylene oxide, polyacrylates, potato starch, pregelatinized starch, sodium alginate, sodium starch, sodium carboxymethylcellulose, starch, and mixtures of any of the foregoing.

[0041] In some embodiments, the disintegrant is selected from the group consisting of alginic acid, croscarmellose sodium, cellulose, calcium carboxymethylcellulose, sodium carboxymethylcellulose, microcrystalline cellulose, crospovidone, sodium starch glycolate, low-substituted hydroxypropylcellulose, polacrilin potassium, pregelatinized starch, partially hydrolyzed starch, sodium carboxymethylstarch, starch, sodium alginate, sodium carboxymethylcellulose, and mixtures of any of the foregoing.

[0042] In some embodiments, the surfactant is cetylpyridine chloride, heptadecaethyleneoxycetanol, lecithin, polyoxyethylene stearate, nonoxynol 9, nonoxynol 10, octoxynol 9, sorbitan fatty acid esters, Span 20, Span 40, Span 60, Span 80, Span 85, polysorbate, polysorbate 20, polysorbate 21, polysorbate 40, polysorbate 60, polysorbate 61, polysorbate 65, polysorbate 80, sodium sulfate of fatty alcohol sulfate esters. The fatty acid esters are selected from the group consisting of sodium salts, sodium lauryl sulfate, sodium salts of sulfosuccinic acid esters, sodium dioctyl sulfosuccinate, partial esters of fatty acids and alcohols, glyceryl monostearate, glyceryl monooleate, ethers of fatty alcohols and polyoxyethylene, esters of fatty acids and polyoxyethylene, copolymers of ethylene oxide and propylene oxide (Pluronic®), benzalkonium chloride, ethoxylated triglycerides, and mixtures of any of the foregoing.

[0043] In some embodiments, the lubricant is selected from the group consisting of hydrogenated castor oil, magnesium stearate, glyceryl monostearate, calcium stearate, glyceryl behenate, glycerol distearate, glyceryl dipalmitostearate, behenoyl polyoxyl-8 glyceride, sodium stearyl fumarate, stearic acid, talc, zinc stearate, mineral oil, polyethylene glycol, polaxamer, sodium lauryl sulfate, and mixtures of any of the foregoing.

[0044] In some embodiments, the formulation comprises: (i) about 1% to about 80% by weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (ii) about 15% to about 90% by weight of a filler; (iii) about 0.1% to about 10% by weight of a binder; (iv) about 1% to about 10% by weight of a disintegrant; (v) about 0.1% to about 10% by weight of a surfactant; and (vi) about 0.1% to about 10% by weight of a lubricant.

[0045] In some embodiments, the formulation comprises: (i) about 1% to about 80% by weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide; (ii) about 15% to about 90% by weight of a filler; (iii) about 0.1% to about 10% by weight of a binder; (iv) about 1% to about 10% by weight of a disintegrant; (v) about 0.1% to about 10% by weight of a surfactant; and (vi) about 0.1% to about 10% by weight of a lubricant.

[0046] In some embodiments, the formulation comprises: (i) about 1% to about 50% by weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (ii) about 40% to about 80% by weight of a filler; (iii) about 0.5% to about 5% by weight of a binder; (iv) about 2% to about 8% by weight of a disintegrant; (v) about 0.5% to about 5% by weight of a surfactant; and (vi) about 0.5% to about 5% by weight of a lubricant.

[0047] In some embodiments, the formulation comprises: (i) about 1% to about 50% by weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide; (ii) about 40% to about 80% by weight of a filler; (iii) about 0.5% to about 5% by weight of a binder; (iv) about 2% to about 8% by weight of a disintegrant; (v) about 0.5% to about 5% by weight of a surfactant; and (vi) about 0.5% to about 5% by weight of a lubricant.

[0048] In some embodiments, the formulation comprises: (i) about 10% to about 30% by weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (ii) about 60% to about 80% by weight of a filler; (iii) about 1% to about 3% by weight of a binder; (iv) about 4% to about 6% by weight of a disintegrant; (v) about 1% to about 3% by weight of a surfactant; and (vi) about 0.5% to about 1.5% by weight of a lubricant.

[0049] In some embodiments, the formulation comprises: (i) about 10% to about 30% by weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide; (ii) about 60% to about 80% by weight of a filler; (iii) about 1% to about 3% by weight of a binder; (iv) about 4% to about 6% by weight of a disintegrant; (v) about 1% to about 3% by weight of a surfactant; and (vi) about 0.5% to about 1.5% by weight of a lubricant.

[0050] In some embodiments, the formulation comprises: (i) about 20% by weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or a pharma- ceutically acceptable salt thereof; (ii) about 70% by weight of a filler; (iii) about 2% by weight of a binder; (iv) about 5% by weight of a disintegrant; (v) about 2% by weight of a surfactant; and (vi) about 1% by weight of a lubricant.

[0051] In some embodiments, the formulation comprises: (i) about 20% by weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide; (ii) about 70% by weight of a filler; (iii) about 2% by weight of a binder; (iv) about 5% by weight of a disintegrant; (v) about 2% by weight of a surfactant; and (vi) about 1% by weight of a lubricant.

[0052] In some embodiments, the formulation comprises: (i) about 1% to about 10% by weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (ii) about 70% to about 90% by weight of a filler; (iii) about 1% to about 3% by weight of a binder; (iv) about 4% to about 6% by weight of a disintegrant; (v) about 1% to about 3% by weight of a surfactant; and (vi) about 0.5% to about 1.5% by weight of a lubricant.

[0053] In some embodiments, the formulation comprises: (i) about 1% to about 10% by weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide; (ii) about 70% to about 90% by weight of a filler; (iii) about 1% to about 3% by weight of a binder; (iv) about 4% to about 6% by weight of a disintegrant; (v) about 1% to about 3% by weight of a surfactant; and (vi) about 0.5% to about 1.5% by weight of a lubricant.

[0054] In some embodiments, the formulation comprises: (i) about 5% by weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or a pharma- ceutically acceptable salt thereof; (ii) about 85% by weight of a filler; (iii) about 2% by weight of a binder; (iv) about 5% by weight of a disintegrant; (v) about 2% by weight of a surfactant; and (vi) about 1% by weight of a lubricant.

[0055] In some embodiments, the formulation comprises: (i) about 5% by weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide; (ii) about 85% by weight of a filler; (iii) about 2% by weight of a binder; (iv) about 5% by weight of a disintegrant; (v) about 2% by weight of a surfactant; and (vi) about 1% by weight of a lubricant.

[0056] In some embodiments, the formulation comprises: (i) about 10% by weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or a pharma- ceutically acceptable salt thereof; (ii) about 80% by weight of a filler; (iii) about 2% by weight of a binder; (iv) about 5% by weight of a disintegrant; (v) about 2% by weight of a surfactant; and (vi) about 1% by weight of a lubricant.

[0057] In some embodiments, the formulation comprises: (i) about 10% by weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide; (ii) about 80% by weight of a filler; (iii) about 2% by weight of a binder; (iv) about 5% by weight of a disintegrant; (v) about 2% by weight of a surfactant; and (vi) about 1% by weight of a lubricant.

[0058] In some embodiments, the filler comprises mannitol. In some embodiments, the filler comprises microcrystalline cellulose. In some embodiments, the filler consists of mannitol and microcrystalline cellulose. In some embodiments, the binder is hydroxypropyl cellulose. In some embodiments, the disintegrant is croscarmellose sodium. In some embodiments, the surfactant is sodium lauryl sulfate. In some embodiments, the lubricant is magnesium stearate.

[0059] In some embodiments, the formulation comprises: (i) about 1% to about 50% by weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (ii-1) about 10% to about 60% by weight of mannitol; (ii-2) about 5% to about 45% by weight of microcrystalline cellulose; (iii) about 0.1% to about 10% by weight of hydroxypropylcellulose; (iv) about 1% to about 10% by weight of croscarmellose sodium; (v) about 0.1% to about 10% by weight of sodium lauryl sulfate; and (vi) about 0.1% to about 10% by weight of magnesium stearate.

[0060] In some embodiments, the formulation comprises: (i) about 1% to about 50% by weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide; (ii-1) about 10% to about 60% by weight of mannitol; (ii-2) about 5% to about 45% by weight of microcrystalline cellulose; (iii) about 0.1% to about 10% by weight of hydroxypropylcellulose; (iv) about 1% to about 10% by weight of croscarmellose sodium; (v) about 0.1% to about 10% by weight of sodium lauryl sulfate; and (vi) about 0.1% to about 10% by weight of magnesium stearate.

[0061] In some embodiments, the formulation comprises: (i) about 10% to about 30% by weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (ii-1) about 40% to about 50% by weight of mannitol; (ii-2) about 20% to about 30% by weight of microcrystalline cellulose; (iii) about 1% to about 3% by weight of hydroxypropylcellulose; (iv) about 4% to about 6% by weight of croscarmellose sodium; (v) about 1% to about 3% by weight of sodium lauryl sulfate; and (vi) about 0.5% to about 1.5% by weight of magnesium stearate.

[0062] In some embodiments, the formulation comprises: (i) about 10% to about 30% by weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide; (ii-1) about 40% to about 50% by weight of mannitol; (ii-2) about 20% to about 30% by weight of microcrystalline cellulose; (iii) about 1% to about 3% by weight of hydroxypropylcellulose; (iv) about 4% to about 6% by weight of croscarmellose sodium; (v) about 1% to about 3% by weight of sodium lauryl sulfate; and (vi) about 0.5% to about 1.5% by weight of magnesium stearate.

[0063] In some embodiments, the formulation comprises: (i) about 1% to about 10% by weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (ii-1) about 50% to about 60% by weight of mannitol; (ii-2) about 25% to about 35% by weight of microcrystalline cellulose; (iii) about 1% to about 3% by weight of hydroxypropylcellulose; (iv) about 4% to about 6% by weight of croscarmellose sodium; (v) about 1% to about 3% by weight of sodium lauryl sulfate; and (vi) about 0.5% to about 1.5% by weight of magnesium stearate.

[0064] In some embodiments, the formulation comprises: (i) about 1% to about 10% by weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide; (ii-1) about 50% to about 60% by weight of mannitol; (ii-2) about 25% to about 35% by weight of microcrystalline cellulose; (iii) about 1% to about 3% by weight of hydroxypropylcellulose; (iv) about 4% to about 6% by weight of croscarmellose sodium; (v) about 1% to about 3% by weight of sodium lauryl sulfate; and (vi) about 0.5% to about 1.5% by weight of magnesium stearate.

[0065] In some embodiments, the formulation comprises: (i) about 20% by weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (ii-1) about 44% by weight of mannitol; (ii-2) about 26% by weight of microcrystalline cellulose; (iii) about 2% by weight of hydroxypropylcellulose; (iv) about 5% by weight of croscarmellose sodium; (v) about 2% by weight of sodium lauryl sulfate; and (vi) about 1% by weight of magnesium stearate.

[0066] In some embodiments, the formulation comprises: (i) about 20% by weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide; (ii-1) about 44% by weight of mannitol; (ii-2) about 26% by weight of microcrystalline cellulose; (iii) about 2% by weight of hydroxypropylcellulose; (iv) about 5% by weight of croscarmellose sodium; (v) about 2% by weight of sodium lauryl sulfate; and (vi) about 1% by weight of magnesium stearate.

[0067] In some embodiments, the formulation comprises: (i) about 10% by weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (ii-1) about 50% by weight of mannitol; (ii-2) about 30% by weight of microcrystalline cellulose; (iii) about 2% by weight of hydroxypropylcellulose; (iv) about 5% by weight of croscarmellose sodium; (v) about 2% by weight of sodium lauryl sulfate; and (vi) about 1% by weight of magnesium stearate.

[0068] In some embodiments, the formulation comprises: (i) about 10% by weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide; (ii-1) about 50% by weight of mannitol; (ii-2) about 30% by weight of microcrystalline cellulose; (iii) about 2% by weight of hydroxypropylcellulose; (iv) about 5% by weight of croscarmellose sodium; (v) about 2% by weight of sodium lauryl sulfate; and (vi) about 1% by weight of magnesium stearate.

[0069] In some embodiments, the formulation comprises: (i) about 5% by weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (ii-1) about 54% by weight of mannitol; (ii-2) about 31% by weight of microcrystalline cellulose; (iii) about 2% by weight of hydroxypropylcellulose; (iv) about 5% by weight of croscarmellose sodium; (v) about 2% by weight of sodium lauryl sulfate; and (vi) about 1% by weight of magnesium stearate.

[0070] In some embodiments, the formulation comprises: (i) about 5% by weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide; (ii-1) about 54% by weight of mannitol; (ii-2) about 31% by weight of microcrystalline cellulose; (iii) about 2% by weight of hydroxypropylcellulose; (iv) about 5% by weight of croscarmellose sodium; (v) about 2% by weight of sodium lauryl sulfate; and (vi) about 1% by weight of magnesium stearate.

[0071] The administration of the compositions disclosed herein can be by any of the modes of administration accepted for solid and semi-solid formulations, including but not limited to oral, sublingual, subcutaneous, parenteral, intranasal, topical, transdermal, intraperitoneal, intramuscular, pulmonary, intravaginal, rectal or intraocular administration.In some embodiments, the formulation is for oral or sublingual administration.In some embodiments, the formulation is for oral administration.

[0072] In some embodiments, the formulation is for administration once a day. In some embodiments, the formulation is for administration twice a day. In some embodiments, the formulation is for administration three times a day. In some embodiments, the formulation is for administration four times a day. In some embodiments, the formulation is for administration five times a day.

[0073] In some embodiments, the formulation is in the form of a pill, capsule or tablet, hi some embodiments, the formulation is a tablet. tablet

[0074] Provided herein is a tablet comprising: (i) a core, the core having a total core weight including intragranular components, the total core weight including (a)(ai) (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii) an intragranular filler; (a-iii) an intragranular binder; (a-iv) an intragranular disintegrant; and (av) an intragranular surfactant; and (b) an extragranular component, the total core weight including (bi) an extragranular filler; (b-ii) an extragranular disintegrant; and (b-iii) an extragranular lubricant; and optionally (ii) a coating layer comprising a coating agent.

[0075] In some embodiments, there is provided a tablet comprising: (i) a core, the core having a total core weight including intragranular components comprising: (a)(ai) (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide; (a-ii) intragranular filler; (a-iii) intragranular binder; (a-iv) intragranular disintegrant; and (av) intragranular surfactant; and (b)(bi) extragranular filler; (b-ii) extragranular disintegrant; and (b-iii) extragranular lubricant; and optionally (ii) a coating layer comprising a coating agent.

[0076] In some embodiments, the intragranular filler is selected from the group consisting of powdered cellulose, microcrystalline cellulose, silicified microcrystalline cellulose, kaolin, corn starch, maize starch, starch derivatives, pregelatinized starch, calcium phosphate, calcium hydrogen phosphate, dicalcium phosphate, tricalcium phosphate, compressible sugar, sugar alcohols, mannitol, sorbitol, maltitol, xylitol, lactitol, lactose, dextrose, maltose, sucrose, glucose, fructose, saccharose, raffinose, dextrates, trehalose, maltodextrin, and mixtures of any of the foregoing.

[0077] In some embodiments, the intragranular binder is selected from the group consisting of gum arabic, gum acacia, alginates, alginic acid, corn starch, copolyvidone, polyvinylpyrrolidone, gelatin, glyceryl behenate, hydroxyethyl cellulose, hydroxypropyl cellulose, carboxymethyl cellulose, calcium carboxymethyl cellulose, sodium carboxymethyl cellulose, methyl cellulose, hypromellose, lactose, polyvinyl alcohol, povidone, polyethylene oxide, polyacrylates, potato starch, pregelatinized starch, sodium alginate, sodium starch, sodium carboxymethyl cellulose, starch, and mixtures of any of the foregoing.

[0078] In some embodiments, the intragranular disintegrant is selected from the group consisting of alginic acid, croscarmellose sodium, cellulose, calcium carboxymethylcellulose, sodium carboxymethylcellulose, microcrystalline cellulose, crospovidone, sodium starch glycolate, low substituted hydroxypropylcellulose, polacrilin potassium, pregelatinized starch, partially hydrolyzed starch, sodium carboxymethylstarch, starch, sodium alginate, sodium carboxymethylcellulose, and mixtures of any of the foregoing.

[0079] In some embodiments, the intragranular surfactant is cetylpyridine chloride, heptadecaethyleneoxycetanol, lecithin, polyoxyethylene stearate, nonoxynol 9, nonoxynol 10, octoxynol 9, sorbitan fatty acid esters, Span 20, Span 40, Span 60, Span 80, Span 85, polysorbate, polysorbate 20, polysorbate 21, polysorbate 40, polysorbate 60, polysorbate 61, polysorbate 65, polysorbate 80, sodium fatty alcohol sulfate esters. The fatty acid esters are selected from the group consisting of trisodium salts, sodium lauryl sulfate, sodium salts of sulfosuccinic acid esters, sodium dioctyl sulfosuccinate, partial esters of fatty acids and alcohols, glyceryl monostearate, glyceryl monooleate, ethers of fatty alcohols and polyoxyethylene, esters of fatty acids and polyoxyethylene, copolymers of ethylene oxide and propylene oxide (Pluronic®), benzalkonium chloride, ethoxylated triglycerides, and mixtures of any of the foregoing.

[0080] In some embodiments, the extragranular filler is selected from the group consisting of powdered cellulose, microcrystalline cellulose, silicified microcrystalline cellulose, kaolin, corn starch, maize starch, starch derivatives, pregelatinized starch, calcium phosphate, calcium hydrogen phosphate, dicalcium phosphate, tricalcium phosphate, compressible sugar, sugar alcohols, mannitol, sorbitol, maltitol, xylitol, lactitol, lactose, dextrose, maltose, sucrose, glucose, fructose, saccharose, raffinose, dextrates, trehalose, maltodextrin, and mixtures of any of the foregoing.

[0081] In some embodiments, the extragranular disintegrant is selected from the group consisting of alginic acid, croscarmellose sodium, cellulose, calcium carboxymethylcellulose, sodium carboxymethylcellulose, microcrystalline cellulose, crospovidone, sodium starch glycolate, low substituted hydroxypropylcellulose, polacrilin potassium, pregelatinized starch, partially hydrolyzed starch, sodium carboxymethylstarch, starch, sodium alginate, sodium carboxymethylcellulose, and mixtures of any of the foregoing.

[0082] In some embodiments, the extragranular lubricant is selected from the group consisting of hydrogenated castor oil, magnesium stearate, glyceryl monostearate, calcium stearate, glyceryl behenate, glycerol distearate, glyceryl dipalmitostearate, behenoyl polyoxyl-8 glyceride, sodium stearyl fumarate, stearic acid, talc, zinc stearate, mineral oil, polyethylene glycol, poloxamer, sodium lauryl sulfate, and mixtures of any of the foregoing.

[0083] In some embodiments, the core comprises: (a)(ai) about 1% to about 80% of the total core weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii) about 10% to about 80% of the total core weight of intragranular filler; (a-iii) about 10% to about 80% of the total core weight of intragranular filler; (a-iv) from about 0.1% to about 5% of the total core weight of an intragranular binder; and (av) from about 0.1% to about 5% of the total core weight of an intragranular disintegrant; and (b) from about 0.1% to about 5% of the total core weight of an intragranular surfactant; and (b) from about 5% to about 15% of the total core weight of an extragranular filler; (b-ii) from about 0.1% to about 5% of the total core weight of an extragranular disintegrant; and (b-iii) from about 0.1% to about 5% of the total core weight of an extragranular lubricant.

[0084] In some embodiments, the core comprises: (a) (ai) from about 1% to about 80% of the total core weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide; (a-ii) from about 10% to about 80% of the total core weight of intragranular filler; (a-iii) from about 0.1% to about 10% of the total core weight of intragranular binder; (a-iv) from about 0.1% to about 5% of the total core weight of an intragranular disintegrant; and (av) from about 0.1% to about 5% of the total core weight of an intragranular surfactant; and (b) (bi) from about 5% to about 15% of the total core weight of an extragranular filler; (b-ii) from about 0.1% to about 5% of the total core weight of an extragranular disintegrant; and (b-iii) from about 0.1% to about 5% of the total core weight of an extragranular lubricant.

[0085] In some embodiments, the core comprises: (a)(ai) about 1% to about 50% of the total core weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii) about 40% to about 80% of the total core weight of an intragranular filler; (a-iii) (a-iv) an intragranular binder of about 1% to about 5% of the total core weight; and (av) an intragranular surfactant of about 1% to about 5% of the total core weight; and (b) an extragranular component comprising (bi) an extragranular filler of about 5% to about 15% of the total core weight; (b-ii) an extragranular disintegrant of about 1% to about 5% of the total core weight; and (b-iii) an extragranular lubricant of about 0.1% to about 2% of the total core weight.

[0086] In some embodiments, the core comprises: (a) (ai) from about 1% to about 50% of the total core weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide; (a-ii) from about 40% to about 80% of the total core weight of intragranular filler; (a-iii) from about 1% to about 5% of the total core weight of intragranular filler; (a-iv) intragranular components including an intragranular disintegrant of about 1% to about 5% of the total core weight; and (av) intragranular surfactant of about 1% to about 5% of the total core weight; and (b) extragranular components including (bi) extragranular filler of about 5% to about 15% of the total core weight; (b-ii) extragranular disintegrant of about 1% to about 5% of the total core weight; and (b-iii) extragranular lubricant of about 0.1% to about 2% of the total core weight.

[0087] In some embodiments, the core comprises: (a)(ai) about 10% to about 30% of the total core weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii) about 50% to about 70% of the total core weight of intragranular filler; (a-iii) about 10% to about 30% of the total core weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii) about 50% to about 70% of the total core weight of intragranular filler; (a-iv) intragranular binder at about 1% to about 3% of the total core weight; (a-iv) intragranular disintegrant at about 2% to about 4% of the total core weight; and (av) intragranular surfactant at about 1% to about 3% of the total core weight; and (b) extragranular components including (bi) extragranular filler at about 5% to about 15% of the total core weight; (b-ii) extragranular disintegrant at about 1% to about 3% of the total core weight; and (b-iii) extragranular lubricant at about 0.1% to about 1.5% of the total core weight.

[0088] In some embodiments, the core comprises: (a) (ai) from about 10% to about 30% of the total core weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide; (a-ii) from about 50% to about 70% of the total core weight of intragranular filler; (a-iii) from about 1% to about 3% of the total core weight of intragranular filler; (a-iv) intragranular components including an intragranular disintegrant, from about 2% to about 4% of the total core weight; and (av) intragranular surfactant, from about 1% to about 3% of the total core weight; and (b) extragranular components including (bi) extragranular filler, from about 5% to about 15% of the total core weight; (b-ii) extragranular disintegrant, from about 1% to about 3% of the total core weight; and (b-iii) extragranular lubricant, from about 0.1% to about 1.5% of the total core weight.

[0089] In some embodiments, the core comprises: (a)(ai) about 1% to about 10% of the total core weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii) about 60% to about 80% of the total core weight of intragranular filler; (a-iii) about 10% to about 20% of the total core weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii) about 60% to about 80% of the total core weight of intragranular filler; (a-iv) intragranular binder at about 1% to about 3% of the total core weight; (a-iv) intragranular disintegrant at about 2% to about 4% of the total core weight; and (av) intragranular surfactant at about 1% to about 3% of the total core weight; and (b) extragranular components including (bi) extragranular filler at about 5% to about 15% of the total core weight; (b-ii) extragranular disintegrant at about 1% to about 3% of the total core weight; and (b-iii) extragranular lubricant at about 0.1% to about 1.5% of the total core weight.

[0090] In some embodiments, the core comprises: (a) (ai) from about 1% to about 10% of the total core weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide; (a-ii) from about 60% to about 80% of the total core weight of intragranular filler; (a-iii) from about 1% to about 3% of the total core weight of intragranular binder; (a-iv) intragranular components including an intragranular disintegrant of about 2% to about 4% of the total core weight; and (av) intragranular surfactant of about 1% to about 3% of the total core weight; and (b) extragranular components including (bi) extragranular filler of about 5% to about 15% of the total core weight; (b-ii) extragranular disintegrant of about 1% to about 3% of the total core weight; and (b-iii) extragranular lubricant of about 0.1% to about 1.5% of the total core weight.

[0091] In some embodiments, the core comprises: (a)(ai) about 5% of the total core weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii) about 74% of the total core weight of an intragranular filler; (a-iii) intragranular components comprising: (a-iv) intragranular disintegrant of about 3% of the total core weight; and (av) intragranular surfactant of about 2% of the total core weight; and (b)(bi) extragranular filler of about 11% of the total core weight; (b-ii) extragranular disintegrant of about 2% of the total core weight; and (b-iii) extragranular lubricant of about 1% of the total core weight.

[0092] In some embodiments, the core comprises: (a)(ai) about 5% of the total core weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide; (a-ii) about 74% of the total core weight of intragranular filler; (a-iii) about 2% of the total core weight of intragranular binder; (a-iv) about 3% of the total core weight of intragranular disintegrant; and (av) about 2% of the total core weight of intragranular surfactant; and (b)(bi) about 11% of the total core weight of extragranular filler; (b-ii) about 2% of the total core weight of extragranular disintegrant; and (b-iii) about 1% of the total core weight of extragranular lubricant.

[0093] In some embodiments, the core comprises: (a)(ai) about 10% of the total core weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii) about 69% intragranular loading of the total core weight. (a-iii) an intragranular binder of about 2% of the total core weight; (a-iv) an intragranular disintegrant of about 3% of the total core weight; and (av) an intragranular surfactant of about 2% of the total core weight; and (b) an extragranular component comprising (bi) an extragranular filler of about 11% of the total core weight; (b-ii) an extragranular disintegrant of about 2% of the total core weight; and (b-iii) an extragranular lubricant of about 1% of the total core weight.

[0094] In some embodiments, the core comprises: (a)(ai) about 10% of the total core weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide; (a-ii) about 69% of the total core weight of intragranular filler; (a-iii) about 2% of the total core weight of intragranular binder; (a-iv) about 3% of the total core weight of intragranular disintegrant; and (av) about 2% of the total core weight of intragranular surfactant; and (b)(bi) about 11% of the total core weight of extragranular filler; (b-ii) about 2% of the total core weight of extragranular disintegrant; and (b-iii) about 1% of the total core weight of extragranular lubricant.

[0095] In some embodiments, the core comprises: (a)(ai) about 20% of the total core weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii) about 59% intragranular loading of the total core weight. (a-iii) an intragranular binder of about 2% of the total core weight; (a-iv) an intragranular disintegrant of about 3% of the total core weight; and (av) an intragranular surfactant of about 2% of the total core weight; and (b) an extragranular component comprising (bi) an extragranular filler of about 11% of the total core weight; (b-ii) an extragranular disintegrant of about 2% of the total core weight; and (b-iii) an extragranular lubricant of about 1% of the total core weight.

[0096] In some embodiments, the core comprises: (a)(ai) about 20% of the total core weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide; (a-ii) about 59% of the total core weight of intragranular filler; (a-iii) about 2% of the total core weight of intragranular binder; (a-iv) about 3% of the total core weight of intragranular disintegrant; and (av) about 2% of the total core weight of intragranular surfactant; and (b)(bi) about 11% of the total core weight of extragranular filler; (b-ii) about 2% of the total core weight of extragranular disintegrant; and (b-iii) about 1% of the total core weight of extragranular lubricant.

[0097] In some embodiments, the intragranular filler comprises mannitol. In some embodiments, the intragranular filler comprises microcrystalline cellulose. In some embodiments, the intragranular filler consists of mannitol and microcrystalline cellulose. In some embodiments, the intragranular binder is hydroxypropyl cellulose. In some embodiments, the intragranular disintegrant is croscarmellose sodium. In some embodiments, the intragranular surfactant is sodium lauryl sulfate. In some embodiments, the extragranular filler is microcrystalline cellulose. In some embodiments, the extragranular disintegrant is croscarmellose sodium. In some embodiments, the extragranular lubricant is magnesium stearate.

[0098] In some embodiments, the core comprises: (a) (ai) about 1% to about 50% of the total core weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii-1) about 40% to about 60% of the total core weight of mannitol; (a-ii-2) about 10% to about 30% of the total core weight of microcrystalline cellulose; (a-iii) ) intragranular components including: (a-iv) hydroxypropylcellulose at about 1% to about 5% of the total core weight; (a-iv) croscarmellose sodium at about 1% to about 5% of the total core weight; and (av) sodium lauryl sulfate at about 1% to about 5% of the total core weight; and (b) extragranular components including: (bi) microcrystalline cellulose at about 5% to about 15% of the total core weight; (b-ii) croscarmellose sodium at about 1% to about 5% of the total core weight; and (b-iii) extragranular lubricant at about 0.1% to about 2% of the total core weight.

[0099] In some embodiments, the core comprises: (a) (ai) about 1% to about 50% of the total core weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii-1) about 40% to about 60% of the total core weight of mannitol; (a-ii-2) about 10% to about 30% of the total core weight of microcrystalline cellulose; (a-iii) about 10% to about 30% of the total core weight of microcrystalline cellulose; (a-iv) croscarmellose sodium, about 1% to about 5% by weight of the total core; and (av) intragranular components comprising: (b) (bi) microcrystalline cellulose, about 5% to about 15% by weight of the total core; (b-ii) croscarmellose sodium, about 1% to about 5% by weight of the total core; and (b-iii) magnesium stearate, about 0.1% to about 2% by weight of the total core.

[0100] In some embodiments, the core comprises: (a) (ai) about 1% to about 50% of the total core weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide; (a-ii-1) about 40% to about 60% of the total core weight of mannitol; (a-ii-2) about 10% to about 30% of the total core weight of microcrystalline cellulose; (a-iii) about 1% to about 5% of the total core weight of hydroxypropyl cellulose; (a-iv) croscarmellose sodium, about 1% to about 5% of the total core weight; and (av) intragranular components comprising: (b) (bi) microcrystalline cellulose, about 5% to about 15% of the total core weight; (b-ii) croscarmellose sodium, about 1% to about 5% of the total core weight; and (b-iii) magnesium stearate, about 0.1% to about 2% of the total core weight.

[0101] In some embodiments, the core comprises: (a)(ai) about 10% to about 30% of the total core weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii-1) about 40% to about 50% of the total core weight of mannitol; (a-ii-2) about 10% to about 20% of the total core weight of microcrystalline cellulose; (a-iii) (a-iv) croscarmellose sodium, about 2% to about 4% of the total core weight; and (av) intragranular components including sodium lauryl sulfate, about 1% to about 3% of the total core weight; and (b) extragranular components including (bi) microcrystalline cellulose, about 5% to about 15% of the total core weight; (b-ii) croscarmellose sodium, about 1% to about 3% of the total core weight; and (b-iii) extragranular lubricant, about 0.1% to about 1.5% of the total core weight.

[0102] In some embodiments, the core comprises: (a) (ai) about 10% to about 30% of the total core weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii-1) about 40% to about 50% of the total core weight of mannitol; (a-ii-2) about 10% to about 20% of the total core weight of microcrystalline cellulose; (a-iii) about 10% to about 20% of the total core weight of microcrystalline cellulose; (a-iv) croscarmellose sodium, about 2% to about 4% by weight of the total core weight; and (av) intragranular components comprising: (b) (bi) microcrystalline cellulose, about 5% to about 15% by weight of the total core weight; (b-ii) croscarmellose sodium, about 1% to about 3% by weight of the total core weight; and (b-iii) magnesium stearate, about 0.1% to about 1.5% by weight of the total core weight.

[0103] In some embodiments, the core comprises: (a) (ai) about 10% to about 30% of the total core weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide; (a-ii-1) about 40% to about 50% of the total core weight of mannitol; (a-ii-2) about 10% to about 20% of the total core weight of microcrystalline cellulose; (a-iii) about 1% to about 3% of the total core weight of hydroxypropyl cellulose; propyl cellulose; (a-iv) croscarmellose sodium, about 2% to about 4% of the total core weight; and (av) sodium lauryl sulfate, about 1% to about 3% of the total core weight; and (b) extragranular components, including (bi) microcrystalline cellulose, about 5% to about 15% of the total core weight; (b-ii) croscarmellose sodium, about 1% to about 3% of the total core weight; and (b-iii) magnesium stearate, about 0.1% to about 1.5% of the total core weight.

[0104] In some embodiments, the core comprises: (a) (ai) about 1% to about 10% by weight of the total core weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii-1) about 50% to about 60% by weight of the total core weight of mannitol; (a-ii-2) about 15% to about 25% by weight of the total core weight of microcrystalline cellulose; (a-iii) ) intragranular components including: (a-iv) hydroxypropylcellulose at about 1% to about 3% of the total core weight; (a-iv) croscarmellose sodium at about 2% to about 4% of the total core weight; and (av) sodium lauryl sulfate at about 1% to about 3% of the total core weight; and (b) extragranular components including: (bi) microcrystalline cellulose at about 5% to about 15% of the total core weight; (b-ii) croscarmellose sodium at about 1% to about 3% of the total core weight; and (b-iii) extragranular lubricant at about 0.1% to about 1.5% of the total core weight.

[0105] In some embodiments, the core comprises: (a) (ai) about 1% to about 10% by weight of the total core weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii-1) about 50% to about 60% by weight of the total core weight of mannitol; (a-ii-2) about 15% to about 25% by weight of the total core weight of microcrystalline cellulose; (a-iii) about 10% by weight of the total core weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii-3) about 10% by weight of the total core weight of mannitol; (a-ii-4) about 10% by weight of the total core weight of crystalline cellulose; (a-iv) croscarmellose sodium, about 2% to about 4% by weight of the total core weight; and (av) intragranular components comprising: (b) (bi) microcrystalline cellulose, about 5% to about 15% by weight of the total core weight; (b-ii) croscarmellose sodium, about 1% to about 3% by weight of the total core weight; and (b-iii) magnesium stearate, about 0.1% to about 1.5% by weight of the total core weight.

[0106] In some embodiments, the core comprises: (a) (ai) about 1% to about 10% by weight of the total core weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide; (a-ii-1) about 50% to about 60% by weight of the total core weight of mannitol; (a-ii-2) about 15% to about 25% by weight of the total core weight of microcrystalline cellulose; (a-iii) about 1% to about 3% by weight of the total core weight of hydroxypropyl cellulose; (a-iv) intragranular components comprising: cyclopropyl cellulose; (a-iv) croscarmellose sodium, about 2% to about 4% of the total core weight; and (av) sodium lauryl sulfate, about 1% to about 3% of the total core weight; and (b) extragranular components comprising: (bi) microcrystalline cellulose, about 5% to about 15% of the total core weight; (b-ii) croscarmellose sodium, about 1% to about 3% of the total core weight; and (b-iii) magnesium stearate, about 0.1% to about 1.5% of the total core weight.

[0107] In some embodiments, the core comprises: (a)(ai) about 20% of the total core weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii-1) about 44% of the total core weight of mannitol; (a-ii-2) about 15% of the total core weight of microcrystalline cellulose; (a-iii) intragranular components including hydroxypropyl cellulose at about 2% of the total core weight; (a-iv) croscarmellose sodium at about 3% of the total core weight; and (av) sodium lauryl sulfate at about 2% of the total core weight; and (b) extragranular components including (bi) microcrystalline cellulose at about 11% of the total core weight; (b-ii) croscarmellose sodium at about 2% of the total core weight; and (b-iii) extragranular lubricant at about 1% of the total core weight.

[0108] In some embodiments, the core comprises: (a) (ai) about 20% of the total core weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii-1) about 44% of the total core weight of mannitol; (a-ii-2) about 15% of the total core weight of microcrystalline cellulose; (a-i ii) intragranular components comprising: (a-iv) croscarmellose sodium at about 3% of the total core weight; and (av) sodium lauryl sulfate at about 2% of the total core weight; and (b) extragranular components comprising: (bi) microcrystalline cellulose at about 11% of the total core weight; (b-ii) croscarmellose sodium at about 2% of the total core weight; and (b-iii) magnesium stearate at about 1% of the total core weight.

[0109] In some embodiments, the core comprises: (a) (ai) about 20% (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide by weight of the total core; (a-ii-1) about 44% mannitol by weight of the total core; (a-ii-2) about 15% microcrystalline cellulose by weight of the total core; (a-iii) about 2% hydrazine by weight of the total core. (a-iv) intragranular components comprising croscarmellose sodium at about 3% of the total core weight; and (av) sodium lauryl sulfate at about 2% of the total core weight; and (b) extragranular components comprising (bi) microcrystalline cellulose at about 11% of the total core weight; (b-ii) croscarmellose sodium at about 2% of the total core weight; and (b-iii) magnesium stearate at about 1% of the total core weight.

[0110] In some embodiments, the core comprises: (a)(ai) about 10% of the total core weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii-1) about 50% of the total core weight of mannitol; (a-ii-2) about 19% of the total core weight of microcrystalline cellulose; (a-iii) intragranular components including hydroxypropyl cellulose at about 2% of the total core weight; (a-iv) croscarmellose sodium at about 3% of the total core weight; and (av) sodium lauryl sulfate at about 2% of the total core weight; and (b) extragranular components including (bi) microcrystalline cellulose at about 11% of the total core weight; (b-ii) croscarmellose sodium at about 2% of the total core weight; and (b-iii) extragranular lubricant at about 1% of the total core weight.

[0111] In some embodiments, the core comprises: (a) (ai) about 10% of the total core weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii-1) about 50% of the total core weight of mannitol; (a-ii-2) about 19% of the total core weight of microcrystalline cellulose; (a-i ii) intragranular components comprising: (a-iv) croscarmellose sodium at about 3% of the total core weight; and (av) sodium lauryl sulfate at about 2% of the total core weight; and (b) extragranular components comprising: (bi) microcrystalline cellulose at about 11% of the total core weight; (b-ii) croscarmellose sodium at about 2% of the total core weight; and (b-iii) magnesium stearate at about 1% of the total core weight.

[0112] In some embodiments, the core comprises: (a) (ai) about 10% (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide by weight of the total core; (a-ii-1) about 50% mannitol by weight of the total core; (a-ii-2) about 19% microcrystalline cellulose by weight of the total core; (a-iii) about 2% hydrazine by weight of the total core. (a-iv) intragranular components comprising croscarmellose sodium at about 3% of the total core weight; and (av) sodium lauryl sulfate at about 2% of the total core weight; and (b) extragranular components comprising (bi) microcrystalline cellulose at about 11% of the total core weight; (b-ii) croscarmellose sodium at about 2% of the total core weight; and (b-iii) magnesium stearate at about 1% of the total core weight.

[0113] In some embodiments, the core comprises: (a)(ai) about 5% by weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii-1) about 54% by weight of mannitol; (a-ii-2) about 20% by weight of microcrystalline cellulose; (a-iii) about 2% by weight of hydroxypropylcellulose; (a-iv) about 3% by weight of croscarmellose sodium; and (av) about 2% by weight of sodium lauryl sulfate; and (b)(bi) about 11% by weight of microcrystalline cellulose; (b-ii) about 2% by weight of croscarmellose sodium; and (b-iii) about 1% by weight of an extragranular lubricant.

[0114] In some embodiments, the core comprises: (a)(ai) about 5% by weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii-1) about 54% by weight of mannitol; (a-ii-2) about 20% by weight of microcrystalline cellulose; (a-iii) about 2% by weight of hydroxypropylcellulose; (a-iv) about 3% by weight of croscarmellose sodium; and (av) about 2% by weight of sodium lauryl sulfate; and (b)(bi) about 11% by weight of microcrystalline cellulose; (b-ii) about 2% by weight of croscarmellose sodium; and (b-iii) about 1% by weight of magnesium stearate.

[0115] In some embodiments, the core comprises (a)(ai) intragranular components comprising about 5% by weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide; (a-ii-1) about 54% by weight of mannitol; (a-ii-2) about 20% by weight of microcrystalline cellulose; (a-iii) about 2% by weight of hydroxypropylcellulose; (a-iv) about 3% by weight of croscarmellose sodium; and (av) about 2% by weight of sodium lauryl sulfate; and (b)(bi) about 11% by weight of microcrystalline cellulose; (b-ii) about 2% by weight of croscarmellose sodium; and (b-iii) about 1% by weight of magnesium stearate.

[0116] In some embodiments, the tablet comprises a coating layer comprising a coating agent. In some embodiments, the coating agent is selected from the group consisting of Opadry QX White 21A180025, Opadry I and Opadry II. In some embodiments, the coating agent is Opadry QX White 21A180025. In some embodiments, the tablet comprises about 0.5% to about 10% of the total core weight of the coating agent. In some embodiments, the tablet comprises about 1% to about 5% of the total core weight of the coating agent. In some embodiments, the tablet comprises about 2% to about 4% of the total core weight of the coating agent. In some embodiments, the tablet comprises about 3% of the total core weight of the coating agent. In some embodiments, the tablet comprises about 0.5% to about 10% of the total core weight of Opadry QX White 21A180025. In some embodiments, the tablet comprises about 1% to about 5% of the total core weight of Opadry QX White 21A180025. In some embodiments, the tablet comprises about 2% to about 4% of the total core weight of Opadry QX White 21A180025. In some embodiments, the tablet comprises about 3% of the total core weight of Opadry QX White 21A180025.

[0117] In some embodiments, the total core weight is about 50 mg. In some embodiments, the core comprises: (a)(ai) about 2.5 mg of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii-1) about 27 mg of mannitol of the total core weight; (a-ii-2) about 10 mg of microcrystalline cellulose of the total core weight; (a-iii) (a-iv) intragranular components comprising about 1 mg of hydroxypropylcellulose by total core weight; (a-iv) about 1.5 mg of croscarmellose sodium by total core weight; and (av) about 1 mg of sodium lauryl sulfate by total core weight; and (b) extragranular components comprising (bi) about 5.5 mg of microcrystalline cellulose by total core weight; (b-ii) about 1 mg of croscarmellose sodium by total core weight; and (b-iii) about 0.5 mg of extragranular lubricant by total core weight. In some embodiments, the core comprises: (a)(ai) about 2.5 mg of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii-1) about 27 mg of mannitol by total core weight; (a-ii-2) about 10 mg of microcrystalline cellulose by total core weight; (a-iii) about 10 mg of microcrystalline cellulose by total core weight; (a-iv) intragranular components comprising about 1 mg of hydroxypropylcellulose by weight of the total core; (a-iv) about 1.5 mg of croscarmellose sodium by weight of the total core; and (av) about 1 mg of sodium lauryl sulfate by weight of the total core; and (b) extragranular components comprising: (bi) about 5.5 mg of microcrystalline cellulose by weight of the total core; (b-ii) about 1 mg of croscarmellose sodium by weight of the total core; and (b-iii) about 0.5 mg of magnesium stearate by weight of the total core.In some embodiments, the core comprises: (a)(ai) about 2.5 mg of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide; (a-ii-1) about 27 mg of mannitol by total core weight; (a-ii-2) about 10 mg of microcrystalline cellulose by total core weight; (a-iii) about 1 mg of hydroxypropyl cellulose by total core weight. (a-iv) about 1.5 mg of croscarmellose sodium by total core weight; and (av) about 1 mg of sodium lauryl sulfate by total core weight; and (b) about 5.5 mg of croscarmellose sodium by total core weight; (b-ii) about 1 mg of croscarmellose sodium by total core weight; and (b-iii) about 0.5 mg of magnesium stearate by total core weight. In some embodiments, the tablet comprises about 1.5 mg of a coating agent. In some embodiments, the coating agent is Opadry QX White 21A180025.

[0118] In some embodiments, the total core weight is about 100 mg. In some embodiments, the core comprises: (a)(ai) about 20 mg of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii-1) about 44 mg of mannitol of the total core weight; (a-ii-2) about 15 mg of microcrystalline cellulose of the total core weight; (a-ii-3) about 15 mg of microcrystalline cellulose of the total core weight; (a-ii-4) about 15 mg of microcrystalline cellulose of the total core weight; (a-ii-5) about 15 mg of microcrystalline cellulose of the total core weight; (a-ii-6) about 15 mg of microcrystalline cellulose of the total core weight; (a-ii-7) about 15 mg of microcrystalline cellulose of the total core weight; (a-ii-8) about 15 mg of microcrystalline cellulose of the total core weight; (a-ii-9) about 15 mg of microcrystalline cellulose of the total core weight; (a-ii-10) about 15 mg of microcrystalline cellulose of the total core weight; (a-ii-11) about 15 mg of microcrystalline cellulose of the total core weight; (a-ii-12) about 15 mg of microcrystalline cellulose of the total core weight; (a-ii-13) about 15 mg of microcrystalline cellulose of the total core weight; (a-ii-14) about 15 mg of microcrystalline cellulose of the total core weight; (a-ii-15) about 15 mg of microcrystalline cellulose of the total core weight; (a-ii-16) about 15 mg of microcrystalline cellulose of the total core weight; (a-ii-17) about (i) intragranular components comprising: (a-iv) croscarmellose sodium, about 3 mg by total core weight; and (av) sodium lauryl sulfate, about 2 mg by total core weight; and (b) extragranular components comprising: (bi) microcrystalline cellulose, about 11 mg by total core weight; (b-ii) croscarmellose sodium, about 2 mg by total core weight; and (b-iii) extragranular lubricant, about 1 mg by total core weight. In some embodiments, the core comprises: (a)(ai) about 20 mg of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii-1) about 44 mg of mannitol of total core weight; (a-ii-2) about 15 mg of microcrystalline cellulose of total core weight; (a-iii) about 10 mg of cellulose of total core weight; (a-iv) intragranular components comprising about 2 mg of hydroxypropylcellulose by total core weight; (a-iv) about 3 mg of croscarmellose sodium by total core weight; and (av) about 2 mg of sodium lauryl sulfate by total core weight; and (b) extragranular components comprising: (bi) about 11 mg of microcrystalline cellulose by total core weight; (b-ii) about 2 mg of croscarmellose sodium by total core weight; and (b-iii) about 1 mg of magnesium stearate by total core weight.In some embodiments, the core comprises: (a)(ai) about 20 mg of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide; (a-ii-1) about 44 mg of mannitol by total core weight; (a-ii-2) about 15 mg of microcrystalline cellulose by total core weight; (a-iii) about 2 mg of hydroxypropyl cellulose by total core weight; (a-iv) intragranular components comprising about 3 mg of croscarmellose sodium by total core weight; and (av) about 2 mg of sodium lauryl sulfate by total core weight; and (b) extragranular components comprising: (bi) about 11 mg of microcrystalline cellulose by total core weight; (b-ii) about 2 mg of croscarmellose sodium by total core weight; and (b-iii) about 1 mg of magnesium stearate by total core weight. In some embodiments, the core comprises: (a)(ai) about 5 mg of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii-1) about 54 mg of mannitol; (a-ii-2) about 20 mg of microcrystalline cellulose; (a-iii) about 2 mg of hydroxypropylcellulose; (a-iv) about 3 mg of croscarmellose sodium; and (av) about 2 mg of sodium lauryl sulfate; and (b)(bi) about 11 mg of microcrystalline cellulose; (b-ii) about 2 mg of croscarmellose sodium; and (b-iii) about 1 mg of extragranular lubricant.In some embodiments, the core comprises: (a)(ai) intragranular components comprising about 5 mg of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii-1) about 54 mg of mannitol; (a-ii-2) about 20 mg of microcrystalline cellulose; (a-iii) about 2 mg of hydroxypropylcellulose; (a-iv) about 3 mg of croscarmellose sodium; and (av) about 2 mg of sodium lauryl sulfate; and (b)(bi) about 11 mg of microcrystalline cellulose; (b-ii) about 2 mg of croscarmellose sodium; and (b-iii) about 1 mg of magnesium stearate. In some embodiments, the core comprises (a)(ai) about 5 mg of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide; (a-ii-1) about 54 mg of mannitol; (a-ii-2) about 20 mg of microcrystalline cellulose; (a-iii) about 2 mg of hydroxypropylcellulose; (a-iv) about 3 mg of croscarmellose sodium; and (av) about 2 mg of sodium lauryl sulfate; and (b)(bi) about 11 mg of microcrystalline cellulose; (b-ii) about 2 mg of croscarmellose sodium; and (b-iii) about 1 mg of magnesium stearate. In some embodiments, the tablet comprises about 3 mg of a coating agent. In some embodiments, the coating is Opadry QX White 21A180025.

[0119] In some embodiments, the total core weight is about 200 mg. In some embodiments, the core comprises: (a)(ai) about 40 mg of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof, of the total core weight; (a-ii-1) about 88 mg of mannitol, of the total core weight; (a-ii-2) about 30 mg of microcrystalline cellulose, of the total core weight; (a-ii-3) about 30 mg of microcrystalline cellulose, of the total core weight; (a-ii-4) about 30 mg of microcrystalline cellulose, of the total core weight; (a-ii-5) about 30 mg of microcrystalline cellulose, of the total core weight; (a-ii-6) about 30 mg of microcrystalline cellulose, of the total core weight; (a-ii-7) about 30 mg of microcrystalline cellulose, of the total core weight; (a-ii-8) about 30 mg of microcrystalline cellulose, of the total core weight; (a-ii-9) about 30 mg of microcrystalline cellulose, of the total core weight; (a-ii-10) about 30 mg of microcrystalline cellulose, of the total core weight; (a-ii-11) about 30 mg of microcrystalline cellulose, of the total core weight; (a-ii-12) about 30 mg of microcrystalline cellulose, of the total core weight; (a-ii-13) about 30 mg of microcrystalline cellulose, of the total core weight; (a-ii-14) about 30 mg of microcrystalline cellulose, of the total core weight; (a-ii-15) about 30 mg of microcrystalline cellulose, of the total core weight; (a-ii-16) about 30 mg (a-iii) intragranular components comprising: (a-iv) croscarmellose sodium, about 6 mg by total core weight; and (av) sodium lauryl sulfate, about 4 mg by total core weight; and (b) extragranular components comprising: (bi) microcrystalline cellulose, about 22 mg by total core weight; (b-ii) croscarmellose sodium, about 4 mg by total core weight; and (b-iii) extragranular lubricant, about 2 mg by total core weight. In some embodiments, the core comprises: (a)(ai) about 40 mg of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof, of total core weight; (a-ii-1) about 88 mg of mannitol, of total core weight; (a-ii-2) about 30 mg of microcrystalline cellulose, of total core weight; (a-ii-3) about 30 mg of microcrystalline cellulose, of total core weight; (i) intragranular components comprising: (a-iv) croscarmellose sodium, about 6 mg by total core weight; and (av) sodium lauryl sulfate, about 4 mg by total core weight; and (b) extragranular components comprising: (bi) microcrystalline cellulose, about 22 mg by total core weight; (b-ii) croscarmellose sodium, about 4 mg by total core weight; and (b-iii) magnesium stearate, about 2 mg by total core weight.In some embodiments, the core comprises: (a)(ai) about 40 mg of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide by total core weight; (a-ii-1) about 88 mg of mannitol by total core weight; (a-ii-2) about 30 mg of microcrystalline cellulose by total core weight; (a-iii) about 4 mg of hydrochloride by total core weight; (a-iv) intragranular components comprising about 6 mg of croscarmellose sodium by total core weight; and (av) about 4 mg of sodium lauryl sulfate by total core weight; and (b) extragranular components comprising: (bi) about 22 mg of microcrystalline cellulose by total core weight; (b-ii) about 4 mg of croscarmellose sodium by total core weight; and (b-iii) about 2 mg of magnesium stearate by total core weight. In some embodiments, the core comprises: (a)(ai) intragranular components comprising about 10 mg of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii-1) about 108 mg of mannitol; (a-ii-2) about 40 mg of microcrystalline cellulose; (a-iii) about 4 mg of hydroxypropylcellulose; (a-iv) about 6 mg of croscarmellose sodium; and (av) about 4 mg of sodium lauryl sulfate; and (b)(bi) about 22 mg of microcrystalline cellulose; (b-ii) about 4 mg of croscarmellose sodium; and (b-iii) about 2 mg of extragranular lubricant.In some embodiments, the core comprises: (a)(ai) intragranular components comprising about 10 mg of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii-1) about 108 mg of mannitol; (a-ii-2) about 40 mg of microcrystalline cellulose; (a-iii) about 4 mg of hydroxypropylcellulose; (a-iv) about 6 mg of croscarmellose sodium; and (av) about 4 mg of sodium lauryl sulfate; and (b)(bi) about 22 mg of microcrystalline cellulose; (b-ii) about 4 mg of croscarmellose sodium; and (b-iii) about 2 mg of magnesium stearate. In some embodiments, the core comprises (a)(ai) about 10 mg of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide; (a-ii-1) about 108 mg of mannitol; (a-ii-2) about 40 mg of microcrystalline cellulose; (a-iii) about 4 mg of hydroxypropylcellulose; (a-iv) about 6 mg of croscarmellose sodium; and (av) about 4 mg of sodium lauryl sulfate; and (b)(bi) about 22 mg of microcrystalline cellulose; (b-ii) about 4 mg of croscarmellose sodium; and (b-iii) about 2 mg of magnesium stearate. In some embodiments, the tablet comprises about 6 mg of a coating agent. In some embodiments, the coating is Opadry QX White 21A180025.

[0120] In some embodiments, the total core weight is about 70 mg. In some embodiments, the core comprises: (a)(ai) about 7 mg of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii-1) about 35 mg of mannitol; (a-ii-2) about 13.3 mg of crystalline cellulose; (a-iii) about 1.4 mg hydroxypropyl cellulose; (a-iv) about 2.1 mg croscarmellose sodium; and (av) about 1.4 mg sodium lauryl sulfate; and (b) about 7.7 mg microcrystalline cellulose; (b-ii) about 1.4 mg croscarmellose sodium; and (b-iii) about 0.7 mg extragranular lubricant. In some embodiments, the core comprises: (a)(ai) about 7 mg of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii-1) about 35 mg of mannitol; (a-ii-2) about 13.3 mg of crystalline cellulose; (a-iii) about 1.4 mg hydroxypropylcellulose; (a-iv) about 2.1 mg croscarmellose sodium; and (av) about 1.4 mg magnesium stearate; and (b) about 7.7 mg microcrystalline cellulose; (b-ii) about 1.4 mg croscarmellose sodium; and (b-iii) about 0.7 mg extragranular lubricant.In some embodiments, the core comprises (a)(ai) about 7 mg of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide; (a-ii-1) about 35 mg of mannitol; (a-ii-2) about 13.3 mg of microcrystalline cellulose; (a-iii) about 1.4 mg of hydroxypropylcellulose; (a-iv) about 2.1 mg of croscarmellose sodium; and (av) about 1.4 mg of magnesium stearate; and (b)(bi) about 7.7 mg of microcrystalline cellulose; (b-ii) about 1.4 mg of croscarmellose sodium; and (b-iii) about 0.7 mg of extragranular lubricant. In some embodiments, the tablet comprises about 2.1 mg of coating agent. In some embodiments, the coating is Opadry QX White 21A180025.

[0121] In some embodiments, the total core weight is about 400 mg. In some embodiments, the core comprises: (a)(ai) about 40 mg of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii-1) about 200 mg of mannitol; (a-ii-2) about 76 mg of microcrystalline cellulose; (a-iii) about 8 mg of hydroxypropylcellulose; (a-iv) about 12 mg of croscarmellose sodium; and (av) about 8 mg of sodium lauryl sulfate; and (b)(bi) about 44 mg of microcrystalline cellulose; (b-ii) about 8 mg of croscarmellose sodium; and (b-iii) about 4 mg of extragranular lubricant. In some embodiments, the core comprises: (a)(ai) intragranular components comprising about 40 mg of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii-1) about 200 mg of mannitol; (a-ii-2) about 76 mg of microcrystalline cellulose; (a-iii) about 8 mg of hydroxypropylcellulose; (a-iv) about 12 mg of croscarmellose sodium; and (av) about 8 mg of sodium lauryl sulfate; and (b)(bi) about 44 mg of microcrystalline cellulose; (b-ii) about 8 mg of croscarmellose sodium; and (b-iii) about 4 mg of magnesium stearate.In some embodiments, the core comprises (a)(ai) about 40 mg of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide; (a-ii-1) about 200 mg of mannitol; (a-ii-2) about 76 mg of microcrystalline cellulose; (a-iii) about 8 mg of hydroxypropylcellulose; (a-iv) about 12 mg of croscarmellose sodium; and (av) about 8 mg of sodium lauryl sulfate; and (b)(bi) about 44 mg of microcrystalline cellulose; (b-ii) about 8 mg of croscarmellose sodium; and (b-iii) about 4 mg of magnesium stearate. In some embodiments, the tablet comprises about 12 mg of a coating agent. In some embodiments, the coating is Opadry QX White 21A180025. Filler

[0122] Fillers are substances that can be added to the components of pharmaceutical compositions or formulations to increase the bulk weight of the substance to be formulated, for example tableted, to achieve the desired weight. Fillers include, but are not limited to, powdered cellulose, microcrystalline cellulose, silicified microcrystalline cellulose, kaolin, corn starch, maize starch, starch derivatives, pregelatinized starch, calcium phosphate, calcium hydrogen phosphate, dicalcium phosphate, tricalcium phosphate, compressible sugar, sugar alcohol, mannitol, sorbitol, maltitol, xylitol, lactitol, lactose, dextrose, maltose, sucrose, glucose, fructose, saccharose, raffinose, dextrates, trehalose, maltodextrin, etc. In some embodiments, the filler is selected from the group consisting of powdered cellulose, microcrystalline cellulose, silicified microcrystalline cellulose, kaolin, corn starch, maize starch, starch derivatives, pregelatinized starch, calcium phosphate, calcium hydrogen phosphate, dicalcium phosphate, tricalcium phosphate, compressible sugar, sugar alcohol, mannitol, sorbitol, maltitol, xylitol, lactitol, lactose, dextrose, maltose, sucrose, glucose, fructose, saccharose, raffinose, dextrates, trehalose, maltodextrin, and mixtures of any of the above. In some embodiments, the filler is selected from the group consisting of microcrystalline cellulose, mannitol, and mixtures of any of the above. In some embodiments, the filler comprises mannitol. In some embodiments, the filler comprises microcrystalline cellulose. In some embodiments, the filler comprises microcrystalline cellulose and mannitol. Binder

[0123] Binders are substances that can be added to the components of a pharmaceutical composition or formulation to act as an adhesive to bind together powders, granules, and other dry ingredients contained in the pharmaceutical composition or formulation, and impart the desired mechanical strength to the pharmaceutical composition or formulation. Binders include, but are not limited to, gum arabic, gum acacia, alginates, alginic acid, corn starch, copolyvidone, polyvinylpyrrolidone, gelatin, glyceryl behenate, hydroxyethylcellulose, hydroxypropylcellulose, carboxymethylcellulose, calcium carboxymethylcellulose, sodium carboxymethylcellulose, methylcellulose, hypromellose, lactose, polyvinyl alcohol, povidone, polyethylene oxide, polyacrylates, potato starch, pregelatinized starch, sodium alginate, sodium starch, sodium carboxymethylcellulose, starch, and the like. In some embodiments, the binder is selected from the group consisting of gum arabic, gum acacia, alginate, alginic acid, corn starch, copolyvidone, polyvinylpyrrolidone, gelatin, glyceryl behenate, hydroxyethyl cellulose, hydroxypropyl cellulose, carboxymethyl cellulose, calcium carboxymethyl cellulose, sodium carboxymethyl cellulose, methyl cellulose, hypromellose, lactose, polyvinyl alcohol, povidone, polyethylene oxide, polyacrylate, potato starch, pregelatinized starch, sodium alginate, sodium starch, sodium carboxymethyl cellulose, starch, and mixtures of any of the above. In some embodiments, the binder is selected from the group consisting of hydroxyethyl cellulose, hydroxypropyl cellulose, carboxymethyl cellulose, calcium carboxymethyl cellulose, sodium carboxymethyl cellulose, methyl cellulose, hypromellose, sodium carboxymethyl cellulose, and mixtures of any of the above. In some embodiments, the binder is hydroxypropyl cellulose. Disintegrants

[0124] Disintegrants are substances that can be added to pharmaceutical compositions or formulations to aid in their deagglomeration. Disintegrants can be formulated to cause rapid disintegration of solid pharmaceutical compositions or formulations when exposed to moisture. Disintegrants include, but are not limited to, alginic acid, croscarmellose sodium, cellulose, calcium carboxymethylcellulose, sodium carboxymethylcellulose, microcrystalline cellulose, crospovidone, sodium starch glycolate, low-substituted hydroxypropylcellulose, polacrilin potassium, pregelatinized starch, partially hydrolyzed starch, sodium carboxymethyl starch, starch, sodium alginate, sodium carboxymethylcellulose, and mixtures of any of the above. In some embodiments, the disintegrant is selected from the group consisting of alginic acid, croscarmellose sodium, cellulose, carboxymethylcellulose calcium, carboxymethylcellulose sodium, microcrystalline cellulose, crospovidone, sodium starch glycolate, low-substituted hydroxypropylcellulose, polacrilin potassium, pregelatinized starch, partially hydrolyzed starch, sodium carboxymethylstarch, starch, sodium alginate, sodium carboxymethylcellulose, and mixtures of any of the above. In some embodiments, the disintegrant is selected from the group consisting of croscarmellose sodium, cellulose, carboxymethylcellulose calcium, carboxymethylcellulose sodium, microcrystalline cellulose, low-substituted hydroxypropylcellulose, and mixtures of any of the above. In some embodiments, the disintegrant is croscarmellose sodium. Surfactants

[0125] A surfactant is a substance that can be added to a pharmaceutical composition or formulation to reduce the surface tension between two liquids or between a solid and a liquid, thereby improving solubility. Surfactants include, but are not limited to, cetylpyridine chloride, heptadecaethyleneoxycetanol, lecithin, polyoxyethylene stearate, nonoxynol 9, nonoxynol 10, octoxynol 9, sorbitan fatty acid esters, Span 20, Span 40, Span 60, Span 80, Span 85, polysorbate, polysorbate 20, polysorbate 21, polysorbate 40, polysorbate 60, polysorbate 61, polysorbate 65, polysorbate 80, fatty alginate, and the like. These include sodium cholate sulfate, sodium lauryl sulfate, sodium sulfosuccinate, sodium dioctyl sulfosuccinate, partial esters of fatty acids and alcohols, glyceryl monostearate, glyceryl monooleate, ethers of fatty alcohols and polyoxyethylene, esters of fatty acids and polyoxyethylene, copolymers of ethylene oxide and propylene oxide (Pluronic®), benzalkonium chloride, ethoxylated triglycerides, and the like. In some embodiments, the surfactant is selected from the group consisting of sodium salts of fatty alcohol sulfates, sodium lauryl sulfate, sodium dodecyl sulfate, and mixtures of any of the foregoing. In some embodiments, the surfactant is sodium lauryl sulfate. lubricant

[0126] A lubricant is a substance that can be added to the components of the composition of the present invention to reduce adhesion of the solid formulation to the equipment used to produce the unit dose form. Lubricants include, but are not limited to, hydrogenated castor oil, magnesium stearate, glyceryl monostearate, calcium stearate, glyceryl behenate, glycerol distearate, glyceryl dipalmitostearate, behenoyl polyoxyl-8 glyceride, sodium stearyl fumarate, stearic acid, talc, zinc stearate, mineral oil, polyethylene glycol, poloxamer, sodium lauryl sulfate, and the like. In some embodiments, the lubricant is selected from the group consisting of hydrogenated castor oil, magnesium stearate, calcium stearate, zinc stearate, and mixtures of any of the above. In some embodiments, the lubricant is magnesium stearate. Coating Agent

[0127] A coating agent is a substance that can be added as an outer layer surrounding a component of a pharmaceutical composition or formulation. Surfactants include, but are not limited to, Opadry QX White 21A180025, Opadry I, Opadry II, and the like. In some embodiments, the coating agent is selected from the group consisting of Opadry QX White 21A180025, Opadry I, and Opadry II. In some embodiments, the coating agent is Opadry QX White 21A180025. Additional Agents

[0128] Pharmaceutical compositions or formulations intended for the preparation of oral dosage forms (e.g., tablets and capsules) may further contain one or more agents selected from the group consisting of sweetening agents, flavoring agents, coloring agents and preservatives in order to obtain pharma- ceutically elegant and palatable preparations. method

[0129] Similarly, the present invention relates to a method for preparing a granule comprising the steps of: (1) preparing a granule comprising (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph or pharma- ceutically acceptable salt thereof, an intragranular filler, an intragranular binder, an intragranular disintegrant and an intragranular surfactant; Provided herein is a method for making the tablets described herein, comprising the steps of: (1) milling granules comprising 1,2,3,4,5-trimethylsilyl ether, or a hydrate, solvate, polymorph or pharma- ceutically acceptable salt thereof, an intragranular filler, an intragranular binder, an intragranular disintegrant and an intragranular surfactant to form an intragranular component; (2) blending the intragranular component with an extragranular filler, an extragranular disintegrant and an extragranular lubricant to form a final blended mixture; (3) compressing the final blended mixture to form cores; and (4) optionally coating the cores with a coating layer.

[0130] In some embodiments, the step of preparing a granule comprising (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph or pharma- ceutically acceptable salt thereof, an intragranular filler, an intragranular binder, an intragranular disintegrant and an intragranular surfactant comprises a wet granulation step. In some embodiments, the wet granulation step is carried out using a high shear granulator. In some embodiments, the wet granulation step is carried out using a fluid bed granulator. In some embodiments, the wet granulation step is carried out using a granulator drum. In some embodiments, the wet granulation step further comprises a wet milling step. In some embodiments, the wet milling step is carried out using a conical mill. In some embodiments, the wet milling step is carried out using a turbo mill or a hammer mill. In some embodiments, the step of preparing a granule comprising (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph or pharma- ceutically acceptable salt thereof, an intragranular filler, an intragranular binder, an intragranular disintegrant and an intragranular surfactant further comprises drying the granule. In some embodiments, drying the granule is performed in a fluid bed dryer. In some embodiments, drying the granule is performed in a tray dryer. In some embodiments, drying the granule is performed in a belt dryer. In some embodiments, drying the granule is performed in a vacuum tray dryer. In some embodiments, drying the granule is performed in a rotary dryer.

[0131] In some embodiments, the step of milling the granules comprising (R)—N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph or pharma- ceutically acceptable salt thereof, an intragranular filler, an intragranular binder, an intragranular disintegrant and an intragranular surfactant is performed using a conical mill. In some embodiments, the step of milling the granules comprising (R)—N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph or pharma- ceutically acceptable salt thereof, intragranular filler, intragranular binder, intragranular disintegrant and intragranular surfactant is performed using a turbo mill or a hammer mill.

[0132] In some embodiments, the step of blending the intragranular component with the extragranular filler, the extragranular disintegrant and the extragranular lubricant is carried out in a V-blender. In some embodiments, the step of blending the intragranular component with the extragranular filler, the extragranular disintegrant and the extragranular lubricant is carried out in an octagonal blender. In some embodiments, the step of blending the intragranular component with the extragranular filler, the extragranular disintegrant and the extragranular lubricant is carried out in a mass blender. In some embodiments, the step of blending the intragranular component with the extragranular filler, the extragranular disintegrant and the extragranular lubricant is carried out in a double cone blender. In some embodiments, the step of blending the intragranular component with the extragranular filler, the extragranular disintegrant and the extragranular lubricant is carried out in a vertical blender.

[0133] In some embodiments, compressing the final blended mixture to form cores is performed using a rotary tablet press. In some embodiments, compressing the final blended mixture to form cores is performed using a single punch tablet press.

[0134] In some embodiments, the method includes coating the core with a coating layer. In some embodiments, coating the core with the coating layer is performed using a conventional coating pan, such as a Pelligrini pan, an immersion sword pan, or an immersion tube pan. In some embodiments, coating the core with the coating layer is performed using a perforated coating pan, such as an Accela-Cota pan, a Hi-Coater, a Doria Coater, a Glatt pan coating apparatus, a Huttlin butterfly pan, or a Dumoulin coating apparatus.

[0135] In some embodiments, the method includes the steps of: (1) preparing a granule comprising (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, an intragranular filler, an intragranular binder, an intragranular disintegrant, and an intragranular surfactant; (2) preparing a granule comprising (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, an intragranular filler, an intragranular binder, an intragranular disintegrant, and an intragranular surfactant; There is provided a method of making the tablets described herein, comprising the steps of: (1) milling granules comprising 4-carboxamide, intragranular filler, intragranular binder, intragranular disintegrant and intragranular surfactant to form an intragranular component; (2) blending the intragranular component with an extragranular filler, an extragranular disintegrant and an extragranular lubricant to form a final blended mixture; (3) compressing the final blended mixture to form cores; and (4) optionally coating the cores with a coating layer.

[0136] In some embodiments, the step of preparing a granule comprising (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, an intragranular filler, an intragranular binder, an intragranular disintegrant and an intragranular surfactant comprises a wet granulation step. In some embodiments, the wet granulation step is carried out using a high shear granulator. In some embodiments, the wet granulation step is carried out using a fluid bed granulator. In some embodiments, the wet granulation step is carried out using a granulator drum. In some embodiments, the wet granulation step further comprises a wet milling step. In some embodiments, the wet milling step is carried out using a conical mill. In some embodiments, the wet milling step is carried out using a turbo mill or a hammer mill. In some embodiments, the step of preparing a granule comprising (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, an intragranular filler, an intragranular binder, an intragranular disintegrant, and an intragranular surfactant further comprises drying the granule. In some embodiments, drying the granule is performed in a fluid bed dryer. In some embodiments, drying the granule is performed in a tray dryer. In some embodiments, drying the granule is performed in a belt dryer. In some embodiments, drying the granule is performed in a vacuum tray dryer. In some embodiments, drying the granule is performed in a rotary dryer.

[0137] In some embodiments, the step of milling the granules containing (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, intragranular filler, intragranular binder, intragranular disintegrant and intragranular surfactant is carried out using a conical mill. In some embodiments, the step of milling the granules containing (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, intragranular filler, intragranular binder, intragranular disintegrant and intragranular surfactant is carried out using a turbo mill or a hammer mill.

[0138] In some embodiments, the step of blending the intragranular component with the extragranular filler, the extragranular disintegrant and the extragranular lubricant is carried out in a V-blender. In some embodiments, the step of blending the intragranular component with the extragranular filler, the extragranular disintegrant and the extragranular lubricant is carried out in an octagonal blender. In some embodiments, the step of blending the intragranular component with the extragranular filler, the extragranular disintegrant and the extragranular lubricant is carried out in a mass blender. In some embodiments, the step of blending the intragranular component with the extragranular filler, the extragranular disintegrant and the extragranular lubricant is carried out in a double cone blender. In some embodiments, the step of blending the intragranular component with the extragranular filler, the extragranular disintegrant and the extragranular lubricant is carried out in a vertical blender.

[0139] In some embodiments, compressing the final blended mixture to form cores is performed using a rotary tablet press. In some embodiments, compressing the final blended mixture to form cores is performed using a single punch tablet press.

[0140] In some embodiments, the method includes coating the core with a coating layer. In some embodiments, coating the core with the coating layer is performed using a conventional coating pan, such as a Pelligrini pan, an immersion sword pan, or an immersion tube pan. In some embodiments, coating the core with the coating layer is performed using a perforated coating pan, such as an Accela-Cota pan, a Hi-Coater, a Doria Coater, a Glatt pan coating apparatus, a Huttlin butterfly pan, or a Dumoulin coating apparatus. How to use

[0141] The formulations or tablets described and / or disclosed herein may be used to treat or prevent a disease or condition in a subject.

[0142] Without wishing to be bound by theory, (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide is believed to act by inhibiting myosin. This inhibition potentially reduces the number of independent myosin heads that interact with actin filaments, reducing the amount of contraction. Reducing myocardial contraction can be important for the treatment of cardiac diseases where excessive contraction is a problem. In some embodiments, a method of treating or preventing cardiac disease in a subject is provided, comprising administering to a subject in need thereof a formulation or tablet as described herein. In some embodiments, a method of treating or preventing cardiac disease in a subject in need thereof is provided, comprising administering to the subject a therapeutically effective amount of a formulation or tablet as described herein. In some embodiments, a method of treating a cardiac disease in a subject in need of treating the cardiac disease is provided, comprising administering to the subject a therapeutically effective amount of a formulation or tablet described herein. In some embodiments, a method of treating an established or diagnosed cardiac disease in a subject in need of treating the established or diagnosed cardiac disease is provided, comprising administering to the subject a therapeutically effective amount of a formulation or tablet described herein. In some embodiments, a method of preventing a cardiac disease in a subject in need of preventing the cardiac disease is provided, comprising administering to the subject a therapeutically effective amount of a formulation or tablet described herein.

[0143] Also provided herein is the use of the formulation or tablet described herein in the manufacture of a medicament for treating a cardiac disease in a subject. In some aspects, a formulation or tablet described herein is provided for use in a method of treating a human or animal body by therapy. In some embodiments herein, a formulation or tablet described herein is provided for use in a method of treating a human or animal body by therapy. In some embodiments herein, a formulation or tablet described herein is provided for use in treating or preventing a cardiac disease. In some embodiments herein, a formulation or tablet described herein is provided for use in treating a cardiac disease. In some embodiments herein, a formulation or tablet described herein is provided for use in treating an established or diagnosed cardiac disease. In other embodiments herein, a formulation or tablet described herein is provided for use in preventing a cardiac disease. In some embodiments herein, a formulation or tablet described herein is provided for use in treating a disease or condition associated with HCM. In some embodiments herein, a formulation or tablet described herein is provided for use in treating a disease or condition associated with secondary left ventricular wall thickening. In some embodiments herein, a formulation or tablet as described herein is provided for use in ameliorating symptoms associated with heart disease. In some embodiments herein, a formulation or tablet as described herein is provided for use in reducing the risk of symptoms associated with heart disease. In some embodiments herein, a formulation or tablet as described herein is provided for use in treating diseases or conditions associated with small left ventricular cavity, cavity obstruction, hyperkinetic left ventricular contraction, obstruction of blood flow out of the left ventricle, cardiac hypertrophy, reduced cardiac output, left ventricular relaxation failure, high left ventricular filling pressure, myocardial ischemia, or cardiac fibrosis. In some embodiments herein, a formulation or tablet as described herein is provided for use in treating diseases or conditions associated with small left ventricular cavity and cavity obstruction, hyperkinetic left ventricular contraction, myocardial ischemia, or cardiac fibrosis.Provided herein in some embodiments is a formulation or tablet as described herein for use in treating muscular dystrophy. Provided herein in some embodiments is a formulation or tablet as described herein for use in treating glycogen storage disease. Provided herein in some embodiments is a formulation or tablet as described herein for use in modulating cardiac sarcomere, for example inhibiting cardiac sarcomere. Provided herein in some embodiments is a formulation or tablet as described herein for use in enhancing cardiac myosin.

[0144] In some embodiments, the subject is a mammal. In some embodiments, the subject is a mouse, rat, dog, cat, pig, sheep, horse, cow, or human. In some embodiments, the subject is a human. In some embodiments, the subject has established or diagnosed cardiac disease. In some embodiments, the subject has established or diagnosed hypertrophic cardiomyopathy (HCM). In some embodiments, the subject is at risk of developing cardiac disease. In some embodiments, the subject has a mutation that increases the risk of cardiac disease. In some embodiments, the subject has a mutation that increases the risk of hypertrophic cardiomyopathy (HCM). In some embodiments, the mutation is a sarcomere mutation. In some embodiments, the mutation is in myosin heavy chain beta (MHC-β), cardiac troponin T (cTnT), tropomyosin alpha-1 chain (TPM1), myosin binding protein C cardiac type (MYBPC3), cardiac troponin I (cTnI), myosin essential light chain (ELC), titin (TTN), myosin regulatory light chain 2 ventricular / cardiac isoform (MLC-2), cardiac alpha actin, muscle LIM protein (MLP), or protein kinase AMP activating non-catalytic subunit gamma 2 (PRKAG2). In some embodiments, the mutation is in MHC-β. In some embodiments, the subject has established or diagnosed hypertrophic cardiomyopathy without a confirmed genetic etiology.

[0145] In some embodiments, the subject has a high risk of progressive symptoms. In some embodiments, the subject has a high risk of atrial fibrillation, ventricular tachyarrhythmia, stroke, and / or sudden death. In some embodiments, the subject has a reduced exercise capacity. In some embodiments, the reduced exercise capacity is compared with a control population of the same age. In some embodiments, the subject is eligible for surgical intervention or percutaneous ablation to treat heart disease.

[0146] In some embodiments, the cardiac disease is hypertrophic cardiomyopathy (HCM). In some embodiments, the cardiac disease is obstructive HCM. In some embodiments, the cardiac disease is non-obstructive HCM. In some embodiments, the HCM is associated with a sarcomere mutation. In some embodiments, the HCM is associated with a non-sarcomere mutation. In some embodiments, the cardiac disease is obstructive or non-obstructive HCM caused by a sarcomere and / or non-sarcomere mutation. In some embodiments, the sarcomere mutation is a mutation in myosin heavy chain beta (MHC-β), cardiac troponin T (cTnT), tropomyosin alpha-1 chain (TPM1), myosin binding protein C cardiac type (MYBPC3), cardiac troponin I (cTnI), myosin essential light chain (ELC), titin (TTN), myosin regulatory light chain 2 ventricular / cardiac isoform (MLC-2), cardiac alpha actin, or muscle LIM protein (MLP). In some embodiments, the sarcomeric mutation is a mutation in MHC-β. In some embodiments, the non-sarcomeric mutation is a mutation in protein kinase AMP-activated non-catalytic subunit gamma 2 (PRKAG2).

[0147] Provided herein in some embodiments is a method for treating a disease or condition associated with HCM, comprising administering to a subject in need thereof a formulation or tablet as described herein. In some embodiments, the disease or condition is Fabry disease, Danon disease, mitochondrial cardiomyopathy, and Noonan syndrome.

[0148] Also provided herein is the use of a formulation or tablet described herein in the manufacture of a medicament for treating a disease or condition associated with HCM.

[0149] In some embodiments, the cardiac disease is heart failure with preserved ejection fraction (HFpEF). In some embodiments, the cardiac disease is diastolic dysfunction. In some embodiments, the cardiac disease is cardiomyopathy. In some embodiments, the cardiac disease is primary or secondary restrictive cardiomyopathy. In some embodiments, the cardiac disease is a condition or symptom caused by coronary artery disease. In some embodiments, the cardiac disease is myocardial infarction or angina pectoris. In some embodiments, the cardiac disease is left ventricular outflow tract obstruction. In some embodiments, the cardiac disease is hypertensive heart disease. In some embodiments, the cardiac disease is congenital heart disease. In some embodiments, the cardiac disease is cardiac ischemia and / or coronary heart disease. In some embodiments, the cardiac disease is diabetic heart disease. In other embodiments, the cardiac disease is congestive heart failure. In some embodiments, the cardiac disease is right heart failure. In other embodiments, the cardiac disease is cardiorenal syndrome. In some embodiments, the cardiac disease is infiltrative cardiomyopathy. In some embodiments, the cardiac disease is or is related to diastolic dysfunction resulting from cardiac aging or aging. In some embodiments, the cardiac disease is or is related to left ventricular hypertrophy and / or concentric left ventricular remodeling.

[0150] In some embodiments, a method for treating a disease or condition associated with secondary left ventricular wall thickening in a subject is provided, comprising administering to a subject in need thereof a formulation or tablet as described herein. In some embodiments, the disease is hypertension, valvular heart disease (aortic stenosis, mitral regurgitation), metabolic syndrome (diabetes, obesity), end-stage renal disease, scleroderma, sleep apnea, amyloidosis, Fabry disease, Friedreich's ataxia, Danon disease, Noonan syndrome, or Pompe disease.

[0151] Also provided herein is the use of a formulation or tablet as described herein in the manufacture of a medicament for treating a disease or condition associated with secondary left ventricular wall thickening.

[0152] In some embodiments, there is provided a method of ameliorating a symptom associated with a cardiac disease in a subject, comprising administering to a subject in need thereof a formulation or tablet as described herein, wherein the symptom is one or more selected from poor or reduced cardiac elasticity, poor or reduced left ventricular diastolic relaxation, left atrial pressure abnormalities (e.g., abnormally high left atrial pressure), paroxysmal or permanent atrial fibrillation, increased left atrial and pulmonary capillary wedge pressure, increased left ventricular diastolic pressure, syncope, ventricular relaxation during diastole, ventricular fibrosis, left ventricular hypertrophy, left ventricular mass, increased left ventricular wall thickening, left ventricular mid-cavity obstruction, increased systolic anterior motion of the mitral valve, left ventricular outflow tract obstruction, chest pain, dyspnea on exertion, presyncope, abnormal exercise capacity, and fatigue.

[0153] In some embodiments, there is provided a method of reducing the risk of a symptom associated with cardiac disease in a subject comprising administering to a subject in need thereof a formulation or tablet as described herein, wherein the symptom is one or more selected from sudden cardiac death, poor or reduced cardiac elasticity, poor or reduced left ventricular diastolic relaxation, left atrial pressure abnormalities (e.g., abnormally high left atrial pressure), paroxysmal or permanent atrial fibrillation, increased left atrial and pulmonary capillary wedge pressure, increased left ventricular diastolic pressure, syncope, ventricular relaxation during diastole, ventricular fibrosis, left ventricular hypertrophy, left ventricular mass, increased left ventricular wall thickness, left ventricular mid-lumen obstruction, increased systolic anterior motion of the mitral valve, left ventricular outflow tract obstruction, chest pain, dyspnea on exertion, presyncope, abnormal exercise performance, and fatigue.

[0154] In some embodiments, there is provided a method of treating a disease or condition associated with a small left ventricular cavity, lumen obstruction, hyperkinetic left ventricular contractions, obstruction of blood flow out of the left ventricle, cardiac hypertrophy, reduced cardiac output, impaired left ventricular relaxation, high left ventricular filling pressure, myocardial ischemia, or cardiac fibrosis in an individual or subject, comprising administering to a subject in need thereof a formulation or tablet as described herein.

[0155] In some embodiments, a method is provided for treating a disease or condition associated with small left ventricular cavity and lumen obstruction, hyperdynamic left ventricular contraction, myocardial ischemia, or cardiac fibrosis in a subject, comprising administering to a subject in need thereof a formulation or tablet described herein.

[0156] Also provided herein is the use of a formulation or tablet as described herein in the manufacture of a medicament for treating a disease or condition associated with small left ventricular lumen and lumen obstruction, hyperdynamic left ventricular contraction, myocardial ischemia, or cardiac fibrosis.

[0157] In some embodiments, there is provided a method of treating muscular dystrophy (e.g., Duchenne muscular dystrophy) in a subject, comprising administering to a subject in need thereof a formulation or tablet described herein. Also provided herein is the use of a formulation or tablet described herein in the manufacture of a medicament for treating muscular dystrophy (e.g., Duchenne muscular dystrophy).

[0158] In some embodiments, provided herein is a method of treating glycogen storage disease in a subject, the method comprising administering to an individual or subject in need thereof a formulation or tablet described herein.Also provided herein is the use of a formulation or tablet described herein in the manufacture of a medicament for treating glycogen storage disease.

[0159] Also provided is a method for modulating cardiac sarcomere in a subject, comprising administering to a subject in need thereof a therapeutically effective amount of a formulation or tablet described herein. In some embodiments, provided is a method for inhibiting cardiac sarcomere, comprising contacting cardiac sarcomere with a formulation or tablet described herein. Further provided herein is the use of a formulation or tablet described herein in the manufacture of a medicament for inhibiting cardiac sarcomere in a subject.

[0160] Also provided is a method for enhancing cardiac myosin in a subject, comprising administering to a subject in need thereof a therapeutically effective amount of a formulation or tablet described herein. Further provided herein is the use of a formulation or tablet described herein in the manufacture of a medicament for enhancing cardiac myosin in an individual or subject.

[0161] In some embodiments, the method provided herein further comprises monitoring the effectiveness of treatment.Examples of indicators include, but are not limited to, one or more improvements in the following: New York Heart Association (NYHA) functional class, exercise capacity, cardiac elasticity, diastolic left ventricular relaxation, left atrial pressure, paroxysmal or permanent atrial fibrillation, left atrial and pulmonary capillary wedge pressure, left ventricular diastolic pressure, syncope, ventricular relaxation during diastole, ventricular fibrosis, left ventricular hypertrophy, left ventricular mass, left ventricular wall thickness, left ventricular mid-lumen obstruction, systolic anterior motion of mitral valve, left ventricular outflow tract obstruction, chest pain, exertional dyspnea, presyncope, exercise capacity abnormality, and fatigue.These indicators can be monitored by techniques known in the art, including self-report, ECG, including ambulatory ECG, echocardiography, cardiac MRI, CT, biopsy, cardiopulmonary exercise testing (CPET), and actigraphy.

[0162] In some embodiments, the formulations or tablets described and / or disclosed herein reduce the contractility of cardiomyocytes. In some embodiments, the formulations or tablets described and / or disclosed herein reduce the contractility of cardiomyocytes by more than 40%, such as more than 45%, more than 50%, more than 60%, more than 70%, more than 80%, or more than 90%. In some embodiments, the formulations or tablets described and / or disclosed herein reduce the contractility of cardiomyocytes by 40%-90%, such as 40%-80%, 40-70%, 50%-90%, 50%-80%, or 50%-70%. In some embodiments, the formulations or tablets described and / or disclosed herein do not significantly alter calcium transients in cardiomyocytes. In some embodiments, the formulations or tablets described and / or disclosed herein reduce ATPase activity in cardiomyocytes. Methods for measuring contractility, ATPase activity, and calcium transients are known in the art, for example, by calcium labeling, electrophysiological recording, and microscopic imaging. In some embodiments, the formulations or tablets described and / or disclosed herein do not significantly inhibit or induce cytochrome P450 (CYP) proteins.

[0163] In some embodiments, the subject has a left ventricular wall thicker than normal before treatment.In some embodiments, the subject has a left ventricular wall thickness of more than 15 mm, for example more than 18 mm, more than 20 mm, more than 22 mm, more than 25 mm, or more than 30 mm before treatment.In some embodiments, the left ventricular wall thickness is reduced by more than 5%, for example more than 8%, more than 10%, more than 12%, more than 15%, more than 20%, or more than 30% after treatment.The left ventricular wall thickness can be measured by methods known in the art, for example by echocardiography, CT scan, or cardiac MRI.

[0164] In some embodiments, the subject has abnormal cardiac fibrosis before treatment.In some embodiments, abnormal cardiac fibrosis is reduced by more than 5%, for example, more than 8%, more than 10%, more than 12%, more than 15%, more than 20%, or more than 30% after treatment.Cardiac fibrosis can be measured by methods known in the art, for example, by biopsy or cardiac MRI.

[0165] In some embodiments, the subject has a reduced exercise capacity prior to treatment. In some embodiments, the subject's exercise capacity increases by more than 5%, e.g., more than 8%, more than 10%, more than 12%, more than 15%, more than 20%, or more than 30% after treatment. In some embodiments, exercise capacity is measured by cardiopulmonary exercise testing (CPET). CPET measures changes in oxygen consumption (VO2 max). Methods for measuring CPET and VO2 max are well known in the art (Malhotra et al., JACC:Heart Failure, 2016, 4(8):607-616; Guazzi et al., J Amer College Cardiol, 2017, 70 (13):1618-1636; Rowin et al., JACC:Cariovasc Imaging, 2017, 10(11):1374-1386). In some embodiments, VO2 max increases by more than 1 mL / kg / m after treatment. 2 Greater than, for example, 1.2 mL / kg / m 2 Ultra, 1.4mL / kg / m 2 Ultra, 1.5mL / kg / m 2 Ultra, 1.7mL / kg / m 2 Ultra, 2mL / kg / m 2 Ultra, 2.2mL / kg / m 2 Ultra, 2.5mL / kg / m 2 Ultra, 3mL / kg / m 2 Ultra, 3.2mL / kg / m 2 > 3.5 mL / kg / m 2 Super improved.

[0166] In some embodiments, the subject has a New York Heart Association (NYHA) functional class of II, III or IV before treatment.In some embodiments, the subject has a New York Heart Association (NYHA) functional class of III or IV before treatment.In some embodiments, the subject has a New York Heart Association (NYHA) functional class of IV before treatment.In some embodiments, the subject maintains the same NYHA functional class or has a reduced NYHA functional class after treatment.

[0167] In some embodiments, VO2 max is greater than or equal to 1 mL / kg / m after treatment. 2 Greater than, for example, 1.2 mL / kg / m 2 Ultra, 1.4mL / kg / m 2 Ultra, 1.5mL / kg / m 2 Ultra, 1.7mL / kg / m 2 > 2 mL / kg / m 2 In some embodiments, the VO2 max is greater than or equal to 2.5 mL / kg / m after treatment, and the subject has a reduced NYHA functional class. 2 Ultra, 3mL / kg / m 2 Ultra, 3.2mL / kg / m 2 > 3.5 mL / kg / m 2 Super-improved, subjects maintain the same NYHA functional class or experience a decrease in NYHA functional class.

[0168] In some embodiments, the subject's daily function and / or activity level is improved after treatment. The improvement in daily function and / or activity level can be measured, for example, by journaling or actigraphy, such as FITBIT® or FITBIT®-like monitors.

[0169] In some embodiments, the subject has one or more of reduced shortness of breath, reduced chest pain, reduced arrhythmia burden, e.g., atrial fibrillation and ventricular arrhythmias, reduced incidence of heart failure, and reduced ventricular outflow tract obstruction after treatment. kit

[0170] Also provided are articles of manufacture and kits that include any of the formulations or tablets provided herein. The articles of manufacture can include a container with a label. Suitable containers include, for example, bottles, vials, and test tubes. The container can be formed from a variety of materials, such as glass or plastic. The container can hold the pharmaceutical composition provided herein. The label on the container can indicate that the pharmaceutical composition is used to prevent, treat, or suppress a condition described herein, and can also indicate instructions for use either in vivo or in vitro.

[0171] In one aspect, a kit is provided herein that includes the formulation or tablet described herein and instructions for use.The kit can include instructions for use in treating cardiac disease in a subject that requires cardiac disease treatment.The kit can also include sterile packaging. Combination

[0172] The formulations or tablets described and / or disclosed herein can be administered alone or in combination with other therapeutic agents and / or therapeutic agents useful in the treatment of the aforementioned disorders, diseases or conditions.

[0173] The formulation or tablet described and / or disclosed herein can be combined with one or more other therapeutic agents for treating cardiac disease, such as HCM or HFpEF. In some embodiments, the one or more therapeutic agents include therapeutic agents that attempt to slow the progression of heart failure and prevent cardiac remodeling by downregulating cardiac neurohormonal stimulation (e.g., ACE inhibitors, angiotensin receptor blockers (ARBs), β-blockers, aldosterone receptor antagonists, or neuroendopeptidase inhibitors). In some embodiments, the one or more therapeutic agents include therapeutic agents that improve cardiac function by stimulating cardiac contractility (e.g., positive inotropic agents, such as the β-adrenergic agonist dobutamine or the phosphodiesterase inhibitor milrinone). In other embodiments, the one or more therapeutic agents include a therapeutic agent that reduces cardiac preload (e.g., a diuretic, such as furosemide) or a therapeutic agent that reduces afterload (a vasodilator of any class, including but not limited to, a calcium channel blocker, a phosphodiesterase inhibitor, an endothelin receptor antagonist, a renin inhibitor, or a smooth muscle myosin modulator).

[0174] The formulations or tablets described and / or disclosed herein can be combined with one or more other therapeutic agents for treating HCM or HFpEF. In some embodiments, the formulations or tablets described and / or disclosed herein can be combined with β-blockers, verapamil, and / or disopyramide. Enumerated Embodiments

[0175] Embodiment 1. (i) (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (ii) filler; (iii) a binder; (iv) a disintegrant; (v) surfactants; and (vi) Lubricants 13. A formulation comprising:

[0176] Embodiment 2. The formulation of embodiment 1, wherein the filler is selected from the group consisting of powdered cellulose, microcrystalline cellulose, silicified microcrystalline cellulose, kaolin, corn starch, maize starch, starch derivatives, pregelatinized starch, calcium phosphate, calcium hydrogen phosphate, dicalcium phosphate, tricalcium phosphate, compressible sugar, sugar alcohols, mannitol, sorbitol, maltitol, xylitol, lactitol, lactose, dextrose, maltose, sucrose, glucose, fructose, saccharose, raffinose, dextrates, trehalose, maltodextrin, and mixtures of any of the foregoing.

[0177] Embodiment 3. The formulation of embodiment 1 or 2, wherein the binder is selected from the group consisting of gum arabic, gum acacia, alginate, alginic acid, corn starch, copolyvidone, polyvinylpyrrolidone, gelatin, glyceryl behenate, hydroxyethylcellulose, hydroxypropylcellulose, carboxymethylcellulose, calcium carboxymethylcellulose, sodium carboxymethylcellulose, methylcellulose, hypromellose, lactose, polyvinyl alcohol, povidone, polyethylene oxide, polyacrylates, potato starch, pregelatinized starch, sodium alginate, sodium starch, sodium carboxymethylcellulose, starch, and mixtures of any of the foregoing.

[0178] Embodiment 4. The formulation of any one of embodiments 1-3, wherein the disintegrant is selected from the group consisting of alginic acid, croscarmellose sodium, cellulose, calcium carboxymethylcellulose, sodium carboxymethylcellulose, microcrystalline cellulose, crospovidone, sodium starch glycolate, low substituted hydroxypropylcellulose, polacrilin potassium, pregelatinized starch, partially hydrolyzed starch, sodium carboxymethylstarch, starch, sodium alginate, sodium carboxymethylcellulose, and mixtures of any of the foregoing.

[0179] Embodiment 5. The surfactants are cetylpyridine chloride, heptadecaethyleneoxycetanol, lecithin, polyoxyethylene stearate, nonoxynol 9, nonoxynol 10, octoxynol 9, sorbitan fatty acid ester, Span 20, Span 40, Span 60, Span 80, Span 85, polysorbate, polysorbate 20, polysorbate 21, polysorbate 40, polysorbate 60, polysorbate 61, polysorbate 65, polysorbate 80, sodium salt of fatty alcohol sulfate, sodium lauryl sulfate. The formulation of any one of embodiments 1-4, wherein the isopropyl alcohol is selected from the group consisting of glyceryl monostearate, sodium salts of sulfosuccinates, sodium dioctyl sulfosuccinate, partial esters of fatty acids and alcohols, glyceryl monostearate, glyceryl monooleate, ethers of fatty alcohols and polyoxyethylene, esters of fatty acids and polyoxyethylene, copolymers of ethylene oxide and propylene oxide (Pluronic®), benzalkonium chloride, ethoxylated triglycerides, and mixtures of any of the foregoing.

[0180] Embodiment 6. The formulation of any one of embodiments 1-5, wherein the lubricant is selected from the group consisting of hydrogenated castor oil, magnesium stearate, glyceryl monostearate, calcium stearate, glyceryl behenate, glycerol distearate, glyceryl dipalmitostearate, behenoyl polyoxyl-8 glyceride, sodium stearyl fumarate, stearic acid, talc, zinc stearate, mineral oil, polyethylene glycol, poloxamer, sodium lauryl sulfate, and mixtures of any of the foregoing.

[0181] Embodiment 7. The formulation, (i) about 1% to about 80% by weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (ii) about 15% to about 90% by weight of a filler; (iii) about 0.1% to about 10% by weight of a binder; (iv) about 1% to about 10% by weight of a disintegrant; (v) about 0.1% to about 10% by weight of a surfactant; and (vi) from about 0.1% to about 10% by weight; The formulation of any one of embodiments 1-6, comprising:

[0182] Embodiment 8. The formulation, (i) about 1% to about 50% by weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (ii) about 40% to about 80% by weight of a filler; (iii) about 0.5% to about 5% by weight of a binder; (iv) about 2% to about 8% by weight of a disintegrant; (v) about 0.5% to about 5% by weight of a surfactant; and (vi) from about 0.5% by weight to about 5% by weight; The formulation of any one of embodiments 1-7, comprising:

[0183] EMBODIMENT 9. The formulation, (i) about 10% to about 30% by weight of (R)—N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (ii) about 60% to about 80% by weight of a filler; (iii) about 1% to about 3% by weight of a binder; (iv) about 4% to about 6% by weight of a disintegrant; (v) about 1% to about 3% by weight of a surfactant; and (vi) from about 0.5% by weight to about 1.5% by weight; The formulation of any one of embodiments 1-8, comprising:

[0184] Embodiment 10. The formulation, (i) about 20% by weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (ii) about 70% by weight of a filler; (iii) about 2% by weight of a binder; (iv) about 5% by weight of a disintegrant; (v) about 2% by weight of a surfactant; and (vi) about 1% by weight of a lubricant; The formulation of any one of embodiments 1-9, comprising:

[0185] Embodiment 11. The formulation, (i) about 1% to about 10% by weight of (R)—N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (ii) about 70% to about 90% by weight of a filler; (iii) about 1% to about 3% by weight of a binder; (iv) about 4% to about 6% by weight of a disintegrant; (v) about 1% to about 3% by weight of a surfactant; and (vi) from about 0.5% by weight to about 1.5% by weight; The formulation of any one of embodiments 1-8, comprising:

[0186] Embodiment 12. The formulation, (i) about 5% by weight of (R)—N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (ii) about 85% by weight of a filler; (iii) about 2% by weight of a binder; (iv) about 5% by weight of a disintegrant; (v) about 2% by weight of a surfactant; and (vi) about 1% by weight of a lubricant; The formulation of any one of embodiments 1-8 and 11, comprising:

[0187] Embodiment 13. The formulation, (i) about 10% by weight of (R)—N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (ii) about 80% by weight of a filler; (iii) about 2% by weight of a binder; (iv) about 5% by weight of a disintegrant; (v) about 2% by weight of a surfactant; and (vi) about 1% by weight of a lubricant; The formulation of any one of embodiments 1-9 and 11, comprising:

[0188] Embodiment 14. The formulation of any one of embodiments 1-13, wherein the bulking agent comprises mannitol.

[0189] EMBODIMENT 15. The formulation of any one of embodiments 1-14, wherein the filler comprises microcrystalline cellulose.

[0190] Embodiment 16. The formulation of any one of embodiments 1-15, wherein the filler consists of mannitol and microcrystalline cellulose.

[0191] EMBODIMENT 17. The formulation of any one of embodiments 1-16, wherein the binder is hydroxypropyl cellulose.

[0192] Embodiment 18. The formulation of any one of embodiments 1-17, wherein the disintegrant is croscarmellose sodium.

[0193] EMBODIMENT 19. The formulation of any one of embodiments 1-18, wherein the surfactant is sodium lauryl sulfate.

[0194] EMBODIMENT 20. The formulation of any one of embodiments 1-19, wherein the lubricant is magnesium stearate.

[0195] EMBODIMENT 21. The formulation, (i) about 1% to about 50% by weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (ii-1) about 10% by weight to about 60% by weight of mannitol; (ii-2) about 5% by weight to about 45% by weight of crystalline cellulose; (iii) about 0.1% to about 10% by weight of hydroxypropylcellulose; (iv) about 1% to about 10% by weight of croscarmellose sodium; (v) about 0.1% to about 10% by weight of sodium lauryl sulfate; and (vi) about 0.1% to about 10% by weight of magnesium stearate; The formulation of any one of embodiments 1-8, comprising:

[0196] EMBODIMENT 22. The formulation, (i) about 10% to about 30% by weight of (R)—N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (ii-1) about 40% by weight to about 50% by weight of mannitol; (ii-2) about 20% by weight to about 30% by weight of crystalline cellulose; (iii) about 1% to about 3% by weight of hydroxypropylcellulose; (iv) about 4% to about 6% by weight of croscarmellose sodium; (v) about 1% to about 3% by weight of sodium lauryl sulfate; and (vi) about 0.5% to about 1.5% by weight of magnesium stearate; The formulation of any one of embodiments 1-8 and 21, comprising:

[0197] EMBODIMENT 23. The formulation, (i) about 1% to about 10% by weight of (R)—N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (ii-1) about 50% by weight to about 60% by weight of mannitol; (ii-2) about 25% by weight to about 35% by weight of crystalline cellulose; (iii) about 1% to about 3% by weight of hydroxypropylcellulose; (iv) about 4% to about 6% by weight of croscarmellose sodium; (v) about 1% to about 3% by weight of sodium lauryl sulfate; and (vi) about 0.5% to about 1.5% by weight of magnesium stearate; The formulation of any one of embodiments 1-8 and 21, comprising:

[0198] EMBODIMENT 24. The formulation, (i) about 20% by weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (ii-1) about 44% by weight of mannitol; (ii-2) about 26% by weight of crystalline cellulose; (iii) about 2% by weight of hydroxypropylcellulose; (iv) about 5% by weight of croscarmellose sodium; (v) about 2% by weight of sodium lauryl sulfate; and (vi) about 1% by weight of magnesium stearate; The formulation of any one of embodiments 1-8, 21 and 22, comprising:

[0199] EMBODIMENT 25. The formulation, (i) about 10% by weight of (R)—N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (ii-1) about 50% by weight of mannitol; (ii-2) about 30% by weight of crystalline cellulose; (iii) about 2% by weight of hydroxypropylcellulose; (iv) about 5% by weight of croscarmellose sodium; (v) about 2% by weight of sodium lauryl sulfate; and (vi) about 1% by weight of magnesium stearate; The formulation of any one of embodiments 1-8, 21-23, comprising:

[0200] 26. The formulation, (i) about 5% by weight of (R)—N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (ii-1) about 54% by weight of mannitol; (ii-2) about 31% by weight of crystalline cellulose; (iii) about 2% by weight of hydroxypropylcellulose; (iv) about 5% by weight of croscarmellose sodium; (v) about 2% by weight of sodium lauryl sulfate; and (vi) about 1% by weight of magnesium stearate; The formulation of any one of embodiments 1-8, 21 and 23, comprising:

[0201] EMBODIMENT 27. The formulation of any of the previous embodiments, wherein the formulation is for oral administration.

[0202] 28. The formulation of any of the previous embodiments, wherein the formulation is for once daily administration.

[0203] 29. The formulation of any of the previous embodiments, wherein the (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph or pharma- ceutically acceptable salt thereof is (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide.

[0204] EMBODIMENT 30. (i) a core, (a) (ai) (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii) intragranular fillers; (a-iii) intragranular binders; (a-iv) an intragranular disintegrant; and (av) Intragranular surfactant Intragranular constituents, including; And (b) (bi) extragranular fillers; (b-ii) an extragranular disintegrant; and (b-iii) Extragranular lubricant Extragranular constituents, including Core with total core weight including; And, where necessary, (ii) a coating layer containing a coating agent Tablets containing:

[0205] EMBODIMENT 31. The tablet of embodiment 30, wherein the intragranular filler is selected from the group consisting of powdered cellulose, microcrystalline cellulose, silicified microcrystalline cellulose, kaolin, corn starch, maize starch, starch derivatives, pregelatinized starch, calcium phosphate, calcium hydrogen phosphate, dicalcium phosphate, tricalcium phosphate, compressible sugar, sugar alcohols, mannitol, sorbitol, maltitol, xylitol, lactitol, lactose, dextrose, maltose, sucrose, glucose, fructose, saccharose, raffinose, dextrates, trehalose, maltodextrin, and mixtures of any of the foregoing.

[0206] EMBODIMENT 32. 32. The tablet of embodiment 30 or 31, wherein the intragranular binder is selected from the group consisting of gum arabic, gum acacia, alginates, alginic acid, corn starch, copolyvidone, polyvinylpyrrolidone, gelatin, glyceryl behenate, hydroxyethylcellulose, hydroxypropylcellulose, carboxymethylcellulose, calcium carboxymethylcellulose, sodium carboxymethylcellulose, methylcellulose, hypromellose, lactose, polyvinyl alcohol, povidone, polyethylene oxide, polyacrylates, potato starch, pregelatinized starch, sodium alginate, sodium starch, sodium carboxymethylcellulose, starch, and mixtures of any of the foregoing.

[0207] EMBODIMENT 33. The tablet of any one of embodiments 30-32, wherein the intragranular disintegrant is selected from the group consisting of alginic acid, croscarmellose sodium, cellulose, calcium carboxymethylcellulose, sodium carboxymethylcellulose, microcrystalline cellulose, crospovidone, sodium starch glycolate, low-substituted hydroxypropylcellulose, polacrilin potassium, pregelatinized starch, partially hydrolyzed starch, sodium carboxymethylstarch, starch, sodium alginate, sodium carboxymethylcellulose, and mixtures of any of the foregoing.

[0208] EMBODIMENT 34. Intragranular surfactants include cetylpyridine chloride, heptadecaethyleneoxycetanol, lecithin, polyoxyethylene stearate, nonoxynol 9, nonoxynol 10, octoxynol 9, sorbitan fatty acid ester, Span 20, Span 40, Span 60, Span 80, Span 85, polysorbate, polysorbate 20, polysorbate 21, polysorbate 40, polysorbate 60, polysorbate 61, polysorbate 65, polysorbate 80, sodium salt of fatty alcohol sulfate, sodium lauryl sulfate. 34. The tablet of any one of embodiments 30 to 33, wherein the glyceryl monostearate, glyceryl monooleate, ethers of fatty alcohols and polyoxyethylene, esters of fatty acids and polyoxyethylene, copolymers of ethylene oxide and propylene oxide (Pluronic®), benzalkonium chloride, ethoxylated triglycerides, and mixtures of any of the foregoing.

[0209] EMBODIMENT 35. The tablet of any one of embodiments 30 to 34, wherein the extragranular filler is selected from the group consisting of powdered cellulose, microcrystalline cellulose, silicified microcrystalline cellulose, kaolin, corn starch, maize starch, starch derivatives, pregelatinized starch, calcium phosphate, calcium hydrogen phosphate, dicalcium phosphate, tricalcium phosphate, compressible sugar, sugar alcohols, mannitol, sorbitol, maltitol, xylitol, lactitol, lactose, dextrose, maltose, sucrose, glucose, fructose, saccharose, raffinose, dextrates, trehalose, maltodextrin, and mixtures of any of the above.

[0210] EMBODIMENT 36. The tablet of any one of embodiments 30-35, wherein the extragranular disintegrant is selected from the group consisting of alginic acid, croscarmellose sodium, cellulose, calcium carboxymethylcellulose, sodium carboxymethylcellulose, microcrystalline cellulose, crospovidone, sodium starch glycolate, low-substituted hydroxypropylcellulose, polacrilin potassium, pregelatinized starch, partially hydrolyzed starch, sodium carboxymethylstarch, starch, sodium alginate, sodium carboxymethylcellulose, and mixtures of any of the foregoing.

[0211] 37. The tablet of any one of embodiments 30-36, wherein the extragranular lubricant is selected from the group consisting of hydrogenated castor oil, magnesium stearate, glyceryl monostearate, calcium stearate, glyceryl behenate, glycerol distearate, glyceryl dipalmitostearate, behenoyl polyoxyl-8 glyceride, sodium stearyl fumarate, stearic acid, talc, zinc stearate, mineral oil, polyethylene glycol, poloxamer, sodium lauryl sulfate, and mixtures of any of the foregoing.

[0212] 38. The core, (a) (ai) from about 1% to about 80% of the total core weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii) about 10% to about 80% of the total core weight of intragranular fillers; (a-iii) about 0.1% to about 10% of the total core weight of an intragranular binder; (a-iv) about 0.1% to about 5% by weight of the total core of an intragranular disintegrant; and (av) about 0.1% to about 5% of the total core weight of an intragranular surfactant; Intragranular constituents, including; And (b) (bi) about 5% to about 15% of the total core weight of extragranular filler; (b-ii) about 0.1% to about 5% of the total core weight of an extragranular disintegrant; and (b-iii) about 0.1% to about 5% of the total core weight of an extragranular lubricant Extragranular constituents, including; The tablet of any one of embodiments 30 to 37, comprising:

[0213] 39. The core, (a) (ai) from about 1% to about 50% of the total core weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii) about 40% to about 80% of the total core weight of intragranular fillers; (a-iii) about 1% to about 5% of the total core weight of an intragranular binder; (a-iv) about 1% to about 5% by weight of the total core of an intragranular disintegrant; and (av) about 1% to about 5% of the total core weight of intragranular surfactant Intragranular constituents including; And (b) (bi) about 5% to about 15% of the total core weight of extragranular filler; (b-ii) about 1% to about 5% by weight of the total core of an extragranular disintegrant; and (b-iii) about 0.1% to about 2% of the total core weight of an extragranular lubricant Extragranular constituents, including; The tablet of any one of embodiments 30 to 38, comprising:

[0214] EMBODIMENT 40. The core, (a) (ai) about 10% to about 30% of the total core weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii) about 50% to about 70% of the total core weight of intragranular filler; (a-iii) about 1% to about 3% of the total core weight of an intragranular binder; (a-iv) about 2% to about 4% by weight of the total core of an intragranular disintegrant; and (av) Intragranular surfactant of about 1% to about 3% of the total core weight Intragranular constituents, including; And (b) (bi) about 5% to about 15% of the total core weight of extragranular filler; (b-ii) about 1% to about 3% of the total core weight of an extragranular disintegrant; and (b-iii) about 0.1% to about 1.5% of the total core weight of an extragranular lubricant Extragranular constituents, including; The tablet of any one of embodiments 30 to 39, comprising:

[0215] EMBODIMENT 41. The core, (a) (ai) about 1% to about 10% of the total core weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii) about 60% to about 80% of the total core weight of intragranular filler; (a-iii) about 1% to about 3% of the total core weight of an intragranular binder; (a-iv) about 2% to about 4% by weight of the total core of an intragranular disintegrant; and (av) about 1% to about 3% of the total core weight of intragranular surfactant; Intragranular constituents, including; And (b) (bi) about 5% to about 15% of the total core weight of extragranular filler; (b-ii) about 1% to about 3% of the total core weight of an extragranular disintegrant; and (b-iii) about 0.1% to about 1.5% of the total core weight of an extragranular lubricant Extragranular constituents, including; The tablet of any one of embodiments 30 to 39, comprising:

[0216] EMBODIMENT 42. The core, (a) (ai) about 5% by weight of the total core of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii) intragranular filler of about 74% of the total core weight; (a-iii) intragranular binders, approximately 2% of the total core weight; (a-iv) about 3% of the total core weight of an intragranular disintegrant; and (av) Intragranular surfactant, approximately 2% of the total core weight Intragranular constituents, including; And (b) (bi) extragranular filler, approximately 11% of the total core weight; (b-ii) an extragranular disintegrant, about 2% by weight of the total core; and (b-iii) an extragranular lubricant, approximately 1% of the total core weight Extragranular constituents, including; The tablet of any one of embodiments 30 to 39, and 41, comprising:

[0217] EMBODIMENT 43. The core, (a) (ai) about 10% by weight of the total core of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii) intragranular filler of about 69% of the total core weight; (a-iii) intragranular binders, approximately 2% of the total core weight; (a-iv) about 3% of the total core weight of an intragranular disintegrant; and (av) Intragranular surfactant, approximately 2% of the total core weight Intragranular constituents, including; And (b) (bi) extragranular filler, approximately 11% of the total core weight; (b-ii) an extragranular disintegrant, about 2% by weight of the total core; and (b-iii) an extragranular lubricant, approximately 1% of the total core weight Extragranular constituents, including; The tablet of any one of embodiments 30 to 41, comprising:

[0218] EMBODIMENT 44. The core, (a) (ai) about 20% by weight of the total core of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii) intragranular filler of about 59% of the total core weight; (a-iii) intragranular binders, approximately 2% of the total core weight; (a-iv) about 3% of the total core weight of an intragranular disintegrant; and (av) Intragranular surfactant, approximately 2% of the total core weight Intragranular constituents, including; And (b) (bi) extragranular filler, approximately 11% of the total core weight; (b-ii) an extragranular disintegrant, about 2% by weight of the total core; and (b-iii) an extragranular lubricant, approximately 1% of the total core weight Extragranular constituents, including; The tablet of any one of embodiments 30 to 40, comprising:

[0219] EMBODIMENT 45. The tablet of any one of embodiments 30-44, wherein the intragranular filler comprises mannitol.

[0220] EMBODIMENT 46. The tablet of any one of embodiments 30 to 45, wherein the intragranular filler comprises microcrystalline cellulose.

[0221] EMBODIMENT 47. The tablet of any one of embodiments 30 to 46, wherein the intragranular filler consists of mannitol and microcrystalline cellulose.

[0222] 48. The tablet of any one of embodiments 30-47, wherein the intragranular binder is hydroxypropyl cellulose.

[0223] 49. The tablet of any one of embodiments 30-48, wherein the intragranular disintegrant is croscarmellose sodium.

[0224] EMBODIMENT 50. The tablet of any one of embodiments 30-49, wherein the intragranular surfactant is sodium lauryl sulfate.

[0225] EMBODIMENT 51. The tablet of any one of embodiments 30 to 50, wherein the extragranular filler is microcrystalline cellulose.

[0226] EMBODIMENT 52. The tablet of any one of embodiments 30-51, wherein the extragranular disintegrant is croscarmellose sodium.

[0227] EMBODIMENT 53. The tablet of any one of embodiments 30-52, wherein the extragranular lubricant is magnesium stearate.

[0228] EMBODIMENT 54. The core, (a) (ai) from about 1% to about 50% of the total core weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii-1) mannitol, about 40% to about 60% by weight of the total core; (a-ii-2) about 10% to about 30% of the total core weight of crystalline cellulose; (a-iii) about 1% to about 5% by weight of the total core of hydroxypropylcellulose; (a-iv) about 1% to about 5% of the total core weight of croscarmellose sodium; and (av) Sodium lauryl sulfate, from about 1% to about 5% by weight of the total core Intragranular constituents, including; And (b) (bi) about 5% to about 15% by weight of the total core of microcrystalline cellulose; (b-ii) about 1% to about 5% of the total core weight of croscarmellose sodium; and (b-iii) about 0.1% to about 2% of the total core weight of an extragranular lubricant Extragranular constituents, including; The tablet of any one of embodiments 30 to 39 and 45 to 52, comprising:

[0229] EMBODIMENT 55. The core, (a) (ai) from about 1% to about 50% of the total core weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii-1) mannitol, about 40% to about 60% by weight of the total core; (a-ii-2) about 10% to about 30% of the total core weight of crystalline cellulose; (a-iii) about 1% to about 5% by weight of the total core of hydroxypropylcellulose; (a-iv) about 1% to about 5% of the total core weight of croscarmellose sodium; and (av) Sodium lauryl sulfate, from about 1% to about 5% by weight of the total core Intragranular constituents, including; And (b) (bi) about 5% to about 15% by weight of the total core of microcrystalline cellulose; (b-ii) about 1% to about 5% of the total core weight of croscarmellose sodium; and (b-iii) magnesium stearate, from about 0.1% to about 2% by weight of the total core Extragranular constituents, including; The tablet of any one of embodiments 30 to 39 and 45 to 53, comprising:

[0230] EMBODIMENT 56. The core, (a) (ai) about 10% to about 30% of the total core weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii-1) mannitol, about 40% to about 50% by weight of the total core; (a-ii-2) about 10% to about 20% of the total core weight of crystalline cellulose; (a-iii) about 1% to about 3% by weight of the total core of hydroxypropylcellulose; (a-iv) about 2% to about 4% of the total core weight of croscarmellose sodium; and (av) sodium lauryl sulfate, from about 1% to about 3% by weight of the total core Intragranular constituents, including; And (b) (bi) about 5% to about 15% by weight of the total core of microcrystalline cellulose; (b-ii) about 1% to about 3% of the total core weight of croscarmellose sodium; and (b-iii) about 0.1% to about 1.5% of the total core weight of an extragranular lubricant Extragranular constituents, including; The tablet of any one of embodiments 30-40, 45-52 and 54, comprising:

[0231] EMBODIMENT 57. The core, (a) (ai) about 10% to about 30% of the total core weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii-1) mannitol, about 40% to about 50% by weight of the total core; (a-ii-2) about 10% to about 20% of the total core weight of crystalline cellulose; (a-iii) about 1% to about 3% by weight of the total core of hydroxypropylcellulose; (a-iv) about 2% to about 4% of the total core weight of croscarmellose sodium; and (av) sodium lauryl sulfate, from about 1% to about 3% by weight of the total core Intragranular constituents, including; And (b) (bi) about 5% to about 15% by weight of the total core of microcrystalline cellulose; (b-ii) about 1% to about 3% of the total core weight of croscarmellose sodium; and (b-iii) magnesium stearate, from about 0.1% to about 1.5% by weight of the total core Extragranular constituents, including; The tablet of any one of embodiments 30 to 40, 45 to 56, comprising:

[0232] EMBODIMENT 58. The core, (a) (ai) about 1% by weight to about 10% by weight of the total core weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii-1) mannitol, about 50% to about 60% by weight of the total core; (a-ii-2) about 15% to about 25% of the total core weight of crystalline cellulose; (a-iii) about 1% to about 3% by weight of the total core of hydroxypropylcellulose; (a-iv) about 2% to about 4% of the total core weight of croscarmellose sodium; and (av) sodium lauryl sulfate, from about 1% to about 3% by weight of the total core Intragranular constituents, including; And (b) (bi) about 5% to about 15% by weight of the total core of microcrystalline cellulose; (b-ii) about 1% to about 3% of the total core weight of croscarmellose sodium; and (b-iii) about 0.1% to about 1.5% of the total core weight of an extragranular lubricant Extragranular constituents, including; The tablet of any one of embodiments 30 to 39, 41, 45 to 52 and 54, comprising:

[0233] EMBODIMENT 59. The core, (a) (ai) about 1% by weight to about 10% by weight of the total core weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii-1) mannitol, about 50% to about 60% by weight of the total core; (a-ii-2) about 15% to about 25% of the total core weight of crystalline cellulose; (a-iii) about 1% to about 3% by weight of the total core of hydroxypropylcellulose; (a-iv) about 2% to about 4% of the total core weight of croscarmellose sodium; and (av) sodium lauryl sulfate, from about 1% to about 3% by weight of the total core Intragranular constituents, including; And (b) (bi) about 5% to about 15% by weight of the total core of microcrystalline cellulose; (b-ii) about 1% to about 3% of the total core weight of croscarmellose sodium; and (b-iii) magnesium stearate, from about 0.1% to about 1.5% by weight of the total core Extragranular constituents, including; The tablet of any one of embodiments 30 to 39, 41, 45 to 55, comprising:

[0234] 60. The core, (a) (ai) about 5% by weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii-1) about 54% by weight of mannitol; (a-ii-2) about 20% by weight of crystalline cellulose; (a-iii) about 2% by weight of hydroxypropylcellulose; (a-iv) about 3% by weight of croscarmellose sodium; and (av) about 2% by weight of sodium lauryl sulfate Intragranular constituents, including; And (b) (bi) about 11% by weight of microcrystalline cellulose; (b-ii) about 2% by weight of croscarmellose sodium; and (b-iii) about 1% by weight of an extragranular lubricant Extragranular constituents, including; The tablet of any one of embodiments 30-39, 41, 42, 45-52, 54 and 58, comprising:

[0235] 61. The core, (a) (ai) about 5% by weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii-1) about 54% by weight of mannitol; (a-ii-2) about 20% by weight of crystalline cellulose; (a-iii) about 2% by weight of hydroxypropylcellulose; (a-iv) about 3% by weight of croscarmellose sodium; and (av) about 2% by weight of sodium lauryl sulfate Intragranular constituents, including; And (b) (bi) about 11% by weight of microcrystalline cellulose; (b-ii) about 2% by weight of croscarmellose sodium; and (b-iii) about 1% by weight of magnesium stearate Extragranular constituents, including; The tablet of any one of embodiments 30 to 39, 41, 42, 45 to 55, 58 and 59, comprising:

[0236] 62. The core, (a) (ai) about 10% by weight of the total core of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii-1) mannitol, approximately 50% of the total core weight; (a-ii-2) crystalline cellulose, about 19% of the total core weight; (a-iii) hydroxypropylcellulose, approximately 2% of the total core weight; (a-iv) croscarmellose sodium, about 3% by weight of the total core; and (av) Sodium lauryl sulfate, approximately 2% of the total core weight Intragranular constituents, including; And (b) (bi) crystalline cellulose, approximately 11% of the total core weight; (b-ii) croscarmellose sodium, about 2% by weight of the total core; and (b-iii) an extragranular lubricant, approximately 1% of the total core weight Extragranular constituents, including; The tablet of any one of embodiments 30 to 41, 45 to 52, 54, 56 and 58, comprising:

[0237] 63. The core, (a) (ai) about 10% by weight of the total core of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii-1) mannitol, approximately 50% of the total core weight; (a-ii-2) crystalline cellulose, about 19% of the total core weight; (a-iii) hydroxypropylcellulose, approximately 2% of the total core weight; (a-iv) croscarmellose sodium, about 3% by weight of the total core; and (av) Sodium lauryl sulfate, approximately 2% of the total core weight Intragranular constituents, including; And (b) (bi) crystalline cellulose, approximately 11% of the total core weight; (b-ii) croscarmellose sodium, about 2% by weight of the total core; and (b-iii) Magnesium stearate, approximately 1% of the total core weight Extragranular constituents, including; The tablet of any one of embodiments 30 to 41, and 45 to 59, comprising:

[0238] 64. The core, (a) (ai) about 20% by weight of the total core of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii-1) mannitol, approximately 44% of the total core weight; (a-ii-2) Microcrystalline cellulose, approximately 15% of the total core weight; (a-iii) hydroxypropylcellulose, approximately 2% of the total core weight; (a-iv) croscarmellose sodium, about 3% by weight of the total core; and (av) Sodium lauryl sulfate, approximately 2% of the total core weight Intragranular constituents, including; And (b) (bi) crystalline cellulose, approximately 11% of the total core weight; (b-ii) croscarmellose sodium, about 2% by weight of the total core; and (b-iii) an extragranular lubricant, approximately 1% of the total core weight Extragranular constituents, including; The tablet of any one of embodiments 30-40, 44-52, 54 and 56, comprising:

[0239] 65. The core, (a) (ai) about 20% by weight of the total core of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii-1) mannitol, approximately 44% of the total core weight; (a-ii-2) Microcrystalline cellulose, approximately 15% of the total core weight; (a-iii) hydroxypropylcellulose, approximately 2% of the total core weight; (a-iv) croscarmellose sodium, about 3% by weight of the total core; and (av) Sodium lauryl sulfate, approximately 2% of the total core weight Intragranular constituents, including; And (b) (bi) crystalline cellulose, approximately 11% of the total core weight; (b-ii) croscarmellose sodium, about 2% by weight of the total core; and (b-iii) Magnesium stearate, approximately 1% of the total core weight Extragranular constituents, including; The tablet of any one of embodiments 30 to 40, 44 to 57, comprising:

[0240] 66. The tablet of any one of embodiments 30 to 65, comprising a coating layer.

[0241] 67. The tablet of any one of embodiments 30 to 66, wherein the coating agent is selected from the group consisting of Opadry QX White 21A180025, Opadry I and Opadry II.

[0242] 68. The tablet of any one of embodiments 30 to 67, wherein the coating agent is Opadry QX White 21A180025.

[0243] 69. The tablet of any one of embodiments 30 to 68, wherein the tablet comprises from about 0.5% to about 10% of the total core weight of a coating agent.

[0244] EMBODIMENT 70. The tablet of any one of embodiments 30 to 69, wherein the tablet comprises from about 1% to about 5% of the total core weight of a coating agent.

[0245] EMBODIMENT 71. The tablet of any one of embodiments 30 to 71, wherein the tablet comprises about 2% to about 4% of the total core weight of a coating agent.

[0246] EMBODIMENT 72. The tablet of any one of embodiments 30 to 71, wherein the tablet comprises about 3% of the total core weight of a coating agent.

[0247] EMBODIMENT 73. The tablet of any one of embodiments 30 to 72, wherein the total core weight is about 50 mg.

[0248] 74. The core, (a) (ai) about 2.5 mg of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii-1) about 27 mg of mannitol; (a-ii-2) about 10 mg of crystalline cellulose; (a-iii) about 1 mg of hydroxypropylcellulose; (a-iv) about 1.5 mg of croscarmellose sodium; and (av) Approximately 1 mg of sodium lauryl sulfate Intragranular constituents, including; And (b) (bi) approximately 5.5 mg of crystalline cellulose; (b-ii) about 1 mg of croscarmellose sodium; and (b-iii) about 0.5 mg of extragranular lubricant Extragranular constituents, including; 74. The tablet of embodiment 73, comprising:

[0249] 75. The core, (a) (ai) about 2.5 mg of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii-1) about 27 mg of mannitol; (a-ii-2) about 10 mg of crystalline cellulose; (a-iii) about 1 mg of hydroxypropylcellulose; (a-iv) about 1.5 mg of croscarmellose sodium; and (av) Approximately 1 mg of sodium lauryl sulfate Intragranular constituents, including; And (b) (bi) approximately 5.5 mg of crystalline cellulose; (b-ii) about 1 mg of croscarmellose sodium; and (b-iii) about 0.5 mg of magnesium stearate Extragranular constituents, including; 75. The tablet of embodiment 73 or 74, comprising:

[0250] 76. The tablet of any one of embodiments 73 to 75, wherein the tablet comprises about 1.5 mg of a coating agent.

[0251] EMBODIMENT 77. The tablet of embodiment 76, wherein the coating agent is Opadry QX White 21A180025.

[0252] 78. The tablet of any one of embodiments 30 to 72, wherein the total core weight is about 100 mg.

[0253] 79. The core, (a) (ai) about 5 mg of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii-1) about 54 mg of mannitol; (a-ii-2) about 20 mg of crystalline cellulose; (a-iii) about 2 mg of hydroxypropylcellulose; (a-iv) about 3 mg of croscarmellose sodium; and (av) Approximately 2 mg of sodium lauryl sulfate Intragranular constituents, including; And (b) (bi) about 11 mg of crystalline cellulose; (b-ii) about 2 mg of croscarmellose sodium; and (b-iii) Approximately 1 mg of extragranular lubricant Extragranular constituents, including; 79. The tablet of embodiment 78, comprising:

[0254] 80. The core, (a) (ai) about 5 mg of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii-1) about 54 mg of mannitol; (a-ii-2) about 20 mg of crystalline cellulose; (a-iii) about 2 mg of hydroxypropylcellulose; (a-iv) about 3 mg of croscarmellose sodium; and (av) Approximately 2 mg of sodium lauryl sulfate Intragranular constituents, including; and (b) (bi) about 11 mg of crystalline cellulose; (b-ii) about 2 mg of croscarmellose sodium; and (b-iii) Approximately 1 mg of magnesium stearate Extragranular constituents, including; 80. The tablet of embodiment 78 or 79, comprising:

[0255] 81. The core, (a) (ai) about 20 mg of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii-1) mannitol, approximately 44 mg of total core weight; (a-ii-2) crystalline cellulose of about 15 mg of total core weight; (a-iii) hydroxypropylcellulose, approximately 2 mg of total core weight; (a-iv) croscarmellose sodium, about 3 mg by total core weight; and (av) Sodium lauryl sulfate, approximately 2 mg of total core weight Intragranular constituents, including; And (b) (bi) crystalline cellulose, approximately 11 mg of total core weight; (b-ii) croscarmellose sodium, about 2 mg of total core weight; and (b-iii) Approximately 1 mg of extragranular lubricant of the total core weight Extragranular constituents, including; 79. The tablet of embodiment 78, comprising:

[0256] 82. The core, (a) (ai) about 20 mg of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii-1) mannitol, approximately 44 mg of total core weight; (a-ii-2) crystalline cellulose of about 15 mg of total core weight; (a-iii) hydroxypropylcellulose, approximately 2 mg of total core weight; (a-iv) croscarmellose sodium, about 3 mg by total core weight; and (av) Sodium lauryl sulfate, approximately 2 mg of total core weight Intragranular constituents, including; And (b) (bi) crystalline cellulose, approximately 11 mg of total core weight; (b-ii) croscarmellose sodium, about 2 mg of total core weight; and (b-iii) Magnesium stearate, approximately 1 mg of total core weight Extragranular constituents, including; The tablet of embodiment 78 or 81, comprising:

[0257] 83. The tablet of any one of embodiments 78 to 82, wherein the tablet comprises about 3 mg of a coating agent.

[0258] 84. A tablet according to embodiment 83, wherein the coating agent is Opadry QX White 21A180025.

[0259] 85. The tablet of any one of embodiments 30 to 72, wherein the total core weight is about 200 mg.

[0260] 86. The core, (a) (ai) about 10 mg of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii-1) about 108 mg of mannitol; (a-ii-2) about 40 mg of crystalline cellulose; (a-iii) about 4 mg of hydroxypropylcellulose; (a-iv) about 6 mg of croscarmellose sodium; and (av) Approximately 4 mg of sodium lauryl sulfate Intragranular constituents, including; And (b) (bi) about 22 mg of crystalline cellulose; (b-ii) about 4 mg of croscarmellose sodium; and (b-iii) Approximately 2 mg of extragranular lubricant Extragranular constituents, including; The tablet of embodiment 85, comprising:

[0261] 87. The core, (a) (ai) about 10 mg of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii-1) about 108 mg of mannitol; (a-ii-2) about 40 mg of crystalline cellulose; (a-iii) about 4 mg of hydroxypropylcellulose; (a-iv) about 6 mg of croscarmellose sodium; and (av) Approximately 4 mg of sodium lauryl sulfate Intragranular constituents, including; And (b) (bi) about 22 mg of crystalline cellulose; (b-ii) about 4 mg of croscarmellose sodium; and (b-iii) Approximately 2 mg of magnesium stearate Extragranular constituents, including; The tablet of embodiment 85 or 86, comprising:

[0262] 88. The core, (a) (ai) about 40 mg of total core weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii-1) mannitol, approximately 88 mg of total core weight; (a-ii-2) crystalline cellulose, approximately 30 mg of total core weight; (a-iii) hydroxypropylcellulose, approximately 4 mg of total core weight; (a-iv) croscarmellose sodium, about 6 mg by total core weight; and (av) Sodium lauryl sulfate, approximately 4 mg of total core weight Intragranular constituents, including; And (b) (bi) crystalline cellulose, approximately 22 mg of total core weight; (b-ii) croscarmellose sodium, about 4 mg of total core weight; and (b-iii) Approximately 2 mg of extragranular lubricant of the total core weight Extragranular constituents, including; The tablet of embodiment 85, comprising:

[0263] 89. The core, (a) (ai) about 40 mg of total core weight of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii-1) mannitol, approximately 88 mg of total core weight; (a-ii-2) crystalline cellulose, approximately 30 mg of total core weight; (a-iii) hydroxypropylcellulose, approximately 4 mg of total core weight; (a-iv) croscarmellose sodium, about 6 mg by total core weight; and (av) Sodium lauryl sulfate, approximately 4 mg of total core weight Intragranular constituents, including; And (b) (bi) crystalline cellulose, approximately 22 mg of total core weight; (b-ii) croscarmellose sodium, about 4 mg of total core weight; and (b-iii) Magnesium stearate, approximately 2 mg of total core weight Extragranular constituents, including; The tablet of embodiment 85 or 88, comprising:

[0264] EMBODIMENT 90. The tablet of any one of embodiments 85 to 89, wherein the tablet comprises about 6 mg of a coating agent.

[0265] EMBODIMENT 91. The tablet of embodiment 90, wherein the coating agent is Opadry QX White 21A180025.

[0266] EMBODIMENT 92. The tablet of any one of embodiments 30 to 72, wherein the total core weight is about 70 mg.

[0267] EMBODIMENT 93. Core (a) (ai) about 7 mg of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii-1) about 35 mg of mannitol; (a-ii-2) about 13.3 mg of crystalline cellulose; (a-iii) about 1.4 mg of hydroxypropylcellulose; (a-iv) about 2.1 mg of croscarmellose sodium; and (av) Approximately 1.4 mg of sodium lauryl sulfate Intragranular constituents, including; And (b) (bi) approximately 7.7 mg of crystalline cellulose; (b-ii) about 1.4 mg of croscarmellose sodium; and (b-iii) about 0.7 mg of extragranular lubricant Extragranular constituents, including; 93. The tablet of embodiment 92, comprising:

[0268] EMBODIMENT 94. The core, (a) (ai) about 7 mg of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii-1) about 35 mg of mannitol; (a-ii-2) about 13.3 mg of crystalline cellulose; (a-iii) about 1.4 mg of hydroxypropylcellulose; (a-iv) about 2.1 mg of croscarmellose sodium; and (av) about 1.4 mg sodium lauryl sulfate; Intragranular constituents, including; And (b) (bi) approximately 7.7 mg of crystalline cellulose; (b-ii) about 1.4 mg of croscarmellose sodium; and (b-iii) Approximately 0.7 mg of magnesium stearate Extragranular constituents, including; 94. The tablet of embodiment 92 or 93, comprising:

[0269] EMBODIMENT 95. The tablet of any one of embodiments 92 to 94, wherein the tablet comprises about 2.1 mg of a coating agent.

[0270] EMBODIMENT 96. The tablet of embodiment 95, wherein the coating agent is Opadry QX White 21A180025.

[0271] EMBODIMENT 97. The tablet of any one of embodiments 30 to 72, wherein the total core weight is about 400 mg.

[0272] EMBODIMENT 98. The core, (a) (ai) about 40 mg of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii-1) about 200 mg of mannitol; (a-ii-2) about 76 mg of crystalline cellulose; (a-iii) about 8 mg of hydroxypropylcellulose; (a-iv) about 12 mg of croscarmellose sodium; and (av) Approximately 8 mg of sodium lauryl sulfate Intragranular constituents, including; And (b) (bi) about 44 mg of crystalline cellulose; (b-ii) about 8 mg of croscarmellose sodium; and (b-iii) Approximately 4 mg of extragranular lubricant Extragranular constituents, including; 98. The tablet of embodiment 97, comprising:

[0273] EMBODIMENT 99. The core, (a) (ai) about 40 mg of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii-1) about 200 mg of mannitol; (a-ii-2) about 76 mg of crystalline cellulose; (a-iii) about 8 mg of hydroxypropylcellulose; (a-iv) about 12 mg of croscarmellose sodium; and (av) Approximately 8 mg of sodium lauryl sulfate Intragranular constituents, including; And (b) (bi) about 44 mg of crystalline cellulose; (b-ii) about 8 mg of croscarmellose sodium; and (b-iii) Approximately 4 mg of magnesium stearate Extragranular constituents, including; 99. The tablet of embodiment 97 or 98, comprising:

[0274] EMBODIMENT 100. The tablet of any one of embodiments 97 to 98, wherein the tablet comprises about 12 mg of a coating agent.

[0275] EMBODIMENT 101. The tablet of embodiment 100, wherein the coating agent is Opadry QX White 21A180025.

[0276] EMBODIMENT 102. The tablet of any one of embodiments 30 to 101, wherein the (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph or pharma- ceutically acceptable salt thereof is (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide.

[0277] EMBODIMENT 103. A method of making a tablet according to any one of embodiments 30 to 102, comprising the steps of: (1) preparing a granule comprising (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph or pharma- ceutically acceptable salt thereof, an intragranular filler, an intragranular binder, an intragranular disintegrant and an intragranular surfactant; (2) milling a granule comprising (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof, an intragranular filler, an intragranular binder, an intragranular disintegrant, and an intragranular surfactant to form an intragranular component; (3) blending the intragranular components with the extragranular filler, the extragranular disintegrant and the extragranular lubricant to form a final blended mixture; (4) compressing the final blended mixture to form a core; (5) optionally coating the core with a coating layer; A method comprising:

[0278] EMBODIMENT 104. The method of embodiment 102, wherein the step of preparing granules comprising (R)—N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph or pharma- ceutically acceptable salt thereof, an intragranular filler, an intragranular binder, an intragranular disintegrant and an intragranular surfactant comprises a wet granulation process.

[0279] EMBODIMENT 105. The method of embodiment 104, wherein the wet granulation step is carried out using a high shear granulator.

[0280] EMBODIMENT 106. The method of embodiment 104 or 105, wherein the wet granulation step further comprises a wet milling step.

[0281] EMBODIMENT 107. The method of embodiment 106, wherein the wet milling step is carried out using a conical mill.

[0282] EMBODIMENT 108. The method of any one of embodiments 103-107, wherein the step of preparing a granule comprising (R)—N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph or pharma- ceutically acceptable salt thereof, an intragranular filler, an intragranular binder, an intragranular disintegrant and an intragranular surfactant further comprises the step of drying the granule.

[0283] EMBODIMENT 109. The method of embodiment 108, wherein the step of drying the granules is carried out in a fluid bed dryer.

[0284] EMBODIMENT 110. The method of any one of embodiments 103-109, wherein the step of milling the granules comprising (R)—N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph or pharma- ceutically acceptable salt thereof, an intragranular filler, an intragranular binder, an intragranular disintegrant and an intragranular surfactant is performed using a conical mill.

[0285] EMBODIMENT 111. The method of any one of embodiments 103-110, wherein the step of blending the intragranular component with the extragranular filler, the extragranular disintegrant and the extragranular lubricant is carried out in a V-blender.

[0286] EMBODIMENT 112. The method of any one of embodiments 103-111, wherein the step of compressing the final blended mixture to form the cores is carried out using a rotary tablet press.

[0287] EMBODIMENT 113. The method of any one of embodiments 103 to 112, comprising coating the core with a coating layer.

[0288] EMBODIMENT 114. The method of any one of embodiments 103-113, comprising coating the cores with the coating layer using a conventional coating pan.

[0289] EMBODIMENT 115. The method of any one of embodiments 103-114, wherein the (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph or pharma- ceutically acceptable salt thereof is (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide.

[0290] EMBODIMENT 116. (i) a core, (a) (ai) (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide; or a hydrate, solvate, polymorph or pharma- ceutically acceptable salt thereof; (a-ii) intragranular fillers; (a-iii) intragranular binders; (a-iv) an intragranular disintegrant; and (av) Intragranular surfactant Intragranular constituents, including; And (b) (bi) extragranular fillers; (b-ii) an extragranular disintegrant; and (b-iii) Extragranular lubricant a core having a total core weight including extragranular constituents, And (ii) a coating layer containing a coating agent 1. A method of making a tablet comprising: (1) preparing a granule comprising (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph or pharma- ceutically acceptable salt thereof, an intragranular filler, an intragranular binder, an intragranular disintegrant and an intragranular surfactant; (2) milling a granule comprising (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof, an intragranular filler, an intragranular binder, an intragranular disintegrant, and an intragranular surfactant to form an intragranular component; (3) blending the intragranular components with the extragranular filler, the extragranular disintegrant and the extragranular lubricant to form a final blended mixture; (4) compressing the final blended mixture to form a core; (5) coating the core with a coating layer A method comprising:

[0291] EMBODIMENT 117. The method of embodiment 116, wherein the step of preparing granules comprising (R)—N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph or pharma- ceutically acceptable salt thereof, an intragranular filler, an intragranular binder, an intragranular disintegrant and an intragranular surfactant comprises a wet granulation process.

[0292] EMBODIMENT 118. The method of embodiment 117, wherein the wet granulation step is carried out using a high shear granulator.

[0293] EMBODIMENT 119. The method of embodiment 117 or 118, wherein the wet granulation step further comprises a wet milling step.

[0294] EMBODIMENT 120. The method of embodiment 119, wherein the wet milling step is carried out using a conical mill.

[0295] EMBODIMENT 121. The method of any one of embodiments 116-120, wherein the step of preparing a granule comprising (R)—N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph or pharma- ceutically acceptable salt thereof, an intragranular filler, an intragranular binder, an intragranular disintegrant and an intragranular surfactant further comprises the step of drying the granule.

[0296] EMBODIMENT 122. The method of embodiment 121, wherein the step of drying the granules is carried out in a fluid bed dryer.

[0297] EMBODIMENT 123. The method of any one of embodiments 116-122, wherein the step of milling the granules comprising (R)—N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph or pharma- ceutically acceptable salt thereof, an intragranular filler, an intragranular binder, an intragranular disintegrant and an intragranular surfactant is performed using a conical mill.

[0298] EMBODIMENT 124. The method of any one of embodiments 116-123, wherein the step of blending the intragranular components with the extragranular filler, the extragranular disintegrant and the extragranular lubricant is carried out in a V-blender.

[0299] EMBODIMENT 125. The method of any one of embodiments 116-124, wherein the step of compressing the final blended mixture to form the cores is carried out using a rotary tablet press.

[0300] Embodiment 126. The method of any one of embodiments 116 to 125, comprising coating the core with a coating layer.

[0301] EMBODIMENT 127. The method of any one of embodiments 116-126, comprising coating the cores with the coating layer using a coating pan.

[0302] EMBODIMENT 128. The method of any one of embodiments 116-127, wherein the (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph or pharma- ceutically acceptable salt thereof is (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide.

[0303] EMBODIMENT 129. A method of treating a cardiac disease in a subject in need thereof, comprising administering to the subject a formulation of any one of embodiments 1-29, or a tablet of any one of embodiments 30-102.

[0304] EMBODIMENT 130. 130. The method of embodiment 129, wherein the cardiac disease is hypertrophic cardiomyopathy (HCM).

[0305] EMBODIMENT 131. The method of embodiment 130, wherein the HCM is obstructive or non-obstructive, or associated with sarcomeric and / or non-sarcomeric mutations.

[0306] EMBODIMENT 132. The method of embodiment 129, wherein the cardiac disease is heart failure with preserved ejection fraction (HFpEF).

[0307] EMBODIMENT 133. The method of embodiment 129, wherein the cardiac disease is selected from the group consisting of diastolic dysfunction, primary or secondary restrictive cardiomyopathy, myocardial infarction and angina pectoris, left ventricular outflow tract obstruction, hypertensive heart disease, congenital heart disease, cardiac ischemia, coronary heart disease, diabetic heart disease, congestive heart failure, right heart failure, cardiorenal syndrome, and infiltrative cardiomyopathy.

[0308] EMBODIMENT 134. The method of embodiment 129, wherein the cardiac disease is or is associated with one or more conditions selected from the group consisting of cardiac aging, age-related diastolic dysfunction, left ventricular hypertrophy and concentric left ventricular remodeling.

[0309] EMBODIMENT 135. A method of treating a disease or condition associated with hypertrophic cardiomyopathy in a subject in need of such treatment, comprising administering to the subject a formulation of any one of embodiments 1-29, or a tablet of any one of embodiments 30-102.

[0310] EMBODIMENT 136. The method of embodiment 135, wherein the disease or condition is selected from the group consisting of Fabry disease, Danon disease, mitochondrial cardiomyopathy, and Noonan syndrome.

[0311] EMBODIMENT 137. A method for treating a disease or condition associated with secondary left ventricular wall thickening in a subject in need thereof, comprising administering to the subject a formulation of any one of embodiments 1-29 or a tablet of any one of embodiments 30-102.

[0312] EMBODIMENT 138. The method of embodiment 137, wherein the disease or condition is selected from the group consisting of hypertension, valvular heart disease, metabolic syndrome, end stage renal disease, scleroderma, sleep apnea, amyloidosis, Fabry disease, Friedreich's ataxia, Danon disease, Noonan syndrome, and Pompe disease.

[0313] EMBODIMENT 139. A method for treating a disease or condition associated with small left ventricular cavity and lumen obstruction, hyperdynamic left ventricular contraction, myocardial ischemia, or cardiac fibrosis in a subject in need thereof, comprising administering to the subject a formulation according to any one of embodiments 1-29 or a tablet according to any one of embodiments 30-102.

[0314] EMBODIMENT 140. A method for treating a disease or condition selected from muscular dystrophy and glycogen storage disease in a subject in need thereof, comprising administering to the subject a formulation of any one of embodiments 1-29, or a tablet of any one of embodiments 30-102.

[0315] EMBODIMENT 141. A method for inhibiting cardiac sarcomeres, comprising contacting cardiac sarcomeres with the formulation of any one of embodiments 1-29, or the tablet of any one of embodiments 30-102. EXAMPLES

[0316] The following examples are presented to illustrate, but not limit, the compositions, uses and methods presented herein.

[0317] The following abbreviations are used throughout the examples: TEA (trimethylamine), DCM (dichloromethane), (Boc)2O (di-tert-butyl dicarbonate), EA (ethyl acetate), PE (petroleum ether), DMF (N,N-dimethylformamide), DIEA (N-ethyl-N-isopropylpropan-2-amine), HATU (1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate), HOAt (1-hydroxy-7-azabenzotriazole), HOBt (hydroxybenzotriazole), EDCI (1-ethyl-3-(3-dimethylaminopropyl)carbodiimide), MeOH (methanol), EtO H (ethanol), iPrOH (propan-2-ol), ACN (acetonitrile), TFA (trifluoroacetic acid), DPPA (diphenylphosphoryl azide), DBU (1,8-diazabicyclo(5.4.0)undec-7-ene), THF (tetrahydrofuran), PPh3 (triphenylphosphane), SM (starting material), Hex (hexane), NCS (N-chlorosuccinimide), rt (room temperature), DCE (dichloroethane), FA (formic acid), CHCl3 (chloroform), BnBr (benzyl bromide), HCl (hydrogen chloride), equiv (equivalent), DSC (bis(2,5-dioxopyrrolidin-1-yl)carbonate), RH (relative humidity), QL (quantitation limit), RRT (relative retention time), RS (related substances). Example 1 Synthesis of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide (i) Synthesis of intermediate A [ka]

[0318] To a solution of tert-butyl N-[(1R)-5-(N-hydroxycarbamimidoyl)-2,3-dihydro-1H-inden-1-yl]carbamate (16 g, 54.9 mmol, 1.0 equiv.) in dioxane (300 mL) was added propanoyl propanoate (8.4 g, 64.5 mmol, 1.2 equiv.). The mixture was stirred at 105° C. for 8 h, cooled to room temperature, concentrated under reduced pressure, and purified by silica gel chromatography (EA / PE, 1 / 9) to give 17.5 g (97%) of tert-butyl N-[(1R)-5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl]carbamate as a white solid. (ii) Synthesis of intermediate B [ka]

[0319] To a solution of tert-butyl N-[(1R)-5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl]carbamate (17.6 g, 53.4 mmol, 1.0 equiv) in DCM (120 mL) was added TFA (24 mL). The mixture was stirred at room temperature overnight and concentrated under reduced pressure. The mixture was then poured into ethanol (50 mL) and water (5 mL) and the pH was adjusted to 12 with sodium hydroxide solution (2N). The mixture was then extracted three times with dichloromethane (200 mL). The combined organic layers were dried over anhydrous sodium sulfate and concentrated under reduced pressure to give 11.2 g of (1R)-5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-amine as a brown oil. (iii) Synthesis of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide: [ka]

[0320] To a solution of 1-methyl-1H-pyrazole-4-carboxylic acid (6.1 g, 48.4 mmol, 1.0 equiv.) in DMF (300 mL) was added DIEA (12.6 g, 97.5 mmol, 2.0 equiv.), HOAt (19.8 g, 145.8 mmol, 3.0 equiv.) and EDCI (28 g, 146.1 mmol, 3.0 equiv.). The mixture was stirred for 15 min, and then (1R)-5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-amine (11.2 g, 48.9 mmol, 1.0 equiv.) was added. The mixture was then stirred for 3 h, diluted with DCM, washed three times with NH4Cl solution, dried over sodium sulfate, concentrated under reduced pressure and purified by silica gel chromatography (EA / PE, 74 / 26) to give the intermediate product, which was triturated with a mixture of EA and PE (1 / 10) to give 14.5 g (88%) of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide as a white solid. LRMS (ES) m / z 338 (M+H). 1 H-NMR: (DMSO, 300MHz, ppm): δ 8.41 (1H, d, J = 8.4 Hz), 8.16 (1H, s), 7.91-7.79 (3H, m), 7.34 (1H, d, J = 7.9 Hz), 5.53 (1H, q, J = 8.3 Hz), 3.84 (3H, s), 3.13-2.81 (4H, m), 2.44 (1H, dd, J = 7.9, 4.7 Hz), 1.95 (1H, m), 1.33 (3H, t, J = 7.5 Hz). Example 2 Preparation of Exemplary Formulations

[0321] FIG. 1 depicts a flow chart illustrating unit operations in the preparation of the formulations described herein.

[0322] (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, microcrystalline cellulose, mannitol, croscarmellose sodium, hydroxypropyl cellulose and sodium lauryl sulfate were sieved by hand. Magnesium stearate was sieved by hand. (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, microcrystalline cellulose, mannitol, croscarmellose sodium, hydroxypropyl cellulose and sodium lauryl sulfate were mixed in a high shear granulator and subjected to a wet granulation process, followed by wet milling, drying and dry milling. The resulting solid mixture was blended with microcrystalline cellulose and croscarmellose sodium. Finally, the resulting mixture was blended with magnesium stearate to obtain a formulation containing (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide. Example 3 Preparation of uncoated tablets

[0323] FIG. 2 depicts a flow chart illustrating the unit operations in the preparation of the uncoated tablets described herein.

[0324] (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, microcrystalline cellulose, mannitol, croscarmellose sodium, hydroxypropyl cellulose and sodium lauryl sulfate were sieved by hand. Magnesium stearate was sieved by hand. (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, microcrystalline cellulose, mannitol, croscarmellose sodium, hydroxypropyl cellulose and sodium lauryl sulfate were mixed in a high shear granulator and subjected to a wet granulation process, followed by wet milling, drying and dry milling. The resulting solid mixture was blended with microcrystalline cellulose and croscarmellose sodium. The resulting mixture is blended with magnesium stearate. This final mixture is then compressed into tablets to obtain uncoated tablets. Example 4 Preparation of coated tablets

[0325] FIG. 3 depicts a flow chart illustrating the unit operations in the preparation of the coated tablets described herein.

[0326] (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, microcrystalline cellulose, mannitol, croscarmellose sodium, hydroxypropyl cellulose and sodium lauryl sulfate were sieved by hand. Magnesium stearate was sieved by hand. (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, microcrystalline cellulose, mannitol, croscarmellose sodium, hydroxypropyl cellulose and sodium lauryl sulfate were mixed in a high shear granulator and subjected to a wet granulation process, followed by wet milling, drying and dry milling. The resulting solid mixture was blended with microcrystalline cellulose and croscarmellose sodium. The resulting mixture is blended with magnesium stearate. This final mixture is then compressed into tablets to obtain uncoated tablets. These uncoated tablets are then coated with Opadry White QX to obtain coated tablets. Example 5 2.5mg formulation

[0327] A tablet containing 5 mg of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide was prepared according to the method of Example 4, the flow chart of which is shown in Figure 3. The following ingredients and amounts were used in this method: [Table 1] Example 6 5 mg formulation

[0328] A tablet containing 5 mg of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide was prepared according to the method of Example 4, the flow chart of which is shown in Figure 3. The following ingredients and amounts were used in this method: [Table 2] Example 7 10 mg formulation

[0329] Tablets containing 10 mg of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide were prepared according to the method of Example 4, the flow chart of which is shown in Figure 3. The following ingredients and amounts were used in this method: [Table 3] Example 8 20 mg formulation

[0330] Tablets containing 20 mg of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide were prepared according to the method of Example 4, the flow chart of which is shown in Figure 3. The following ingredients and amounts were used in this method: [Table 4] Example 9 40 mg formulation

[0331] Tablets containing 40 mg of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide were prepared according to the method of Example 4, the flow chart of which is shown in Figure 3. The following ingredients and amounts were used in this method: [Table 5] Example 10 7 mg formulation

[0332] A tablet containing 7 mg of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide was prepared according to the method of Example 4, the flow chart of which is shown in Figure 3. The following ingredients and amounts were used in this method: [Table 6] Example 11 40 mg formulation

[0333] Tablets containing 40 mg of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide were prepared according to the method of Example 4, the flow chart of which is shown in Figure 3. The following ingredients and amounts were used in this method: [Table 7] Example 11 Long-term stability of 5mg formulation

[0334] Tablets containing 5 mg of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide as described in Example 6. The tablets were packaged in white 30cc round wide mouth HDPE bottles with induction seal and 28mm Securx cap, SG-75M liner. Each bottle contained 40 tablets. The tablets were stored at 30°C + / - 2°C and 65% RH + / - 5% RH for 12 months. After the 12 month period, the tablets were analyzed for appearance, potency, presence of unknown compounds, ability to release active ingredient upon dissolution and moisture content. The results are shown in Table 8. [Table 8] Example 12 Long-term stability of the 40mg formulation

[0335] Tablets containing 40 mg of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide as described in Example 9. The tablets were packaged in white 30 cc round wide mouth HDPE bottles with induction seal and 28 mm Securx cap, SG-75M liner. Each bottle contained 40 tablets. The tablets were stored at 30° C.+ / -2° C. and 65% RH+ / -5% RH for 12 months. After the 12 month period, the tablets were analyzed for appearance, potency, presence of unknown compounds, ability to release active ingredient upon dissolution and moisture content. The results are shown in Table 9. [Table 9] (Biological Example B-1) Myofibril assay

[0336] To evaluate the effect of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide on the ATPase activity of full-length cardiac myosin in the context of native sarcomeres, a stripped myofibril assay was performed. Bovine cardiac myofibrils were obtained by homogenizing left ventricular tissue of bovine hearts in the presence of detergents such as Triton X-100. Such treatment removes most of the membrane and soluble cytoplasmic proteins but leaves the cardiac sarcomeric actomyosin apparatus intact. Myofibril preparations were enriched in Ca 2+ Ca2+ activates the ATPase activity of such myofibrillar preparations to defined maximal fractions (i.e., 25%, 75%) in the presence and absence of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, retaining the ability to hydrolyze ATP in a regulated manner. 2+ (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide was assessed for their ability to inhibit steady-state ATPase activity of bovine cardiac myofibrils using a pyruvate kinase and lactate dehydrogenase (PK / LDH) coupled enzyme system. This assay regenerates ADP produced by myosin to ATP by oxidizing NADH resulting in an absorbance change at 340 nm. Prior to testing (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, bovine cardiac myofibrils were assessed for their calcium responsiveness and were assayed to determine whether they were at 50% of the myofibrillar system (pCa 50 ) or 75%(pCa 75) activation was selected as the final condition for assessing the inhibitory activity of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide. All enzyme activities were measured in a buffer solution containing 12 mM PIPES (piperazine-N,N'-bis(2-ethanesulfonic acid), 2 mM magnesium chloride at pH 6.8 (PM12 buffer). The final assay conditions were 1 mg / mL bovine cardiac myofibrils, 4 U / mL pyruvate kinase, 6 U / mL lactate dehydrogenase, 50 μM ATP, 0.1 mg / mL BSA (bovine serum albumin), 10 ppm antifoam, 1 mM DTT, 0.5 mM NADH, 1.5 mM PEP, 0.6 mM EGTA, and myofibrillar ATP acetate. The amount of CaCl2 was sufficient to achieve either 50% or 75% activation of the enzyme activity. The results for (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide are provided in Table A. (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide was prepared according to the synthetic procedures described herein. [Table 1A] (Biological Example B-2) Myocyte assay (i) Preparation of adult rat ventricular myocytes:

[0337] Adult male Sprague-Dawley rats were anesthetized, the hearts were rapidly excised, rinsed, and the ascending aorta was cannulated. Continuous retrograde perfusion was initiated through the hearts at a perfusion pressure of 60 cmH2O. Hearts were first perfused nominally with Ca 2+The hearts were perfused with modified Krebs solution of the following composition without Sigma: 113 mM NaCl, 4.7 mM KCl, 0.6 mM KH2PO4, 0.6 mM Na2HPO4, 1.2 mM MgSO4, 12 mM NaHCO3, 10 mM KHCO3, 30 mM taurine, 5.5 mM glucose and 10 mM Hepes (all Sigma). This medium is not recirculated and is constantly aerated with a 95% O2 / 5% CO2 mixture. After approximately 3 minutes, the hearts were perfused with modified Krebs buffer supplemented with collagenase (Worthington) and a final calcium concentration of 12.5 μM. After the heart appeared white and soft in appearance, it was removed from the cannula. The atria and blood vessels were removed and the ventricles were carefully dissected into smaller pieces with forceps. Tissues were homogenized by repeated pipette trituration, collagenase reactions were stopped with 10% bovine calf serum (BCS), precipitated, and resuspended in perfusion buffer containing 5% BCS and 12.5 uM CaCl2. Myocytes were made calcium tolerant by stepwise addition of CaCl2 solution to a final concentration of 1.2 mM. Cells were then washed and resuspended in Tyrode's buffer (137 mM NaCl, 3.7 mM KCl, 0.5 mM MgCl2, 11 mM glucose, 4 mM Hepes, and 1.2 mM CaCl2, pH 7.4). Cells were kept at 37°C for 60 minutes before starting the experiment and were used within 5 hours of isolation. Cell preparations were used only if the cells initially passed QC criteria by demonstrating contractile responses to standard (>150% of basal) and isoproterenol (ISO, >250% of basal) treatments. Furthermore, only cells whose basal contractility was between 3-8% were used in subsequent experiments with compounds. (ii) Adult ventricular myocyte contraction experiments:

[0338] An aliquot of myocytes in Tyrode's buffer was placed in a perfusion chamber equipped with a heating platform (series 20 RC-27NE, Warner Instruments). Myocytes were allowed to attach, the chamber was heated to 37°C, and the cells were perfused with Tyrode's buffer at 37°C. Myocytes were field stimulated at 1 Hz with platinum electrodes (20% above threshold). Only cells that had clear striations and were quiescent before pacing were used for contractility experiments. To determine basal contractility, myocytes were imaged with a 40x objective. Images were digitized using a charge-coupled device camera with variable frame rates (60-240 Hz) and displayed on a computer screen at a sampling rate of 240 Hz (IonOptix Milton, MA). Once cell contraction was stable over time, (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide (0.01-15 µM) was perfused for 5 min over the myocyte in the chamber. Myocyte contractility, as well as the rate of contraction and relaxation, were then recorded using edge detection. (iii) Contractility analysis:

[0339] Five or more individual myocytes from two or more different myocyte preparations were tested. For each cell, 20 or more contractile transients at basal (defined as 1 minute before compound injection) and after compound addition (defined as 5 minutes after starting compound perfusion) were averaged and compared. These averaged transients were analyzed using IonWizard software (IonOptix) to determine the change in diastolic length and fractional shortening. Fractional shortening was calculated as ((resting length-peak contraction length) divided by resting length). Percentage change in fractional shortening from baseline was calculated as ((fractional shortening after dosing / basal fractional shortening) x 100). Percentage reduction in fractional shortening from baseline was calculated as (100-percentage change in fractional shortening from baseline). Maximum contraction and relaxation velocities (um / sec) were also determined. Results from individual cells were averaged and SEM was calculated.

[0340] The effect of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide on the fractional shortening (FS) of muscle cells is shown in Table B. [Table 1B] FS% = average of (post-baseline peak height percent / pre-baseline peak height percent) x 100 for each cell (Biological Example B-3) Echocardiographic assessment of acute pharmacodynamic effects on cardiac contractility in rats.

[0341] Assessment of in vivo cardiac function by echocardiography was performed in male Sprague Dawley rats under isoflurane (1–3%) anesthesia. 2-D M-mode images of the left ventricle were acquired in the parasternal long axis view before, during, and after administration of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide by continuous IV infusion or oral gavage. In vivo fractional shortening was determined by M-mode image analysis using the following calculation: ((end-diastolic diameter - end-systolic diameter) / end-diastolic diameter × 100). In the continuous IV infusion study, three pre-dose baseline M-mode images were obtained at 1 minute intervals prior to infusion of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide. (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide was formulated in 50% propylene glycol (PG):16% Captisol:10% dimethylacetamide (DMA) and delivered at a rate of 1 mL / kg / hr via a jugular catheter. During the infusion, M-mode images were obtained at 5 minute intervals. The infusion was stopped when fractional shortening was reduced by a maximum of 60% from baseline. Blood samples were taken to determine the plasma concentration of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide. Data are based on estimated IC, the concentration at which fractional shortening is 50% of pre-dose baseline contractility. 50 The values ​​were reported as IC 50 The results are summarized in Table C. [Table 1C]

[0342] For oral dosing studies, three pre-dose baseline M-mode images were obtained 1 min apart before compound administration. (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide was formulated in 0.5% hydroxypropyl methylcellulose 2910 (HPMC2910):0.1% Tween 80 suspension and delivered by oral gavage as a single dose (5 mL / kg). Rats were lightly anesthetized for M-mode echocardiography measurements at selected time points over a 24-hour period. Various dose levels were evaluated for (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide. The effect of the compounds on cardiac shunt fraction at the highest dose evaluated is shown in Table D as the percent reduction of baseline fractional shortening (=100%). [Table 1D]

[0343] Concurrent with the echocardiographic measurements, blood samples were taken to determine the plasma concentrations of the corresponding (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide. The data in Table E are the estimated IC, the concentrations at which fractional shortening was 50% and 10% of the predose baseline contractility, respectively. 50 and I.C. 10 The values ​​are summarized. [Table 1E]

[0344] All documents cited in this specification, including all patents, patent applications, and publications, including all documents cited in this specification, tables, and figures, are expressly incorporated by reference in their entirety for all purposes.

[0345] The foregoing description of the compounds, uses, and methods described herein allows one skilled in the art to make and use the compounds, uses, and methods described herein, but one skilled in the art will understand and appreciate the existence of variations, combinations, and equivalents of the specific embodiments, methods, and examples herein. Thus, the compounds, uses, and methods provided herein should not be limited by the foregoing embodiments, methods, or examples, but rather encompass any and all embodiments and methods that fall within the scope and spirit of the compounds, uses, and methods provided herein. The present invention provides, for example, the following: (Item 1) (i) (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide; (ii) filler; (iii) a binder; (iv) a disintegrant; (v) surfactants; and (vi) Lubricants 13. A formulation comprising: (Item 2) 2. The formulation of item 1, wherein the filler is selected from the group consisting of powdered cellulose, microcrystalline cellulose, silicified microcrystalline cellulose, kaolin, corn starch, maize starch, starch derivatives, pregelatinized starch, calcium phosphate, calcium hydrogen phosphate, dicalcium phosphate, tricalcium phosphate, compressible sugar, sugar alcohols, mannitol, sorbitol, maltitol, xylitol, lactitol, lactose, dextrose, maltose, sucrose, glucose, fructose, saccharose, raffinose, dextrates, trehalose, maltodextrin, and mixtures of any of the above. (Item 3) 3. The formulation according to item 1 or 2, wherein the binder is selected from the group consisting of gum arabic, gum acacia, alginate, alginic acid, corn starch, copolyvidone, polyvinylpyrrolidone, gelatin, glyceryl behenate, hydroxyethylcellulose, hydroxypropylcellulose, carboxymethylcellulose, calcium carboxymethylcellulose, sodium carboxymethylcellulose, methylcellulose, hypromellose, lactose, polyvinyl alcohol, povidone, polyethylene oxide, polyacrylates, potato starch, pregelatinized starch, sodium alginate, sodium starch, sodium carboxymethylcellulose, starch, and mixtures of any of the above. (Item 4) 4. The formulation according to any one of items 1 to 3, wherein the disintegrant is selected from the group consisting of alginic acid, croscarmellose sodium, cellulose, calcium carboxymethylcellulose, sodium carboxymethylcellulose, microcrystalline cellulose, crospovidone, sodium starch glycolate, low substituted hydroxypropylcellulose, polacrilin potassium, pregelatinized starch, partially hydrolyzed starch, sodium carboxymethylstarch, starch, sodium alginate, sodium carboxymethylcellulose, and mixtures of any of the above. (Item 5) The surfactant may be cetylpyridine chloride, heptadecaethyleneoxycetanol, lecithin, polyoxyethylene stearate, nonoxynol 9, nonoxynol 10, octoxynol 9, sorbitan fatty acid ester, Span 20, Span 40, Span 60, Span 80, Span 85, polysorbate, polysorbate 20, polysorbate 21, polysorbate 40, polysorbate 60, polysorbate 61, polysorbate 65, polysorbate 80, sodium salt of fatty alcohol sulfate, sodium lauryl sulfate. 5. The formulation according to any one of items 1 to 4, wherein the glyceryl monostearate, glyceryl monooleate, ethers of fatty alcohols and polyoxyethylene, esters of fatty acids and polyoxyethylene, copolymers of ethylene oxide and propylene oxide (Pluronic®), benzalkonium chloride, ethoxylated triglycerides, and mixtures of any of the above. (Item 6) 6. The formulation according to any one of items 1 to 5, wherein the lubricant is selected from the group consisting of hydrogenated castor oil, magnesium stearate, glyceryl monostearate, calcium stearate, glyceryl behenate, glycerol distearate, glyceryl dipalmitostearate, behenoyl polyoxyl-8 glyceride, sodium stearyl fumarate, stearic acid, talc, zinc stearate, mineral oil, polyethylene glycol, poloxamer, sodium lauryl sulfate, and mixtures of any of the above. (Item 7) The formulation comprises: (i) about 1% by weight to about 80% by weight of the (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide; (ii) about 15% to about 90% by weight of said filler; (iii) about 0.1% to about 10% by weight of the binder; (iv) about 1% by weight to about 10% by weight of the disintegrant; (v) about 0.1% to about 10% by weight of the surfactant; and (vi) about 0.1% to about 10% by weight of said lubricant; 7. The formulation according to any one of items 1 to 6, comprising: (Item 8) The formulation comprises: (i) about 20% by weight of said (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide; (ii) about 70% by weight of said filler; (iii) about 2% by weight of said binder; (iv) about 5% by weight of said disintegrant; (v) about 2% by weight of said surfactant; and (vi) about 1% by weight of said lubricant; 8. The formulation according to any one of items 1 to 7, comprising: (Item 9) The formulation comprises: (i) about 10% by weight of said (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide; (ii) about 80% by weight of said filler; (iii) about 2% by weight of said binder; (iv) about 5% by weight of said disintegrant; (v) about 2% by weight of said surfactant; and (vi) about 1% by weight of said lubricant; 8. The formulation according to any one of items 1 to 7, comprising: (Item 10) The formulation comprises: (i) about 5% by weight of said (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide; (ii) about 85% by weight of said filler; (iii) about 2% by weight of said binder; (iv) about 5% by weight of said disintegrant; (v) about 2% by weight of said surfactant; and (vi) about 1% by weight of said lubricant; 8. The formulation according to any one of items 1 to 7, comprising: (Item 11) The formulation comprises: (i) about 20% by weight of said (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide; (ii-1) about 44% by weight of mannitol; (ii-2) about 26% by weight of crystalline cellulose; (iii) about 2% by weight of hydroxypropylcellulose; (iv) about 5% by weight of croscarmellose sodium; (v) about 2% by weight of sodium lauryl sulfate; and (vi) about 1% by weight of magnesium stearate; 8. The formulation according to any one of items 1 to 7, comprising: (Item 12) The formulation comprises: (i) about 10% by weight of said (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide; (ii-1) about 50% by weight of mannitol; (ii-2) about 30% by weight of crystalline cellulose; (iii) about 2% by weight of hydroxypropylcellulose; (iv) about 5% by weight of croscarmellose sodium; (v) about 2% by weight of sodium lauryl sulfate; and (vi) about 1% by weight of magnesium stearate; 8. The formulation according to any one of items 1 to 7, comprising: (Item 13) The formulation comprises: (i) about 5% by weight of said (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide; (ii-1) about 54% by weight of mannitol; (ii-2) about 31% by weight of crystalline cellulose; (iii) about 2% by weight of hydroxypropylcellulose; (iv) about 5% by weight of croscarmellose sodium; (v) about 2% by weight of sodium lauryl sulfate; and (vi) about 1% by weight of magnesium stearate; 8. The formulation according to any one of items 1 to 7, comprising: (Item 14) The formulation of any of the preceding items, wherein the formulation is for oral administration. (Item 15) The formulation of any of the preceding items, wherein the formulation is for once-daily administration. (Item 16) (i) a core, (a) (ai) (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide; (a-ii) intragranular fillers; (a-iii) intragranular binders; (a-iv) an intragranular disintegrant; and (av) Intragranular surfactant Intragranular constituents, including; And (b) (bi) extragranular fillers; (b-ii) an extragranular disintegrant; and (b-iii) Extragranular lubricant Extragranular constituents, including said core having a total core weight including: And, where necessary, (ii) a coating layer containing a coating agent Tablets containing: (Item 17) Item 17. The tablet according to item 16, wherein the intragranular filler is selected from the group consisting of powdered cellulose, microcrystalline cellulose, silicified microcrystalline cellulose, kaolin, corn starch, maize starch, starch derivatives, pregelatinized starch, calcium phosphate, calcium hydrogen phosphate, dicalcium phosphate, tricalcium phosphate, compressible sugar, sugar alcohols, mannitol, sorbitol, maltitol, xylitol, lactitol, lactose, dextrose, maltose, sucrose, glucose, fructose, saccharose, raffinose, dextrates, trehalose, maltodextrin, and mixtures of any of the above. (Item 18) 18. The tablet according to item 16 or 17, wherein the intragranular binder is selected from the group consisting of gum arabic, gum acacia, alginates, alginic acid, corn starch, copolyvidone, polyvinylpyrrolidone, gelatin, glyceryl behenate, hydroxyethylcellulose, hydroxypropylcellulose, carboxymethylcellulose, calcium carboxymethylcellulose, sodium carboxymethylcellulose, methylcellulose, hypromellose, lactose, polyvinyl alcohol, povidone, polyethylene oxide, polyacrylates, potato starch, pregelatinized starch, sodium alginate, sodium starch, sodium carboxymethylcellulose, starch, and mixtures of any of the above. (Item 19) 19. The tablet according to any one of items 16 to 18, wherein the intragranular disintegrant is selected from the group consisting of alginic acid, croscarmellose sodium, cellulose, carboxymethylcellulose calcium, carboxymethylcellulose sodium, microcrystalline cellulose, crospovidone, sodium starch glycolate, low substituted hydroxypropylcellulose, polacrilin potassium, pregelatinized starch, partially hydrolyzed starch, sodium carboxymethylstarch, starch, sodium alginate, sodium carboxymethylcellulose, and mixtures of any of the above. (Item 20) The intragranular surfactant may be cetylpyridine chloride, heptadecaethyleneoxycetanol, lecithin, polyoxyethylene stearate, nonoxynol 9, nonoxynol 10, octoxynol 9, sorbitan fatty acid ester, Span 20, Span 40, Span 60, Span 80, Span 85, polysorbate, polysorbate 20, polysorbate 21, polysorbate 40, polysorbate 60, polysorbate 61, polysorbate 65, polysorbate 80, sodium salt of fatty alcohol sulfate, sodium lauryl sulfate. 20. The tablet according to any one of items 16 to 19, wherein the fatty acid is selected from the group consisting of sodium salts of sulfosuccinic acid esters, sodium dioctyl sulfosuccinate, partial esters of fatty acids and alcohols, glyceryl monostearate, glyceryl monooleate, ethers of fatty alcohols and polyoxyethylene, esters of fatty acids and polyoxyethylene, copolymers of ethylene oxide and propylene oxide (Pluronic®), benzalkonium chloride, ethoxylated triglycerides, and mixtures of any of the above. (Item 21) 21. The tablet according to any one of items 16 to 20, wherein the extragranular filler is selected from the group consisting of powdered cellulose, microcrystalline cellulose, silicified microcrystalline cellulose, kaolin, corn starch, maize starch, starch derivatives, pregelatinized starch, calcium phosphate, calcium hydrogen phosphate, dicalcium phosphate, tricalcium phosphate, compressible sugar, sugar alcohols, mannitol, sorbitol, maltitol, xylitol, lactitol, lactose, dextrose, maltose, sucrose, glucose, fructose, saccharose, raffinose, dextrates, trehalose, maltodextrin, and mixtures of any of the above. (Item 22) 22. The tablet according to any one of items 16 to 21, wherein the extragranular disintegrant is selected from the group consisting of alginic acid, croscarmellose sodium, cellulose, carboxymethylcellulose calcium, carboxymethylcellulose sodium, microcrystalline cellulose, crospovidone, sodium starch glycolate, low substituted hydroxypropylcellulose, polacrilin potassium, pregelatinized starch, partially hydrolyzed starch, sodium carboxymethylstarch, starch, sodium alginate, sodium carboxymethylcellulose, and mixtures of any of the above. (Item 23) 23. The tablet according to any one of items 16 to 22, wherein the extragranular lubricant is selected from the group consisting of hydrogenated castor oil, magnesium stearate, glyceryl monostearate, calcium stearate, glyceryl behenate, glycerol distearate, glyceryl dipalmitostearate, behenoyl polyoxyl-8 glyceride, sodium stearyl fumarate, stearic acid, talc, zinc stearate, mineral oil, polyethylene glycol, poloxamer, sodium lauryl sulfate, and mixtures of any of the above. (Item 24) The core is (a) (ai) about 1% to about 80% of the total core weight of the (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide; (a-ii) about 10% to about 80% of the intragranular filler by weight of the total core; (a-iii) about 0.1% to about 10% of the total core weight of the intragranular binder; (a-iv) about 0.1% to about 5% of the intragranular disintegrant by weight of the total core; and (av) about 0.1% to about 5% of the total core weight of the intragranular surfactant; Intragranular constituents, including; And (b) (bi) about 5% to about 15% of the total core weight of said extragranular filler; (b-ii) about 0.1% to about 5% of the total core weight of the extragranular disintegrant; and (b-iii) about 0.1% to about 5% of the extragranular lubricant by weight of the total core. Extragranular constituents, including; 24. The tablet according to any one of items 16 to 23, comprising: (Item 25) The core is (a) (ai) about 20% by weight of the total core of the (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide; (a-ii-1) about 44% mannitol by weight of the total core; (a-ii-2) about 15% by weight of the total core of microcrystalline cellulose; (a-iii) about 2% by weight of the total core of hydroxypropyl cellulose; (a-iv) about 3% by weight of the total core of croscarmellose sodium; and (av) sodium lauryl sulfate, about 2% by weight of the total core Intragranular constituents, including; And (b) (bi) about 11% by weight of the total core of microcrystalline cellulose; (b-ii) about 2% of the total core weight of croscarmellose sodium; and (b-iii) magnesium stearate, about 1% by weight of the total core; Extragranular constituents, including The tablet according to any one of items 16 to 24, comprising: (Item 26) The core is (a) (ai) about 10% by weight of the total core of the (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide; (a-ii-1) about 50% mannitol by weight of the total core; (a-ii-2) about 19% by weight of the total core of microcrystalline cellulose; (a-iii) about 2% by weight of the total core of hydroxypropyl cellulose; (a-iv) about 3% by weight of the total core of croscarmellose sodium; and (av) sodium lauryl sulfate, about 2% by weight of the total core Intragranular constituents, including; And (b) (bi) about 11% by weight of the total core of microcrystalline cellulose; (b-ii) about 2% of the total core weight of croscarmellose sodium; and (b-iii) magnesium stearate, about 1% by weight of the total core; Extragranular constituents, including; The tablet according to any one of items 16 to 24, comprising: (Item 27) The core is (a) (ai) about 5% by weight of said (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide; (a-ii-1) about 54% by weight of mannitol; (a-ii-2) about 20% by weight of crystalline cellulose; (a-iii) about 2% by weight of hydroxypropylcellulose; (a-iv) about 3% by weight of croscarmellose sodium; and (av) about 2% by weight of sodium lauryl sulfate Intragranular constituents, including; And (b) (bi) about 11% by weight of microcrystalline cellulose; (b-ii) about 2% by weight of croscarmellose sodium; and (b-iii) about 1% by weight of magnesium stearate Extragranular constituents, including; The tablet according to any one of items 16 to 24, comprising: (Item 28) 28. The tablet according to any one of items 16 to 27, comprising a coating layer comprising a coating agent. (Item 29) 29. The tablet according to item 28, wherein the coating is selected from the group consisting of Opadry QX White 21A180025, Opadry I and Opadry II. (Item 30) 30. The tablet according to item 28 or 29, wherein the coating is Opadry QX White 21A180025. (Item 31) The core is (a) (ai) about 2.5 mg of the (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide; (a-ii-1) about 27 mg of mannitol; (a-ii-2) about 10 mg of crystalline cellulose; (a-iii) about 1 mg of hydroxypropylcellulose; (a-iv) about 1.5 mg of croscarmellose sodium; and (av) Approximately 1 mg of sodium lauryl sulfate Intragranular constituents, including; And (b) (bi) approximately 5.5 mg of crystalline cellulose; (b-ii) about 1 mg of croscarmellose sodium; and (b-iii) about 0.5 mg of magnesium stearate Extragranular constituents, including; The tablet according to items 16 to 24, comprising: (Item 32) The core is (a) (ai) about 20 mg of the (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide; (a-ii-1) about 44 mg of mannitol based on the total core weight; (a-ii-2) about 15 mg of microcrystalline cellulose based on the total core weight; (a-iii) about 2 mg of hydroxypropylcellulose based on the total core weight; (a-iv) about 3 mg of croscarmellose sodium by weight of the total cores; and (av) about 2 mg of sodium lauryl sulfate based on the total core weight; Intragranular constituents, including; And (b) (bi) about 11 milligrams of microcrystalline cellulose of said total core weight; (b-ii) about 2 mg of croscarmellose sodium by weight of the total cores; and (b-iii) about 1 mg of magnesium stearate based on the total core weight; Extragranular constituents, including; The tablet according to items 16 to 24, comprising: (Item 33) The core is (a) (ai) about 5 mg of the (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide; (a-ii-1) about 54 mg of mannitol; (a-ii-2) about 20 mg of crystalline cellulose; (a-iii) about 2 mg of hydroxypropylcellulose; (a-iv) about 3 mg of croscarmellose sodium; and (av) Approximately 2 mg of sodium lauryl sulfate Intragranular constituents, including; And (b) (bi) about 11 mg of crystalline cellulose; (b-ii) about 2 mg of croscarmellose sodium; and (b-iii) Approximately 1 mg of magnesium stearate Extragranular constituents, including; The tablet according to items 16 to 24, comprising: (Item 34) The core is (a) (ai) about 40 mg of the (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide of the total core weight; (a-ii-1) about 88 mg of mannitol based on the total core weight; (a-ii-2) about 30 mg of microcrystalline cellulose based on the total core weight; (a-iii) about 4 mg of hydroxypropylcellulose based on the total core weight; (a-iv) about 6 mg of croscarmellose sodium by weight of the total cores; and (av) about 4 mg of sodium lauryl sulfate based on the total core weight; Intragranular constituents, including; And (b) (bi) about 22 milligrams of microcrystalline cellulose of said total core weight; (b-ii) about 4 mg of croscarmellose sodium by weight of the total cores; and (b-iii) about 2 mg of magnesium stearate based on the total core weight; Extragranular constituents, including; The tablet according to items 16 to 24, comprising: (Item 35) The core is (a) (ai) about 10 mg of the (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide; (a-ii-1) about 108 mg of mannitol; (a-ii-2) about 40 mg of crystalline cellulose; (a-iii) about 4 mg of hydroxypropylcellulose; (a-iv) about 6 mg of croscarmellose sodium; and (av) Approximately 4 mg of sodium lauryl sulfate Intragranular constituents, including; And (b) (bi) about 22 mg of crystalline cellulose; (b-ii) about 4 mg of croscarmellose sodium; and (b-iii) containing about 2 mg of magnesium stearate; extragranular components; The tablet according to items 16 to 24, comprising: (Item 36) The core (a) (ai) about 7 mg of the (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide; (a-ii-1) about 35 mg of mannitol; (a-ii-2) about 13.3 mg of crystalline cellulose; (a-iii) about 1.4 mg of hydroxypropylcellulose; (a-iv) about 2.1 mg of croscarmellose sodium; and (av) Approximately 1.4 mg of sodium lauryl sulfate Intragranular constituents, including; And (b) (bi) approximately 7.7 mg of crystalline cellulose; (b-ii) about 1.4 mg of croscarmellose sodium; and (b-iii) Approximately 0.7 mg of magnesium stearate Extragranular constituents, including; The tablet according to items 16 to 24, comprising: (Item 37) The core is (a) (ai) about 40 mg of the (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide; (a-ii-1) about 200 mg of mannitol; (a-ii-2) about 76 mg of crystalline cellulose; (a-iii) about 8 mg of hydroxypropylcellulose; (a-iv) about 12 mg of croscarmellose sodium; and (av) Approximately 8 mg of sodium lauryl sulfate Intragranular constituents, including; And (b) (bi) about 44 mg of crystalline cellulose; (b-ii) about 8 mg of croscarmellose sodium; and (b-iii) Approximately 4 mg of magnesium stearate Extragranular constituents, including; The tablet according to items 16 to 24, comprising: (Item 38) A method for producing the tablet according to any one of items 16 to 37, comprising: (1) preparing a granule comprising (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, the intragranular filler, the intragranular binder, the intragranular disintegrant and the intragranular surfactant; (2) milling the granules comprising (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, the intragranular filler, the intragranular binder, the intragranular disintegrant, and the intragranular surfactant to form the intragranular component; (3) blending the intragranular components with the extragranular filler, the extragranular disintegrant and the extragranular lubricant to form a final blended mixture; (4) compressing the final blended mixture to form the core; (5) optionally coating said core with said coating layer. (Item 39) Item 39. The method according to item 38, wherein the step of preparing granules comprising (R)—N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, the intragranular filler, the intragranular binder, the intragranular disintegrant and the intragranular surfactant comprises a wet granulation process. (Item 40) 40. The method according to claim 38 or 39, wherein the wet granulation step further comprises a wet milling step. (Item 41) 41. The method according to any one of items 38 to 40, wherein the step of preparing granules comprising (R)—N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, the intragranular filler, the intragranular binder, the intragranular disintegrant and the intragranular surfactant further comprises a step of drying the granules. (Item 42) 42. The method according to any one of items 38 to 41, comprising a step of coating the core with the coating layer. (Item 43) A method for treating a cardiac disease in a subject in need thereof, comprising administering to the subject a formulation according to any one of items 1 to 15, or a tablet according to any one of items 16 to 37. (Item 44) 44. The method of claim 43, wherein the heart disease is hypertrophic cardiomyopathy (HCM). (Item 45) 45. The method of claim 44, wherein the HCM is obstructive or non-obstructive, or is associated with sarcomeric and / or non-sarcomeric mutations. (Item 46) 44. The method of item 43, wherein the cardiac disease is heart failure with preserved ejection fraction (HFpEF).

Claims

1. (i) (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (ii) a filler; (iii) a binder; (iv) disintegrants; (v) a surfactant; and (vi) lubricant 13. A formulation comprising:

2. The formulation of claim 1, wherein the (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph or pharma- ceutically acceptable salt thereof is (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide.

3. (a) the filler is selected from the group consisting of powdered cellulose, microcrystalline cellulose, silicified microcrystalline cellulose, kaolin, corn starch, maize starch, starch derivatives, pregelatinized starch, calcium phosphate, calcium hydrogen phosphate, dicalcium phosphate, tricalcium phosphate, compressible sugar, sugar alcohols, mannitol, sorbitol, maltitol, xylitol, lactitol, lactose, dextrose, maltose, sucrose, glucose, fructose, saccharose, raffinose, dextrates, trehalose, maltodextrin, and mixtures of any of the foregoing; and / or (b) the binder is selected from the group consisting of gum arabic, gum acacia, alginate, alginic acid, corn starch, copolyvidone, polyvinylpyrrolidone, gelatin, glyceryl behenate, hydroxyethylcellulose, hydroxypropylcellulose, carboxymethylcellulose, calcium carboxymethylcellulose, sodium carboxymethylcellulose, methylcellulose, hypromellose, lactose, polyvinyl alcohol, povidone, polyethylene oxide, polyacrylates, potato starch, pregelatinized starch, sodium alginate, sodium starch, sodium carboxymethylcellulose, starch, and mixtures of any of the foregoing; and / or (c) the disintegrant is selected from the group consisting of alginic acid, croscarmellose sodium, cellulose, calcium carboxymethylcellulose, sodium carboxymethylcellulose, microcrystalline cellulose, crospovidone, sodium starch glycolate, low-substituted hydroxypropylcellulose, polacrilin potassium, pregelatinized starch, partially hydrolyzed starch, sodium carboxymethylstarch, starch, sodium alginate, sodium carboxymethylcellulose, and mixtures of any of the foregoing; and / or (d) The surfactant is selected from the group consisting of cetylpyridine chloride, heptadecaethyleneoxycetanol, lecithin, polyoxyethylene stearate, nonoxynol 9, nonoxynol 10, octoxynol 9, sorbitan fatty acid esters, Span 20, Span 40, Span 60, Span 80, Span 85, polysorbate, polysorbate 20, polysorbate 21, polysorbate 40, polysorbate 60, polysorbate 61, polysorbate 65, polysorbate 80, sodium salts of fatty alcohol sulfates, lauric acid, glyceryl stearate ... and / or selected from the group consisting of sodium glyceryl sulfate, sodium salts of sulfosuccinates, sodium dioctyl sulfosuccinate, partial esters of fatty acids and alcohols, glyceryl monostearate, glyceryl monooleate, ethers of fatty alcohols and polyoxyethylene, esters of fatty acids and polyoxyethylene, copolymers of ethylene oxide and propylene oxide (Pluronic®), benzalkonium chloride, ethoxylated triglycerides, and mixtures of any of the foregoing; and / or (e) the lubricant is selected from the group consisting of hydrogenated castor oil, magnesium stearate, glyceryl monostearate, calcium stearate, glyceryl behenate, glycerol distearate, glyceryl dipalmitostearate, behenoyl polyoxyl-8 glyceride, sodium stearyl fumarate, stearic acid, talc, zinc stearate, mineral oil, polyethylene glycol, poloxamer, sodium lauryl sulfate, and mixtures of any of the foregoing; and / or (f) the formulation comprises (i) 1% to 80% by weight of said (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (ii) 15% to 90% by weight of said filler; (iii) 0.1% to 10% by weight of said binder; (iv) 1% to 10% by weight of said disintegrant; (v) 0.1% to 10% by weight of said surfactant; and (vi) 0.1% to 10% by weight of said lubricant; 3. The formulation of claim 1 or 2, comprising:

4. The formulation, (i) 1% to 50% by weight of the (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a pharma- ceutically acceptable salt thereof; (ii) 40% to 80% by weight of said filler; (iii) 0.5% to 5% by weight of said binder; (iv) 2% to 8% by weight of said disintegrant; (v) 0.5% to 5% by weight of said surfactant; and (vi) 0.5% to 5% by weight of said lubricant; The formulation according to any one of claims 1 to 3, comprising:

5. The formulation, (i) 10% to 30% by weight of the (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a pharma- ceutically acceptable salt thereof; (ii) 60% to 80% by weight of said filler; (iii) 1% to 3% by weight of said binder; (iv) 4% to 6% by weight of said disintegrant; (v) 1% to 3% by weight of said surfactant; and (vi) 0.5% to 1.5% by weight of said lubricant; The formulation according to any one of claims 1 to 3, comprising:

6. The formulation, (i) 1% to 10% by weight of the (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a pharma- ceutically acceptable salt thereof; (ii) 70% to 90% by weight of said filler; (iii) 1% to 3% by weight of said binder; (iv) 4% to 6% by weight of said disintegrant; (v) 1% to 3% by weight of said surfactant; and (vi) 0.5% to 1.5% by weight of said lubricant; The formulation according to any one of claims 1 to 3, comprising:

7. The formulation, (i) 1% to 50% by weight of the (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a pharma- ceutically acceptable salt thereof; (ii-1) 10% by weight to 60% by weight of mannitol; (ii-2) 5% by weight to 45% by weight of crystalline cellulose; (iii) 0.1% to 10% by weight of hydroxypropylcellulose; (iv) 1% to 10% by weight of croscarmellose sodium; (v) 0.1% to 10% by weight of sodium lauryl sulfate; and (vi) 0.1% to 10% by weight of magnesium stearate; The formulation according to any one of claims 1 to 3, comprising:

8. The formulation, (i) 10% to 30% by weight of the (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a pharma- ceutically acceptable salt thereof; (ii-1) 40% to 50% by weight of mannitol; (ii-2) 20% by weight to 35% by weight of crystalline cellulose; (iii) 1% to 3% by weight of hydroxypropylcellulose; (iv) 4% to 6% by weight of croscarmellose sodium; (v) 1% to 3% by weight of sodium lauryl sulfate; and (vi) 0.5% to 1.5% by weight of magnesium stearate; The formulation according to any one of claims 1 to 3, comprising:

9. The formulation, (i) 1% to 10% by weight of the (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a pharma- ceutically acceptable salt thereof; (ii-1) 50% to 60% by weight of mannitol; (ii-2) 25% to 35% by weight of crystalline cellulose; (iii) 1% to 3% by weight of hydroxypropylcellulose; (iv) 4% to 6% by weight of croscarmellose sodium; (v) 1% to 3% by weight of sodium lauryl sulfate; and (vi) 0.5% to 1.5% by weight of magnesium stearate; The formulation according to any one of claims 1 to 3, comprising:

10. (a) the formulation comprises: (i) about 20% by weight of said (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (ii) about 70% by weight of said filler; (iii) about 2% by weight of said binder; (iv) about 5% by weight of said disintegrant; (v) about 2% by weight of said surfactant; and (vi) about 1% by weight of said lubricant; Including, (b) the formulation comprises (i) about 10% by weight of said (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (ii) about 80% by weight of said filler; (iii) about 2% by weight of said binder; (iv) about 5% by weight of said disintegrant; (v) about 2% by weight of said surfactant; and (vi) about 1% by weight of said lubricant; Including, (c) the formulation comprises (i) about 5% by weight of said (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (ii) about 85% by weight of said filler; (iii) about 2% by weight of said binder; (iv) about 5% by weight of said disintegrant; (v) about 2% by weight of said surfactant; and (vi) about 1% by weight of said lubricant; Including, (d) the formulation comprises (i) about 20% by weight of said (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (ii-1) about 44% by weight of mannitol; (ii-2) about 26% by weight of crystalline cellulose; (iii) about 2% by weight of hydroxypropylcellulose; (iv) about 5% by weight of croscarmellose sodium; (v) about 2% by weight of sodium lauryl sulfate; and (vi) about 1% by weight of magnesium stearate; Including, (e) the formulation comprises (i) about 10% by weight of said (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (ii-1) about 50% by weight of mannitol; (ii-2) about 30% by weight of crystalline cellulose; (iii) about 2% by weight of hydroxypropylcellulose; (iv) about 5% by weight of croscarmellose sodium; (v) about 2% by weight of sodium lauryl sulfate; and (vi) about 1% by weight of magnesium stearate; or (f) the formulation comprises (i) about 5% by weight of said (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (ii-1) about 54% by weight of mannitol; (ii-2) about 31% by weight of crystalline cellulose; (iii) about 2% by weight of hydroxypropylcellulose; (iv) about 5% by weight of croscarmellose sodium; (v) about 2% by weight of sodium lauryl sulfate; and (vi) about 1% by weight of magnesium stearate; The formulation according to any one of claims 1 to 3, comprising:

11. the formulation is for oral administration; and / or The formulation of any one of claims 1 to 10, wherein the formulation is for once-daily administration.

12. (i) a core, (a) (a-i) (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii) intragranular fillers; (a-iii) intragranular binders; (a-iv) intragranular disintegrants; and (a-v) Intragranular surfactant Intragranular constituents including: And (b) (bi) extragranular fillers; (b-ii) an extragranular disintegrant; and (b-iii) extragranular lubricant Extragranular constituents, including The core having a total core weight including Tablets containing:

13. (a) the intragranular filler is selected from the group consisting of powdered cellulose, microcrystalline cellulose, silicified microcrystalline cellulose, kaolin, corn starch, maize starch, starch derivatives, pregelatinized starch, calcium phosphate, calcium hydrogen phosphate, dicalcium phosphate, tricalcium phosphate, compressible sugar, sugar alcohols, mannitol, sorbitol, maltitol, xylitol, lactitol, lactose, dextrose, maltose, sucrose, glucose, fructose, saccharose, raffinose, dextrates, trehalose, maltodextrin, and mixtures of any of the foregoing; and / or (b) the intragranular binder is selected from the group consisting of gum arabic, gum acacia, alginate, alginic acid, corn starch, copolyvidone, polyvinylpyrrolidone, gelatin, glyceryl behenate, hydroxyethylcellulose, hydroxypropylcellulose, carboxymethylcellulose, calcium carboxymethylcellulose, sodium carboxymethylcellulose, methylcellulose, hypromellose, lactose, polyvinyl alcohol, povidone, polyethylene oxide, polyacrylates, potato starch, pregelatinized starch, sodium alginate, sodium starch, sodium carboxymethylcellulose, starch, and mixtures of any of the foregoing; and / or (c) the intragranular disintegrant is selected from the group consisting of alginic acid, croscarmellose sodium, cellulose, calcium carboxymethylcellulose, sodium carboxymethylcellulose, microcrystalline cellulose, crospovidone, sodium starch glycolate, low-substituted hydroxypropylcellulose, polacrilin potassium, pregelatinized starch, partially hydrolyzed starch, sodium carboxymethylstarch, starch, sodium alginate, sodium carboxymethylcellulose, and mixtures of any of the foregoing; and / or (d) The intragranular surfactant is selected from the group consisting of cetylpyridine chloride, heptadecaethyleneoxycetanol, lecithin, polyoxyethylene stearate, nonoxynol 9, nonoxynol 10, octoxynol 9, sorbitan fatty acid ester, Span 20, Span 40, Span 60, Span 80, Span 85, polysorbate, polysorbate 20, polysorbate 21, polysorbate 40, polysorbate 60, polysorbate 61, polysorbate 65, polysorbate 80, sodium salt of fatty alcohol sulfate, la and / or selected from the group consisting of sodium uryl sulfate, sodium salts of sulfosuccinic acid esters, sodium dioctyl sulfosuccinate, partial esters of fatty acids and alcohols, glyceryl monostearate, glyceryl monooleate, ethers of fatty alcohols and polyoxyethylene, esters of fatty acids and polyoxyethylene, copolymers of ethylene oxide and propylene oxide (Pluronic®), benzalkonium chloride, ethoxylated triglycerides, and mixtures of any of the foregoing; and / or (e) the extragranular filler is selected from the group consisting of powdered cellulose, microcrystalline cellulose, silicified microcrystalline cellulose, kaolin, corn starch, maize starch, starch derivatives, pregelatinized starch, calcium phosphate, calcium hydrogen phosphate, dicalcium phosphate, tricalcium phosphate, compressible sugar, sugar alcohols, mannitol, sorbitol, maltitol, xylitol, lactitol, lactose, dextrose, maltose, sucrose, glucose, fructose, saccharose, raffinose, dextrates, trehalose, maltodextrin, and mixtures of any of the foregoing; and / or (f) the extragranular disintegrant is selected from the group consisting of alginic acid, croscarmellose sodium, cellulose, calcium carboxymethylcellulose, sodium carboxymethylcellulose, microcrystalline cellulose, crospovidone, sodium starch glycolate, low-substituted hydroxypropylcellulose, polacrilin potassium, pregelatinized starch, partially hydrolyzed starch, sodium carboxymethylstarch, starch, sodium alginate, sodium carboxymethylcellulose, and mixtures of any of the foregoing; and / or 13. The tablet of claim 12, wherein (g) the extragranular lubricant is selected from the group consisting of hydrogenated castor oil, magnesium stearate, glyceryl monostearate, calcium stearate, glyceryl behenate, glycerol distearate, glyceryl dipalmitostearate, behenoyl polyoxyl-8 glyceride, sodium stearyl fumarate, stearic acid, talc, zinc stearate, mineral oil, polyethylene glycol, poloxamer, sodium lauryl sulfate, and mixtures of any of the foregoing.

14. The core is (a) (ai) 1% to 80% of the total core weight of the (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii) 10% to 80% of the total core weight of said intragranular filler; (a-iii) 0.1% to 10% of the total core weight of the intragranular binder; (a-iv) 0.1% to 5% of the total core weight of the intragranular disintegrant; and (av) 0.1% to 5% of the total core weight of said intragranular surfactant; Intragranular constituents including: And (b) (bi) 5% to 15% of the total core weight of said extragranular filler; (b-ii) 0.1% to 5% of the total core weight of the extragranular disintegrant; and (b-iii) 0.1% to 5% of the total core weight of said extragranular lubricant Extragranular components including:

14. The tablet of claim 12 or 13, comprising:

15. The core, (a) (ai) 1% to 50% of the total core weight of the (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a pharma- ceutically acceptable salt thereof; (a-ii) 40% to 80% of the total core weight of said intragranular filler; (a-iii) 1% to 5% of the total core weight of the intragranular binder; (a-iv) 1% to 5% of the total core weight of the intragranular disintegrant; and (av) 1% to 5% of the total core weight of said intragranular surfactant; Intragranular constituents including: And (b) (bi) 5% to 15% of the total core weight of said extragranular filler; (b-ii) 1% to 5% of the total core weight of the extragranular disintegrant; and (b-iii) 0.1% to 2% of the total core weight of said extragranular lubricant Extragranular components including: The tablet according to any one of claims 12 to 14, comprising:

16. The core, (a) (ai) 10% to 30% of the total core weight of the (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a pharma- ceutically acceptable salt thereof; (a-ii) 50% to 70% of the total core weight of said intragranular filler; (a-iii) 1% to 3% of the total core weight of the intragranular binder; (a-iv) 2% to 4% of the total core weight of the intragranular disintegrant; and (av) 1% to 3% of the total core weight of said intragranular surfactant; Intragranular constituents including: And (b) (bi) 5% to 15% of the total core weight of said extragranular filler; (b-ii) 1% to 3% of the total core weight of the extragranular disintegrant; and (b-iii) 0.1% to 1.5% of the total core weight of said extragranular lubricant Extragranular components including: The tablet according to any one of claims 12 to 14, comprising:

17. The core, (a) (ai) 1% to 10% of the total core weight of the (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a pharma- ceutically acceptable salt thereof; (a-ii) 60% to 80% of the intragranular filler by weight of the total core; (a-iii) 1% to 3% of the total core weight of the intragranular binder; (a-iv) 2% to 4% of the total core weight of the intragranular disintegrant; and (av) 1% to 3% of the total core weight of said intragranular surfactant; Intragranular constituents including: And (b) (bi) 5% to 15% of the total core weight of said extragranular filler; (b-ii) 1% to 3% of the total core weight of the extragranular disintegrant; and (b-iii) 0.1% to 1.5% of the total core weight of said extragranular lubricant Extragranular components including: The tablet according to any one of claims 12 to 14, comprising:

18. The core, (a) (ai) 1% to 50% of the total core weight of the (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a pharma- ceutically acceptable salt thereof; (a-ii-1) mannitol, from 40% to 60% by weight of the total core; (a-ii-1) 10% to 30% by weight of the total core of microcrystalline cellulose; (a-iii) 1% to 5% of the total core weight of hydroxypropylcellulose; (a-iv) 1% to 5% of the total core weight of croscarmellose sodium; and (av) sodium lauryl sulfate, from 1% to 5% by weight of the total core; Intragranular constituents including: And (b) (bi) 5% to 15% of the total core weight of microcrystalline cellulose; (b-ii) 1% to 5% of the total core weight of croscarmellose sodium; and (b-iii) 0.1% to 2% of the total core weight of said extragranular lubricant Extragranular components including:

14. The tablet of claim 12 or 13, comprising:

19. The core, (a) (ai) 10% to 30% of the total core weight of the (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a pharma- ceutically acceptable salt thereof; (a-ii-1) mannitol, from 40% to 50% by weight of the total core; (a-ii-1) 10% to 20% by weight of the total core of microcrystalline cellulose; (a-iii) 1% to 3% of the total core weight of hydroxypropylcellulose; (a-iv) 2% to 4% of the total core weight of croscarmellose sodium; and (av) sodium lauryl sulfate, from 1% to 3% by weight of the total core; Intragranular constituents including: And (b) (bi) 5% to 15% of the total core weight of microcrystalline cellulose; (b-ii) 1% to 3% of the total core weight of croscarmellose sodium; and (b-iii) 0.1% to 1.5% of the total core weight of said extragranular lubricant Extragranular components including:

19. The tablet of any one of claims 12, 13 and 18, comprising:

20. The core, (a) (ai) 1% to 10% of the total core weight of the (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a pharma- ceutically acceptable salt thereof; (a-ii-1) mannitol, from 50% to 60% by weight of the total core; (a-ii-1) 15% to 25% of the total core weight of microcrystalline cellulose; (a-iii) 1% to 3% of the total core weight of hydroxypropylcellulose; (a-iv) 2% to 4% of the total core weight of croscarmellose sodium; and (av) sodium lauryl sulfate, from 1% to 3% by weight of the total core; Intragranular constituents including: And (b) (bi) 5% to 15% of the total core weight of microcrystalline cellulose; (b-ii) 1% to 3% of the total core weight of croscarmellose sodium; and (b-iii) 0.1% to 1.5% of the total core weight of said extragranular lubricant Extragranular components including:

19. The tablet of any one of claims 12, 13 and 18, comprising:

21. (A) the core, (a) (ai) about 20% by weight of the total core of said (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph or pharma- ceutically acceptable salt thereof; (a-ii-1) about 44% mannitol by weight of the total core; (a-ii-2) about 15% by weight of the total core of microcrystalline cellulose; (a-iii) about 2% hydroxypropyl cellulose by weight of the total core; (a-iv) about 3% of the total core weight of croscarmellose sodium; and (av) about 2% by weight of the total core, of sodium lauryl sulfate Intragranular constituents including: And (b) (bi) about 11% microcrystalline cellulose by weight of the total core; (b-ii) about 2% of the total core weight of croscarmellose sodium; and (b-iii) magnesium stearate, about 1% by weight of the total core; Extragranular constituents, including Including, (B) the core is (a) (ai) about 10% by weight of the total core of said (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph or pharma- ceutically acceptable salt thereof; (a-ii-1) about 50% mannitol by weight of the total core; (a-ii-2) about 19% microcrystalline cellulose by weight of the total core; (a-iii) about 2% hydroxypropyl cellulose by weight of the total core; (a-iv) about 3% of the total core weight of croscarmellose sodium; and (av) about 2% by weight of the total core, of sodium lauryl sulfate Intragranular constituents including: And (b) (bi) about 11% microcrystalline cellulose by weight of the total core; (b-ii) about 2% of the total core weight of croscarmellose sodium; and (b-iii) magnesium stearate, about 1% of the total core weight Extragranular components including: or (C) the core, (a) (a-i) about 5% by weight of said (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii-1) about 54% by weight of mannitol; (a-ii-2) about 20% by weight of crystalline cellulose; (a-iii) about 2% by weight of hydroxypropylcellulose; (a-iv) about 3% by weight of croscarmellose sodium; and (a-v) about 2% by weight of sodium lauryl sulfate Intragranular constituents including: And (b) (bi) about 11% by weight of microcrystalline cellulose; (b-ii) about 2% by weight of croscarmellose sodium; and (b-iii) about 1% by weight of magnesium stearate Extragranular components including:

19. The tablet of any one of claims 12, 13 and 18, comprising:

22. The core, (a) (ai) about 10% by weight of the total core of said (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph or pharma- ceutically acceptable salt thereof; (a-ii-1) about 50% mannitol by weight of the total core; (a-ii-1) about 19% microcrystalline cellulose by weight of the total core; (a-iii) about 2% hydroxypropyl cellulose by weight of the total core; (a-iv) about 3% of the total core weight of croscarmellose sodium; and (av) about 2% by weight of the total core, of sodium lauryl sulfate; Intragranular constituents including: And (b) (bi) about 11% microcrystalline cellulose by weight of the total core; (b-ii) about 2% of the total core weight of croscarmellose sodium; and (b-iii) magnesium stearate, about 1% of the total core weight Extragranular components including:

22. The tablet of any one of claims 12, 13, 18 and 21, comprising:

23. The tablet of claim 12, comprising 5 mg, 10 mg, or 20 mg of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide.

24. The coating layer includes a coating agent, for example The coating agent is selected from the group consisting of Opadry QX White 21A180025, Opadry I and Opadry II, for example: The tablet according to any one of claims 12 to 23, wherein the coating agent is Opadry QX White 21A180025.

25. (A) the core, (a) (a-i) about 2.5 mg of the (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii-1) about 27 mg of mannitol; (a-ii-2) about 10 mg of crystalline cellulose; (a-iii) about 1 mg of hydroxypropylcellulose; (a-iv) about 1.5 mg of croscarmellose sodium; and (a-v) about 1 mg of sodium lauryl sulfate Intragranular constituents including: And (b) (b-i) about 5.5 mg of crystalline cellulose; (b-ii) about 1 mg of croscarmellose sodium; and (b-iii) about 0.5 mg of magnesium stearate Extragranular components including: Including, (B) the core is (a) (a-i) about 20 mg of said (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii-1) about 44 mg of mannitol based on the total core weight; (a-ii-2) about 15 mg of microcrystalline cellulose based on the total core weight; (a-iii) about 2 mg of hydroxypropylcellulose based on the total core weight; (a-iv) about 3 mg of croscarmellose sodium by weight of the total core; and (av) about 2 mg of sodium lauryl sulfate based on the total core weight. Intragranular constituents including: And (b) (bi) about 11 mg of microcrystalline cellulose of the total core weight; (b-ii) about 2 mg of croscarmellose sodium by weight of the total core; and (b-iii) about 1 mg of magnesium stearate based on the total core weight Extragranular components including: Including, (C) the core, (a) (a-i) about 5 mg of the (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii-1) about 54 mg of mannitol; (a-ii-2) about 20 mg of crystalline cellulose; (a-iii) about 2 mg of hydroxypropylcellulose; (a-iv) about 3 mg of croscarmellose sodium; and (a-v) about 2 mg of sodium lauryl sulfate Intragranular constituents including: And (b) (b-i) about 11 mg of crystalline cellulose; (b-ii) about 2 mg of croscarmellose sodium; and (b-iii) about 1 mg of magnesium stearate Extragranular components including: Including, (D) the core is (a) (ai) about 40 mg of the (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof, based on the total core weight; (a-ii-1) about 88 mg of mannitol based on the total core weight; (a-ii-2) about 30 mg of microcrystalline cellulose based on the total core weight; (a-iii) about 4 mg of hydroxypropylcellulose by weight of the total core; (a-iv) about 6 mg of croscarmellose sodium by total core weight; and (av) about 4 mg of sodium lauryl sulfate based on the total core weight; Intragranular constituents including: And (b) (bi) about 22 mg of microcrystalline cellulose of the total core weight; (b-ii) about 4 mg of croscarmellose sodium by weight of the total core; and (b-iii) about 2 mg of magnesium stearate based on the total core weight. Extragranular components including: Including, (E) the core is (a) (a-i) about 10 mg of said (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii-1) about 108 mg mannitol; (a-ii-2) about 40 mg of crystalline cellulose; (a-iii) about 4 mg of hydroxypropylcellulose; (a-iv) about 6 mg of croscarmellose sodium; and (a-v) about 4 mg of sodium lauryl sulfate Intragranular constituents including: And (b) (b-i) about 22 mg of crystalline cellulose; (b-ii) about 4 mg of croscarmellose sodium; and (b-iii) containing about 2 mg of magnesium stearate; Extragranular components; Including, (F) the core (a) (a-i) about 7 mg of the (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii-1) about 35 mg mannitol; (a-ii-2) about 13.3 mg of crystalline cellulose; (a-iii) about 1.4 mg hydroxypropylcellulose; (a-iv) about 2.1 mg of croscarmellose sodium; and (a-v) about 1.4 mg of sodium lauryl sulfate Intragranular constituents including: And (b) (b-i) about 7.7 mg of crystalline cellulose; (b-ii) about 1.4 mg of croscarmellose sodium; and (b-iii) about 0.7 mg of magnesium stearate Extragranular components including: or (G) the core, (a) (a-i) about 40 mg of the (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof; (a-ii-1) about 200 mg of mannitol; (a-ii-2) about 76 mg of crystalline cellulose; (a-iii) about 8 mg of hydroxypropylcellulose; (a-iv) about 12 mg of croscarmellose sodium; and (a-v) about 8 mg of sodium lauryl sulfate Intragranular constituents including: And (b) (b-i) about 44 mg of crystalline cellulose; (b-ii) about 8 mg of croscarmellose sodium; and (b-iii) about 4 mg of magnesium stearate Extragranular components including: The tablet according to any one of claims 12 to 14, comprising:

26. A method for making a tablet according to any one of claims 12 to 25, said method comprising: (1) preparing a granule comprising (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof, said intragranular filler, said intragranular binder, said intragranular disintegrant, and said intragranular surfactant; (2) milling the granules comprising (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph, or pharma- ceutically acceptable salt thereof, the intragranular filler, the intragranular binder, the intragranular disintegrant, and the intragranular surfactant to form the intragranular component; (3) blending the intragranular components with the extragranular filler, the extragranular disintegrant and the extragranular lubricant to form a final blended mixture; (4) compressing the final blended mixture to form the core. Including, For example, the method wherein the step of preparing granules comprising (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph or pharma- ceutically acceptable salt thereof, said intragranular filler, said intragranular binder, said intragranular disintegrant and said intragranular surfactant comprises a wet granulation step, for example, said wet granulation step further comprises a wet milling step.

27. 27. The method of claim 26, wherein the step of preparing granules comprising (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, or a hydrate, solvate, polymorph or pharma- ceutically acceptable salt thereof, the intragranular filler, the intragranular binder, the intragranular disintegrant and the intragranular surfactant further comprises the step of drying the granules.

28. 28. The method of claim 26 or 27, comprising the step of coating the core with a coating layer.

29. A formulation according to any one of claims 1 to 11, or a tablet according to any one of claims 12 to 25, for use in treating a cardiac disease in a subject in need thereof.

30. 30. The formulation or tablet for use according to claim 29, wherein the cardiac disease is hypertrophic cardiomyopathy (HCM).

31. 31. The formulation or tablet for use according to claim 30, wherein the HCM is obstructive or non-obstructive or associated with sarcomeric and / or non-sarcomeric mutations.

32. 30. The formulation or tablet for use according to claim 29, wherein the cardiac disease is heart failure with preserved ejection fraction (HFpEF).

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