Methods for the administration of CRF antagonist

Abstract

Provided are methods for the treatment of congenital adrenal hyperplasia.

Description

Attorney Docket No. 46696-0217WO1 / 377.WO1.PCTMETHODS FOR THE ADMINISTRATION OF CRF ANTAGONISTTECHNICAL FIELD

[0001] The present disclosure relates to methods of administering 4-(2-chloro-4-methoxy-5- methylphenyl)-A-[(15)-2-cyclopropyl-l-(3-fluoro-4-methylphenyl)ethyl]-5-methyl-7V-prop-2- ynyl-l,3-thiazol-2-amine, or a pharmaceutically acceptable salt thereof, as well as pharmaceutical formulations thereof, to a patient.BACKGROUND

[0002] Classic congenital adrenal hyperplasia (CAH) is a disease that includes a group of autosomal recessive disorders that result in an enzyme deficiency that alters the production of adrenal steroids due to 21 -hydroxylase deficiency, a condition that results in little or no cortisol biosynthesis. One clinical manifestation of the absence of cortisol is the lack of feedback inhibition of pituitary adrenocorticotropic hormone (ACTH) secretion. Increased ACTH levels cause adrenal hyperplasia and the enzyme mutation causes a shunting of cortisol precursor steroids to alternate pathways. Most notably, the shunting of androgens leads to virilization and other developmental complications in females and the overaccumulation of ACTH is associated with the formation of testicular adrenal rest tumors in males. In addition, since the same enzyme (21 -hydroxylase) is used in the pathway for the biosynthesis of the mineralocorticoids, a number of these patients suffer from aldosterone deficiency which can result in dehydration and death due to salt- wasting. For a long time, exogenous corticosteroids have been the standard of care for treating patients with classic CAH. This treatment is used to correct the cortisol deficiency and reduce the excessive ACTH levels and androgen excess. However, the dosage and duration of steroid use required to suppress ACTH are typically well above the normal physiological level used for cortisol replacement alone (as in patients with Addison’s disease). This increased exposure to glucocorticoids can lead to iatrogenic Cushing’s syndrome, increased cardiovascular risk factors, glucose intolerance, reduced growth velocity, and decreased bone mineral density in CAH patients. Corticotropin releasing factor (CRF) is a hypothalamic hormone released directly into the hypophyseal portal vasculature and acts on specific corticotropin releasing factor 1 (CRF i) receptors on corticotropes in the anterior pituitary to stimulate the release of ACTH. Blockade of these receptors has been shown to decrease the release of ACTH in both animals and humans.Attorney Docket No. 46696-0217WO1 / 377.WO1.PCT

[0003] Compound A, 4-(2-chloro-4-methoxy-5-methylphenyl)-A-[(lN)-2-cyclopropyl-l-(3- fluoro-4- methylphenyl)ethyl]-5-methyl-7V-prop-2-ynyl-l,3-thiazol-2-amine, or a pharmaceutically acceptable salt thereof, (also referred to herein as crinecerfont) is a selective CRFi receptor antagonist that has been developed for the treatment of CAH associated with high ACTH levels and adrenal steroid insufficiency. Compound A, or a pharmaceutically acceptable salt thereof, can be prepared according to the methods described in WO 2021 / 252669 and U.S. Patent Nos. 6,586,456 and 8,314,249, each of which is hereby incorporated by reference in its entirety.

[0004] Crinecerfont is the first new treatment available in 70 years to the classic congenital adrenal hyperplasia (CAH) community that was approved by the US Food and Drug Administration (FDA) under the tradename CRENESSITY® in December 2024. Its approval was supported by data from the largest-ever clinical trial program in pediatric and adult patients with classic CAH. The data from the CAHtalyst™ Phase 3 global registrational studies in pediatric and adult patients with classic CAH were published in The New England Journal of Medicine (Sarafoglou, K., et al., New England Journal of Medicine, 391 (6), 493- 503 (Phase 3 trial of crinecerfont in pediatric congenital adrenal hyperplasia) and Auchus, R. J, et al., New England Journal of Medicine, 391 (6), 504-514 (Phase 3 trial of crinecerfont in adult congenital adrenal hyperplasia)).

[0005] In the CAHtalyst™ pediatric phase 3 trial, crinecerfont was superior to placebo in reducing elevated androstenedione levels in pediatric participants with classic CAH and was also associated with a decrease in the glucocorticoid dose from supraphysiologic to physiologic levels while androstenedione control was maintained. In addition, in the CAHtalyst™ phase 3 trial of adults with classic CAH, the use of crinecerfont resulted in a greater decrease from baseline in the mean daily glucocorticoid dose, including a reduction to the physiologic range, than placebo following evaluation of adrenal androgen levels. In both the pediatric and adult CAHtalyst™ studies, crinecerfont enabled lower steroid doses and decreased androgen levels, which led to the approval of CRENESSITY® by the FDA in December 2024. CRENESSITY® is now approved as adjunctive treatment to glucocorticoid replacement to control androgens in adults and pediatric patients 4 years of age and older with classic congenital adrenal hyperplasia (CAH).

[0006] There is a significant, unmet need for methods for treating congenital adrenal hyperplasia. The present disclosure fulfills these and other needs, as evident in reference to the following disclosure.Attorney Docket No. 46696-0217WO1 / 377.WO1.PCTSUMMARY

[0007] Provided is a method of administering 4-(2-chloro-4-methoxy-5-methylphenyl)-A- [(15)-2-cyclopropyl-l-(3-fluoro-4-methylphenyl)ethyl]-5-methyl-7V-prop-2-ynyl-l,3-thiazol- 2-amine (Compound A),(Compound A) or a pharmaceutically acceptable salt thereof, to a patient, said method comprising: administering to the patient a therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof; monitoring the patient for a hypersensitivity reaction associated with the administration of Compound A, or a pharmaceutically acceptable salt thereof; and discontinuing administration of Compound A, or a pharmaceutically acceptable salt thereof, if the patient is not able to tolerate the hypersensitivity reaction.

[0008] Also provided is a method of administering 4-(2-chloro-4-methoxy-5-methylphenyl)-A-[(15)-2-cyclopropyl-l-(3-fluoro-4-methylphenyl)ethyl]-5-methyl-7V-prop-2-ynyl-l,3- thiazol-2-amine (Compound A),(Compound A) to a patient, said method comprising: administering to the patient a therapeutically effective amount of Compound A; monitoring the patient for a hypersensitivity reaction associated with the administration of Compound A; and discontinuing administration of Compound A, if the patient is not able to tolerate the hypersensitivity reaction.

[0009] Also provided is a method of administering a pharmaceutical composition comprising a therapeutically effective amount of 4-(2-chloro-4-methoxy-5-methylphenyl)-7V-[(15)-2- cyclopropyl-l-(3-fluoro-4-methylphenyl)ethyl]-5-methyl-7V-prop-2-ynyl-l,3-thiazol-2-amine (Compound A),Attorney Docket No. 46696-0217WO1 / 377.WO1.PCT(Compound A) or a pharmaceutically acceptable salt thereof, to a patient, said method comprising: administering to the patient the pharmaceutical composition; monitoring the patient for a hypersensitivity reaction associated with the administration of the pharmaceutical composition; and discontinuing administration of the pharmaceutical composition if the patient is not able to tolerate the hypersensitivity reaction.

[0010] Also provided is a method of administering a pharmaceutical composition comprising a therapeutically effective amount of 4-(2-chloro-4-methoxy-5-methylphenyl)-A-[(15)-2- cyclopropyl-l-(3-fluoro-4-methylphenyl)ethyl]-5-methyl-A-prop-2-ynyl-l,3-thiazol-2-amine (Compound A),(Compound A) to a patient, said method comprising: administering to the patient the pharmaceutical composition; monitoring the patient for a hypersensitivity reaction associated with the administration of the pharmaceutical composition; and discontinuing administration of the pharmaceutical composition, if the patient is not able to tolerate the hypersensitivity reaction.

[0011] Also provided is a method of treating a patient with congenital adrenal hyperplasia (CAH), said method comprising: administering to the patient a therapeutically effective amount of 4-(2-chloro-4- methoxy-5-methylphenyl)-A-[(15)-2-cyclopropyl-l-(3-fluoro-4-methylphenyl)ethyl]-5- methyl-A-prop-2-ynyl-l,3-thiazol-2-amine (Compound A),Attorney Docket No. 46696-0217WO1 / 377.WO1.PCT(Compound A) or a pharmaceutically acceptable salt thereof; monitoring the patient for a hypersensitivity reaction associated with the administration of Compound A, or a pharmaceutically acceptable salt thereof; and discontinuing administration of Compound A, or a pharmaceutically acceptable salt thereof, if the patient is not able to tolerate the hypersensitivity reaction.

[0012] Also provided is a method of treating a patient with congenital adrenal hyperplasia (CAH), said method comprising: administering a therapeutically effective amount of 4-(2-chloro-4-methoxy-5- methylphenyl)-A-[(15)-2-cyclopropyl-l-(3-fluoro-4-methylphenyl)ethyl]-5-methyl-A-prop-2- ynyl-l,3-thiazol-2-amine (Compound A),(Compound A) to the patient, monitoring the patient for a hypersensitivity reaction associated with the administration of Compound A, and discontinuing administration of Compound A, if the patient is not able to tolerate the hypersensitivity reaction.

[0013] Also provided is a method of treating a patient with congenital adrenal hyperplasia (CAH), said method comprising: administering a pharmaceutical composition comprising a therapeutically effective amount of 4-(2-chloro-4-methoxy-5-methylphenyl)-A-[(lN)-2-cyclopropyl-l-(3-fluoro-4- methylphenyl)ethyl]-5-methyl-A-prop-2-ynyl-l,3-thiazol-2-amine (Compound A),Attorney Docket No. 46696-0217WO1 / 377.WO1.PCT(Compound A) or a pharmaceutically acceptable salt thereof, to the patient, monitoring the patient for a hypersensitivity reaction associated with the administration of the pharmaceutical composition, and discontinuing administration of the pharmaceutical composition if the patient is not able to tolerate the hypersensitivity reaction.

[0014] Also provided is a method of treating a patient with congenital adrenal hyperplasia (CAH), said method comprising: administering a pharmaceutical composition comprising a therapeutically effective amount of 4-(2-chloro-4-methoxy-5-methylphenyl)-A-[(lN)-2-cyclopropyl-l-(3-fluoro-4- methylphenyl)ethyl]-5-methyl-A-prop-2-ynyl-l,3-thiazol-2-amine (Compound A),(Compound A) to the patient, monitoring the patient for a hypersensitivity reaction associated with the administration of the pharmaceutical composition, and discontinuing administration of the pharmaceutical composition, if the patient is not able to tolerate the hypersensitivity reaction.

[0015] Also provided is a method of treating a patient with congenital adrenal hyperplasia (CAH), said method comprising: administering a therapeutically effective amount of 4-(2-chloro-4-methoxy-5- methylphenyl)-A-[(15)-2-cyclopropyl-l-(3-fluoro-4-methylphenyl)ethyl]-5-methyl-A-prop-2- ynyl-l,3-thiazol-2-amine (Compound A),Attorney Docket No. 46696-0217WO1 / 377.WO1.PCT(Compound A) or a pharmaceutically acceptable salt thereof, to the patient, monitoring the patient for a hypersensitivity reaction associated with the administration of Compound A, or a pharmaceutically acceptable salt thereof; and if the patient demonstrates the hypersensitivity reaction, discontinuing administration of Compound A, or a pharmaceutically acceptable salt thereof.

[0016] Also provided is a method of treating a patient with congenital adrenal hyperplasia (CAH), said method comprising: administering a therapeutically effective amount of 4-(2-chloro-4-methoxy-5- methylphenyl)-A-[(15)-2-cyclopropyl-l-(3-fluoro-4-methylphenyl)ethyl]-5-methyl-A-prop-2- ynyl-l,3-thiazol-2-amine (Compound A),(Compound A) to the patient, monitoring the patient for a hypersensitivity reaction associated with the administration of Compound A; and if the patient demonstrates the hypersensitivity reaction, discontinuing administration of Compound A.

[0017] Also provided is a method of treating a patient with congenital adrenal hyperplasia (CAH), said method comprising: administering a pharmaceutical composition comprising a therapeutically effective amount of 4-(2-chloro-4-methoxy-5-methylphenyl)-A-[(lN)-2-cyclopropyl-l-(3-fluoro-4- methylphenyl)ethyl]-5-methyl-A-prop-2-ynyl-l,3-thiazol-2-amine (Compound A),Attorney Docket No. 46696-0217WO1 / 377.WO1.PCT(Compound A) or a pharmaceutically acceptable salt thereof, to the patient, monitoring the patient for a hypersensitivity reaction associated with the administration of the pharmaceutical composition; and if the patient demonstrates the hypersensitivity reaction, discontinuing administration of the pharmaceutical composition.

[0018] Also provided is a method of treating a patient with congenital adrenal hyperplasia (CAH), said method comprising: administering a pharmaceutical composition comprising a therapeutically effective amount of 4-(2-chloro-4-methoxy-5-methylphenyl)-A-[(lN)-2-cyclopropyl-l-(3-fluoro-4- methylphenyl)ethyl]-5-methyl-A-prop-2-ynyl-l,3-thiazol-2-amine (Compound A),(Compound A) to the patient, monitoring the patient for a hypersensitivity reaction associated with the administration of the pharmaceutical composition; and if the patient demonstrates the hypersensitivity reaction, discontinuing administration of the pharmaceutical composition.

[0019] Also provided is a method of treating a patient with congenital adrenal hyperplasia (CAH), said method comprising: administering a therapeutically effective amount of 4-(2-chloro-4-methoxy-5- methylphenyl)-A-[(15)-2-cyclopropyl-l-(3-fluoro-4-methylphenyl)ethyl]-5-methyl-A-prop-2- ynyl-l,3-thiazol-2-amine (Compound A),Attorney Docket No. 46696-0217WO1 / 377.WO1.PCT(Compound A) or a pharmaceutically acceptable salt thereof, to the patient, monitoring the patient for the presence or absence of a hypersensitivity reaction associated with the administration of Compound A, or a pharmaceutically acceptable salt thereof, and if the hypersensitivity reaction is present, discontinuing administration of Compound A, or a pharmaceutically acceptable salt thereof, or if the hypersensitivity reaction is absent, continuing administering the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof, to the patient.

[0020] Also provided is a method of treating a patient with congenital adrenal hyperplasia (CAH), said method comprising: administering a therapeutically effective amount of 4-(2-chloro-4-methoxy-5- methylphenyl)-A-[(15)-2-cyclopropyl-l-(3-fluoro-4-methylphenyl)ethyl]-5-methyl-A-prop-2- ynyl-l,3-thiazol-2-amine (Compound A),(Compound A) to the patient, monitoring the patient for the presence or absence of a hypersensitivity reaction associated with the administration of Compound A, and if the hypersensitivity reaction is present, discontinuing administration of Compound A, or if the hypersensitivity reaction is absent, continuing administering the therapeutically effective amount of Compound A to the patient.

[0021] Also provided is a method of treating a patient with congenital adrenal hyperplasia(CAH), said method comprising:Attomey Docket No. 46696-0217WO1 / 377.WO1.PCT administering a pharmaceutical composition comprising a therapeutically effective amount of 4-(2-chloro-4-methoxy-5-methylphenyl)-A-[(lN)-2-cyclopropyl-l-(3-fluoro-4- methylphenyl)ethyl]-5-methyl-A-prop-2-ynyl-l,3-thiazol-2-amine (Compound A),(Compound A) or a pharmaceutically acceptable salt thereof, to the patient, monitoring the patient for the presence or absence of a hypersensitivity reaction associated with the administration of the pharmaceutical composition, and if the hypersensitivity reaction is present, discontinuing administration of the pharmaceutical composition, or if the hypersensitivity reaction is absent, continuing administering the pharmaceutical composition to the patient.

[0022] Also provided is a method of treating a patient with congenital adrenal hyperplasia (CAH), said method comprising: administering a pharmaceutical composition comprising a therapeutically effective amount of 4-(2-chloro-4-methoxy-5-methylphenyl)-A-[(lN)-2-cyclopropyl-l-(3-fluoro-4- methylphenyl)ethyl]-5-methyl-A-prop-2-ynyl-l,3-thiazol-2-amine (Compound A),(Compound A) to the patient, monitoring the patient for the presence or absence of a hypersensitivity reaction associated with the administration of the pharmaceutical composition, and if the hypersensitivity reaction is present, discontinuing administration of the pharmaceutical composition, or if the hypersensitivity reaction is absent, continuing administering the pharmaceutical composition to the patient.

[0023] Also provided is a method of treating a patient with classic congenital adrenal hyperplasia (CAH), using 4-(2-chloro-4-methoxy-5-methylphenyl)-A-[(lN)-2-cyclopropyl-l-Atorney Docket No. 46696-0217WO1 / 377.WO1.PCT(3-fluoro-4-methylphenyl)ethyl]-5-methyl-A-prop-2-ynyl-l,3-thiazol-2-amine (CompoundA),(Compound A) or a pharmaceutically acceptable salt thereof, as adjunctive treatment to glucocorticoid replacement therapy to control androgens in the patient, said method comprising: administering to the patient a therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof, monitoring the patient for the occurrence of a hypersensitivity reaction associated with the administration of Compound A, or a pharmaceutically acceptable salt thereof, and if the hypersensitivity reaction occurs, discontinuing administration of Compound A, or a pharmaceutically acceptable salt thereof.

[0024] Also provided is a method of treating a patient with classic congenital adrenal hyperplasia (CAH), using 4-(2-chloro-4-methoxy-5-methylphenyl)-A-[(lN)-2-cyclopropyl-l- (3-fluoro-4-methylphenyl)ethyl]-5-methyl-A-prop-2-ynyl-l,3-thiazol-2-amine (Compound A),(Compound A) as adjunctive treatment to glucocorticoid replacement therapy to control androgens in the patient, said method comprising: administering to the patient a therapeutically effective amount of Compound A, monitoring the patient for the occurrence of a hypersensitivity reaction associated with the administration of Compound A, and if the hypersensitivity reaction occurs, discontinuing administration of Compound A.

[0025] Also provided is a method of treating a patient with classic congenital adrenal hyperplasia (CAH), using a pharmaceutical composition comprising a therapeuticallyAttorney Docket No. 46696-0217WO1 / 377.WO1.PCT effective amount of 4-(2-chloro-4-methoxy-5-methylphenyl)-A-[(15)-2-cyclopropyl-l-(3- fluoro-4-methylphenyl)ethyl]-5-methyl-A-prop-2-ynyl-l,3-thiazol-2-amine (Compound A),(Compound A) or a pharmaceutically acceptable salt thereof, as adjunctive treatment to glucocorticoid replacement therapy to control androgens in the patient, said method comprising: administering to the patient the pharmaceutical composition, monitoring the patient for the occurrence of a hypersensitivity reaction associated with the administration of the pharmaceutical composition, and if the hypersensitivity reaction occurs, discontinuing administration of the pharmaceutical composition.

[0026] Also provided is a method of treating a patient with classic congenital adrenal hyperplasia (CAH), using a pharmaceutical composition comprising a therapeutically effective amount of 4-(2-chloro-4-methoxy-5-methylphenyl)-A-[(15)-2-cyclopropyl-l-(3- fluoro-4-methylphenyl)ethyl]-5-methyl-A-prop-2-ynyl-l,3-thiazol-2-amine (Compound A),(Compound A) as adjunctive treatment to glucocorticoid replacement therapy to control androgens in the patient, said method comprising: administering to the patient the pharmaceutical composition, monitoring the patient for the occurrence of a hypersensitivity reaction associated with the administration of the pharmaceutical composition, and if the hypersensitivity reaction occurs, discontinuing administration of the pharmaceutical composition.

[0027] These and other aspects of the invention disclosed herein will be set forth in greater detail as the patent disclosure proceeds.Attorney Docket No. 46696-0217WO1 / 377.WO1.PCTDETAILED DESCRIPTION

[0028] In the following description, certain specific details are set forth in order to provide a thorough understanding of various embodiments. However, one skilled in the art will understand that the invention may be practiced without these details. In other instances, well- known structures have not been shown or described in detail to avoid unnecessarily obscuring descriptions of the embodiments. Unless the context requires otherwise, throughout the specification and claims which follow, the word “comprise” and variations thereof, such as, “comprises” and “comprising” are to be construed in an open, inclusive sense, that is, as “including, but not limited to.” Further, headings provided herein are for convenience only and do not interpret the scope or meaning of the claimed invention.

[0029] Reference throughout this specification to “one embodiment” or “an embodiment” or “some embodiments” or “a certain embodiment” means that a particular feature, structure or characteristic described in connection with the embodiment is included in at least one embodiment. Thus, the appearances of the phrases “in one embodiment” or “in an embodiment” or “in some embodiments” or “in a certain embodiment” in various places throughout this specification are not necessarily all referring to the same embodiment. Furthermore, the particular features, structures, or characteristics may be combined in any suitable manner in one or more embodiments.

[0030] Also, as used in this specification and the appended claims, the singular forms “a,” “an,” and “the” include plural referents unless the content clearly dictates otherwise.

[0031] Compound A and its pharmaceutically acceptable salts may form solvates, including hydrates. Solvates are formed by the incorporation into the solid-state structure (e.g., crystal structure) of the compounds and salts described herein of molecules of a non-toxic pharmaceutically acceptable solvent. Examples of such solvents include water, alcohols (such as ethanol, isopropanol and butanol), and dimethyl sulfoxide. Solvates can be prepared by recrystallizing the compounds and salts with a solvent, or a mixture of solvents, containing the solvating solvent. Whether or not a solvate has been formed in any given instance can be determined by subjecting crystals to analysis using well known and standard techniques such as thermogravimetric analysis (TGE), differential scanning calorimetry (DSC), and X-ray crystallography. The solvates can be stoichiometric or nonstoichiometric solvates. In some embodiments, the solvate is a hydrate, such as a hemihydrate, monohydrate, or dihydrate.

[0032] As used herein, “about” means ± 20% of the stated value, and includes more specifically values of ± 10%, ± 5%, ± 2%, and ± 1% of the stated value.Attorney Docket No. 46696-0217WO1 / 377.WO1.PCT

[0033] As used herein, “administering to a patient” refers to the process of introducing a composition or dosage form or generally any amount of the drug compound into the patient via an art-recognized means of introduction.

[0034] As used herein, “adjusting administration,” “altering administration,” “adjusting dosing,” or “altering dosing” are all equivalent and mean tapering off, reducing, or increasing the dose of the substance, ceasing to administer the substance to the patient, or substituting a different active agent for the substance.

[0035] As used herein, “treat,” “treating,” and “treatment” are meant to include alleviating or abrogating a disorder, disease, or condition, or one or more of the symptoms associated with the disorder, disease, or condition; or alleviating or eradicating the cause(s) of the disorder, disease, or condition itself.

[0036] As used herein, “co-administer” and “co-admini strati on” and variants thereof mean the administration of at least two drugs to a patient either subsequently, simultaneously, or consequently proximate in time to one another (e.g., within the same day, or week or period of 30 days, or sufficiently proximate that each of the at least two drugs can be simultaneously detected in the blood plasma). When co-administered, two or more active agents can be coformulated as part of the same composition, or administered as separate formulations. This also may be referred to herein as “concomitant” administration or variants thereof.

[0037] As used herein, “amelioration of the symptoms” of a particular disorder by administration of a particular pharmaceutical composition refers to any lessening, whether permanent or temporary, lasting or transient, that can be attributed to or associated with administration of the composition.

[0038] As used herein, “baseline” refers to the period of time just prior to initiation of therapy. The patient's condition just prior to initiation of therapy can be referred to as the patient's baseline condition.

[0039] As used herein the term “disorder” is intended to be generally synonymous, and is used interchangeably with, the terms “disease,” “syndrome,” and “condition” (as in medical condition), in that all reflect an abnormal condition of the human or animal body or of one of its parts that impairs normal functioning, is typically manifested by distinguishing signs and symptoms.

[0040] As used herein, a “dosage” is the prescribed administration of a specific amount, number, and frequency of doses over a specific period of time.

[0041] As used herein, a “dosage form” refers to a form of the active agent suitable for administration of a specific dosage.Attorney Docket No. 46696-0217WO1 / 377.WO1.PCT

[0042] As used herein, a “dose” means the measured quantity of an active agent to be taken at one time by a patient. In certain embodiments, wherein the active agent is not a free base, the quantity is the molar equivalent to the corresponding amount of free base.

[0043] As used herein, “effective amount” and “therapeutically effective amount” of an agent, compound, drug, composition, or combination is an amount which is nontoxic and effective for producing some desired therapeutic effect upon administration to a subject or patient (e.g., a human subject or patient). The precise therapeutically effective amount for a subject may depend upon, e.g., the subject’s size and health, the nature and extent of the condition, the therapeutics or combination of therapeutics selected for administration, and other variables known to those of skill in the art. The effective amount for a given situation is determined by routine experimentation and is within the judgment of the clinician.

[0044] In the context of the present disclosure, the amount (as weight, typically in mg) of crinecerfont or a pharmaceutically acceptable salt thereof in a dosage form is always expressed as the equivalent amount of crinecerfont free base, regardless of the form used, i.e., the crinecerfont free base or a pharmaceutically acceptable salt. If a pharmaceutically acceptable salt of crinecerfont was used, the amount of the respective crinecerfont salt would be higher in order to match the equimolar amount of the crinecerfont free base form used.

[0045] As used herein “hypersensitivity” or “hypersensitivity reaction” refers to an immunological sensitization due to a drug and / or its metabolites, or due to an excipient or other component of the pharmaceutical formulation. Generally, there are four types of hypersensitivity :Type I, IgE mediated-immediate-type hypersensitivity, including systemic hypersensitivity (e.g., anaphylaxis and urticarial) and respiratory hypersensitivity (e.g., asthma);Type II, IgG or IgM mediated-antibody-mediated cytotoxic reaction and Type III, IgG mediated-immune complex reaction, which often occur simultaneously and are commonly associated with systemic or organ hypersensitivity reactions. Type II and III immunopathies include anemia, leukopenia, thrombocytopenia, pneumonitis, vasculitis, lupus-like reactions or glomerulonephritis; andType IV, T lymphocyte mediated-delayed-type hypersensitivity response, which most commonly occurs as a delayed-type hypersensitivity skin reaction.

[0046] As used herein, “informing” means referring to or providing published material, for example, providing an active agent with published material to a user; or presenting information orally, for example, by presentation at a seminar, conference, or otherAttorney Docket No. 46696-0217WO1 / 377.WO1.PCT educational presentation, by conversation between a pharmaceutical sales representative and a medical care worker, or by conversation between a medical care worker and a patient; or demonstrating the intended information to a user for the purpose of comprehension.

[0047] As used herein, “labeling” means all labels or other means of written, printed, graphic, electronic, verbal, or demonstrative communication that is upon a pharmaceutical product or a dosage form or accompanying such pharmaceutical product or dosage form.

[0048] As used herein, the terms “manage,” “managing,” and “management” refer to preventing or slowing the progression, spread, or worsening of a disease or disorder, or of one or more symptoms thereof. Often, the beneficial effects that a subject derives from a prophylactic and / or therapeutic agent do not result in a cure of the disease or disorder. In this regard, the term "managing" encompasses treating a subject who had suffered from the particular disease in an attempt to prevent or minimize the recurrence of the disease.

[0049] As used herein, “a medical care worker" means a worker in the health care field who may need or utilize information regarding an active agent, including a dosage form thereof, including information on safety, efficacy, dosing, administration, or pharmacokinetics. Examples of medical care workers include physicians, pharmacists, physician's assistants, nurses, aides, caretakers (which can include family members or guardians), emergency medical workers, and veterinarians.

[0050] As used herein, “Medication Guide” means an FDA-approved patient labeling for a pharmaceutical product conforming to the specifications set forth in 21 C.F.R. §208 and other applicable regulations which contains information for patients on how to safely use a pharmaceutical product. A medication guide is scientifically accurate and is based on, and does not conflict with, the approved professional labeling for the pharmaceutical product under 21 C.F.R. §201.57, but the language need not be identical to the sections of approved labeling to which it corresponds. A medication guide is typically available for a pharmaceutical product with special risk management information.

[0051] As used herein, “patient” or “individual” or “subject” means a mammal, including a human, for whom or which therapy is desired, and generally refers to the recipient of the therapy.

[0052] As used herein, a “pediatric” patient is from 4 years to less than 18 years of age.

[0053] As used herein, an “adult” or “adult patient” is 18 years of age or older.

[0054] As used herein, “pharmaceutically acceptable” refers to a material that is not biologically or otherwise undesirable, / .< ., the material may be incorporated into a pharmaceutical composition administered to a patient without causing any undesirableAttorney Docket No. 46696-0217WO1 / 377.WO1.PCT biological effects or interacting in a deleterious manner with any of the other components of the composition in which it is contained. When the term “pharmaceutically acceptable” is used to refer to a pharmaceutical carrier or excipient, it is implied that the carrier or excipient has met the required standards of toxicological and manufacturing testing or that it is included on the Inactive Ingredient Guide prepared by the U.S. Food and Drug administration. “Pharmacologically active” (or simply “active”) as in a “pharmacologically active” (or “active”) derivative or analog, refers to a derivative or analog having the same type of pharmacological activity as the parent compound and approximately equivalent in degree.

[0055] As used herein, in some embodiments, “pharmaceutically acceptable salt” refers to acid addition salts with an inorganic or an organic acid. Lists of suitable salts are found in WO 87 / 05297, Johnston et al., published September 11, 1987; Remington’s Pharmaceutical Sciences, 17th ed., Mack Publishing Company, Easton, Pa., 1985, p. 1418; and J. Pharm. Sci., 66, 2 (1977), each of which is incorporated herein by reference in its entirety. A reference for the preparation and selection of pharmaceutical salts of the present disclosure is P. H. Stahl & C. G. Wermuth “Handbook of Pharmaceutical Salts,” Ver lag Helvetica Chimica Acta, Zurich, 2002 which is incorporated herein by reference in its entirety. The organic or inorganic acids include, but are not limited to, hydrochloric, hydrobromic, sulfuric, nitric, phosphoric, sulfamic, acetic, trifluoroacetic, trichloroacetic, propionic, hexanoic, cyclopentylpropionic, glycolic, glutaric, pyruvic, lactic, malonic, succinic, sorbic, ascorbic, malic, maleic, fumaric, tartaric, citric, benzoic, 3-(4-hydroxybenzoyl)benzoic, picric, cinnamic, mandelic, phthalic, lauric, methanesulfonic, ethanesulfonic, 1,2-ethane-disulfonic, 2-hydroxyethanesulfonic, benzenesulfonic, 4-chlorobenzenesulfonic, 2-naphthalenesulfonic, 4-toluenesulfonic, camphoric, camphorsulfonic, 4-methylbicyclo[2.2.2]-oct-2-ene-l- carboxylic, glucoheptonic, 3 -phenylpropionic, trimethylacetic, tert-butyl acetic, lauryl sulfuric, gluconic, benzoic, glutamic, hydroxynaphthoic, salicylic, stearic, cyclohexylsulfamic, quinic, muconic acid, and the like. In some embodiments, “pharmaceutically acceptable salt” refers to base addition salts with an inorganic or an organic base. Inorganic bases which may be used to prepare salts include, for example, sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, manganese, aluminum hydroxides, carbonates, bicarbonates, phosphates, and the like; particularly preferred are the ammonium, potassium, sodium, calcium, and magnesium hydroxides, carbonates, bicarbonates, or phosphates. Organic bases from which may be used to prepare salts include, for example, primary, secondary, and tertiary amines, substituted aminesAttorney Docket No. 46696-0217WO1 / 377.WO1.PCT including naturally occurring substituted amines, cyclic amines, basic ion exchange resins, and the like, e.g., isopropylamine, trimethylamine, di ethylamine, tri ethylamine, tripropylamine, and ethanolamine.

[0056] As used herein, “prevent,” “preventing,” and “prevention” are meant to include a method of delaying and / or precluding the onset of a disorder, disease, or condition, and / or its attendant symptoms; barring a subject from acquiring a disorder, disease, or condition; or reducing a subject's risk of acquiring a disorder, disease, or condition.

[0057] As used herein, a “product” or “pharmaceutical product” means a dosage form of an active agent plus published material, and optionally packaging.

[0058] As used herein, “product insert” means the professional labeling (prescribing information) for a pharmaceutical product, a patient package insert for the pharmaceutical product, or a medication guide for the pharmaceutical product.

[0059] As used herein, “professional labeling” or “prescribing information” means the official description of a pharmaceutical product approved by a regulatory agency (e.g., FDA or EMEA) regulating marketing of the pharmaceutical product, which includes a summary of the essential scientific information needed for the safe and effective use of the drug, such as, for example indication and usage; dosage and administration; who should take it; adverse events (side effects); instructions for use in special populations (pregnant women, children, geriatric, etc.); safety information for the patient, and the like.

[0060] As used herein, “published material” means a medium providing information, including printed, audio, visual, or electronic medium, for example a flyer, an advertisement, a product insert, printed labeling, an internet web site, an internet web page, an internet popup window, a radio or television broadcast, a compact disk, a DVD, an audio recording, or other recording or electronic medium.

[0061] As used herein, the phrases “wherein the administration of Compound A (or a pharmaceutically acceptable salt thereof) improves androgen control and / or enables a reduced glucocorticoid dose while maintaining androgen control in the patient” or “wherein the administration of Compound A (or a pharmaceutically acceptable salt thereof) reduces androgen levels and / or enables a reduced glucocorticoid dose while maintaining androgen control in the patient” mean that the patient being administered Compound A (or a pharmaceutically acceptable salt thereof) demonstrates lower levels of androgens, including androstenedione, and / or demonstrates the ability to receive a reduced daily glucocorticoid dose compared to prior to starting treatment of Compound A.Attomey Docket No. 46696-0217WO1 / 377.WO1.PCTMethods of Treatment

[0062] Provided is a method of administering 4-(2-chloro-4-methoxy-5-methylphenyl)-7V-[(15)-2-cyclopropyl-l-(3-fluoro-4-methylphenyl)ethyl]-5-methyl-7V-prop-2-ynyl-l,3-thiazol-2-amine (Compound A),(Compound A) or a pharmaceutically acceptable salt thereof, to a patient, said method comprising: administering to the patient a therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof; monitoring the patient for a hypersensitivity reaction associated with the administration of Compound A, or a pharmaceutically acceptable salt thereof; and discontinuing administration of Compound A, or a pharmaceutically acceptable salt thereof, if the patient is not able to tolerate the hypersensitivity reaction.

[0063] In an embodiment thereof, the patient has congenital adrenal hyperplasia (CAH).

[0064] Also provided is a method of administering 4-(2-chloro-4-methoxy-5-methylphenyl)-A-[(15)-2-cyclopropyl-l-(3-fluoro-4-methylphenyl)ethyl]-5-methyl-A-prop-2-ynyl-l,3- thiazol-2-amine (Compound A),(Compound A) to a patient, said method comprising: administering to the patient a therapeutically effective amount of Compound A; monitoring the patient for a hypersensitivity reaction associated with the administration of Compound A; and discontinuing administration of Compound A, if the patient is not able to tolerate the hypersensitivity reaction.

[0065] In an embodiment thereof, the patient has congenital adrenal hyperplasia (CAH).

[0066] Also provided is a method of administering a pharmaceutical composition comprising therapeutically effective amount of 4-(2-chloro-4-methoxy-5-methylphenyl)-A-[(lN)-2-Attorney Docket No. 46696-0217WO1 / 377.WO1.PCT cyclopropyl-l-(3-fluoro-4-methylphenyl)ethyl]-5-methyl-A-prop-2-ynyl-l,3-thiazol-2-amine(Compound A),(Compound A) or a pharmaceutically acceptable salt thereof, to a patient, said method comprising: administering to the patient the pharmaceutical composition; monitoring the patient for a hypersensitivity reaction associated with the administration of the pharmaceutical composition; and discontinuing administration of the pharmaceutical composition if the patient is not able to tolerate the hypersensitivity reaction.

[0067] Also provided is a method of administering a pharmaceutical composition comprising a therapeutically effective amount of 4-(2-chloro-4-methoxy-5-methylphenyl)-A-[(15)-2- cyclopropyl-l-(3-fluoro-4-methylphenyl)ethyl]-5-methyl-A-prop-2-ynyl-l,3-thiazol-2-amine (Compound A),(Compound A) to a patient, said method comprising: administering to the patient the pharmaceutical composition; monitoring the patient for a hypersensitivity reaction associated with the administration of the pharmaceutical composition; and discontinuing administration of the pharmaceutical composition, if the patient is not able to tolerate the hypersensitivity reaction.

[0068] Also provided is a method of treating a patient with congenital adrenal hyperplasia (CAH), said method comprising: administering to the patient a therapeutically effective amount of 4-(2-chloro-4- methoxy-5-methylphenyl)-A-[(15)-2-cyclopropyl-l-(3-fluoro-4-methylphenyl)ethyl]-5- methyl-A-prop-2-ynyl-l,3-thiazol-2-amine (Compound A),Attorney Docket No. 46696-0217WO1 / 377.WO1.PCT(Compound A) or a pharmaceutically acceptable salt thereof; monitoring the patient for a hypersensitivity reaction associated with the administration of Compound A, or a pharmaceutically acceptable salt thereof; and discontinuing administration of Compound A, or a pharmaceutically acceptable salt thereof, if the patient is not able to tolerate the hypersensitivity reaction.

[0069] Also provided is a method of treating a patient with congenital adrenal hyperplasia (CAH), said method comprising: administering a therapeutically effective amount of 4-(2-chloro-4-methoxy-5- methylphenyl)-A-[(15)-2-cyclopropyl-l-(3-fluoro-4-methylphenyl)ethyl]-5-methyl-A-prop-2- ynyl-l,3-thiazol-2-amine (Compound A),(Compound A) to the patient, monitoring the patient for a hypersensitivity reaction associated with the administration of Compound A, and discontinuing administration of Compound A, if the patient is not able to tolerate the hypersensitivity reaction.

[0070] Also provided is a method of treating a patient with congenital adrenal hyperplasia (CAH), said method comprising: administering a pharmaceutical composition comprising a therapeutically effective amount of 4-(2-chloro-4-methoxy-5-methylphenyl)-A-[(lN)-2-cyclopropyl-l-(3-fluoro-4- methylphenyl)ethyl]-5-methyl-A-prop-2-ynyl-l,3-thiazol-2-amine (Compound A),Attorney Docket No. 46696-0217WO1 / 377.WO1.PCT(Compound A) or a pharmaceutically acceptable salt thereof, to the patient, monitoring the patient for a hypersensitivity reaction associated with the administration of the pharmaceutical composition, and discontinuing administration of the pharmaceutical composition if the patient is not able to tolerate the hypersensitivity reaction.

[0071] Also provided is a method of treating a patient with congenital adrenal hyperplasia (CAH), said method comprising: administering a pharmaceutical composition comprising a therapeutically effective amount of 4-(2-chloro-4-methoxy-5-methylphenyl)-A-[(lN)-2-cyclopropyl-l-(3-fluoro-4- methylphenyl)ethyl]-5-methyl-A-prop-2-ynyl-l,3-thiazol-2-amine (Compound A),(Compound A) to the patient, monitoring the patient for a hypersensitivity reaction associated with the administration of the pharmaceutical composition, and discontinuing administration of the pharmaceutical composition, if the patient is not able to tolerate the hypersensitivity reaction.

[0072] Also provided is a method of treating a patient with congenital adrenal hyperplasia (CAH), said method comprising: administering a therapeutically effective amount of 4-(2-chloro-4-methoxy-5- methylphenyl)-A-[(15)-2-cyclopropyl-l-(3-fluoro-4-methylphenyl)ethyl]-5-methyl-A-prop-2- ynyl-l,3-thiazol-2-amine (Compound A),Attorney Docket No. 46696-0217WO1 / 377.WO1.PCT(Compound A) or a pharmaceutically acceptable salt thereof, to the patient, monitoring the patient for a hypersensitivity reaction associated with the administration of Compound A, or a pharmaceutically acceptable salt thereof; and if the patient demonstrates the hypersensitivity reaction, discontinuing administration of Compound A, or a pharmaceutically acceptable salt thereof.

[0073] Also provided is a method of treating a patient with congenital adrenal hyperplasia (CAH), said method comprising: administering a therapeutically effective amount of 4-(2-chloro-4-methoxy-5- methylphenyl)-A-[(15)-2-cyclopropyl-l-(3-fluoro-4-methylphenyl)ethyl]-5-methyl-A-prop-2- ynyl-l,3-thiazol-2-amine (Compound A),(Compound A) to the patient, monitoring the patient for a hypersensitivity reaction associated with the administration of Compound A; and if the patient demonstrates the hypersensitivity reaction, discontinuing administration of Compound A.

[0074] Also provided is a method of treating a patient with congenital adrenal hyperplasia (CAH), said method comprising: administering a pharmaceutical composition comprising a therapeutically effective amount of 4-(2-chloro-4-methoxy-5-methylphenyl)-A-[(lN)-2-cyclopropyl-l-(3-fluoro-4- methylphenyl)ethyl]-5-methyl-A-prop-2-ynyl-l,3-thiazol-2-amine (Compound A),Attorney Docket No. 46696-0217WO1 / 377.WO1.PCT(Compound A) or a pharmaceutically acceptable salt thereof, to the patient, monitoring the patient for a hypersensitivity reaction associated with the administration of the pharmaceutical composition; and if the patient demonstrates the hypersensitivity reaction, discontinuing administration of the pharmaceutical composition.

[0075] Also provided is a method of treating a patient with congenital adrenal hyperplasia (CAH), said method comprising: administering a pharmaceutical composition comprising a therapeutically effective amount of 4-(2-chloro-4-methoxy-5-methylphenyl)-A-[(lN)-2-cyclopropyl-l-(3-fluoro-4- methylphenyl)ethyl]-5-methyl-A-prop-2-ynyl-l,3-thiazol-2-amine (Compound A),(Compound A) to the patient, monitoring the patient for a hypersensitivity reaction associated with the administration of the pharmaceutical composition; and if the patient demonstrates the hypersensitivity reaction, discontinuing administration of the pharmaceutical composition.

[0076] Also provided is a method of treating a patient with congenital adrenal hyperplasia (CAH), said method comprising: administering a therapeutically effective amount of 4-(2-chloro-4-methoxy-5- methylphenyl)-A-[(15)-2-cyclopropyl-l-(3-fluoro-4-methylphenyl)ethyl]-5-methyl-A-prop-2- ynyl-l,3-thiazol-2-amine (Compound A),Attorney Docket No. 46696-0217WO1 / 377.WO1.PCT(Compound A) or a pharmaceutically acceptable salt thereof, to the patient, monitoring the patient for the presence or absence of a hypersensitivity reaction associated with the administration of Compound A, or a pharmaceutically acceptable salt thereof, and if the hypersensitivity reaction is present, discontinuing administration of Compound A, or a pharmaceutically acceptable salt thereof, or if the hypersensitivity reaction is absent, continuing administering the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof, to the patient.

[0077] Also provided is a method of treating a patient with congenital adrenal hyperplasia (CAH), said method comprising: administering a therapeutically effective amount of 4-(2-chloro-4-methoxy-5- methylphenyl)-A-[(15)-2-cyclopropyl-l-(3-fluoro-4-methylphenyl)ethyl]-5-methyl-A-prop-2- ynyl-l,3-thiazol-2-amine (Compound A),(Compound A) to the patient, monitoring the patient for the presence or absence of a hypersensitivity reaction associated with the administration of Compound A, and if the hypersensitivity reaction is present, discontinuing administration of Compound A, or if the hypersensitivity reaction is absent, continuing administering the therapeutically effective amount of Compound A to the patient.

[0078] Also provided is a method of treating a patient with congenital adrenal hyperplasia (CAH), said method comprising:Attomey Docket No. 46696-0217WO1 / 377.WO1.PCT administering a pharmaceutical composition comprising a therapeutically effective amount of 4-(2-chloro-4-methoxy-5-methylphenyl)-A-[(lN)-2-cyclopropyl-l-(3-fluoro-4- methylphenyl)ethyl]-5-methyl-A-prop-2-ynyl-l,3-thiazol-2-amine (Compound A),(Compound A) or a pharmaceutically acceptable salt thereof, to the patient, monitoring the patient for the presence or absence of a hypersensitivity reaction associated with the administration of the pharmaceutical composition, and if the hypersensitivity reaction is present, discontinuing administration of the pharmaceutical composition, or if the hypersensitivity reaction is absent, continuing administering the pharmaceutical composition to the patient.

[0079] Also provided is a method of treating a patient with congenital adrenal hyperplasia (CAH), said method comprising: administering a pharmaceutical composition comprising a therapeutically effective amount of 4-(2-chloro-4-methoxy-5-methylphenyl)-A-[(lN)-2-cyclopropyl-l-(3-fluoro-4- methylphenyl)ethyl]-5-methyl-A-prop-2-ynyl-l,3-thiazol-2-amine (Compound A),(Compound A) to the patient, monitoring the patient for the presence or absence of a hypersensitivity reaction associated with the administration of the pharmaceutical composition, and if the hypersensitivity reaction is present, discontinuing administration of the pharmaceutical composition, or if the hypersensitivity reaction is absent, continuing administering the pharmaceutical composition to the patient.

[0080] Also provided is a method of treating a patient with classic congenital adrenal hyperplasia (CAH), using 4-(2-chloro-4-methoxy-5-methylphenyl)-A-[(lN)-2-cyclopropyl-l-Atorney Docket No. 46696-0217WO1 / 377.WO1.PCT(3-fluoro-4-methylphenyl)ethyl]-5-methyl-A-prop-2-ynyl-l,3-thiazol-2-amine (CompoundA),(Compound A) or a pharmaceutically acceptable salt thereof, as adjunctive treatment to glucocorticoid replacement therapy to control androgens in the patient, said method comprising: administering to the patient a therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof, monitoring the patient for the occurrence of a hypersensitivity reaction associated with the administration of Compound A, or a pharmaceutically acceptable salt thereof, and if the hypersensitivity reaction occurs, discontinuing administration of Compound A, or a pharmaceutically acceptable salt thereof.

[0081] Also provided is a method of treating a patient with classic congenital adrenal hyperplasia (CAH), using 4-(2-chloro-4-methoxy-5-methylphenyl)-A-[(lN)-2-cyclopropyl-l- (3-fluoro-4-methylphenyl)ethyl]-5-methyl-A-prop-2-ynyl-l,3-thiazol-2-amine (Compound A),(Compound A) as adjunctive treatment to glucocorticoid replacement therapy to control androgens in the patient, said method comprising: administering to the patient a therapeutically effective amount of Compound A, monitoring the patient for the occurrence of a hypersensitivity reaction associated with the administration of Compound A, and if the hypersensitivity reaction occurs, discontinuing administration of Compound A.

[0082] Also provided is a method of treating a patient with classic congenital adrenal hyperplasia (CAH), using a pharmaceutical composition comprising a therapeuticallyAttorney Docket No. 46696-0217WO1 / 377.WO1.PCT effective amount of 4-(2-chloro-4-methoxy-5-methylphenyl)-A-[(15)-2-cyclopropyl-l-(3- fluoro-4-methylphenyl)ethyl]-5-methyl-A-prop-2-ynyl-l,3-thiazol-2-amine (Compound A),(Compound A) or a pharmaceutically acceptable salt thereof, as adjunctive treatment to glucocorticoid replacement therapy to control androgens in the patient, said method comprising: administering to the patient the pharmaceutical composition, monitoring the patient for the occurrence of a hypersensitivity reaction associated with the administration of the pharmaceutical composition, and if the hypersensitivity reaction occurs, discontinuing administration of the pharmaceutical composition.

[0083] Also provided is a method of treating a patient with classic congenital adrenal hyperplasia (CAH), using a pharmaceutical composition comprising a therapeutically effective amount of 4-(2-chloro-4-methoxy-5-methylphenyl)-A-[(15)-2-cyclopropyl-l-(3- fluoro-4-methylphenyl)ethyl]-5-methyl-A-prop-2-ynyl-l,3-thiazol-2-amine (Compound A),(Compound A) as adjunctive treatment to glucocorticoid replacement therapy to control androgens in the patient, said method comprising: administering to the patient the pharmaceutical composition, monitoring the patient for the occurrence of a hypersensitivity reaction associated with the administration of the pharmaceutical composition, and if the hypersensitivity reaction occurs, discontinuing administration of the pharmaceutical composition.

[0084] In some embodiments, the method further comprises informing the patient or a medical care worker that administration of Compound A, or a pharmaceutically acceptable salt thereof, to a patient may result in one or more exposure-related adverse reactions.Attorney Docket No. 46696-0217WO1 / 377.WO1.PCT

[0085] In some embodiments, the method further comprises informing the patient or a medical care worker that administration of Compound A, or a pharmaceutically acceptable salt thereof, to a patient may result in increased risk of one or more exposure-related adverse reactions.

[0086] In some embodiments, the method further comprises informing the patient to report to a medical care worker any exposure-related adverse reactions.

[0087] In some embodiments, the one or more exposure-related adverse reactions is chosen from hypersensitivity reactions. In some embodiments, the one or more exposure-related adverse reactions is chosen from hypersensitivity reactions with or without dermatological reactions. In some embodiments, the one or more exposure-related adverse reactions is chosen from hypersensitivity reactions with dermatological reactions. In some embodiments, the one or more exposure-related adverse reactions is chosen from hypersensitivity reactions without dermatological reactions.

[0088] In some embodiments, hypersensitivity is Type I hypersensitivity. In some embodiments, hypersensitivity is Type IV hypersensitivity.

[0089] In some embodiments, the hypersensitivity manifests in one or more symptoms selected from throat tightness, angioedema, and generalized rash.

[0090] In a further embodiment, the hypersensitivity reaction might manifest in one or more symptoms selected from rash pruritic, dermatitis allergic, dermatitis bullous, eczema, laryngitis allergic, and urticaria.

[0091] In some embodiments, the hypersensitivity reaction manifests in one or more immediate-type symptoms. In some embodiments, the hypersensitivity reaction manifests in one or more delayed-type symptoms. In some embodiments, the hypersensitivity reaction manifests in one or more symptoms selected from immediate-type symptoms and delayed- type symptoms.

[0092] In some embodiments, Compound A is administered as the free base.

[0093] In some embodiments, Compound A is administered as a pharmaceutically acceptable salt.

[0094] In some embodiments, the patient is an adult and the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof, is about 200 mg Compound A (based on the weight of the free base) administered daily.

[0095] In some embodiments, the patient is a pediatric patient weighing > 55 kg and the therapeutically effective amount of Compound A, or a pharmaceutically acceptable saltAttorney Docket No. 46696-0217WO1 / 377.WO1.PCT thereof, is administered at an amount of about 200 mg Compound A (based on the weight of the free base) administered daily.

[0096] In some embodiments, the patient is a pediatric patient weighing 20 kg to < 55 kg and the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof, is administered at an amount of about 100 mg Compound A (based on the weight of the free base) administered daily.

[0097] In some embodiments, the patient is a pediatric patient weighing 10 kg to < 20 kg and the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof, is administered at an amount of about 50 mg Compound A (based on the weight of the free base) administered daily.

[0098] In some embodiments, Compound A, or a pharmaceutically acceptable salt thereof, is administered twice daily.

[0099] In some embodiments, Compound A, or a pharmaceutically acceptable salt thereof, is administered twice daily, in the morning and in the evening.

[0100] In some embodiments, the patient is an adult and the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof, is about 100 mg Compound A (based on the weight of the free base) administered twice daily.

[0101] In some embodiments, the patient is a pediatric patient weighing > 55 kg and the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof, is administered at an amount of about 100 mg Compound A (based on the weight of the free base) administered twice daily.

[0102] In some embodiments, the patient is a pediatric patient weighing 20 kg to < 55 kg and the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof, is administered at an amount of about 50 mg Compound A (based on the weight of the free base) administered twice daily.

[0103] In some embodiments, the patient is a pediatric patient weighing 10 kg to < 20 kg and the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof, is administered at an amount of about 25 mg Compound A (based on the weight of the free base) administered twice daily.

[0104] In some embodiments, the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof, is increased. In some embodiments, the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof, is increased, when used concomitantly with strong CYP3 A4 inducers.Attorney Docket No. 46696-0217WO1 / 377.WO1.PCT

[0105] In some embodiments, the increased amount of Compound A, or a pharmaceutically acceptable salt thereof, is double (2-fold) the amount that would be administered to a patient not concomitantly using a strong cytochrome P450 3 A4 (CYP3 A4) inducer.

[0106] In some embodiments, the increased amount of Compound A, or a pharmaceutically acceptable salt thereof, is only increased for one of the daily administrations in case of twice daily administration.

[0107] In some embodiments, the patient is an adult and the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof, is about 400 mg Compound A (based on the weight of the free base) administered daily.

[0108] In some embodiments, the patient is a pediatric patient weighing > 55 kg and the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof, is administered at an amount of about 400 mg Compound A (based on the weight of the free base) administered daily.

[0109] In some embodiments, the patient is a pediatric patient weighing 20 kg to < 55 kg and the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof, is administered at an amount of about 200 mg Compound A (based on the weight of the free base) administered daily.

[0110] In some embodiments, the patient is a pediatric patient weighing 10 kg to < 20 kg and the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof, is administered at an amount of about 100 mg Compound A (based on the weight of the free base) administered daily.

[0111] In some embodiments, the patient is an adult and the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof, is about 200 mg Compound A (based on the weight of the free base) administered twice daily.

[0112] In some embodiments, the patient is a pediatric patient weighing > 55 kg and the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof, is administered at an amount of about 200 mg Compound A (based on the weight of the free base) administered twice daily.

[0113] In some embodiments, the patient is a pediatric patient weighing 20 kg to < 55 kg and the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof, is administered at an amount of about 100 mg Compound A (based on the weight of the free base) administered twice daily.

[0114] In some embodiments, the patient is a pediatric patient weighing 10 kg to < 20 kg and the therapeutically effective amount of Compound A, or a pharmaceutically acceptableAttorney Docket No. 46696-0217WO1 / 377.WO1.PCT salt thereof, is administered at an amount of about 50 mg Compound A (based on the weight of the free base) administered twice daily.

[0115] In some embodiments, the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof, is adjusted to a double dose in the evening.

[0116] In some embodiments, the patient is an adult and the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof, is about 100 mg of Compound A (based on the weight of the free base) administered in the morning and about 200 mg of Compound A (based on the weight of the free base) administered in the evening.

[0117] In some embodiments, the patient is a pediatric patient weighing > 55 kg and the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof, is about 100 mg of Compound A (based on the weight of the free base) administered in the morning and about 200 mg of Compound A (based on the weight of the free base) administered in the evening, .

[0118] In some embodiments, the patient is a pediatric patient weighing 20 kg to < 55 kg and the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof, is about 50 mg of Compound A (based on the weight of the free base) administered in the morning and about 100 mg of Compound A (based on the weight of the free base) administered in the evening.

[0119] In some embodiments, the patient is a pediatric patient weighing 10 kg to < 20 kg and the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof, is about 25 mg of Compound A (based on the weight of the free base) administered in the morning and about 50 mg of Compound A (based on the weight of the free base) administered in the evening.

[0120] In some embodiments, the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof, is adjusted to a double dose in the evening, but no administration of a Compound A, or a pharmaceutically acceptable salt thereof, in the morning.

[0121] In some embodiments, the patient is an adult and the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof, is about 200 mg of Compound A (based on the weight of the free base) administered in the evening.

[0122] In some embodiments, the patient is a pediatric patient weighing > 55 kg and the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof, is about 200 mg of Compound A (based on the weight of the free base) administered in the evening.Attorney Docket No. 46696-0217WO1 / 377.WO1.PCT

[0123] In some embodiments, the patient is a pediatric patient weighing 20 kg to < 55 kg and the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof, is about 100 mg of Compound A (based on the weight of the free base) administered in the evening.

[0124] In some embodiments, the patient is a pediatric patient weighing 10 kg to < 20 kg and the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof, is about 50 mg of Compound A (based on the weight of the free base) administered in the evening.

[0125] Several dosing regimens for the administration of Compound A, or a pharmaceutically acceptable salt thereof, for a patient not concomitantly using a strong cytochrome P450 3 A4 (CYP3 A4) inducer are described in published patent applications WO 2021 / 252669, WO 2024 / 206769 and WO 2024 / 233525, which are herewith incorporated by reference in their entireties.

[0126] In some embodiments, Compound A, or a pharmaceutically acceptable salt thereof, is administered orally.

[0127] In some embodiments, Compound A, or a pharmaceutically acceptable salt thereof, is administered with food.

[0128] In some embodiments, Compound A, or a pharmaceutically acceptable salt thereof, is administered with a meal.

[0129] In some embodiments, Compound A, or a pharmaceutically acceptable salt thereof, is administered orally, twice daily with a meal in the morning and evening.

[0130] In some embodiments, Compound A, or a pharmaceutically acceptable salt thereof, is administered as an adjunctive treatment to glucocorticoid replacement therapy.

[0131] In some embodiments, the glucocorticoid replacement therapy is administered daily to the patient.

[0132] In some embodiments, the glucocorticoid replacement therapy comprises once daily administration or multiple daily administrations of a glucocorticoid.

[0133] In some embodiments, the glucocorticoid is selected from hydrocortisone, prednisone, methylprednisolone, prednisolone, and dexamethasone, or a combination thereof.

[0134] In some embodiments, the administration of Compound A, or a pharmaceutically acceptable salt thereof, improves androgen control in the patient. In some embodiments, the administration of Compound A, or a pharmaceutically acceptable salt thereof, enables a reduced glucocorticoid dose in the patient. In some embodiments, the administration of Compound A, or a pharmaceutically acceptable salt thereof, enables a reduced glucocorticoidAttorney Docket No. 46696-0217WO1 / 377.WO1.PCT dose while maintaining androgen control in the patient. In some embodiments, the administration of Compound A, or a pharmaceutically acceptable salt thereof, improves androgen control and enables a reduced glucocorticoid dose while maintaining androgen control in the patient. In some embodiments, the administration of Compound A, or a pharmaceutically acceptable salt thereof, enables androgen control in the patient.

[0135] In some embodiments, the patient is an adult patient. In some embodiments, the patient is a pediatric patient.

[0136] In some embodiments, the administration of Compound A, or a pharmaceutically acceptable salt thereof, improves androgen control and / or enables a reduced glucocorticoid dose while maintaining androgen control in pediatric patients with classic CAH.

[0137] In some embodiments, the administration of Compound A, or a pharmaceutically acceptable salt thereof, reduces androgen levels and / or enables a reduced glucocorticoid dose while maintaining androgen control in adult patients with CAH.

[0138] In some embodiments, CAH is classic CAH.

[0139] In some embodiments, Compound A may be used to treat or prevent adrenal myelolipoma in patients with CAH.

[0140] While it may be possible for the compounds and salts of the subject disclosure to be administered as the raw chemical, it is also possible to present them as a pharmaceutical formulation. Accordingly, provided herein are pharmaceutical formulations which comprise one or more of certain compounds disclosed herein, or one or more pharmaceutically acceptable salts thereof, together with one or more pharmaceutically acceptable carriers thereof and optionally one or more other therapeutic ingredients. The carrier(s) must be “acceptable” in the sense of being compatible with the other ingredients of the formulation and not deleterious to the recipient thereof. Proper formulation is dependent upon the route of administration chosen. Any of the well-known techniques, carriers, and excipients may be used as suitable and as understood in the art. The pharmaceutical formulations disclosed herein may be manufactured in any manner known in the art, e.g., by means of conventional mixing, dissolving, granulating, dragee-making, levigating, emulsifying, encapsulating, entrapping, or compression processes. Exemplary pharmaceutical compositions are disclosed in published patent application WO 2021 / 115555, which is hereby incorporated by reference in its entirety.

[0141] In one embodiment, a pharmaceutical composition for Compound A, or a pharmaceutically acceptable salt thereof, is in the form of a self-emulsifying drug deliveryAttorney Docket No. 46696-0217WO1 / 377.WO1.PCT system formulation comprising an oily phase vehicle, a non-ionic surfactant, and optionally an emulsifying agent and / or a solubilizing agent.

[0142] In one embodiment, the formulation is in the form of a capsule.

[0143] In one embodiment, the pharmaceutical composition comprises(a) about 5 wt% to about 15 wt% of Compound A, or a pharmaceutically acceptable salt thereof, based on the weight of the free base;(b) about 35 wt% to about 45 wt% of an oily phase vehicle;(c) about 15 wt% to about 25 wt% of an emulsifying agent;(d) about 15 wt% to about 25 wt% of a nonionic surfactant; and(e) about 5 wt% to about 15 wt% of a solubilizing agent.

[0144] In one embodiment, the pharmaceutical composition comprises(a) about 10 wt% of Compound A, or a pharmaceutically acceptable salt thereof, based on the weight of the free base;(b) about 39 wt% of an oily phase vehicle;(c) about 20 wt% of an emulsifying agent;(d) about 19 wt% of a nonionic surfactant; and(e) about 11 wt% of a solubilizing agent.

[0145] In one embodiment, the oily phase vehicle is medium-chain triglycerides. In one embodiment, the medium-chain triglycerides are caprylic / capric triglycerides.

[0146] In one embodiment, the emulsifying agent is propylene glycol di capryl ate / di caprate.

[0147] In one embodiment, the non-ionic surfactant is lauroyl polyoxyl-32 glycerides.

[0148] In one embodiment, the solubilizing agent is vitamin E polyethylene glycol succinate.

[0149] In one embodiment, the pharmaceutical composition is in the form of a capsule and comprises 25 mg of Compound A, or a pharmaceutically acceptable salt thereof (based on the weight of the free base). In one embodiment, the pharmaceutical composition is in the form of a capsule and comprises 50 mg of Compound A, or a pharmaceutically acceptable salt thereof (based on the weight of the free base). In one embodiment, the pharmaceutical composition is in the form of a capsule and comprises 100 mg of Compound A, or a pharmaceutically acceptable salt thereof (based on the weight of the free base).

[0150] In one embodiment, when the patient is administered 200 mg of Compound A (based on the weight of the free base) at one time point AND if a pharmaceutical composition comprising 200 mg of Compound A (based on the weight of the free base) in one form does not exist, then the patient has to be administered two dosage forms of the pharmaceuticalAttorney Docket No. 46696-0217WO1 / 377.WO1.PCT composition comprising 100 mg of Compound A, or a pharmaceutically acceptable salt thereof (based on the weight of the free base), at that time point.

[0151] In another embodiment, a pharmaceutical composition for Compound A, or a pharmaceutically acceptable salt thereof, is an oral solution dosage form comprising a liquid vehicle and one or more of a sweetener, an anti-oxidant, and a flavor, and optionally a surfactant.

[0152] In one embodiment, the liquid pharmaceutical composition comprises(a) about 4 w / v% to about 6 w / v% of Compound A, or a pharmaceutically acceptable salt thereof, based on the weight of the free base;(b) about 0.1 w / v% to about 0.2 w / v% of a sweetener;(c) about 0.1 w / v% to about 0.2 w / v% of an anti-oxidant;(d) about 0.05 w / v% to about 0.2 w / v% of a flavor; and(e) about 92 w / v% to about 97 w / v% of a liquid vehicle.

[0153] In one embodiment thereof, the liquid pharmaceutical composition comprises(a) about 5 w / v% of Compound A, or a pharmaceutically acceptable salt thereof, based on the weight of the free base;(b) about 0.15 w / v% of a sweetener;(c) about 0.17 w / v% of an anti-oxidant;(d) about 0.1 w / v% of a flavor; and(e) about 94.6 w / v% of a liquid vehicle.

[0154] In one embodiment, the liquid pharmaceutical composition comprises(a) about 4 w / v% to about 6 w / v% of Compound A, or a pharmaceutically acceptable salt thereof, based on the weight of the free base;(b) about 0.1 w / v% to about 0.2 w / v% of a sweetener;(c) about 0.1 w / v% to about 0.2 w / v% of an anti-oxidant;(d) about 0.05 w / v% to about 0.2 w / v% of a flavor;(e) about 15 w / v% to about 25 w / v% of a surfactant; and(f) about 70 w / v% to about 80 w / v% of a liquid vehicle.

[0155] In one embodiment thereof, the liquid pharmaceutical composition comprises(a) about 5 w / v% of Compound A, or a pharmaceutically acceptable salt thereof, based on the weight of the free base;(b) about 0.15 w / v% of a sweetener;(c) about 0.17 w / v% of an anti-oxidant;(d) about 0.1 w / v% of a flavor;Attorney Docket No. 46696-0217WO1 / 377.WO1.PCT(e) about 20 w / v% of a surfactant; and(f) about 75 w / v% of a liquid vehicle.

[0156] In one embodiment, the sweetener is saccharin.

[0157] In one embodiment, the anti-oxidant is butylated hydroxytoluene.

[0158] In one embodiment, the flavor is an orange flavor.

[0159] In one embodiment, the surfactant is oleoyl polyoxyl-6-glycerides.

[0160] In one embodiment, the liquid vehicle is medium-chain triglycerides. In one embodiment, the medium-chain triglycerides are caprylic / capric triglycerides.

[0161] In some embodiments, the hypersensitivity reaction is associated with the administration of Compound A, or a pharmaceutically acceptable salt thereof. In some embodiments, the hypersensitivity reaction is associated with the administration of the pharmaceutical composition comprising Compound A, or a pharmaceutically acceptable salt thereof, as well as certain excipients.

[0162] In some embodiments, the pharmaceutical composition is a capsule and comprises 25 mg, 50 mg, or 100 mg of Compound A as free base, as well. Inactive ingredients of said composition include lauroyl polyoxyl-32 glycerides, medium chain triglycerides, propylene glycol dicaprylate / dicaprate, and Vitamin E polyethylene glycol succinate. The capsule shell contains gelatin, glycerin, red iron oxide, Sorbitol glycerin blend, titanium dioxide, and yellow iron oxide.

[0163] In some embodiments, the pharmaceutical composition is an oral solution and contains 50 mg / mL Compound A as free base. Inactive ingredients include butylated hydroxytoluene, medium-chain triglycerides, oleoyl polyoxyl glycerides, orange flavor, and saccharin.

[0164] In some embodiments, the hypersensitivity reaction is a clinically significant hypersensitivity reaction. In some embodiments, the clinically significant hypersensitivity reaction is not momentary and requires medical attention by a medical care worker.

[0165] In some embodiments, if a clinically significant hypersensitivity reaction occurs, appropriate therapy for the patient should be initiated. The appropriate therapy is to be determine by the medical care worker and will depend on the nature of the hypersensitivity reaction and the severity of the symptoms, and might include symptomatic treatment.

[0166] All the aforementioned embodiments for the methods of treatment according to the present disclosure are equally applicable to:Compound A, or a pharmaceutically acceptable salt thereof, for use in a method of treatment according to the present disclosure;Attorney Docket No. 46696-0217WO1 / 377.WO1.PCT the use of Compound A, or a pharmaceutically acceptable salt thereof, for the manufacture of a medicament for a method of treatment according to the present disclosure; the use of Compound A, or a pharmaceutically acceptable salt thereof, in a method of treatment according to the present disclosure; the use of a pharmaceutical composition comprising Compound A, or a pharmaceutically acceptable salt thereof, in a method of treatment according to the present disclosure; or a pharmaceutical composition comprising Compound A, or a pharmaceutically acceptable salt thereof, for use in a method of treatment according to the present disclosure.The different embodiments of methods of treatments depicted in the claims can be reformulated into the appropriate claim format, which shall be considered to form part of the disclosure. Some of these aspects might be further described herein, but this description should not be construed as limiting.

[0167] Examples of embodiments of the present disclosure are provided in the following examples. The following examples are presented only by way of illustration and to assist one of ordinary skill in using the disclosure. The examples are not intended in any way to otherwise limit the scope of the disclosure.EXAMPLESExample 1Study 1: Double-Blind Placebo-Controlled Treatment Period (Day 1 to Week 24)

[0168] Potential hypersensitivity reactions occurred in 9 subjects (7.4%) in the treatment group and 2 subjects (3.4%) in the placebo group during the double-blind period (Table 1). The events were predominantly mild skin reactions that were considered unlikely or not related to study treatment and did not lead to study treatment interruption or discontinuation. None of the events was serious or of severe intensity. There was no pattern with respect to the timing of the events. Brief descriptions of events in the treatment group that resulted in discontinuation or interruption of study treatment as well as an event of bullous dermatitis are described below.

[0169] One subject in the treatment group discontinued study treatment after Month 18 due to a rash (verbatim term: skin rash), listed under the AE category of “hypersensitivity,” that started during the double-blind period. The rash was reported to be mild, intermittent, andAttorney Docket No. 46696-0217WO1 / 377.WO1.PCT possibly related to study treatment. The event started on Day 166, and the subject started the open-label period on Day 172. No treatment was given initially for the rash until Day 336, when clobetasol was initiated; the subject subsequently was treated with various other topical corticosteroids, hydroquinone, and tretinoin, but the rash persisted. The subject then stopped the study medication for about 4 weeks. Following this, the subject switched from hydrocortisone to prednisone and resumed the study drug but subsequently self-discontinued the study drug due to concern over the rash. The subject then discontinued study treatment on Day 589 during the open-label extension period, after completing the initial 18-month study. After discontinuing crinecerfont this second time, the rash improved. The rash was not resolved as of the data cutoff date (Day 671).

[0170] One subject in the treatment group interrupted study treatment dosing due to a moderate-grade, nonserious TEAE of urticaria, listed under the AE categories of “angioedema” and “hypersensitivity,” with onset on Study Day 4 that was reported by the investigator as “hives post-COVID covering entire body.” The event was considered not related to study treatment and resolved after 12 days with treatment (diphenhydramine; cetirizine). There was no recurrence of urticaria in this subject following resumption of treatment.

[0171] One subject in the treatment group experienced an event of dermatitis bullous, listed under the AE categories of “severe cutaneous adverse reactions” and “hypersensitivity.” This was a cutaneous rash with bullous eruptions that was reported as mild and not related to study treatment. No treatment was administered. The event began on Study Day 76 and lasted approximately 1 week. The rash resolved without interruption or discontinuation of study treatment and did not recur.Table 1: Potential Hypersensitivity Adverse EventsAttorney Docket No. 46696-0217WO1 / 377.WO1.PCTAE=adverse event; DB=double-blind; MedDRA=Medical Dictionary for Regulatory Activities; PT=preferred term; TEAE=treatment-emergent adverse event- TEAEs are defined as those that occurred on or after first dose date of study drug and through the date of the last dose of study drug + 28 days. - Data shown are the number of subjects reporting at least 1 occurrence of the event for each AE category and PT. The same event (PT) can fall under multiple categories. - Percentages are based on the number of subjects in the safety analysis set (N). - PTs within each AE category are sorted by descending frequency within the treatment group. - TEAE categories of were defined using standardized MedDRA queries.Open-Label Treatment Period (Week 24 to Month 12)

[0172] In the open-label period, the incidence and types of potential hypersensitivity TEAEs was consistent overall with the double-blind period. Events were reported for 8 subjects (6.8%) in the treatment / treatment group and 3 subjects (5.3%) in the placebo / treatment group. The events were generally skin-related conditions, such as urticaria, eczema, pruritus, or rash. All events were mild or moderate in severity.

[0173] One event of mild urticaria that was considered possibly related to study treatment led to study treatment discontinuation in a subject in the treatment / treatment group.Following discontinuation of treatment, the event was ongoing as of the data cutoff date. No other TEAEs led to study treatment discontinuation. None of the potential hypersensitivity events in the treatment / treatment group were serious.Attorney Docket No. 46696-0217WO1 / 377.WO1.PCTExample 2Study 2: Double-Blind Placebo-Controlled Treatment Period (Day 1 to Week 28)

[0174] Five subjects (7.2%) in the treatment group and 1 subject (3.0%) in the placebo group had a TEAE of a potential hypersensitivity reaction during the double-blind period (Table 2). All of the events were mild or moderate, nonserious, and characterized as a single continuous episode that resolved without action taken with respect to study treatment. All events were considered by the investigators to be unlikely or not related to study treatment, with a causative agent (cat, grass, virus) reported as part of the verbatim report for some events.Table 2: Potential Hypersensitivity Adverse EventsAE=adverse event; DB=double-blind; MedDRA=Medical Dictionary for Regulatory Activities; PT=preferred term; TEAE=treatment-emergent adverse event- TEAEs are defined as those that occurred on or after first dose date of study drug and through the date of the last dose of study drug + 28 days. - Data shown are the number of subjects reporting at least 1 occurrence of the event. The same event (PT) can fall under multiple categories. - Percentages are based on the number of subjects in the safety analysis set (N). - Preferred terms within each AE category are sorted by descending frequency within the treatment group. - TEAE categories of were defined using standardized MedDRA queries.Attorney Docket No. 46696-0217WO1 / 377.WO1.PCTOpen-Label Treatment Period (Week 28 to Week 52)

[0175] Three subjects (4.5%) in the treatment / treatment group and no subjects in the placebo / treatment group had a TEAE of a potential hypersensitivity reaction during the open-label period. The 3 events (eye swelling, rash, and hypersensitivity) were all considered to be not related to study treatment and were mild or moderate and nonserious. One event was ongoing as of the data cutoff date; the other events had resolved. No action was taken with respect to study treatment administration for any of the events.

[0176] The various embodiments described above can be combined to provide further embodiments. All of the U.S. patents, U.S. patent application publications, U.S. patent applications, foreign patents, foreign patent applications and non-patent publications referred to in this specification and / or listed in the Application Data Sheet are incorporated herein by reference in their entirety. Aspects of the embodiments can be modified, if necessary, to employ concepts of the various patents, applications, and publications to provide yet further embodiments.

[0177] These and other changes can be made to the embodiments in light of the above-detailed description. In general, in the following claims, the terms used should not be construed to limit the claims to the specific embodiments disclosed in the specification and the claims, but should be construed to include all possible embodiments, along with the full scope of equivalents to which such claims are entitled. Accordingly, the claims are not limited by the disclosure.

Claims

Attorney Docket No. 46696-0217WO1 / 377.WO1.PCTWhat is claimed is:

1. A method of administering 4-(2-chloro-4-methoxy-5-methylphenyl)-A-[(15)-2- cyclopropyl-l-(3-fluoro-4-methylphenyl)ethyl]-5-methyl-A-prop-2-ynyl-l,3-thiazol- 2-amine (Compound A),(Compound A) or a pharmaceutically acceptable salt thereof, to a patient, said method comprising: administering to the patient a therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof; monitoring the patient for a hypersensitivity reaction associated with the administration of Compound A, or a pharmaceutically acceptable salt thereof; and discontinuing administration of Compound A, or a pharmaceutically acceptable salt thereof, if the patient is not able to tolerate the hypersensitivity reaction.

2. The method of claim 1, wherein the patient has congenital adrenal hyperplasia (CAH).

3. The method of claim 1 or 2, wherein the hypersensitivity reaction manifests in one or more symptoms selected from throat tightness, angioedema, and generalized rash.

4. The method of any one of the preceding claims, wherein the hypersensitivity reaction manifests in one or more symptoms selected from immediate-type symptoms and delayed-type symptoms.

5. The method of any one of the preceding claims, wherein the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof, is: for an adult, about 100 mg of Compound A (based on the weight of the free base) administered twice daily; for a pediatric patient having a body mass of > 55 kg, about 100 mg of Compound A (based on the weight of the free base) administered twice daily;Attorney Docket No. 46696-0217WO1 / 377.WO1.PCT for a pediatric patient having a body mass of 20 kg to < 55 kg, about 50 mg of Compound A (based on the weight of the free base) administered twice daily; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 25 mg of Compound A (based on the weight of the free base) administered twice daily.

6. The method of any one of claims 1 to 4, wherein the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof, is: for an adult, about 200 mg of Compound A (based on the weight of the free base) administered twice daily; for a pediatric patient having a body mass of > 55 kg, about 200 mg of Compound A (based on the weight of the free base) administered twice daily; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 100 mg of Compound A (based on the weight of the free base) administered twice daily; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 50 mg of Compound A (based on the weight of the free base) administered twice daily.

7. The method of any one of claims 1 to 4, wherein the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof, is: for an adult, about 100 mg of Compound A (based on the weight of the free base) administered in the morning and about 200 mg of Compound A (based on the weight of the free base) administered in the evening; for a pediatric patient having a body mass of > 55 kg, about 100 mg of Compound A (based on the weight of the free base) administered in the morning and about 200 mg of Compound A (based on the weight of the free base) administered in the evening; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 50 mg of Compound A (based on the weight of the free base) administered in the morning and about 100 mg of Compound A (based on the weight of the free base) administered in the evening; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 25 mg of Compound A (based on the weight of the free base) administered in the morning and about 50 mg of Compound A (based on the weight of the free base) administered in the evening.Attorney Docket No. 46696-0217WO1 / 377.WO1.PCT8. The method of any one of claims 1 to 4, wherein the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof, is: for an adult, about 200 mg of Compound A (based on the weight of the free base) administered in the evening; for a pediatric patient having a body mass of > 55 kg, about 200 mg of Compound A (based on the weight of the free base) administered in the evening; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 100 mg of Compound A (based on the weight of the free base) administered in the evening; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 50 mg of Compound A (based on the weight of the free base) administered in the evening.

9. The method of any one of the preceding claims, wherein Compound A, or a pharmaceutically acceptable salt thereof is administered as an adjunctive treatment to glucocorticoid replacement therapy.

10. The method of claim 9, wherein the glucocorticoid replacement therapy is administered daily to the patient.

11. The method of claim 10, wherein the glucocorticoid replacement therapy comprises once daily administration or multiple daily administrations of a glucocorticoid.

12. The method of claim 11, wherein the glucocorticoid is selected from hydrocortisone, prednisone, methylprednisolone, prednisolone, and dexamethasone, or a combination thereof.

13. The method of any one of the preceding claims, wherein Compound A, or a pharmaceutically acceptable salt thereof, is administered orally.

14. The method of any one of the preceding claims, wherein Compound A, or a pharmaceutically acceptable salt thereof, is administered with food.Attorney Docket No. 46696-0217WO1 / 377.WO1.PCT15. The method of any one of the preceding claims, wherein the administration of Compound A, or a pharmaceutically acceptable salt thereof, improves androgen control and / or enables a reduced glucocorticoid dose in the patient.

16. The method of any one of claims 2 to 15, wherein the CAH is classic CAH.

17. A method of administering 4-(2-chloro-4-methoxy-5-methylphenyl)-A-[(15)-2- cyclopropyl-l-(3-fluoro-4-methylphenyl)ethyl]-5-methyl-A-prop-2-ynyl-l,3-thiazol- 2-amine (Compound A),(Compound A) to a patient, said method comprising: administering to the patient a therapeutically effective amount of Compound A; monitoring the patient for a hypersensitivity reaction associated with the administration of Compound A; and discontinuing administration of Compound A, if the patient is not able to tolerate the hypersensitivity reaction.

18. The method of claim 17, wherein the patient has congenital adrenal hyperplasia (CAH).

19. The method of claim 17 or 18, wherein the hypersensitivity reaction manifests in one or more symptoms selected from throat tightness, angioedema, and generalized rash.

20. The method of any one of claims 17 to 19, wherein the hypersensitivity reaction manifests in one or more symptoms selected from immediate-type symptoms and delayed-type symptoms.

21. The method of any one of claims 17 to 20, wherein the therapeutically effective amount of Compound A is:Attorney Docket No. 46696-0217WO1 / 377.WO1.PCT for an adult, about 100 mg of Compound A administered twice daily; for a pediatric patient having a body mass of > 55 kg, about 100 mg of Compound A administered twice daily; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 50 mg of Compound A administered twice daily; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 25 mg of Compound A administered twice daily.

22. The method of any one of claims 17 to 20, wherein the therapeutically effective amount of Compound A is: for an adult, about 200 mg of Compound A administered twice daily; for a pediatric patient having a body mass of > 55 kg, about 200 mg of Compound A administered twice daily; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 100 mg of Compound A administered twice daily; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 50 mg of Compound A administered twice daily.

23. The method of any one of claims 17 to 20, wherein the therapeutically effective amount of Compound A is: for an adult, about 100 mg of Compound A administered in the morning and about 200 mg of Compound A administered in the evening; for a pediatric patient having a body mass of > 55 kg, about 100 mg of Compound A administered in the morning and about 200 mg of Compound A administered in the evening; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 50 mg of Compound A administered in the morning and about 100 mg of Compound A administered in the evening; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 25 mg of Compound A administered in the morning and about 50 mg of Compound A administered in the evening.

24. The method of any one of claims 17 to 20, wherein the therapeutically effective amount of Compound A is:Attorney Docket No. 46696-0217WO1 / 377.WO1.PCT for an adult, about 200 mg of Compound A administered in the evening; for a pediatric patient having a body mass of > 55 kg, about 200 mg of Compound A administered in the evening; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 100 mg of Compound A administered in the evening; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 50 mg of Compound A administered in the evening.

25. The method of any one of claims 17 to 24, wherein Compound A is administered as an adjunctive treatment to glucocorticoid replacement therapy.

26. The method of claim 25, wherein the glucocorticoid replacement therapy is administered daily to the patient.

27. The method of claim 26, wherein the glucocorticoid replacement therapy comprises once daily administration or multiple daily administrations of a glucocorticoid.

28. The method of claim 27, wherein the glucocorticoid is selected from hydrocortisone, prednisone, methylprednisolone, prednisolone, and dexamethasone, or a combination thereof.

29. The method of any one of claims 17 to 28, wherein Compound A is administered orally.

30. The method of any one of claims 17 to 29, wherein Compound A is administered with food.

31. The method of any one of claims 17 to 30, wherein the administration of Compound A improves androgen control and / or enables a reduced glucocorticoid dose in the patient.

32. The method of any one of claims 18 to 31, wherein the CAH is classic CAH.Attorney Docket No. 46696-0217WO1 / 377.WO1.PCT33. A method of administering a pharmaceutical composition comprising a therapeutically effective amount of 4-(2-chloro-4-methoxy-5-methylphenyl)-7V-[(15')- 2-cyclopropyl- 1 -(3-fluoro-4-methylphenyl)ethyl]-5-methyl-7V-prop-2-ynyl- 1 ,3- thiazol-2-amine (Compound A),(Compound A) or a pharmaceutically acceptable salt thereof, to a patient, said method comprising: administering to the patient the pharmaceutical composition; monitoring the patient for a hypersensitivity reaction associated with the administration of the pharmaceutical composition; and discontinuing administration of the pharmaceutical composition, if the patient is not able to tolerate the hypersensitivity reaction.

34. The method of claim 33, wherein the patient has congenital adrenal hyperplasia(CAH).

35. The method of claim 33 or 34, wherein the hypersensitivity reaction manifests in one or more symptoms selected from throat tightness, angioedema, and generalized rash.

36. The method of any one of claims 33 to 35, wherein the hypersensitivity reaction manifests in one or more symptoms selected from immediate-type symptoms and delayed-type symptoms.

37. The method of any one of claims 33 to 36, wherein the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof, is: for an adult, about 100 mg of Compound A (based on the weight of the free base) administered twice daily; for a pediatric patient having a body mass of > 55 kg, about 100 mg of Compound A (based on the weight of the free base) administered twice daily; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 50 mg of Compound A (based on the weight of the free base) administered twice daily; andAttorney Docket No. 46696-0217WO1 / 377.WO1.PCT for a pediatric patient having a body mass of 10 kg to < 20 kg, about 25 mg of Compound A (based on the weight of the free base) administered twice daily.

38. The method of any one of claims 33 to 36, wherein the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof, is: for an adult, about 200 mg of Compound A (based on the weight of the free base) administered twice daily; for a pediatric patient having a body mass of > 55 kg, about 200 mg of Compound A (based on the weight of the free base) administered twice daily; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 100 mg of Compound A (based on the weight of the free base) administered twice daily; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 50 mg of Compound A (based on the weight of the free base) administered twice daily.

39. The method of any one of claims 33 to 36, wherein the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof, is: for an adult, about 100 mg of Compound A (based on the weight of the free base) administered in the morning and about 200 mg of Compound A (based on the weight of the free base) administered in the evening; for a pediatric patient having a body mass of > 55 kg, about 100 mg of Compound A (based on the weight of the free base) administered in the morning and about 200 mg of Compound A (based on the weight of the free base) administered in the evening; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 50 mg of Compound A (based on the weight of the free base) administered in the morning and about 100 mg of Compound A (based on the weight of the free base) administered in the evening; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 25 mg of Compound A (based on the weight of the free base) administered in the morning and about 50 mg of Compound A (based on the weight of the free base) administered in the evening.

40. The method of any one of claims 33 to 36, wherein the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof, is:Attorney Docket No. 46696-0217WO1 / 377.WO1.PCT for an adult, about 200 mg of Compound A (based on the weight of the free base) administered in the evening; for a pediatric patient having a body mass of > 55 kg, about 200 mg of Compound A (based on the weight of the free base) administered in the evening; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 100 mg of Compound A (based on the weight of the free base) administered in the evening; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 50 mg of Compound A (based on the weight of the free base) administered in the evening.

41. The method of any one of claims 33 to 40, wherein the pharmaceutical composition is administered as an adjunctive treatment to glucocorticoid replacement therapy.

42. The method of claim 41, wherein the glucocorticoid replacement therapy is administered daily to the patient.

43. The method of claim 42, wherein the glucocorticoid replacement therapy comprises once daily administration or multiple daily administrations of a glucocorticoid.

44. The method of claim 43, wherein the glucocorticoid is selected from hydrocortisone, prednisone, methylprednisolone, prednisolone, and dexamethasone, or a combination thereof.

45. The method of any one of claims 33 to 44, wherein the pharmaceutical composition is administered orally.

46. The method of any one of claims 33 to 45, wherein the pharmaceutical composition is administered with food.

47. The method of any one of claims 33 to 46, wherein the administration of the pharmaceutical composition improves androgen control and / or enables a reduced glucocorticoid dose in the patient.

48. The method of any one of claims 34 to 47, wherein the CAH is classic CAH.Attorney Docket No. 46696-0217WO1 / 377.WO1.PCT49. A method of administering a pharmaceutical composition comprising a therapeutically effective amount of 4-(2-chloro-4-methoxy-5-methylphenyl)-7V-[(15')- 2-cyclopropyl- 1 -(3-fluoro-4-methylphenyl)ethyl]-5-methyl-7V-prop-2-ynyl- 1 ,3- thiazol-2-amine (Compound A),(Compound A) to a patient, said method comprising: administering to the patient the pharmaceutical composition; monitoring the patient for a hypersensitivity reaction associated with the administration of the pharmaceutical composition; and discontinuing administration of the pharmaceutical composition if the patient is not able to tolerate the hypersensitivity reaction.

50. The method of claim 49, wherein the patient has congenital adrenal hyperplasia(CAH).

51. The method of claim 49 or 50, wherein the hypersensitivity reaction manifests in one or more symptoms selected from throat tightness, angioedema, and generalized rash.

52. The method of any one of claims 49 to 51, wherein the hypersensitivity reaction manifests in one or more symptoms selected from immediate-type symptoms and delayed-type symptoms.

53. The method of any one of claims 49 to 52, wherein the therapeutically effective amount of Compound A is: for an adult, about 100 mg of Compound A administered twice daily; for a pediatric patient having a body mass of > 55 kg, about 100 mg of Compound A administered twice daily; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 50 mg of Compound A administered twice daily; andAttorney Docket No. 46696-0217WO1 / 377.WO1.PCT for a pediatric patient having a body mass of 10 kg to < 20 kg, about 25 mg of Compound A administered twice daily.

54. The method of any one of claims 49 to 52, wherein the therapeutically effective amount of Compound A is: for an adult, about 200 mg of Compound A administered twice daily; for a pediatric patient having a body mass of > 55 kg, about 200 mg of Compound A administered twice daily; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 100 mg of Compound A administered twice daily; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 50 mg of Compound A administered twice daily.

55. The method of any one of claims 49 to 52, wherein the therapeutically effective amount of Compound A is: for an adult, about 100 mg of Compound A administered in the morning and about 200 mg of Compound A administered in the evening; for a pediatric patient having a body mass of > 55 kg, about 100 mg of Compound A administered in the morning and about 200 mg of Compound A administered in the evening; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 50 mg of Compound A administered in the morning and about 100 mg of Compound A administered in the evening; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 25 mg of Compound A administered in the morning and about 50 mg of Compound A administered in the evening.

56. The method of any one of claims 49 to 52, wherein the therapeutically effective amount of Compound A is: for an adult, about 200 mg of Compound A administered in the evening; for a pediatric patient having a body mass of > 55 kg, about 200 mg of Compound A administered in the evening; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 100 mg of Compound A administered in the evening; andAttorney Docket No. 46696-0217WO1 / 377.WO1.PCT for a pediatric patient having a body mass of 10 kg to < 20 kg, about 50 mg of Compound A administered in the evening.

57. The method of any one of claims 49 to 56, wherein the pharmaceutical composition is administered as an adjunctive treatment to glucocorticoid replacement therapy.

58. The method of claim 57, wherein the glucocorticoid replacement therapy is administered daily to the patient.

59. The method of claim 58, wherein the glucocorticoid replacement therapy comprises once daily administration or multiple administrations of a glucocorticoid.

60. The method of claim 59, wherein the glucocorticoid is selected from hydrocortisone, prednisone, methylprednisolone, prednisolone, and dexamethasone, or a combination thereof.

61. The method of any one of claims 49 to 60, wherein the pharmaceutical composition is administered orally.

62. The method of any one of claims 49 to 61, wherein the pharmaceutical composition is administered with food.

63. The method of any one of claims 49 to 62, wherein the administration of the pharmaceutical composition improves androgen control and / or enables a reduced glucocorticoid dose in the patient.

64. The method of any one of claims 50 to 63, wherein the CAH is classic CAH.

65. A method of treating a patient with congenital adrenal hyperplasia (CAH), said method comprising: administering to the patient a therapeutically effective amount of 4-(2-chloro- 4-methoxy-5-methylphenyl)-A-[(15)-2-cyclopropyl-l-(3-fluoro-4- methylphenyl)ethyl]-5-methyl-A-prop-2-ynyl-l,3-thiazol-2-amine (Compound A),Attorney Docket No. 46696-0217WO1 / 377.WO1.PCT(Compound A) or a pharmaceutically acceptable salt thereof; monitoring the patient for a hypersensitivity reaction associated with the administration of Compound A, or a pharmaceutically acceptable salt thereof; and discontinuing administration of Compound A, or a pharmaceutically acceptable salt thereof, if the patient is not able to tolerate the hypersensitivity reaction.

66. The method of claim 65, wherein the hypersensitivity reaction manifests in one or more symptoms selected from throat tightness, angioedema, and generalized rash.

67. The method of claim 65 or 66, wherein the hypersensitivity reaction manifests in one or more symptoms selected from immediate-type symptoms and delayed-type symptoms.

68. The method of any one of claims 65 to 67, wherein the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof, is: for an adult, about 100 mg of Compound A (based on the weight of the free base) administered twice daily; for a pediatric patient having a body mass of > 55 kg, about 100 mg of Compound A (based on the weight of the free base) administered twice daily; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 50 mg of Compound A (based on the weight of the free base) administered twice daily; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 25 mg of Compound A (based on the weight of the free base) administered twice daily.

69. The method of any one of claims 65 to 67, wherein the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof, is: for an adult, about 200 mg of Compound A (based on the weight of the free base) administered twice daily;Attorney Docket No. 46696-0217WO1 / 377.WO1.PCT for a pediatric patient having a body mass of > 55 kg, about 200 mg of Compound A (based on the weight of the free base) administered twice daily; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 100 mg of Compound A (based on the weight of the free base) administered twice daily; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 50 mg of Compound A (based on the weight of the free base) administered twice daily.

70. The method of any one of claims 65 to 67, wherein the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof, is: for an adult, about 100 mg of Compound A (based on the weight of the free base) administered in the morning and about 200 mg of Compound A (based on the weight of the free base) administered in the evening; for a pediatric patient having a body mass of > 55 kg, about 100 mg of Compound A (based on the weight of the free base) administered in the morning and about 200 mg of Compound A (based on the weight of the free base) administered in the evening; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 50 mg of Compound A (based on the weight of the free base) administered in the morning and about 100 mg of Compound A (based on the weight of the free base) administered in the evening; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 25 mg of Compound A (based on the weight of the free base) administered in the morning and about 50 mg of Compound A (based on the weight of the free base) administered in the evening.

71. The method of any one of claims 65 to 67, wherein the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof, is: for an adult, about 200 mg of Compound A (based on the weight of the free base) administered in the evening; for a pediatric patient having a body mass of > 55 kg, about 200 mg of Compound A (based on the weight of the free base) administered in the evening; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 100 mg of Compound A (based on the weight of the free base) administered in the evening; andAttorney Docket No. 46696-0217WO1 / 377.WO1.PCT for a pediatric patient having a body mass of 10 kg to < 20 kg, about 50 mg of Compound A (based on the weight of the free base) administered in the evening.

72. The method of any one of claims 65 to 71, wherein Compound A, or a pharmaceutically acceptable salt thereof is administered as an adjunctive treatment to glucocorticoid replacement therapy.

73. The method of claim 72, wherein the glucocorticoid replacement therapy is administered daily to the patient.

74. The method of claim 73, wherein the glucocorticoid replacement therapy comprises once daily administration or multiple daily administrations of a glucocorticoid.

75. The method of claim 74, wherein the glucocorticoid is selected from hydrocortisone, prednisone, methylprednisolone, prednisolone, and dexamethasone, or a combination thereof.

76. The method of any one of claims 65 to 75, wherein Compound A, or a pharmaceutically acceptable salt thereof, is administered orally.

77. The method of any one of claims 65 to 76, wherein Compound A, or a pharmaceutically acceptable salt thereof, is administered with food.

78. The method of any one of claims 65 to 77, wherein the administration of Compound A, or a pharmaceutically acceptable salt thereof, improves androgen control and / or enables a reduced glucocorticoid dose in the patient.

79. The method of any one of claims 65 to 78, wherein the CAH is classic CAH.

80. A method of treating a patient with congenital adrenal hyperplasia (CAH), said method comprising: administering a therapeutically effective amount of 4-(2-chloro-4-methoxy-5- methylphenyl)-A-[(15)-2-cyclopropyl-l-(3-fluoro-4-methylphenyl)ethyl]-5-methyl-A- prop-2-ynyl-l,3-thiazol-2-amine (Compound A),Attorney Docket No. 46696-0217WO1 / 377.WO1.PCT(Compound A) to the patient, monitoring the patient for a hypersensitivity reaction associated with the administration of Compound A, and discontinuing administration of Compound A if the patient is not able to tolerate the hypersensitivity reaction.

81. The method of claim 80, wherein the hypersensitivity reaction manifests in one or more symptoms selected from throat tightness, angioedema, and generalized rash.

82. The method of claim 80 or 81, wherein the hypersensitivity reaction manifests in one or more symptoms selected from immediate-type symptoms and delayed-type symptoms.

83. The method of any one of claims 80 to 82, wherein the therapeutically effective amount of Compound A is: for an adult, about 100 mg of Compound A administered twice daily; for a pediatric patient having a body mass of > 55 kg, about 100 mg of Compound A administered twice daily; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 50 mg of Compound A administered twice daily; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 25 mg of Compound A administered twice daily.

84. The method of any one of claims 80 to 82, wherein the therapeutically effective amount of Compound A is: for an adult, about 200 mg of Compound A administered twice daily; for a pediatric patient having a body mass of > 55 kg, about 200 mg of Compound A administered twice daily;Attorney Docket No. 46696-0217WO1 / 377.WO1.PCT for a pediatric patient having a body mass of 20 kg to < 55 kg, about 100 mg of Compound A administered twice daily; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 50 mg of Compound A administered twice daily.

85. The method of any one of claims 80 to 82, wherein the therapeutically effective amount of Compound A is: for an adult, about 100 mg of Compound A administered in the morning and about 200 mg of Compound A administered in the evening; for a pediatric patient having a body mass of > 55 kg, about 100 mg of Compound A administered in the morning and about 200 mg of Compound A administered in the evening; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 50 mg of Compound A administered in the morning and about 100 mg of Compound A administered in the evening; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 25 mg of Compound A administered in the morning and about 50 mg of Compound A administered in the evening.

86. The method of any one of claims 80 to 82, wherein the therapeutically effective amount of Compound A is: for an adult, about 200 mg of Compound A administered in the evening; for a pediatric patient having a body mass of > 55 kg, about 200 mg of Compound A administered in the evening; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 100 mg of Compound A administered in the evening; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 50 mg of Compound A administered in the evening.

87. The method of any one of claims 80 to 86, wherein Compound A is administered as an adjunctive treatment to glucocorticoid replacement therapy.

88. The method of claim 87, wherein the glucocorticoid replacement therapy is administered daily to the patient.Attorney Docket No. 46696-0217WO1 / 377.WO1.PCT89. The method of claim 88, wherein the glucocorticoid replacement therapy comprises once daily administration or multiple daily administrations of a glucocorticoid.

90. The method of claim 89, wherein the glucocorticoid is selected from hydrocortisone, prednisone, methylprednisolone, prednisolone, and dexamethasone, or a combination thereof.

91. The method of any one of claims 80 to 90, wherein Compound A is administered orally.

92. The method of any one of claims 80 to 91, wherein Compound A is administered with food.

93. The method of any one of claims 80 to 92, wherein the administration of Compound A improves androgen control and / or enables a reduced glucocorticoid dose in the patient.

94. The method of any one of claims 80 to 93, wherein the CAH is classic CAH.

95. A method of treating a patient with congenital adrenal hyperplasia (CAH), said method comprising: administering a pharmaceutical composition comprising a therapeutically effective amount of 4-(2-chloro-4-methoxy-5-methylphenyl)-A-[(15)-2-cyclopropyl- l-(3-fluoro-4-methylphenyl)ethyl]-5-methyl-A-prop-2-ynyl-l,3-thiazol-2-amine (Compound A),(Compound A) or a pharmaceutically acceptable salt thereof, to the patient, monitoring the patient for a hypersensitivity reaction associated with the administration of the pharmaceutical composition, andAttorney Docket No. 46696-0217WO1 / 377.WO1.PCT discontinuing administration of the pharmaceutical composition if the patient is not able to tolerate the hypersensitivity reaction.

96. The method of claim 95, wherein the hypersensitivity reaction manifests in one or more symptoms selected from throat tightness, angioedema, and generalized rash.

97. The method of claim 95 or 96, wherein the hypersensitivity reaction manifests in one or more symptoms selected from immediate-type symptoms and delayed-type symptoms.

98. The method of any one of claims 95 to 97, wherein the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof, is: for an adult, about 100 mg of Compound A (based on the weight of the free base) administered twice daily; for a pediatric patient having a body mass of > 55 kg, about 100 mg of Compound A (based on the weight of the free base) administered twice daily; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 50 mg of Compound A (based on the weight of the free base) administered twice daily; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 25 mg of Compound A (based on the weight of the free base) administered twice daily.

99. The method of any one of claims 95 to 97, wherein the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof, is: for an adult, about 200 mg of Compound A (based on the weight of the free base) administered twice daily; for a pediatric patient having a body mass of > 55 kg, about 200 mg of Compound A (based on the weight of the free base) administered twice daily; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 100 mg of Compound A (based on the weight of the free base) administered twice daily; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 50 mg of Compound A (based on the weight of the free base) administered twice daily.

100. The method of any one of claims 95 to 97, wherein the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof, is:Attorney Docket No. 46696-0217WO1 / 377.WO1.PCT for an adult, about 100 mg of Compound A (based on the weight of the free base) administered in the morning and about 200 mg of Compound A (based on the weight of the free base) administered in the evening; for a pediatric patient having a body mass of > 55 kg, about 100 mg of Compound A (based on the weight of the free base) administered in the morning and about 200 mg of Compound A (based on the weight of the free base) administered in the evening; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 50 mg of Compound A (based on the weight of the free base) administered in the morning and about 100 mg of Compound A (based on the weight of the free base) administered in the evening; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 25 mg of Compound A (based on the weight of the free base) administered in the morning and about 50 mg of Compound A (based on the weight of the free base) administered in the evening.

101. The method of any one of claims 95 to 97, wherein the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof, is: for an adult, about 200 mg of Compound A (based on the weight of the free base) administered in the evening; for a pediatric patient having a body mass of > 55 kg, about 200 mg of Compound A (based on the weight of the free base) administered in the evening; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 100 mg of Compound A (based on the weight of the free base) administered in the evening; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 50 mg of Compound A (based on the weight of the free base) administered in the evening.

102. The method of any one of claims 95 to 101, wherein the pharmaceutical composition is administered as an adjunctive treatment to glucocorticoid replacement therapy.

103. The method of claim 102, wherein the glucocorticoid replacement therapy is administered daily to the patient.Attorney Docket No. 46696-0217WO1 / 377.WO1.PCT104. The method of claim 103, wherein the glucocorticoid replacement therapy comprises once daily administration or multiple daily administrations of a glucocorticoid.

105. The method of claim 104, wherein the glucocorticoid is selected from hydrocortisone, prednisone, methylprednisolone, prednisolone, and dexamethasone, or a combination thereof.

106. The method of any one of claims 95 to 105, wherein the pharmaceutical composition is administered orally.

107. The method of any one of claims 95 to 106, wherein the pharmaceutical composition is administered with food.

108. The method of any one of claims 95 to 107, wherein the administration of the pharmaceutical composition improves androgen control and / or enables a reduced glucocorticoid dose in the patient.

109. The method of any one of claims 95 to 108, wherein the CAH is classic CAH.

110. A method of treating a patient with congenital adrenal hyperplasia (CAH), said method comprising: administering a pharmaceutical composition comprising a therapeutically effective amount of 4-(2-chloro-4-methoxy-5-methylphenyl)-7V-[(15)-2-cyclopropyl- l-(3-fluoro-4-methylphenyl)ethyl]-5-methyl-7V-prop-2-ynyl-l,3-thiazol-2-amine (Compound A),(Compound A) to the patient, monitoring the patient for a hypersensitivity reaction associated with the administration of the pharmaceutical composition, andAttorney Docket No. 46696-0217WO1 / 377.WO1.PCT discontinuing administration of the pharmaceutical composition if the patient is not able to tolerate the hypersensitivity reaction.

111. The method of claim 110, wherein the hypersensitivity reaction manifests in one or more symptoms selected from throat tightness, angioedema, and generalized rash.

112. The method of claim 110 or 111, wherein the hypersensitivity reaction manifests in one or more symptoms selected from immediate-type symptoms and delayed-type symptoms.

113. The method of any one of claims 110 to 112, wherein the therapeutically effective amount of Compound A is: for an adult, about 100 mg of Compound A administered twice daily; for a pediatric patient having a body mass of > 55 kg, about 100 mg of Compound A administered twice daily; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 50 mg of Compound A administered twice daily; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 25 mg of Compound A administered twice daily.

114. The method of any one of claims 110 to 112, wherein the therapeutically effective amount of Compound A is: for an adult, about 200 mg of Compound A administered twice daily; for a pediatric patient having a body mass of > 55 kg, about 200 mg of Compound A administered twice daily; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 100 mg of Compound A administered twice daily; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 50 mg of Compound A administered twice daily.

115. The method of any one of claims 110 to 112, wherein the therapeutically effective amount of Compound A is: for an adult, about 100 mg of Compound A administered in the morning and about 200 mg of Compound A administered in the evening;Attorney Docket No. 46696-0217WO1 / 377.WO1.PCT for a pediatric patient having a body mass of > 55 kg, about 100 mg of Compound A administered in the morning and about 200 mg of Compound A administered in the evening; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 50 mg of Compound A administered in the morning and about 100 mg of Compound A administered in the evening; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 25 mg of Compound A administered in the morning and about 50 mg of Compound A administered in the evening.

116. The method of any one of claims 110 to 112, wherein the therapeutically effective amount of Compound A is: for an adult, about 200 mg of Compound A administered in the evening; for a pediatric patient having a body mass of > 55 kg, about 200 mg of Compound A administered in the evening; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 100 mg of Compound A administered in the evening; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 50 mg of Compound A administered in the evening.

117. The method of any one of claims 110 to 116, wherein the pharmaceutical composition is administered as an adjunctive treatment to glucocorticoid replacement therapy.

118. The method of claim 117, wherein the glucocorticoid replacement therapy is administered daily to the patient.

119. The method of claim 118, wherein the glucocorticoid replacement therapy comprises once daily administration or multiple daily administrations of a glucocorticoid.

120. The method of claim 119, wherein the glucocorticoid is selected from hydrocortisone, prednisone, methylprednisolone, prednisolone, and dexamethasone, or a combination thereof.Attorney Docket No. 46696-0217WO1 / 377.WO1.PCT121. The method of any one of claims 110 to 120, wherein the pharmaceutical composition is administered orally.

122. The method of any one of claims 110 to 121, wherein the pharmaceutical composition is administered with food.

123. The method of any one of claims 110 to 122, wherein the administration of the pharmaceutical composition improves androgen control and / or enables a reduced glucocorticoid dose in the patient.

124. The method of any one of claims 110 to 123, wherein the CAH is classic CAH.

125. A method of treating a patient with congenital adrenal hyperplasia (CAH), said method comprising: administering a therapeutically effective amount of 4-(2-chloro-4-methoxy-5- methylphenyl)-7V-[(15)-2-cyclopropyl-l-(3-fluoro-4-methylphenyl)ethyl]-5-methyl-7V- prop-2-ynyl-l,3-thiazol-2-amine (Compound A),(Compound A) or a pharmaceutically acceptable salt thereof, to the patient, monitoring the patient for a hypersensitivity reaction associated with the administration of Compound A, or a pharmaceutically acceptable salt thereof; and if the patient demonstrates the hypersensitivity reaction, discontinuing administration of Compound A, or a pharmaceutically acceptable salt thereof.

126. The method of claim 125, wherein the hypersensitivity reaction manifests in one or more symptoms selected from throat tightness, angioedema, and generalized rash.

127. The method of claim 125 or 126, wherein the hypersensitivity reaction manifests in one or more symptoms selected from immediate-type symptoms and delayed-type symptoms.Attorney Docket No. 46696-0217WO1 / 377.WO1.PCT128. The method of any one of claims 125 to 127, wherein the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof, is: for an adult, about 100 mg of Compound A (based on the weight of the free base) administered twice daily; for a pediatric patient having a body mass of > 55 kg, about 100 mg of Compound A (based on the weight of the free base) administered twice daily; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 50 mg of Compound A (based on the weight of the free base) administered twice daily; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 25 mg of Compound A (based on the weight of the free base) administered twice daily.

129. The method of any one of claims 125 to 127, wherein the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof, is: for an adult, about 200 mg of Compound A (based on the weight of the free base) administered twice daily; for a pediatric patient having a body mass of > 55 kg, about 200 mg of Compound A (based on the weight of the free base) administered twice daily; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 100 mg of Compound A (based on the weight of the free base) administered twice daily; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 50 mg of Compound A (based on the weight of the free base) administered twice daily.

130. The method of any one of claims 125 to 127, wherein the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof, is: for an adult, about 100 mg of Compound A (based on the weight of the free base) administered in the morning and about 200 mg of Compound A (based on the weight of the free base) administered in the evening; for a pediatric patient having a body mass of > 55 kg, about 100 mg of Compound A (based on the weight of the free base) administered in the morning and about 200 mg of Compound A (based on the weight of the free base) administered in the evening; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 50 mg of Compound A (based on the weight of the free base) administered in the morningAttorney Docket No. 46696-0217WO1 / 377.WO1.PCT and about 100 mg of Compound A (based on the weight of the free base) administered in the evening; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 25 mg of Compound A (based on the weight of the free base) administered in the morning and about 50 mg of Compound A (based on the weight of the free base) administered in the evening.

131. The method of any one of claims 125 to 127, wherein the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof, is: for an adult, about 200 mg of Compound A (based on the weight of the free base) administered in the evening; for a pediatric patient having a body mass of > 55 kg, about 200 mg of Compound A (based on the weight of the free base) administered in the evening; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 100 mg of Compound A (based on the weight of the free base) administered in the evening; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 50 mg of Compound A (based on the weight of the free base) administered in the evening.

132. The method of any one of claims 125 to 131, wherein Compound A, or a pharmaceutically acceptable salt thereof, is administered as an adjunctive treatment to glucocorticoid replacement therapy.

133. The method of claim 132, wherein the glucocorticoid replacement therapy is administered daily to the patient.

134. The method of claim 133, wherein the glucocorticoid replacement therapy comprises once daily administration or multiple daily administrations of a glucocorticoid.

135. The method of claim 134, wherein the glucocorticoid is selected from hydrocortisone, prednisone, methylprednisolone, prednisolone, and dexamethasone, or a combination thereof.Attorney Docket No. 46696-0217WO1 / 377.WO1.PCT136. The method of any one of claims 125 to 135, wherein Compound A, or a pharmaceutically acceptable salt thereof, is administered orally.

137. The method of any one of claims 125 to 136, wherein Compound A, or a pharmaceutically acceptable salt thereof, is administered with food.

138. The method of any one of claims 125 to 137, wherein the administration of Compound A, or a pharmaceutically acceptable salt thereof, improves androgen control and / or enables a reduced glucocorticoid dose in the patient.

139. The method of any one of claims 125 to 138, wherein the CAH is classic CAH.

140. A method of treating a patient with congenital adrenal hyperplasia (CAH), said method comprising: administering a therapeutically effective amount of 4-(2-chloro-4-methoxy-5- methylphenyl)-A-[(15)-2-cyclopropyl-l-(3-fluoro-4-methylphenyl)ethyl]-5-methyl-A- prop-2-ynyl-l,3-thiazol-2-amine (Compound A),(Compound A) to the patient, monitoring the patient for a hypersensitivity reaction associated with the administration of Compound A; and if the patient demonstrates the hypersensitivity reaction, discontinuing administration of Compound A.

141. The method of claim 140, wherein the hypersensitivity reaction manifests in one or more symptoms selected from throat tightness, angioedema, and generalized rash.

142. The method of claim 140 or 141, wherein the hypersensitivity reaction manifests in one or more symptoms selected from immediate-type symptoms and delayed-type symptoms.Attorney Docket No. 46696-0217WO1 / 377.WO1.PCT143. The method of any one of claims 140 to 142, wherein the therapeutically effective amount of Compound A is: for an adult, about 100 mg of Compound A administered twice daily; for a pediatric patient having a body mass of > 55 kg, about 100 mg of Compound A administered twice daily; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 50 mg of Compound A administered twice daily; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 25 mg of Compound A administered twice daily.

144. The method of any one of claims 140 to 142, wherein the therapeutically effective amount of Compound A is: for an adult, about 200 mg of Compound A administered twice daily; for a pediatric patient having a body mass of > 55 kg, about 200 mg of Compound A administered twice daily; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 100 mg of Compound A administered twice daily; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 50 mg of Compound A administered twice daily.

145. The method of any one of claims 140 to 142, wherein the therapeutically effective amount of Compound A is: for an adult, about 100 mg of Compound A administered in the morning and about 200 mg of Compound A administered in the evening; for a pediatric patient having a body mass of > 55 kg, about 100 mg of Compound A administered in the morning and about 200 mg of Compound A administered in the evening; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 50 mg of Compound A administered in the morning and about 100 mg of Compound A administered in the evening; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 25 mg of Compound A administered in the morning and about 50 mg of Compound A administered in the evening.Attorney Docket No. 46696-0217WO1 / 377.WO1.PCT146. The method of any one of claims 140 to 142, wherein the therapeutically effective amount of Compound A is: for an adult, about 200 mg of Compound A administered in the evening; for a pediatric patient having a body mass of > 55 kg, about 200 mg of Compound A administered in the evening; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 100 mg of Compound A administered in the evening; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 50 mg of Compound A administered in the evening.

147. The method of any one of claims 140 to 146, wherein Compound A is administered as an adjunctive treatment to glucocorticoid replacement therapy.

148. The method of claim 147, wherein the glucocorticoid replacement therapy is administered daily to the patient.

149. The method of claim 148, wherein the glucocorticoid replacement therapy comprises once daily administration or multiple daily administrations of a glucocorticoid.

150. The method of claim 149, wherein the glucocorticoid is selected from hydrocortisone, prednisone, methylprednisolone, prednisolone, and dexamethasone, or a combination thereof.

151. The method of any one of claims 140 to 150, wherein Compound A is administered orally.

152. The method of any one of claims 140 to 151, wherein Compound A is administered with food.

153. The method of any one of claims 140 to 152, wherein the administration of Compound A improves androgen control and / or enables a reduced glucocorticoid dose in the patient.

154. The method of any one of claims 140 to 153, wherein the CAH is classic CAH.Attorney Docket No. 46696-0217WO1 / 377.WO1.PCT155. A method of treating a patient with congenital adrenal hyperplasia (CAH), said method comprising: administering a pharmaceutical composition comprising a therapeutically effective amount of 4-(2-chloro-4-methoxy-5-methylphenyl)-A-[(15)-2-cyclopropyl- l-(3-fluoro-4-methylphenyl)ethyl]-5-methyl-A-prop-2-ynyl-l,3-thiazol-2-amine (Compound A),(Compound A) or a pharmaceutically acceptable salt thereof, to the patient, monitoring the patient for a hypersensitivity reaction associated with the administration of the pharmaceutical composition; and if the patient demonstrates the hypersensitivity reaction, discontinuing administration of the pharmaceutical composition.

156. The method of claim 155, wherein the hypersensitivity reaction manifests in one or more symptoms selected from throat tightness, angioedema, and generalized rash.

157. The method of claim 155 or 156, wherein the hypersensitivity reaction manifests in one or more symptoms selected from immediate-type symptoms and delayed-type symptoms.

158. The method of any one of claims 155 to 157, wherein the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof, is: for an adult, about 100 mg of Compound A (based on the weight of the free base) administered twice daily; for a pediatric patient having a body mass of > 55 kg, about 100 mg of Compound A (based on the weight of the free base) administered twice daily; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 50 mg of Compound A (based on the weight of the free base) administered twice daily; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 25 mg of Compound A (based on the weight of the free base) administered twice daily.Attorney Docket No. 46696-0217WO1 / 377.WO1.PCT159. The method of any one of claims 155 to 157, wherein the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof, is: for an adult, about 200 mg of Compound A (based on the weight of the free base) administered twice daily; for a pediatric patient having a body mass of > 55 kg, about 200 mg of Compound A (based on the weight of the free base) administered twice daily; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 100 mg of Compound A (based on the weight of the free base) administered twice daily; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 50 mg of Compound A (based on the weight of the free base) administered twice daily.

160. The method of any one of claims 155 to 157, wherein the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof, is: for an adult, about 100 mg of Compound A (based on the weight of the free base) administered in the morning and about 200 mg of Compound A (based on the weight of the free base) administered in the evening; for a pediatric patient having a body mass of > 55 kg, about 100 mg of Compound A (based on the weight of the free base) administered in the morning and about 200 mg of Compound A (based on the weight of the free base) administered in the evening; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 50 mg of Compound A (based on the weight of the free base) administered in the morning and about 100 mg of Compound A (based on the weight of the free base) administered in the evening; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 25 mg of Compound A (based on the weight of the free base) administered in the morning and about 50 mg of Compound A (based on the weight of the free base) administered in the evening.

161. The method of any one of claims 155 to 157, wherein the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof, is: for an adult, about 200 mg of Compound A (based on the weight of the free base) administered in the evening;Attorney Docket No. 46696-0217WO1 / 377.WO1.PCT for a pediatric patient having a body mass of > 55 kg, about 200 mg of Compound A (based on the weight of the free base) administered in the evening; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 100 mg of Compound A (based on the weight of the free base) administered in the evening; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 50 mg of Compound A (based on the weight of the free base) administered in the evening;162. The method of any one of claims 155 to 161, wherein the pharmaceutical composition is administered as an adjunctive treatment to glucocorticoid replacement therapy.

163. The method of claim 162, wherein the glucocorticoid replacement therapy is administered daily to the patient.

164. The method of claim 163, wherein the glucocorticoid replacement therapy comprises once daily administration or multiple daily administrations of a glucocorticoid.

165. The method of claim 164, wherein the glucocorticoid is selected from hydrocortisone, prednisone, methylprednisolone, prednisolone, and dexamethasone, or a combination thereof.

166. The method of any one of claims 155 to 165, wherein the pharmaceutical composition is administered orally.

167. The method of any one of claims 155 to 166, wherein Compound A, or a pharmaceutically acceptable salt thereof, is administered with food.

168. The method of any one of claims 155 to 167, wherein the administration of Compound A, or a pharmaceutically acceptable salt thereof, improves androgen control and / or enables a reduced glucocorticoid dose in the patient.

169. The method of any one of claims 155 to 168, wherein the CAH is classic CAH.Attorney Docket No. 46696-0217WO1 / 377.WO1.PCT170. A method of treating a patient with congenital adrenal hyperplasia (CAH), said method comprising: administering a pharmaceutical composition comprising a therapeutically effective amount of 4-(2-chloro-4-methoxy-5-methylphenyl)-A-[(15)-2-cyclopropyl- l-(3-fluoro-4-methylphenyl)ethyl]-5-methyl-A-prop-2-ynyl-l,3-thiazol-2-amine(Compound A),(Compound A) to the patient, monitoring the patient for a hypersensitivity reaction associated with the administration of the pharmaceutical composition; and if the patient demonstrates the hypersensitivity reaction, discontinuing administration of the pharmaceutical composition.

171. The method of claim 170, wherein the hypersensitivity reaction manifests in one or more symptoms selected from throat tightness, angioedema, and generalized rash.

172. The method of claim 170 or 171, wherein the hypersensitivity reaction manifests in one or more symptoms selected from immediate-type symptoms and delayed-type symptoms.

173. The method of any one of claims 170 to 172, wherein the therapeutically effective amount of Compound A is: for an adult, about 100 mg of Compound A administered twice daily; for a pediatric patient having a body mass of > 55 kg, about 100 mg of Compound A administered twice daily; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 50 mg of Compound A administered twice daily; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 25 mg of Compound A administered twice daily.Attorney Docket No. 46696-0217WO1 / 377.WO1.PCT174. The method of any one of claims 170 to 172, wherein the therapeutically effective amount of Compound A is: for an adult, about 200 mg of Compound A administered twice daily; for a pediatric patient having a body mass of > 55 kg, about 200 mg of Compound A administered twice daily; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 100 mg of Compound A administered twice daily; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 50 mg of Compound A administered twice daily.

175. The method of any one of claims 170 to 172, wherein the therapeutically effective amount of Compound A is: for an adult, about 100 mg of Compound A administered in the morning and about 200 mg of Compound A administered in the evening; for a pediatric patient having a body mass of > 55 kg, about 100 mg of Compound A administered in the morning and about 200 mg of Compound A administered in the evening; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 50 mg of Compound A administered in the morning and about 100 mg of Compound A administered in the evening; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 25 mg of Compound A administered in the morning and about 50 mg of Compound A administered in the evening.

176. The method of any one of claims 170 to 172, wherein the therapeutically effective amount of Compound A is: for an adult, about 200 mg of Compound A administered in the evening; for a pediatric patient having a body mass of > 55 kg, about 200 mg of Compound A administered in the evening; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 100 mg of Compound A administered in the evening; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 50 mg of Compound A administered in the evening.Attorney Docket No. 46696-0217WO1 / 377.WO1.PCT177. The method of any one of claims 170 to 176, wherein the pharmaceutical composition is administered as an adjunctive treatment to glucocorticoid replacement therapy.

178. The method of claim 177, wherein the glucocorticoid replacement therapy is administered daily to the patient.

179. The method of claim 178, wherein the glucocorticoid replacement therapy comprises once daily administration or multiple daily administrations of a glucocorticoid.

180. The method of claim 179, wherein the glucocorticoid is selected from hydrocortisone, prednisone, methylprednisolone, prednisolone, and dexamethasone, or a combination thereof.

181. The method of any one of claims 170 to 180, wherein the pharmaceutical composition is administered orally.

182. The method of any one of claims 170 to 181, wherein the pharmaceutical composition is administered with food.

183. The method of any one of claims 170 to 182, wherein the administration of the pharmaceutical composition improves androgen control and / or enables a reduced glucocorticoid dose in the patient.

184. The method of any one of claims 170 to 183, wherein the CAH is classic CAH.

185. A method of treating a patient with congenital adrenal hyperplasia (CAH), said method comprising: administering a therapeutically effective amount of 4-(2-chloro-4-methoxy-5- methylphenyl)-7V-[(15)-2-cyclopropyl-l-(3-fluoro-4-methylphenyl)ethyl]-5-methyl-7V- prop-2-ynyl-l,3-thiazol-2-amine (Compound A),Attorney Docket No. 46696-0217WO1 / 377.WO1.PCT(Compound A) or a pharmaceutically acceptable salt thereof, to the patient, monitoring the patient for the presence or absence of a hypersensitivity reaction associated with the administration of Compound A, or a pharmaceutically acceptable salt thereof, and if the hypersensitivity reaction is present, discontinuing administration of Compound A, or a pharmaceutically acceptable salt thereof, or if the hypersensitivity reaction is absent, continuing administering the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof, to the patient.

186. The method of claim 185, wherein the hypersensitivity reaction manifests in one or more symptoms selected from throat tightness, angioedema, and generalized rash.

187. The method of claim 185 or 186, wherein the hypersensitivity reaction manifests in one or more symptoms selected from immediate-type symptoms and delayed-type symptoms.

188. The method of any one of claims 185 to 187, wherein the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof, is: for an adult, about 100 mg of Compound A (based on the weight of the free base) administered twice daily; for a pediatric patient having a body mass of > 55 kg, about 100 mg of Compound A (based on the weight of the free base) administered twice daily; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 50 mg of Compound A (based on the weight of the free base) administered twice daily; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 25 mg of Compound A (based on the weight of the free base) administered twice daily.Attorney Docket No. 46696-0217WO1 / 377.WO1.PCT189. The method of any one of claims 185 to 187, wherein the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof, is: for an adult, about 200 mg of Compound A (based on the weight of the free base) administered twice daily; for a pediatric patient having a body mass of > 55 kg, about 200 mg of Compound A (based on the weight of the free base) administered twice daily; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 100 mg of Compound A (based on the weight of the free base) administered twice daily; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 50 mg of Compound A (based on the weight of the free base) administered twice daily.

190. The method of any one of claims 185 to 187, wherein the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof, is: for an adult, about 100 mg of Compound A (based on the weight of the free base) administered in the morning and about 200 mg of Compound A (based on the weight of the free base) administered in the evening; for a pediatric patient having a body mass of > 55 kg, about 100 mg of Compound A (based on the weight of the free base) administered in the morning and about 200 mg of Compound A (based on the weight of the free base) administered in the evening; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 50 mg of Compound A (based on the weight of the free base) administered in the morning and about 100 mg of Compound A (based on the weight of the free base) administered in the evening; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 25 mg of Compound A (based on the weight of the free base) administered in the morning and about 50 mg of Compound A (based on the weight of the free base) administered in the evening.

191. The method of any one of claims 185 to 187, wherein the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof, is: for an adult, about 200 mg of Compound A (based on the weight of the free base) administered in the evening;Attorney Docket No. 46696-0217WO1 / 377.WO1.PCT for a pediatric patient having a body mass of > 55 kg, about 200 mg of Compound A (based on the weight of the free base) administered in the evening; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 100 mg of Compound A (based on the weight of the free base) administered in the evening; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 50 mg of Compound A (based on the weight of the free base) administered in the evening.

192. The method of any one of claims 185 to 191, wherein Compound A, or a pharmaceutically acceptable salt thereof, is administered as an adjunctive treatment to glucocorticoid replacement therapy.

193. The method of claim 192, wherein the glucocorticoid replacement therapy is administered daily to the patient.

194. The method of claim 193, wherein the glucocorticoid replacement therapy comprises once daily administration or multiple daily administrations of a glucocorticoid.

195. The method of claim 194, wherein the glucocorticoid is selected from hydrocortisone, prednisone, methylprednisolone, prednisolone, and dexamethasone, or a combination thereof.

196. The method of any one of claims 185 to 195, wherein Compound A, or a pharmaceutically acceptable salt thereof, is administered orally.

197. The method of any one of claims 185 to 196, wherein Compound A, or a pharmaceutically acceptable salt thereof, is administered with food.

198. The method of any one of claims 185 to 197, wherein the administration of Compound A, or a pharmaceutically acceptable salt thereof, improves androgen control and / or enables a reduced glucocorticoid dose in the patient.

199. The method of any one of claims 185 to 198, wherein the CAH is classic CAH.Attorney Docket No. 46696-0217WO1 / 377.WO1.PCT200. A method of treating a patient with congenital adrenal hyperplasia (CAH), said method comprising: administering a therapeutically effective amount of 4-(2-chloro-4-methoxy-5- methylphenyl)-A-[(15)-2-cyclopropyl-l-(3-fluoro-4-methylphenyl)ethyl]-5-methyl-A- prop-2-ynyl-l,3-thiazol-2-amine (Compound A),(Compound A) to the patient, monitoring the patient for the presence or absence of a hypersensitivity reaction associated with the administration of Compound A, and if the hypersensitivity reaction is present, discontinuing administration of Compound A, or if the hypersensitivity reaction is absent, continuing administering the therapeutically effective amount of Compound A, to the patient.

201. The method of claim 200, wherein the hypersensitivity reaction manifests in one or more symptoms selected from throat tightness, angioedema, and generalized rash.

202. The method of claim 200 or 201, wherein the hypersensitivity reaction manifests in one or more symptoms selected from immediate-type symptoms and delayed-type symptoms.

203. The method of any one of claims 200 to 202, wherein the therapeutically effective amount of Compound A is: for an adult, about 100 mg of Compound A administered twice daily; for a pediatric patient having a body mass of > 55 kg, about 100 mg of Compound A administered twice daily; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 50 mg of Compound A administered twice daily; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 25 mg of Compound A administered twice daily.Attorney Docket No. 46696-0217WO1 / 377.WO1.PCT204. The method of any one of claims 200 to 202, wherein the therapeutically effective amount of Compound A is: for an adult, about 200 mg of Compound A administered twice daily; for a pediatric patient having a body mass of > 55 kg, about 200 mg of Compound A administered twice daily; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 100 mg of Compound A administered twice daily; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 50 mg of Compound A administered twice daily.

205. The method of any one of claims 200 to 202, wherein the therapeutically effective amount of Compound A is: for an adult, about 100 mg of Compound A administered in the morning and about 200 mg of Compound A administered in the evening; for a pediatric patient having a body mass of > 55 kg, about 100 mg of Compound A administered in the morning and about 200 mg of Compound A administered in the evening; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 50 mg of Compound A administered in the morning and about 100 mg of Compound A administered in the evening; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 25 mg of Compound A administered in the morning and about 50 mg of Compound A administered in the evening.

206. The method of any one of claims 200 to 202, wherein the therapeutically effective amount of Compound A is: for an adult, about 200 mg of Compound A administered in the evening; for a pediatric patient having a body mass of > 55 kg, about 200 mg of Compound A administered in the evening; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 100 mg of Compound A administered in the evening; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 50 mg of Compound A administered in the evening.Attorney Docket No. 46696-0217WO1 / 377.WO1.PCT207. The method of any one of claims 200 to 206, wherein Compound A is administered as an adjunctive treatment to glucocorticoid replacement therapy.

208. The method of claim 207, wherein the glucocorticoid replacement therapy is administered daily to the patient.

209. The method of claim 208, wherein the glucocorticoid replacement therapy comprises once daily administration or multiple daily administrations of a glucocorticoid.

210. The method of claim 209, wherein the glucocorticoid is selected from hydrocortisone, prednisone, methylprednisolone, prednisolone, and dexamethasone, or a combination thereof.

211. The method of any one of claims 200 to 210, wherein Compound A is administered orally.

212. The method of any one of claims 200 to 211, wherein Compound A is administered with food.

213. The method of any one of claims 200 to 212, wherein the administration of Compound A improves androgen control and / or enables a reduced glucocorticoid dose in the patient.

214. The method of any one of claims 200 to 213, wherein the CAH is classic CAH.

215. A method of treating a patient with congenital adrenal hyperplasia (CAH), said method comprising: administering a pharmaceutical composition comprising a therapeutically effective amount of 4-(2-chloro-4-methoxy-5-methylphenyl)-A-[(15)-2-cyclopropyl- l-(3-fluoro-4-methylphenyl)ethyl]-5-methyl-A-prop-2-ynyl-l,3-thiazol-2-amine (Compound A),Attorney Docket No. 46696-0217WO1 / 377.WO1.PCT(Compound A) or a pharmaceutically acceptable salt thereof, to the patient, monitoring the patient for the presence or absence of a hypersensitivity reaction associated with the administration of the pharmaceutical composition, and if the hypersensitivity reaction is present, discontinuing administration of the pharmaceutical composition, or if the hypersensitivity reaction is absent, continuing administering the pharmaceutical composition to the patient.

216. The method of claim 215, wherein the hypersensitivity reaction manifests in one or more symptoms selected from throat tightness, angioedema, and generalized rash.

217. The method of claim 215 or 216, wherein the hypersensitivity reaction manifests in one or more symptoms selected from immediate-type symptoms and delayed-type symptoms.

218. The method of any one of claims 215 to 217, wherein the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof, is: for an adult, about 100 mg of Compound A (based on the weight of the free base) administered twice daily; for a pediatric patient having a body mass of > 55 kg, about 100 mg of Compound A (based on the weight of the free base) administered twice daily; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 50 mg of Compound A (based on the weight of the free base) administered twice daily; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 25 mg of Compound A (based on the weight of the free base) administered twice daily.

219. The method of any one of claims 215 to 217, wherein the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof, is:Attorney Docket No. 46696-0217WO1 / 377.WO1.PCT for an adult, about 200 mg of Compound A (based on the weight of the free base) administered twice daily; for a pediatric patient having a body mass of > 55 kg, about 200 mg of Compound A (based on the weight of the free base) administered twice daily; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 100 mg of Compound A (based on the weight of the free base) administered twice daily; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 50 mg of Compound A (based on the weight of the free base) administered twice daily.

220. The method of any one of claims 215 to 217, wherein the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof, is: for an adult, about 100 mg of Compound A (based on the weight of the free base) administered in the morning and about 200 mg of Compound A (based on the weight of the free base) administered in the evening; for a pediatric patient having a body mass of > 55 kg, about 100 mg of Compound A (based on the weight of the free base) administered in the morning and about 200 mg of Compound A (based on the weight of the free base) administered in the evening; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 50 mg of Compound A (based on the weight of the free base) administered in the morning and about 100 mg of Compound A (based on the weight of the free base) administered in the evening; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 25 mg of Compound A (based on the weight of the free base) administered in the morning and about 50 mg of Compound A (based on the weight of the free base) administered in the evening.

221. The method of any one of claims 215 to 217, wherein the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof, is: for an adult, about 200 mg of Compound A (based on the weight of the free base) administered in the evening; for a pediatric patient having a body mass of > 55 kg, about 200 mg of Compound A (based on the weight of the free base) administered in the evening;Attorney Docket No. 46696-0217WO1 / 377.WO1.PCT for a pediatric patient having a body mass of 20 kg to < 55 kg, about 100 mg of Compound A (based on the weight of the free base) administered in the evening; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 50 mg of Compound A (based on the weight of the free base) administered in the evening.

222. The method of any one of claims 215 to 221, wherein the pharmaceutical composition is administered as an adjunctive treatment to glucocorticoid replacement therapy.

223. The method of claim 222, wherein the glucocorticoid replacement therapy is administered daily to the patient.

224. The method of claim 223, wherein the glucocorticoid replacement therapy comprises once daily administration or multiple daily administrations of a glucocorticoid.

225. The method of claim 224, wherein the glucocorticoid is selected from hydrocortisone, prednisone, methylprednisolone, prednisolone, and dexamethasone, or a combination thereof.

226. The method of any one of claims 215 to 225, wherein the pharmaceutical composition is administered orally.

227. The method of any one of claims 215 to 226, wherein the pharmaceutical composition is administered with food.

228. The method of any one of claims 215 to 227, wherein the administration of the pharmaceutical composition improves androgen control and / or enables a reduced glucocorticoid dose in the patient.

229. The method of any one of claims 215 to 228, wherein the CAH is classic CAH.

230. A method of treating a patient with congenital adrenal hyperplasia (CAH), said method comprising:Attorney Docket No. 46696-0217WO1 / 377.WO1.PCT administering a pharmaceutical composition comprising a therapeutically effective amount of 4-(2-chloro-4-methoxy-5-methylphenyl)-A-[(15)-2-cyclopropyl- l-(3-fluoro-4-methylphenyl)ethyl]-5-methyl-7V-prop-2-ynyl-l,3-thiazol-2-amine (Compound A),(Compound A) to the patient, monitoring the patient for the presence or absence of a hypersensitivity reaction associated with the administration of the pharmaceutical composition, and if the hypersensitivity reaction is present, discontinuing administration of the pharmaceutical composition, or if the hypersensitivity reaction is absent, continuing administering the pharmaceutical composition to the patient.

231. The method of claim 230, wherein the hypersensitivity reaction manifests in one or more symptoms selected from throat tightness, angioedema, and generalized rash.

232. The method of claim 230 or 231, wherein the hypersensitivity reaction manifests in one or more symptoms selected from immediate-type symptoms and delayed-type symptoms.

233. The method of any one of claims 230 to 232, wherein the therapeutically effective amount of Compound A is: for an adult, about 100 mg of Compound A administered twice daily; for a pediatric patient having a body mass of > 55 kg, about 100 mg of Compound A administered twice daily; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 50 mg of Compound A administered twice daily; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 25 mg of Compound A administered twice daily.Attorney Docket No. 46696-0217WO1 / 377.WO1.PCT234. The method of any one of claims 230 to 232, wherein the therapeutically effective amount of Compound A is: for an adult, about 200 mg of Compound A administered twice daily; for a pediatric patient having a body mass of > 55 kg, about 200 mg of Compound A administered twice daily; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 100 mg of Compound A administered twice daily; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 50 mg of Compound A administered twice daily.

235. The method of any one of claims 230 to 232, wherein the therapeutically effective amount of Compound A is: for an adult, about 100 mg of Compound A administered in the morning and about 200 mg of Compound A administered in the evening; for a pediatric patient having a body mass of > 55 kg, about 100 mg of Compound A administered in the morning and about 200 mg of Compound A administered in the evening; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 50 mg of Compound A administered in the morning and about 100 mg of Compound A administered in the evening; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 25 mg of Compound A administered in the morning and about 50 mg of Compound A administered in the evening.

236. The method of any one of claims 230 to 232, wherein the therapeutically effective amount of Compound A is: for an adult, about 200 mg of Compound A administered in the evening; for a pediatric patient having a body mass of > 55 kg, about 200 mg of Compound A administered in the evening; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 100 mg of Compound A administered in the evening; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 50 mg of Compound A administered in the evening.Attorney Docket No. 46696-0217WO1 / 377.WO1.PCT237. The method of any one of claims 230 to 236, wherein the pharmaceutical composition is administered as an adjunctive treatment to glucocorticoid replacement therapy.

238. The method of claim 237, wherein the glucocorticoid replacement therapy is administered daily to the patient.

239. The method of claim 238, wherein the glucocorticoid replacement therapy comprises once daily administration or multiple daily administrations of a glucocorticoid.

240. The method of claim 239, wherein the glucocorticoid is selected from hydrocortisone, prednisone, methylprednisolone, prednisolone, and dexamethasone, or a combination thereof.

241. The method of any one of claims 230 to 240, wherein the pharmaceutical composition is administered orally.

242. The method of any one of claims 230 to 241, wherein the pharmaceutical composition is administered with food.

243. The method of any one of claims 230 to 242, wherein the administration of the pharmaceutical composition improves androgen control and / or enables a reduced glucocorticoid dose in the patient.

244. The method of any one of claims 230 to 243, wherein the CAH is classic CAH.

245. A method of treating a patient with classic congenital adrenal hyperplasia (CAH) using 4-(2-chloro-4-methoxy-5-methylphenyl)-7V-[(15)-2-cyclopropyl-l-(3-fluoro-4- methylphenyl)ethyl]-5-methyl-7V-prop-2-ynyl-l,3-thiazol-2-amine (Compound A),(Compound A) or a pharmaceutically acceptable salt thereof,Attorney Docket No. 46696-0217WO1 / 377.WO1.PCT as adjunctive treatment to glucocorticoid replacement therapy to control androgens in the patient, said method comprising: administering to the patient a therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof; monitoring the patient for the occurrence of a hypersensitivity reaction associated with the administration of Compound A, or a pharmaceutically acceptable salt thereof, and if the hypersensitivity reaction occurs, discontinuing administration of Compound A, or a pharmaceutically acceptable salt thereof.

246. The method of claim 245, wherein the hypersensitivity reaction manifests in one or more symptoms selected from throat tightness, angioedema, and generalized rash.

247. The method of claim 245 or 246, wherein the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof, is: for an adult, about 100 mg of Compound A (based on the weight of the free base) administered orally twice daily with a meal in the morning and evening; for a pediatric patient having a body mass of > 55 kg, about 100 mg of Compound A (based on the weight of the free base) administered orally twice daily with a meal in the morning and evening; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 50 mg of Compound A (based on the weight of the free base) administered orally twice daily with a meal in the morning and evening; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 25 mg of Compound A (based on the weight of the free base) administered orally twice daily with a meal in the morning and evening.

248. The method of claim 245 or 246, wherein the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof, when used concomitantly with strong CYP3A4 inducers, is: for an adult, about 200 mg of Compound A (based on the weight of the free base) administered orally twice daily with a meal in the morning and evening;Attorney Docket No. 46696-0217WO1 / 377.WO1.PCT for a pediatric patient having a body mass of > 55 kg, about 200 mg of Compound A (based on the weight of the free base) administered orally twice daily with a meal in the morning and evening; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 100 mg of Compound A (based on the weight of the free base) administered orally twice daily with a meal in the morning and evening; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 50 mg of Compound A (based on the weight of the free base) administered orally twice daily with a meal in the morning and evening.

249. The method of claim 245 or 246, wherein the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof, is: for an adult, about 100 mg of Compound A (based on the weight of the free base) administered orally with a meal in the morning and about 200 mg of Compound A (based on the weight of the free base) administered orally with a meal in the evening; for a pediatric patient having a body mass of > 55 kg, about 100 mg of Compound A (based on the weight of the free base) administered orally with a meal in the morning and about 200 mg of Compound A (based on the weight of the free base) administered orally with a meal in the evening; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 50 mg of Compound A (based on the weight of the free base) administered orally with a meal in the morning and about 100 mg of Compound A (based on the weight of the free base) administered orally with a meal in the evening; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 25 mg of Compound A (based on the weight of the free base) administered orally with a meal in the morning and about 50 mg of Compound A (based on the weight of the free base) administered orally with a meal in the evening.

250. The method of claim 245 or 246, wherein the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof, is: for an adult, about 200 mg of Compound A (based on the weight of the free base) administered orally with a meal in the evening;Attomey Docket No. 46696-0217WO1 / 377.WO1.PCT for a pediatric patient having a body mass of > 55 kg, about 200 mg of Compound A (based on the weight of the free base) administered orally with a meal in the evening; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 100 mg of Compound A (based on the weight of the free base) administered orally with a meal in the evening; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 50 mg of Compound A (based on the weight of the free base) administered orally with a meal in the evening.

251. The method of any one of claims 245 to 250, wherein the glucocorticoid replacement therapy is administered daily to the patient and comprises once daily administration or multiple daily administrations of a glucocorticoid.

252. The method of claim 251, wherein the glucocorticoid is selected from hydrocortisone, prednisone, methylprednisolone, prednisolone, and dexamethasone, or a combination thereof.

253. A method of treating a patient with classic congenital adrenal hyperplasia (CAH) using 4-(2-chloro-4-methoxy-5-methylphenyl)-A-[(15)-2-cyclopropyl-l-(3-fluoro-4- methylphenyl)ethyl]-5-methyl-A-prop-2-ynyl-l,3-thiazol-2-amine (Compound A),(Compound A) as adjunctive treatment to glucocorticoid replacement therapy to control androgens in the patient, said method comprising: administering to the patient a therapeutically effective amount of CompoundA, monitoring the patient for the occurrence of a hypersensitivity reaction associated with the administration of Compound A, and if the hypersensitivity reaction occurs, discontinuing administration of Compound A.Attorney Docket No. 46696-0217WO1 / 377.WO1.PCT254. The method of claim 253, wherein the hypersensitivity reaction manifests in one or more symptoms selected from throat tightness, angioedema, and generalized rash.

255. The method of claim 253 or 254, wherein the therapeutically effective amount of Compound A is: for an adult, about 100 mg of Compound A administered orally twice daily with a meal in the morning and evening; for a pediatric patient having a body mass of > 55 kg, about 100 mg of Compound A administered orally twice daily with a meal in the morning and evening; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 50 mg of Compound A administered orally twice daily with a meal in the morning and evening; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 25 mg of Compound A administered orally twice daily with a meal in the morning and evening.

256. The method of claim 253 or 254, wherein the therapeutically effective amount of Compound A, when used concomitantly with strong CYP3A4 inducers, is: for an adult, about 200 mg of Compound A administered orally twice daily with a meal in the morning and evening; for a pediatric patient having a body mass of > 55 kg, about 200 mg of Compound A administered orally twice daily with a meal in the morning and evening; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 100 mg of Compound A administered orally twice daily with a meal in the morning and evening; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 50 mg of Compound A administered orally twice daily with a meal in the morning and evening.

257. The method of claim 253 or 254, wherein the therapeutically effective amount of Compound A, is: for an adult, about 100 mg of Compound A administered orally with a meal in the morning and about 200 mg of Compound A administered orally with a meal in the evening;Attorney Docket No. 46696-0217WO1 / 377.WO1.PCT for a pediatric patient having a body mass of > 55 kg, about 100 mg of Compound A administered orally with a meal in the morning and about 200 mg of Compound A administered orally with a meal in the evening; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 50 mg of Compound A administered orally with a meal in the morning and about 100 mg of Compound A administered orally with a meal in the evening; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 25 mg of Compound A administered orally with a meal in the morning and about 50 mg of Compound A administered orally with a meal in the evening.

258. The method of claim 253 or 254, wherein the therapeutically effective amount of Compound A is: for an adult, about 200 mg of Compound A administered orally with a meal in the evening; for a pediatric patient having a body mass of > 55 kg, about 200 mg of Compound A administered orally with a meal in the evening; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 100 mg of Compound A administered orally with a meal in the evening; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 50 mg of Compound A administered orally with a meal in the evening.

259. The method of any one of claims 253 to 258, wherein the glucocorticoid replacement therapy is administered daily to the patient and comprises once daily administration or multiple daily administrations of a glucocorticoid.

260. The method of claim 259, wherein the glucocorticoid is selected from hydrocortisone, prednisone, methylprednisolone, prednisolone, and dexamethasone, or a combination thereof.

261. A method of treating a patient with classic congenital adrenal hyperplasia (CAH) using a pharmaceutical composition comprising a therapeutically effective amount of 4-(2-chloro-4-methoxy-5-methylphenyl)-A-[(lN)-2-cyclopropyl-l-(3-fluoro-4- methylphenyl)ethyl]-5-methyl-A-prop-2-ynyl-l,3-thiazol-2-amine (Compound A),Attorney Docket No. 46696-0217WO1 / 377.WO1.PCT(Compound A) or a pharmaceutically acceptable salt thereof, as adjunctive treatment to glucocorticoid replacement therapy to control androgens in the patient, said method comprising: administering to the patient the pharmaceutical composition, monitoring the patient for the occurrence of a hypersensitivity reaction associated with the administration of the pharmaceutical composition, and if the hypersensitivity reaction occurs, discontinuing administration of the pharmaceutical composition.

262. The method of claim 261, wherein the hypersensitivity reaction manifests in one or more symptoms selected from throat tightness, angioedema, and generalized rash.

263. The method of claim 261 or 262, wherein the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof, is: for an adult, about 100 mg of Compound A (based on the weight of the free base) administered orally twice daily with a meal in the morning and evening; for a pediatric patient having a body mass of > 55 kg, about 100 mg of Compound A (based on the weight of the free base) administered orally twice daily with a meal in the morning and evening; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 50 mg of Compound A (based on the weight of the free base) administered orally twice daily with a meal in the morning and evening; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 25 mg of Compound A (based on the weight of the free base) administered orally twice daily with a meal in the morning and evening.

264. The method of claim 261 or 262, wherein the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof, when used concomitantly with strong CYP3A4 inducers, is:Attorney Docket No. 46696-0217WO1 / 377.WO1.PCT for an adult, about 200 mg of Compound A (based on the weight of the free base) administered orally twice daily with a meal in the morning and evening; for a pediatric patient having a body mass of > 55 kg, about 200 mg of Compound A (based on the weight of the free base) administered orally twice daily with a meal in the morning and evening; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 100 mg of Compound A (based on the weight of the free base) administered orally twice daily with a meal in the morning and evening; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 50 mg of Compound A (based on the weight of the free base) administered orally twice daily with a meal in the morning and evening.

265. The method of claim 261 or 262, wherein the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof, is: for an adult, about 100 mg of Compound A (based on the weight of the free base) administered orally with a meal in the morning and about 200 mg of Compound A (based on the weight of the free base) administered orally with a meal in the evening; for a pediatric patient having a body mass of > 55 kg, about 100 mg of Compound A (based on the weight of the free base) administered orally with a meal in the morning and about 200 mg of Compound A (based on the weight of the free base) administered orally with a meal in the evening; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 50 mg of Compound A (based on the weight of the free base) administered orally with a meal in the morning and about 100 mg of Compound A (based on the weight of the free base) administered orally with a meal in the evening; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 25 mg of Compound A (based on the weight of the free base) administered orally with a meal in the morning and about 50 mg of Compound A (based on the weight of the free base) administered orally with a meal in the evening.

266. The method of claim 261 or 262, wherein the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof, is:Attorney Docket No. 46696-0217WO1 / 377.WO1.PCT for an adult, about 200 mg of Compound A (based on the weight of the free base) administered orally with a meal in the evening; for a pediatric patient having a body mass of > 55 kg, about 200 mg of Compound A (based on the weight of the free base) administered orally with a meal in the evening; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 100 mg of Compound A (based on the weight of the free base) administered orally with a meal in the evening; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 50 mg of Compound A (based on the weight of the free base) administered orally with a meal in the evening.

267. The method of any one of claims 261 to 266, wherein the glucocorticoid replacement therapy is administered daily to the patient and comprises once daily administration or multiple daily administrations of a glucocorticoid.

268. The method of claim 267, wherein the glucocorticoid is selected from hydrocortisone, prednisone, methylprednisolone, prednisolone, and dexamethasone, or a combination thereof.

269. A method of treating a patient with classic congenital adrenal hyperplasia (CAH) using a pharmaceutical composition comprising a therapeutically effective amount of 4-(2-chloro-4-methoxy-5-methylphenyl)-A-[(lN)-2-cyclopropyl-l-(3-fluoro-4- methylphenyl)ethyl]-5-methyl-A-prop-2-ynyl-l,3-thiazol-2-amine (Compound A),(Compound A) as adjunctive treatment to glucocorticoid replacement therapy to control androgens in the patient, said method comprising: administering to the patient the pharmaceutical composition, monitoring the patient for the occurrence of a hypersensitivity reaction associated with the administration of the pharmaceutical composition, andAttorney Docket No. 46696-0217WO1 / 377.WO1.PCT if the hypersensitivity reaction occurs, discontinuing administration of the pharmaceutical composition.

270. The method of claim 269, wherein the hypersensitivity reaction manifests in one or more symptoms selected from throat tightness, angioedema, and generalized rash.

271. The method of claim 269 or 270, wherein the therapeutically effective amount of Compound A is: for an adult, about 100 mg of Compound A administered orally twice daily with a meal in the morning and evening; for a pediatric patient having a body mass of > 55 kg, about 100 mg of Compound A administered orally twice daily with a meal in the morning and evening; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 50 mg of Compound A administered orally twice daily with a meal in the morning and evening; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 25 mg of Compound A administered orally twice daily with a meal in the morning and evening.

272. The method of claim 269 or 270, wherein the therapeutically effective amount of Compound A, when used concomitantly with strong CYP3A4 inducers, is: for an adult, about 200 mg of Compound A administered orally twice daily with a meal in the morning and evening; for a pediatric patient having a body mass of > 55 kg, about 200 mg of Compound A administered orally twice daily with a meal in the morning and evening; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 100 mg of Compound A administered orally twice daily with a meal in the morning and evening; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 50 mg of Compound A administered orally twice daily with a meal in the morning and evening.

273. The method of claim 269 or 270, wherein the therapeutically effective amount of Compound A is:Attorney Docket No. 46696-0217WO1 / 377.WO1.PCT for an adult, about 100 mg of Compound A administered orally with a meal in the morning and about 200 mg of Compound A administered orally with a meal in the evening; for a pediatric patient having a body mass of > 55 kg, about 100 mg of Compound A administered orally with a meal in the morning and about 200 mg of Compound A administered orally with a meal in the evening; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 50 mg of Compound A administered orally with a meal in the morning and about 100 mg of Compound A administered orally with a meal in the evening; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 25 mg of Compound A administered orally with a meal in the morning and about 50 mg of Compound A administered orally with a meal in the evening.

274. The method of claim 269 or 270, wherein the therapeutically effective amount of Compound A is: for an adult, about 200 mg of Compound A administered orally with a meal in the evening; for a pediatric patient having a body mass of > 55 kg, about 200 mg of Compound A administered orally with a meal in the evening; for a pediatric patient having a body mass of 20 kg to < 55 kg, about 100 mg of Compound A administered orally with a meal in the evening; and for a pediatric patient having a body mass of 10 kg to < 20 kg, about 50 mg of Compound A administered orally with a meal in the evening.

275. The method of any one of claims 269 to 274, wherein the glucocorticoid replacement therapy is administered daily to the patient and comprises once daily administration or multiple daily administrations of a glucocorticoid.

276. The method of claim 275, wherein the glucocorticoid is selected from hydrocortisone, prednisone, methylprednisolone, prednisolone, and dexamethasone, or a combination thereof.

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