Methods and compositions are disclosed for diagnosing a patient suspected of suffering from, and for treating a patient suffering from, a disorder such as hypercortisolemia, metabolic syndrome, pre-diabetes, diabetes, Cushing's syndrome, Cushing's Disease, hyperglycemia secondary to hypercortisolemia, a liver disease, a cardiac disorder, high blood pressure, a blood clotting disorder, a cancer, a psychological disorder, weight gain, a disorder of glucose control, a bone disorder (e.g., osteoporosis), hypogonadism, pseudoacromegaly, pituitary tumors, functional hypercortisolism, ACTH secreting tumors, peripheral neuropathy, dyslipidemia and other disorders.

The methods and compositions include administration of a heteroaryl-ketone fused azadecalin glucocorticoid receptor modulator (GRM). The preferred heteroaryl-ketone fused azadecalin GRM is relacorilant ((R)-(1-(4-fluorophenyl)-6-((1-methyl-1H-pyrazol-4-yl)sulfonyl)-4,4a,5,6,7,8-hexahydro-1H-pyrazolo[3,4-g]isoquinolin-4a-yl)(4-(trifluoromethyl)pyridin-2-yl)methanone). In some cases, the GRM (e.g., relacorilant) is orally administered. In some cases, the GRM (e.g., relacorilant) is orally administered without food.

The present invention further provides method of preparing nanocrystals of a hydrophobic therapeutic gent such as fluticasone or triamcinolone, pharmaceutical compositions (e.g., topical or intranasal compositions) thereof and methods for treating and/or preventing the signs and/or symptoms of disorders such as blepharitis, Meibomian gland dysfuntion or skin inflammation or a respiratory disease (e.g., asthma).

Methods and compositions are disclosed for diagnosing a patient suspected of suffering from, and for treating a patient suffering from, a disorder such as hypercortisolemia, metabolic syndrome, pre-diabetes, diabetes, Cushing's syndrome, Cushing's Disease, hyperglycemia secondary to hypercortisolemia, a liver disease, a cardiac disorder, high blood pressure, a blood clotting disorder, a cancer, a psychological disorder, weight gain, a disorder of glucose control, a bone disorder (e.g., osteoporosis), hypogonadism, pseudoacromegaly, pituitary tumors, functional hypercortisolism, ACTH secreting tumors, peripheral neuropathy, dyslipidemia and other disorders.

The methods and compositions include administration of a heteroaryl-ketone fused azadecalin glucocorticoid receptor modulator (GRM). The preferred heteroaryl-ketone fused azadecalin GRM is relacorilant ((R)-(1-(4-fluorophenyl)-6-((1-methyl-1H-pyrazol-4-yl)sulfonyl)-4,4a,5,6,7,8-hexahydro-1H-pyrazolo[3,4-g]isoquinolin-4a-yl)(4-(trifluoromethyl)pyridin-2-yl)methanone). In some cases, the GRM (e.g., relacorilant) is orally administered. In some cases, the GRM (e.g., relacorilant) is orally administered without food.

Methods and compositions are disclosed for diagnosing a patient suspected of suffering from, and for treating a patient suffering from, a disorder such as hypercortisolemia, metabolic syndrome, pre-diabetes, diabetes, Cushing's syndrome, Cushing's Disease, hyperglycemia secondary to hypercortisolemia, a liver disease, a cardiac disorder, high blood pressure, a blood clotting disorder, a cancer, a psychological disorder, weight gain, a disorder of glucose control, a bone disorder (e.g., osteoporosis), hypogonadism, pseudoacromegaly, pituitary tumors, functional hypercortisolism, ACTH secreting tumors, peripheral neuropathy, dyslipidemia and other disorders.

The methods and compositions include administration of a heteroaryl-ketone fused azadecalin glucocorticoid receptor modulator (GRM). The preferred heteroaryl-ketone fused azadecalin GRM is relacorilant ((R)-(1-(4-fluorophenyl)-6-((1-methyl-1H-pyrazol-4-yl)sulfonyl)-4,4a,5,6,7,8-hexahydro-1H-pyrazolo[3,4-g]isoquinolin-4a-yl)(4-(trifluoromethyl)pyridin-2-yl)methanone). In some cases, the GRM (e.g., relacorilant) is orally administered. In some cases, the GRM (e.g., relacorilant) is orally administered without food.

The disclosure provides a method of treatment for glucocorticoid excess in a patient in need thereof, comprising administering to the patient a pseudo-irreversible HSD-1 inhibitor.

The disclosure provides a method of treatment for glucocorticoid excess in a patient in need thereof, comprising administering to the patient a pseudo-irreversible HSD-1 inhibitor.

A pharmaceutical composition is described. The chemically stable pharmaceutical composition comprises a drug component consisting of a) mometasone, mometasone furoate, or a combination thereof and b) formoterol fumarate dihydrate. The chemically stable pharmaceutical composition further comprises a propellant component comprising at least 90 weight % 1,1-difluoroethane (R-152a), and ethanol in an amount of from 0.5 to 10% by weight based on the total weight of the chemically stable pharmaceutical composition. The drug component comprises from 0.01 to 1.0 weight % of the total weight of the chemically stable pharmaceutical composition. The drug component is the sole drug component in the pharmaceutical composition. The chemically stable pharmaceutical composition is free of acid stabilizers. The chemically stable pharmaceutical composition is surfactant-free.

A variety of nanoparticles or microparticles may be used to treat diseases such as restenosis or blood clots. For example, a nanoparticle or microparticle may include a core having a biodegradable polymer, an exterior having hydrophilic moieties. and a therapeutic agent. The nanoparticles may include targeting moieties that target the nanoparticle or microparticle to an arterial lesion. The nanoparticle or microparticle may include an exterior shell around the core to increase stability of the nanoparticle or microparticle. The nanoparticle or microparticle may include a magnetic particle to allow targeted delivery of the nanoparticle or microparticle via a magnetic field. The nanoparticles or microparticles may be coated on a medical device, such as a catheter balloon or a stent, or may be delivered systemically or locally to patients in need thereof.

A variety of nanoparticles or microparticles may be used to treat diseases such as restenosis or blood clots. For example, a nanoparticle or microparticle may include a core having a biodegradable polymer, an exterior having hydrophilic moieties. and a therapeutic agent. The nanoparticles may include targeting moieties that target the nanoparticle or microparticle to an arterial lesion. The nanoparticle or microparticle may include an exterior shell around the core to increase stability of the nanoparticle or microparticle. The nanoparticle or microparticle may include a magnetic particle to allow targeted delivery of the nanoparticle or microparticle via a magnetic field. The nanoparticles or microparticles may be coated on a medical device, such as a catheter balloon or a stent, or may be delivered systemically or locally to patients in need thereof.

The present disclosure relates to stereodefined polycyclic (e.g., tetracyclic) compounds that contain quaternary centers at one or multiple ring fusions, synthetic methods for preparing such compounds, and methods of using such compounds to treat a disease, such as a brain tumor and, particularly, a glioma.