Abstract: The present invention provides octahydro fused azadecalin compounds and methods of using the compounds as glucocorticoid receptor modulators.

Abstract: Many drugs useful in treating cancer are metabolized by CYP2C8 enzymes, by CYP3A4 enzymes, or both. The effects of concomitant administration of relacorilant and paclitaxel, a drug used to treat cancer that is a substrate for both CYP2C8 and CYP3A4, are disclosed herein. Relacorilant potently inhibited CYP2C8 and CYP3A4 in in vitro tests, indicating that co-administration of relacorilant and paclitaxel would increase paclitaxel plasma exposure more than 5-fold in vivo, requiring significant reductions in paclitaxel doses when co-administering paclitaxel with relacorilant. Surprisingly, paclitaxel plasma exposure increased only by about 80% instead of the expected more than 5-fold increase expected with concomitant relacorilant and paclitaxel administration. Applicant discloses safe methods of co-administering relacorilant and paclitaxel by reducing the dose of paclitaxel to about half the paclitaxel dose used when paclitaxel is administered alone.

Abstract: Many drugs useful in treating cancer are metabolized by CYP2C8 enzymes, by CYP3A4 enzymes, or both. The effects of concomitant administration of relacorilant and paclitaxel, a drug used to treat cancer that is a substrate for both CYP2C8 and CYP3A4, are disclosed herein. Relacorilant potently inhibited CYP2C8 and CYP3A4 in in vitro tests, indicating that co-administration of relacorilant and paclitaxel would increase paclitaxel plasma exposure more than 5-fold in vivo, requiring significant reductions in paclitaxel doses when co-administering paclitaxel with relacorilant. Surprisingly, paclitaxel plasma exposure increased only by about 80% instead of the expected more than 5-fold increase expected with concomitant relacorilant and paclitaxel administration. Applicant discloses safe methods of co-administering relacorilant and paclitaxel by reducing the dose of paclitaxel to about half the paclitaxel dose used when paclitaxel is administered alone.

Abstract: Methods are provided for assessing a clinical response to a glucocorticoid receptor antagonist (GRA) in a human subject and for diagnosing Cushing's syndrome.

Abstract: Many drugs useful in treating cancer are metabolized by CYP2C8 enzymes, by CYP3A4 enzymes, or both. The effects of concomitant administration of relacorilant and paclitaxel, a drug used to treat cancer that is a substrate for both CYP2C8 and CYP3A4, are disclosed herein. Relacorilant potently inhibited CYP2C8 and CYP3A4 in in vitro tests, indicating that co-administration of relacorilant and paclitaxel would increase paclitaxel plasma exposure more than 5-fold in vivo, requiring significant reductions in paclitaxel doses when co-administering paclitaxel with relacorilant. Surprisingly, paclitaxel plasma exposure increased only by about 80% instead of the expected more than 5-fold increase expected with concomitant relacorilant and paclitaxel administration. Applicant discloses safe methods of co-administering relacorilant and paclitaxel by reducing the dose of paclitaxel to about half the paclitaxel dose used when paclitaxel is administered alone.

Abstract: The present invention provides heteroaryl ketone fused azadecalin compounds and methods of using the compounds as glucocorticoid receptor modulators, including their use for treating amyotrophic lateral sclerosis (ALS).

Abstract: Relacorilant is useful in the treatment of hypercortisolism and cancer. Many drugs useful in treating hypercortisolism or cancer are metabolized by CYP2C9 enzymes. The effects of concomitant administration of relacorilant and a CYP2C9 substrate are disclosed herein. Relacorilant potently inhibited CYP2C9 in an in vitro test, indicating that co-administration of relacorilant and a CYP2C9 substrate would be expected to increase the CYP2C9 substrate plasma exposure more than five-fold in vivo. Significant reductions in CYP2C9 substrate doses would be expected to be required when administered with relacorilant. Surprisingly, no such increase in plasma exposure was seen in human studies. Applicant discloses that relacorilant may be safely co-administered with unmodified doses of a CYP2C9 substrate such as, e.g., tolbutamide, glimepiride, and glipizide.

Abstract: Relacorilant is useful in the treatment of cancer and hypercortisolism. Many drugs useful in treating cancer or hypercortisolism are metabolized by CYP2C8 enzymes. The effects of concomitant administration of relacorilant and a CYP2C8 substrate are disclosed herein. Relacorilant potently inhibited CYP2C8 in an in vitro test, indicating that co-administration of relacorilant and a CYP2C8 substrate would be expected to increase the CYP2C8 substrate plasma exposure more than five-fold in vivo. Significant reductions in CYP2C8 substrate doses would be expected to be required when administered with relacorilant. Surprisingly, no such increase in plasma exposure was seen in human studies. Applicant discloses that relacorilant may be safely co-administered with unmodified doses of CYP2C8 substrates such as pioglitazone, rosiglitazone, and enzalutamide. Relacorilant and unmodified doses of enzalutamide may be co-administered to treat cancer, e.g., prostate cancer.

Abstract: The present invention provides a class of pyrimidinedione cyclohekenyl compounds and methods of using these compounds as glucocorticoid receptor modulators.

Abstract: This invention provides a method that combines a checkpoint inhibitor and a glucocorticoid receptor modulator to treat cancer, e.g., a checkpoint inhibitor sensitive cancer.

Abstract: Methods of Treating Antipsychotic-Induced Weight Gain with Miricorilant Methods and compositions for treating a subject at risk of, or suffering from antipsychotic-induced weight gain are disclosed. The methods include administration of a cyclohexyl pyrimidine glucocorticoid receptor modulator (GRM) such as miricorilant (CORT118335) to a patient receiving, or who has received, or who is expected to receive, an antipsychotic drug such as olanzapine, risperidone, clozapine, or other weight-inducing antipsychotic medication. The GRM (e.g., miricorilant) may be orally administered. Administration of such a GRM along with antipsychotic medication may reduce the amount of weight, or reduce the rate of weight gain, or prevent weight gain, otherwise due to antipsychotic medication alone. The methods may reverse weight gain in a patient previously administered antipsychotic medication.

Abstract: The present invention provides heteroaryl ketone fused azadecalin compounds and methods of using the compounds as glucocorticoid receptor modulators.

Abstract: The present invention provides octahydro fused azadecalin compounds and methods of using the compounds as glucocorticoid receptor modulators.

Abstract: This invention provides a method that combines a checkpoint inhibitor and a glucocorticoid receptor modulator to treat cancer, e.g., a checkpoint inhibitor sensitive cancer.

Abstract: The present invention provides heteroaryl ketone fused azadecalin compounds and methods of using the compounds as glucocorticoid receptor modulators.

Abstract: The present invention provides treatment of fatty liver disease using a class of pyrimidinedione cyclohexyl compounds.

Abstract: Methods for treating a subject having a cancerous tumor are disclosed. The methods comprise administering to the subject an effective amount of a non-steroidal selective glucocorticoid receptor modulator (SGRM) and an effective amount of a chemotherapeutic agent. The tumor may be cervical cancer. The SGRM may be a fused azadecalin. In embodiments, the SGRM may be a heteroaryl ketone fused azadecalin or an octahydro fused azadecalin.

Abstract: Methods and compositions for treating a subject hosting a non-ACTH-secreting pancreatic tumor are disclosed. The methods include administering to the subject a chemotherapeutic agent and a glucocorticoid receptor modulator (GRM), preferably a selective glucocorticoid receptor modulator (SGRM), to reduce the tumor load in the subject. The GRM may be a nonsteroidal GRM, and may be a nonsteroidal SGRM. The non-ACTH-secreting pancreatic tumor may be an exocrine pancreatic tumor. The nonsteroidal SGRM may be a nonsteroidal compound comprising: a fused azadecalin structure; a heteroaryl ketone fused azadecalin structure; or an octahydro fused azadecalin structure. Pharmaceutical compositions comprising a chemotherapeutic agent and a GRM are disclosed. The GRM in such pharmaceutical compositions may be a nonsteroidal GRM, and may be a SGRM, such as a nonsteroidal SGRM.

Abstract: Methods for treating a subject having a cancerous tumor are disclosed. The methods comprise administering to the subject an effective amount of a non-steroidal selective glucocorticoid receptor modulator (SGRM) and an effective amount of a chemotherapeutic agent. The tumor may be cervical cancer. The SGRM may be a fused azadecalin. In embodiments, the SGRM may be a heteroaryl ketone fused azadecalin or an octahydro fused azadecalin.

Abstract: The present invention provides treatment of fatty liver disease using a class of pyrimidinedione cyclohexyl compounds.