Study to Determine the Prevalence of Hypercortisolism in Patients With Type 2 Diabetes and Treatment With Korlym® (Mifepristone) (CATALYST)

Study Overview
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Brief Summary
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This is a Phase 4 study with 2 parts: Part 1 (Prevalence Phase) is non-interventional and will assess the prevalence of hypercortisolism in a population with difficult to control type 2 diabetes (T2D) (hemoglobin A1c ≥7.5%) despite receiving standard-of-care therapies. Part 2 (Treatment Phase) is a randomized, prospective, placebo-controlled, double-blind multi-center trial that will assess the safety and efficacy of mifepristone treatment in patients with hypercortisolism who have difficult to control T2D despite receiving standard of care therapies.

Detailed Description
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This is a Phase 4 study with 2 parts at approximately 30 sites in the United States (US). Part 1 (Prevalence Phase) is non-interventional and will assess the prevalence of hypercortisolism in a population with difficult to control T2D (HbA1c ≥7.5%) despite receiving standard-of-care therapies. Patients from Part 1 Prevalence Phase who meet eligibility requirements can then enroll in Part 2 and will be randomized 2:1 to receive mifepristone or placebo once daily with food. Randomization will be stratified by presence of adenoma (yes/no). Part 2 (Treatment Phase) is a randomized, prospective, placebo-controlled, double-blind multi-center trial that will assess the safety and efficacy of mifepristone treatment in patients with hypercortisolism who have difficult to control T2D despite receiving standard of care therapies.

Official Title
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Study of Hypercortisolism in Patients With Difficult to Control Type 2 Diabetes Despite Receiving Standard-of-Care Therapies: Prevalence and Treatment With Korlym® (Mifepristone) (CATALYST)

Conditions
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Hypercortisolism, Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Mifepristone 300 MG [Korlym]
* Drug: Placebo for mifepristone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has difficult to control T2D (HbA1c ≥7.5% and ≤11.5%) based on HbA1c performed at screening. AND Taking 3 or more anti-hyperglycemic drugs. OR Taking insulin and other anti-hyperglycemic drugs. OR Taking 2 or more anti-hyperglycemic drugs AND a.) the presence of 1 or more micro-vascular or macro-vascular complication (retinopathy, diabetic nephropathy and chronic kidney disease, diabetic neuropathy, atherosclerotic heart disease with diabetes); AND/OR b.) concomitant hypertension requiring 2 or more anti-hypertension medications. Exclusion Criteria: Has type 1 diabetes mellitus. New-onset diabetes less than 1 year. Systemic glucocorticoid medications exposure (excluding inhalers or topical) within 3 months of screening. Is pregnant or lactating. For women of childbearing potential, have a positive pregnancy test before dexamethasone administration. A woman of childbearing potential includes all women <50 years old, women whose surgical sterilization was performed <6 months ago, and women who have had a menstrual period in the last 12 months. On hemodialysis or has end-stage renal disease. Has severe untreated sleep apnea as judged by the Investigator. Has excessive alcohol consumption (>14 units/week for male, >7 units/week for female) as judged by the Investigator. Has severe psychiatric illness by history (such as schizophrenia or dementia) as judged by the Investigator. Has severe medical or surgical illness as judged by the Investigator. Is a night shift worker, i.e., is awake from approximately 11 PM to 7 AM. Has taken any investigational drug within 4 weeks prior to screening, or within less than 5 times the drug's half-life, whichever is longer. Has had the diagnosis of Cushing syndrome or has used or plans to use any of the following treatments for Cushing syndrome: - Mifepristone, metyrapone, osilodrostat, ketoconazole, fluconazole, aminoglutethimide, etomidate, octreotide, larazotide, pasireotide, long-acting octreotide or pasireotide. Has a history of hypersensitivity or severe reaction to dexamethasone

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mifepristone 300 mg<br>Patients who meet the entry criteria for the Study C-1073-310 will be randomized to receive 600 mg mifepristone for 24 weeks. | Drug: Mifepristone 300 MG [Korlym]<br>* Mifepristone tablets for once daily oral dosing<br>|
| Placebo Comparator: Placebo<br>Patients who meet the entry criteria for the Study C-1073-310 will be randomized to receive placebo for 24 weeks. | Drug: Placebo for mifepristone<br>* Placebo tablets for once daily oral dosing<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prevalence of Hypercortisolism | Prevalence (percentage) of patients with hypercortisolism defined by dexamethasone suppression test (DST) >1.8 μg/dL with dexamethasone level ≥140 ng/dL in patients with difficult to control T2D, defined as HbA1c ≥7.5%. despite receiving standard-of-care therapies. | Screening | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of Treatment on Neoplastic Hypercortisolism | Change in HbA1c from baseline (at randomization) to 24 weeks in patients with neoplastic hypercortisolism who have difficult to control T2D despite receiving standard of care therapies, treated with mifepristone versus placebo. | Baseline Day 1 to week 24 | 
| Effect of Treatment on Non-neoplastic Hypercortisolism | Change in HbA1c from baseline (at randomization) to 24 weeks in patients with non-neoplastic hypercortisolism who have difficult to control T2D despite receiving standard of care therapies, treated with mifepristone versus placebo. | Baseline Day 1 to week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypercortisolism, Diabetes Mellitus, Type 2 Uncontrolled