Study to Determine the Prevalence of Hypercortisolism in Patients With Type 2 Diabetes and Treatment With Korlym® (Mifepristone) (CATALYST)
- Conditions
- HypercortisolismDiabetes Mellitus, Type 2
- Interventions
- Registration Number
- NCT05772169
- Lead Sponsor
- Corcept Therapeutics
- Brief Summary
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
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1113
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.
• Women on oral contraceptive pills (OCPs) may be screened but must be willing and able to stop OCPs for at least 3 weeks prior to the dexamethasone suppression test.
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Has type 1 diabetes mellitus.
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New-onset diabetes less than 1 year.
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Systemic glucocorticoid medications exposure (excluding inhalers or topical) within 3 months of screening.
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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.
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On hemodialysis or has end-stage renal disease.
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Has severe untreated sleep apnea as judged by the Investigator.
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Has excessive alcohol consumption (>14 units/week for male, >7 units/week for female) as judged by the Investigator.
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Has severe psychiatric illness by history (such as schizophrenia or dementia) as judged by the Investigator.
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Has severe medical or surgical illness as judged by the Investigator.
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Is a night shift worker, i.e., is awake from approximately 11 PM to 7 AM.
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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.
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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.
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Has a history of hypersensitivity or severe reaction to dexamethasone
For Part 2:
Inclusion Criteria:
- Has completed Part 1 of the study with post-DST cortisol level of >1.8 μg/dL and dexamethasone level ≥140 ng/dL
- Will have no change in, or initiation of, diabetes medications within 4 weeks prior to first study drug dose
Exclusion Criteria:
- Has any change in status of exclusion criteria from Part 1
- Requires inhaled glucocorticoid use and may require systemic glucocorticoids if their condition deteriorates during study
- Has severe, poorly controlled hypertension at screening (defined as mean systolic BP >160 mmHg or mean diastolic BP >100 mmHg); must be able to correct to a BP of <160/100 mmHg before first dose of study drug
- Has refractory hypokalemia; must be able to correct to potassium level of ≥4.0 mEq/L before first dose of study drug
- Has poorly controlled hyperthyroidism/hypothyroidism before first dose of study drug (confirmed by TSH or free thyroxine)
- Has plans for adrenalectomy or adrenal nodulectomy
- Has renal insufficiency (eGFR <30 mL/min/1.73m2)
- Has liver test results >3x ULN (ALT or AST) or bilirubin >1.5x ULN
- Takes drugs metabolized by CYP3A and CYP3A substrates with narrow therapeutic ranges
- Receiving systemic corticosteroids that cannot be discontinued
- Uses hormonal contraceptives
- Has a history of unexplained vaginal bleeding, endometrial hyperplasia with atypia, or endometrial carcinoma
- Is pregnant or lactating
- Has a known hypersensitivity to mifepristone or any of the product components
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Mifepristone 300 mg Mifepristone 300 MG [Korlym] Randomized to receive 300 mg mifepristone, titrated to 600 mg mifepristone after 4 weeks with an opportunity to increase to 900 mg mifepristone at week 8 or 12 Placebo Placebo for mifepristone Patients who meet the entry criteria for the Study C-1073-310 will be randomized to receive placebo for 24 weeks
- Primary Outcome Measures
Name Time Method Part 1 Prevalence Phase: Prevalence of Hypercortisolism Screening 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.
Part 2 Treatment Phase: Effect of Treatment on Hypercortisolism with Abnormal Adrenal CT Scan Baseline Day 1 to week 24 Change in HbA1c from baseline (at randomization) to 24 weeks in patients with hypercortisolism and abnormal adrenal CT scan who have difficult to control T2D despite receiving standard of care therapies, treated with mifepristone versus placebo.
Part 2 Treatment Phase: Effect of Treatment on Hypercortisolism without Abnormal Adrenal CT Scan Baseline Day 1 to week 24 Change in HbA1c from baseline (at randomization) to 24 weeks in patients with hypercortisolism and normal adrenal CT scan who have difficult to control T2D despite receiving standard of care therapies, treated with mifepristone versus placebo.
- Secondary Outcome Measures
Name Time Method Part 1 Prevalence Phase: Patient Characteristics Screening Clinical and/or laboratory characteristics of patients with hypercortisolism and of patients with hypercortisolism with/without abnormal adrenal CT scan.
Part 1 Prevalence Phase: Origin of Hypercortisolism Screening Percentage of patients with/without abnormal adrenal CT scan.
Part 2 Treatment Phase: Effect of Treatment Baseline Day 1 to week 24 Change from baseline (at randomization) to 24 weeks in body weight, body mass index, waist circumference, other glycemic metrics, blood pressure, quality of life, antihypertensive medications, etc. in patients with hypercortisolism with/without abnormal adrenal CT scan treated with mifepristone versus placebo.
Trial Locations
- Locations (36)
Site 407
🇺🇸Escondido, California, United States
Site 379
🇺🇸Gardena, California, United States
Site 378
🇺🇸Huntington Park, California, United States
Site 406
🇺🇸La Jolla, California, United States
Site 373
🇺🇸Los Angeles, California, United States
Site 387
🇺🇸Tarzana, California, United States
Site 375
🇺🇸Torrance, California, United States
Site 444
🇺🇸Edgewater, Florida, United States
Site 015
🇺🇸Fort Lauderdale, Florida, United States
Site 009
🇺🇸Atlanta, Georgia, United States
Site 097
🇺🇸Atlanta, Georgia, United States
Site 046
🇺🇸Covington, Kentucky, United States
Site 061
🇺🇸Metairie, Louisiana, United States
Site 377
🇺🇸New Orleans, Louisiana, United States
Site 205
🇺🇸New Orleans, Louisiana, United States
Site 410
🇺🇸Baltimore, Maryland, United States
Site 394
🇺🇸Hyattsville, Maryland, United States
Site 067
🇺🇸Boston, Massachusetts, United States
Site 074
🇺🇸Ann Arbor, Michigan, United States
Site 371
🇺🇸Las Vegas, Nevada, United States
Site 070
🇺🇸Albany, New York, United States
Site 411
🇺🇸Smithtown, New York, United States
Site 181
🇺🇸Chapel Hill, North Carolina, United States
Site 059
🇺🇸Wilmington, North Carolina, United States
Site 436
🇺🇸Cincinnati, Ohio, United States
Site 042
🇺🇸Cleveland, Ohio, United States
Site 077
🇺🇸Columbus, Ohio, United States
Site 195
🇺🇸Columbus, Ohio, United States
Site 435
🇺🇸Grants Pass, Oregon, United States
Site 049
🇺🇸Portland, Oregon, United States
Site 456
🇺🇸Cedar Park, Texas, United States
Site 370
🇺🇸Dallas, Texas, United States
Site 408
🇺🇸Lufkin, Texas, United States
Site 054
🇺🇸San Antonio, Texas, United States
Site 369
🇺🇸San Antonio, Texas, United States
Site 405
🇺🇸Seattle, Washington, United States