Study to Determine the Prevalence of Hypercortisolism in Patients With Type 2 Diabetes and Treatment With Korlym® (Mifepristone) (CATALYST)
Status and phase
Conditions
Treatments
Details and patient eligibility
About
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.
Full 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.
Enrollment
Sex
Ages
Volunteers
Inclusion and exclusion criteria
For Part 1:
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.
• 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.
Exclusion Criteria:
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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
Trial design
Primary purpose
Allocation
Interventional model
Masking
1,000 participants in 2 patient groups, including a placebo group
Trial contacts and locations
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Central trial contact
Clinical Trial Lead
Data sourced from clinicaltrials.gov
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