Diabetes Mellitus, Type 2, Hypercortisolism
Conditions
Keywords
Hypercortisolism, Diabetes Mellitus, Type 2 Uncontrolled
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.
Interventions
DRUGMifepristone 300 MG [Korlym]
Mifepristone tablets for once daily oral dosing
DRUGPlacebo for mifepristone
Placebo tablets for once daily oral dosing
Sponsors
Corcept Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
Double Blind
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion 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
* 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 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Part 1 Prevalence Phase: Origin of Hypercortisolism | Screening | Percentage of patients with/without abnormal adrenal CT scan. |
| 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 2 Treatment Phase: Effect of Treatment | Baseline Day 1 to week 24 | Change in anti-diabetes medication from baseline (at randomization) to 24 weeks in patients with hypercortisolism with/without abnormal adrenal CT scan who have difficult to control T2D despite receiving standard-of-care therapies, treated with mifepristone versus placebo. |
Countries
United States
Outcome results
None listed