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)
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 1,113
- 试验地点
- 36
- 主要终点
- Part 1 Prevalence Phase: Prevalence of Hypercortisolism
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
Double Blind
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
- •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
研究组 & 干预措施
Placebo
Patients who meet the entry criteria for the Study C-1073-310 will be randomized to receive placebo for 24 weeks
干预措施: Placebo for mifepristone (Drug)
Mifepristone 300 mg
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
干预措施: Mifepristone 300 MG [Korlym] (Drug)
结局指标
主要结局
Part 1 Prevalence Phase: Prevalence of Hypercortisolism
时间窗: 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
时间窗: 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
时间窗: 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.
次要结局
- Part 1 Prevalence Phase: Patient Characteristics(Screening)
- Part 1 Prevalence Phase: Origin of Hypercortisolism(Screening)
- Part 2 Treatment Phase: Effect of Treatment(Baseline Day 1 to week 24)