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

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05772169
• Other study ID #: C-1073-310
• Status: Recruiting
• Phase: Phase 4
• Start date: March 31, 2023
• Est. completion date: July 2024

Study information

• Verified date: May 2024
• Source: Corcept Therapeutics
• Contact: Clinical Trial Lead
• Phone: 650-688-2858
• Email: corceptstudy310[@]corcept.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 1000
• Est. completion date: July 2024
• Est. primary completion date: May 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

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

Related Conditions & MeSH terms

• Adrenocortical Hyperfunction
• Cushing Syndrome
• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Hypercortisolism

Intervention

Drug:
• Mifepristone 300 MG [Korlym]
Mifepristone tablets for once daily oral dosing
• Placebo for mifepristone
Placebo tablets for once daily oral dosing

Locations

Country	Name	City	State
United States	Site 070	Albany	New York
United States	Site 074	Ann Arbor	Michigan
United States	Site 009	Atlanta	Georgia
United States	Site 097	Atlanta	Georgia
United States	Site 410	Baltimore	Maryland
United States	Site 067	Boston	Massachusetts
United States	Site 456	Cedar Park	Texas
United States	Site 181	Chapel Hill	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 046	Covington	Kentucky
United States	Site 370	Dallas	Texas
United States	Site 444	Edgewater	Florida
United States	Site 407	Escondido	California
United States	Site 015	Fort Lauderdale	Florida
United States	Site 379	Gardena	California
United States	Site 435	Grants Pass	Oregon
United States	Site 378	Huntington Park	California
United States	Site 394	Hyattsville	Maryland
United States	Site 406	La Jolla	California
United States	Site 371	Las Vegas	Nevada
United States	Site 373	Los Angeles	California
United States	Site 408	Lufkin	Texas
United States	Site 061	Metairie	Louisiana
United States	Site 205	New Orleans	Louisiana
United States	Site 377	New Orleans	Louisiana
United States	Site 049	Portland	Oregon
United States	Site 054	San Antonio	Texas
United States	Site 369	San Antonio	Texas
United States	Site 405	Seattle	Washington
United States	Site 411	Smithtown	New York
United States	Site 387	Tarzana	California
United States	Site 375	Torrance	California
United States	Site 059	Wilmington	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Corcept Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1 Prevalence Phase: 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
Primary	Part 2 Treatment Phase: Effect of Treatment on Hypercortisolism with Abnormal Adrenal CT Scan	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.	Baseline Day 1 to week 24
Primary	Part 2 Treatment Phase: Effect of Treatment on Hypercortisolism without Abnormal Adrenal CT Scan	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.	Baseline Day 1 to week 24
Secondary	Part 1 Prevalence Phase: Origin of Hypercortisolism	Percentage of patients with/without abnormal adrenal CT scan.	Screening
Secondary	Part 1 Prevalence Phase: Patient Characteristics	Clinical and/or laboratory characteristics of patients with hypercortisolism and of patients with hypercortisolism with/without abnormal adrenal CT scan.	Screening
Secondary	Part 2 Treatment Phase: Effect of Treatment	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.	Baseline Day 1 to week 24
Secondary	Part 2 Treatment Phase: Effect of Treatment	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.	Baseline Day 1 to week 24