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

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)

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.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2; Hypercortisolism
• Intervention / Treatment: Drug: Mifepristone 300 MG [Korlym]; Drug: Placebo for mifepristone

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.

• Study Type: Interventional
• Enrollment (Actual): 1113
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • Escondido, California, United States, 92025
      • Site 407
    • Gardena, California, United States, 90247
      • Site 379
    • Huntington Park, California, United States, 90255
      • Site 378
    • La Jolla, California, United States, 92037
      • Site 406
    • Los Angeles, California, United States, 90057
      • Site 373
    • Tarzana, California, United States, 91356
      • Site 387
    • Torrance, California, United States, 90502
      • Site 375
  • Florida
    • Edgewater, Florida, United States, 32132
      • Site 444
    • Fort Lauderdale, Florida, United States, 33312
      • Site 015
  • Georgia
    • Atlanta, Georgia, United States, 30303
      • Site 009
    • Atlanta, Georgia, United States, 30318
      • Site 097
  • Kentucky
    • Covington, Kentucky, United States, 41011
      • Site 046
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • Site 061
    • New Orleans, Louisiana, United States, 70112
      • Site 377
    • New Orleans, Louisiana, United States, 70121
      • Site 205
  • Maryland
    • Baltimore, Maryland, United States, 21239
      • Site 410
    • Hyattsville, Maryland, United States, 20782
      • Site 394
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Site 067
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Site 074
  • Nevada
    • Las Vegas, Nevada, United States, 89128
      • Site 371
  • New York
    • Albany, New York, United States, 12208
      • Site 070
    • Smithtown, New York, United States, 11787
      • Site 411
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • Site 181
    • Wilmington, North Carolina, United States, 28401
      • Site 059
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Site 436
    • Cleveland, Ohio, United States, 44195
      • Site 042
    • Columbus, Ohio, United States, 43210
      • Site 077
    • Columbus, Ohio, United States, 43215
      • Site 195
  • Oregon
    • Grants Pass, Oregon, United States, 97527
      • Site 435
    • Portland, Oregon, United States, 97239
      • Site 049
  • Texas
    • Cedar Park, Texas, United States, 78613
      • Site 456
    • Dallas, Texas, United States, 75230
      • Site 370
    • Lufkin, Texas, United States, 75904
      • Site 408
    • San Antonio, Texas, United States, 78207
      • Site 054
    • San Antonio, Texas, United States, 78229
      • Site 369
  • Washington
    • Seattle, Washington, United States, 98108
      • Site 405

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Drug: Mifepristone 300 MG [Korlym]; Mifepristone tablets for once daily oral dosing
Placebo Comparator: Placebo; Patients who meet the entry criteria for the Study C-1073-310 will be randomized to receive placebo for 24 weeks	Drug: Placebo for mifepristone; Placebo tablets for once daily oral dosing

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1 Prevalence Phase: Origin of Hypercortisolism	Percentage of patients with/without abnormal adrenal CT scan.	Screening
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
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
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

Collaborators and Investigators

• Sponsor: Corcept Therapeutics
• Investigators: Study Director: Daniel Einhorn, MD, Corcept Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): March 31, 2023
• Primary Completion (Actual): November 19, 2024
• Study Completion (Actual): December 18, 2024

Study Registration Dates

• First Submitted: March 6, 2023
• First Submitted That Met QC Criteria: March 6, 2023
• First Posted (Actual): March 16, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 17, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Hypercortisolism; Diabetes Mellitus, Type 2 Uncontrolled
• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Adrenal Gland Diseases; Diabetes Mellitus, Type 2; Diabetes Mellitus; Adrenocortical Hyperfunction; Cushing Syndrome; Contraceptive Agents, Hormonal; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Abortifacient Agents; Reproductive Control Agents; Hormone Antagonists; Luteolytic Agents; Contraceptive Agents, Female; Contraceptive Agents; Contraceptives, Oral; Contraceptives, Oral, Synthetic; Abortifacient Agents, Steroidal; Contraceptives, Postcoital, Synthetic; Contraceptives, Postcoital; Menstruation-Inducing Agents; Mifepristone
• Other Study ID Numbers: C-1073-310

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Upon study completion, results will be presented at relevant scientific congresses and published in a peer-reviewed journal.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No