Clinical trial NCT05772169: Study to Determine the Prevalence of Hypercortisolism in Patients With Type 2 Diabetes and Treatment With Korlym® (Mifepristone) (CATALYST)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hypercortisolism
Diabetes Mellitus, Type 2
Keywords: Hypercortisolism
Diabetes Mellitus, Type 2 Uncontrolled
Lead sponsor: Corcept Therapeutics
Sponsor class: INDUSTRY
First posted: 2023-03-16
Enrollment: 1113
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

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

Primary outcomes:
measure: Part 1 Prevalence Phase: Prevalence of Hypercortisolism
timeFrame: Screening
measure: Part 2 Treatment Phase: Effect of Treatment on Hypercortisolism with Abnormal Adrenal CT Scan
timeFrame: Baseline Day 1 to week 24
measure: Part 2 Treatment Phase: Effect of Treatment on Hypercortisolism without Abnormal Adrenal CT Scan
timeFrame: Baseline Day 1 to week 24
Secondary outcomes:
measure: Part 1 Prevalence Phase: Origin of Hypercortisolism
timeFrame: Screening
measure: Part 1 Prevalence Phase: Patient Characteristics
timeFrame: Screening
measure: Part 2 Treatment Phase: Effect of Treatment
timeFrame: Baseline Day 1 to week 24
measure: Part 2 Treatment Phase: Effect of Treatment
timeFrame: Baseline Day 1 to week 24
Other outcomes:
Locations:
city: Escondido
country: United States
facility: Site 407
state: California
city: Gardena
country: United States
facility: Site 379
state: California
city: Huntington Park
country: United States
facility: Site 378
state: California
city: La Jolla
country: United States
facility: Site 406
state: California
city: Los Angeles
country: United States
facility: Site 373
state: California
city: Tarzana
country: United States
facility: Site 387
state: California
city: Torrance
country: United States
facility: Site 375
state: California
city: Edgewater
country: United States
facility: Site 444
state: Florida
city: Fort Lauderdale
country: United States
facility: Site 015
state: Florida
city: Atlanta
country: United States
facility: Site 009
state: Georgia
city: Atlanta
country: United States
facility: Site 097
state: Georgia
city: Covington
country: United States
facility: Site 046
state: Kentucky
city: Metairie
country: United States
facility: Site 061
state: Louisiana
city: New Orleans
country: United States
facility: Site 377
state: Louisiana
city: New Orleans
country: United States
facility: Site 205
state: Louisiana
city: Baltimore
country: United States
facility: Site 410
state: Maryland
city: Hyattsville
country: United States
facility: Site 394
state: Maryland
city: Boston
country: United States
facility: Site 067
state: Massachusetts
city: Ann Arbor
country: United States
facility: Site 074
state: Michigan
city: Las Vegas
country: United States
facility: Site 371
state: Nevada
city: Albany
country: United States
facility: Site 070
state: New York
city: Smithtown
country: United States
facility: Site 411
state: New York
city: Chapel Hill
country: United States
facility: Site 181
state: North Carolina
city: Wilmington
country: United States
facility: Site 059
state: North Carolina
city: Cincinnati
country: United States
facility: Site 436
state: Ohio
city: Cleveland
country: United States
facility: Site 042
state: Ohio
city: Columbus
country: United States
facility: Site 077
state: Ohio
city: Columbus
country: United States
facility: Site 195
state: Ohio
city: Grants Pass
country: United States
facility: Site 435
state: Oregon
city: Portland
country: United States
facility: Site 049
state: Oregon
city: Cedar Park
country: United States
facility: Site 456
state: Texas
city: Dallas
country: United States
facility: Site 370
state: Texas
city: Lufkin
country: United States
facility: Site 408
state: Texas
city: San Antonio
country: United States
facility: Site 054
state: Texas
city: San Antonio
country: United States
facility: Site 369
state: Texas
city: Seattle
country: United States
facility: Site 405
state: Washington
Study officials:
affiliation: Corcept Therapeutics
name: Daniel Einhorn, MD
role: STUDY_DIRECTOR
References: