Glucocorticoid Receptor Antagonism in the Treatment of Hypercortisolism in Patients With Cortisol-Secreting Adrenal Adenomas or Hyperplasia (GRADIENT): A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy and Safety of Relacorilant
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Corcept Therapeutics
- Enrollment
- 137
- Locations
- 45
- Primary Endpoint
- Change in Average 24-hour SBP
Study Overview
Brief Summary
This is a Phase 3, randomized, double-blind, placebo-controlled study to assess the efficacy, and safety of relacorilant to treat hypercortisolism in patients with cortisol-secreting adrenal adenoma or hyperplasia associated with diabetes mellitus/ impaired glucose tolerance (DM/IGT) and/or uncontrolled systolic hypertension (HTN).
Detailed Description
The primary outcome measures of the study are 1) to assess the efficacy of relacorilant based on blood pressure control at Week 22 compared with placebo, and 2) to assess the safety of relacorilant based on adverse events. Patients will be randomized in a 1:1 ratio to treatment with relacorilant (active drug) or placebo. Patients will receive relacorilant or placebo for 22 weeks. Patients who complete the study may also be eligible to roll over into an extension study.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Care Provider, Investigator)
Eligibility Criteria
- Ages
- 18 Years to 80 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Shows lack of cortisol suppression on dexamethasone suppression test
- •Suppressed or low early-morning adrenocorticotropic hormone (ACTH) levels
- •A radiologically confirmed adrenal lesion
- •Has IGT or DM
- •Has uncontrolled HTN
Exclusion Criteria
- •Has severe, uncontrolled HTN
- •Has poorly controlled DM
- •Has DM Type 1
- •Has significantly abnormal liver test results or severe renal insufficiency
- •Has uncontrolled, clinically significant hypothyroidism or hyperthyroidism
Arms & Interventions
Placebo
Patients will receive placebo matched to study drug once daily.
Intervention: Placebo (Other)
Relacorilant
Patients will receive relacorilant increased sequentially from 100 mg once daily to a maximum dose of 400 mg once daily.
Intervention: Placebo (Other)
Relacorilant
Patients will receive relacorilant increased sequentially from 100 mg once daily to a maximum dose of 400 mg once daily.
Intervention: Relacorilant (Drug)
Outcomes
Primary Outcomes
Change in Average 24-hour SBP
Time Frame: Baseline and Week 22
Blood pressure was measured by 24-hour ABPM. The 24-hour average SBP is reported.
Number of Patients With 1 or More Treatment-emergent Adverse Events (TEAEs) as Graded by CTCAE v5.0.
Time Frame: Baseline and up to Week 26
Secondary Outcomes
- Change in Area Under the Concentration-time Curve of Blood Glucose (AUCglucose)(Before and at time intervals up to 2 hours post glucose drink at Baseline and Week 22)
- Change in Average Diastolic Blood Pressure (DBP)(Baseline and Week 22)
- Change in Average Heart Rate (HR)(Baseline and Week 22)
- Change in Average Daytime and Nighttime SBP(Baseline and Week 22)
- Change in Hemoglobin HbA1c for Patients With HbA1c ≥5.7% at Baseline(Baseline and Week 22)
- Change in HbA1c for Patients With HbA1c ≥6.5% at Baseline(Baseline and Week 22)
- Number of Patients With DM Who Achieved 2-hour oGTT Glucose <140 mg/dL(2 hours post glucose drink at Week 22)
- Number of Patients With IGT Who Achieved 2-hour oGTT Glucose <140 mg/dL(2 hours post glucose drink at Week 22)
- Number of Patients With Any Dose Decrease in Antihypertensive Medication(Baseline and Week 22)
- Number of Patients With Any Dose Decrease in Diabetes Medication(Baseline and Week 22)
- Number of Patients With Any Dose Increase or Switch in Antihypertensive Medication(Baseline and Week 22)
- Number of Patients With Any Dose Increase or Switch in Diabetes Medication(Baseline and Week 22)
- Number of Patients With HbA1c ≥6.5% at Baseline Who Achieved HbA1c <6.5%(Baseline and Week 22)
- Number of Patients With Normalization of the 24-hour Average SBP (<130 mm Hg)(Baseline and Week 22)
- Number of Patients With a Reduction in 24-hour Average SBP by ≥5 mm Hg(Baseline and Week 22)