A Study of the Efficacy and Safety of Relacorilant in Patients With Cortisol-Secreting Adrenal Adenomas (GRADIENT)

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

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).

Study Overview

• Status: Completed
• Conditions: Hypercortisolism
• Intervention / Treatment: Drug: Relacorilant; Other: Placebo

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 Type: Interventional
• Enrollment (Actual): 137
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Vienna
    • Vienna, Vienna, Austria, 1090
      • Site 25
• Bulgaria
  • Sofia, Bulgaria, 01431
    • Site 22
• Germany
  • Würzburg, Germany, 97080
    • Site 46
  • Bavaria
    • Munich, Bavaria, Germany, 80336
      • Site 50
• Israel
  • Ramat Gan, Israel, 5265601
    • Site 32
  • Tel Aviv, Israel
    • Site 23
• Italy
  • Milan, Italy
    • Site 34
  • Napoli, Italy, 80131
    • Site 28
  • Padua, Italy, 35128
    • Site 51
  • Rome, Italy, 00161
    • Site 37
  • Torino, Italy, 10126
    • Site 52
  • Milano
    • Milan, Milano, Italy, 20122
      • Site 40
  • Roma
    • Rome, Roma, Italy, 00189
      • Site 31
  • Torino
    • Orbassano, Torino, Italy
      • Site 43
• Poland
  • Gliwice, Poland, 44-102
    • Site 48
  • Krakow, Poland, 31-501
    • Site 47
  • Lublin, Poland
    • Site 35
• Romania
  • Bucharest, Romania, 010825
    • Site 42
  • Bucharest, Romania, 011863
    • Site 38
  • Bucharest, Romania, 011863
    • Site 41
• Spain
  • Málaga, Spain, 29006
    • Site 14
  • Seville, Spain, 41013
    • Site 13
  • Valencia, Spain, 46026
    • Site 26
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Site 27
  • California
    • Stanford, California, United States, 94305
      • Site 17
    • Torrance, California, United States, 90502
      • Site 53
  • Georgia
    • Atlanta, Georgia, United States, 30318
      • Site 07
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Site 16
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • Site 09
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Site 36
  • Massachusetts
    • Fall River, Massachusetts, United States, 02721
      • Site 11
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Site 33
  • Mississippi
    • Jackson, Mississippi, United States, 39202
      • Site 06
  • Nevada
    • Reno, Nevada, United States, 89511
      • Site 54
  • New York
    • Jamaica, New York, United States, 11432
      • Site 10
    • New York, New York, United States, 10021
      • Site 44
  • North Carolina
    • Wilmington, North Carolina, United States, 28401
      • Site 01
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Site 30
    • Columbus, Ohio, United States, 43201-3209
      • Site 21
  • South Carolina
    • Summerville, South Carolina, United States, 29485
      • Site 02
  • Texas
    • Dallas, Texas, United States, 75390
      • Site 20
    • El Paso, Texas, United States, 79935
      • Site 03
    • Fort Worth, Texas, United States, 76132
      • Site 05
    • Houston, Texas, United States, 77079
      • Site 08
  • Washington
    • Spokane, Washington, United States, 99202
      • Site 15

Participation Criteria

Eligibility Criteria

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

Description

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

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: Relacorilant; Patients will receive relacorilant increased sequentially from 100 mg once daily to a maximum dose of 400 mg once daily.	Drug: Relacorilant; Relacorilant is supplied as blister-packed capsules for oral dosing. Relacorilant 400 mg dose consists of 4 relacorilant 100-mg capsules. Relacorilant 100-mg, 200-mg, and 300-mg doses are each given as a combination of 4 capsules containing relacorilant 100-mg and placebo as per the assigned dose.; Other Names: CORT125134; Other: Placebo; Placebo is supplied as blister-packed capsules for oral dosing. Each dose consists of 4 capsules containing placebo.
Placebo Comparator: Placebo; Patients will receive placebo matched to study drug once daily.	Other: Placebo; Placebo is supplied as blister-packed capsules for oral dosing. Each dose consists of 4 capsules containing placebo.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Average 24-hour SBP	Blood pressure was measured by 24-hour ABPM. The 24-hour average SBP is reported.	Baseline and Week 22
Number of Patients With 1 or More Treatment-emergent Adverse Events (TEAEs) as Graded by CTCAE v5.0.		Baseline and up to Week 26

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Area Under the Concentration-time Curve of Blood Glucose (AUCglucose)	AUCglucose was calculated based on results of the plasma 2-hour oGTT.	Before and at time intervals up to 2 hours post glucose drink at Baseline and Week 22
Change in Average Diastolic Blood Pressure (DBP)	Blood pressure was measured by 24-hour ABPM. Daytime average DBP was measured from 06:00 to 21:59. Nighttime average DBP was measure from 22:00 to 05:59.	Baseline and Week 22
Change in Average Heart Rate (HR)	Heart rate was measured by 24-hour ABPM. Daytime average HR was measured from 06:00 to 21:59. Nighttime average HR was measure from 22:00 to 05:59.	Baseline and Week 22
Change in Average Daytime and Nighttime SBP	Blood pressure was measured by 24-hour ABPM. Daytime average SBP was measured from 06:00 to 21:59. Nighttime average SBP was measure from 22:00 to 05:59.	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	Glucose was measured using the 2 hour timepoint of the 2-hour oGTT.	2 hours post glucose drink at Week 22
Number of Patients With IGT Who Achieved 2-hour oGTT Glucose <140 mg/dL	Glucose was measured using the 2 hour timepoint of the 2-hour oGTT.	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)	Blood pressure was measured by 24-hour ABPM Test. Reported is the number of patients with HTN at Baseline who achieved SBP <130 mm Hg at Week 22.	Baseline and Week 22
Number of Patients With a Reduction in 24-hour Average SBP by ≥5 mm Hg	Blood pressure was measured by 24-hour ABPM. Reported is the number of patients with HTN at Baseline who achieved at least a 5 mm Hg reduction in 24-hour average SBP at Week 22.	Baseline and Week 22

Collaborators and Investigators

• Sponsor: Corcept Therapeutics
• Investigators: Study Director: Andreas Moraitis, MD, Corcept Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): July 27, 2020
• Primary Completion (Actual): September 19, 2024
• Study Completion (Actual): September 19, 2024

Study Registration Dates

• First Submitted: February 27, 2020
• First Submitted That Met QC Criteria: March 11, 2020
• First Posted (Actual): March 16, 2020

Study Record Updates

• Last Update Posted (Estimated): September 4, 2025
• Last Update Submitted That Met QC Criteria: August 15, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Hypertension; Type 2 Diabetes; Cortisol; Cushing syndrome; Hypercortisolemia; Impaired Glucose Intolerance; Adrenocorticotropic hormone; Primary Pigmented Nodular Adrenal Disease; Adrenal Adenoma; Adrenal Autonomy; Cushing; Autonomous cortisol secretion; Macronodular adrenal hyperplasia
• Additional Relevant MeSH Terms: Endocrine System Diseases; Vascular Diseases; Cardiovascular Diseases; Neoplasms; Metabolic Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Paraneoplastic Syndromes; Adrenal Gland Diseases; Adrenocortical Hyperfunction; Paraneoplastic Endocrine Syndromes; Nutritional and Metabolic Diseases; Hypertension; Diabetes Mellitus, Type 2; Cushing Syndrome; ACTH Syndrome, Ectopic; Substandard Drugs; Pharmaceutical Preparations; Counterfeit Drugs; relacorilant
• Other Study ID Numbers: CORT125134-456

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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