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Completed

NCT Number: NCT03697109

A Study of the Efficacy and Safety of Relacorilant in Patients With Endogenous Cushing Syndrome

This is a Phase 3, double-blind, placebo-controlled, randomized-withdrawal study to assess the efficacy, safety and pharmacokinetics (PK) of relacorilant in patients with endogenous Cushing syndrome and concurrent type 2 diabetes mellitus/impaired glucose tolerance (DM/IGT) and/or uncontrolled hypertension (HTN).

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Key information

Conditions

Cushing Syndrome ACTH Syndrome, Ectopic Adrenal Gland Diseases Adrenocortical Hyperfunction Brain Diseases Cardiovascular Diseases Central Nervous System Diseases Diabetes Mellitus Diabetes Mellitus, Type 2 Endocrine System Diseases Glucose Metabolism Disorders Hyperpituitarism Hypertension Hypothalamic Diseases Metabolic Diseases Neoplasms Nervous System Diseases Nutritional and Metabolic Diseases Paraneoplastic Endocrine Syndromes Paraneoplastic Syndromes Pituitary ACTH Hypersecretion Pituitary Diseases Vascular Diseases

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Site 47, Vienna, Austria

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About this study

The primary outcome is the assessment of efficacy of relacorilant treatment based on sustained blood pressure control during the Randomized-withdrawal (RW) Phase, wherein patients who had achieved the blood pressure response criteria during the Open-label (OL) Phase are randomized to receive either relacorilant or placebo for 12 weeks.

Patients in the OL Phase will dose-escalate in 100 mg increments to a maximum dose of 400 mg orally once daily. Patients will remain on OL treatment until Week 22 at which time they will be evaluated for the RW Phase based on predefined hyperglycemia and hypertension response criteria. Eligible patients will then be randomized to receive either relacorilant or placebo at a 1:1 ratio for 12 weeks. Patients who do not meet the criteria for the RW Phase will end treatment and may be eligible to roll over into an extension safety study. Patients who complete the RW Phase of the study may also be eligible to roll over into an extension study.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Has a confirmed diagnosis of endogenous Cushing syndrome
  • Meets at least 1 of the following criteria:
  • Has Type 2 diabetes mellitus
  • Has impaired glucose tolerance
  • Has hypertension.

Exclusion criteria

  • Has non-endogenous source of hypercortisolism
  • Has uncontrolled, clinically significant hypothyroidism or hyperthyroidism
  • Has poorly controlled hypertension
  • Has poorly controlled diabetes mellitus
  • Has severe renal insufficiency.

Treatment and study plan

Relacorilant

Drug

Relacorilant is supplied as 100 mg capsules for oral dosing.

Other names: CORT125134

Placebo

Other

Placebo matched to study drug

Primary outcomes

  1. Number of Patients With Loss of Response With Respect to Hypertension During the RW Phase.

    Time frame: Week 22 (end of OL Phase) and Week 36 (Week 12 of RW Phase)

    Loss of response with respect to HTN was measured using 6 criteria: 1) an increase in SBP of at least 5 mm Hg, 2) an increase in DBP of at least 5 mm Hg, 3) an increase in SBP and/or DBP of at least 5 mm Hg, 4) use of HTN rescue medication, 5) treatment discontinuation, and 6) missing 24-hour ambulatory blood pressure monitoring (ABPM) measurement at the end of the RW Phase. Blood pressure was measured using ABPM. Use of rescue medication was defined as any increase, modification, or addition of antihypertensive medication due to worsening HTN. Treatment discontinuation reports the number of patients who discontinued study treatment in the RW Phase for any reason.

  2. Number of Patients With 1 or More Treatment-emergent Adverse Events (TEAEs) as Graded by CTCAE v5.0.

    Time frame: OL Phase: Up to 22 weeks; RW Phase: up to 18 weeks after completion of the OL Phase

Secondary outcomes

  1. Change in Area Under the Concentration-time Curve of Blood Glucose (AUCglucose) During the RW Phase

    Time frame: Before and at time intervals up to 2 hours post glucose drink at Week 22 (end of OL Phase) and Week 36 (Week 12 of RW Phase)

  2. Change in Hemoglobin HbA1c During the RW Phase

    Time frame: Week 22 (end of OL Phase) and Week 36 (Week 12 of RW Phase)

  3. Change in 2-hour Plasma Glucose During the RW Phase

    Time frame: Before and 2 hours post glucose drink at Week 22 (end of OL Phase) and Week 36 (Week 12 of RW Phase)

    Plasma glucose was measured using the 2-hour Oral Glucose Tolerance Test (oGTT).

  4. Change in SBP and DBP During the RW Phase

    Time frame: Week 22 (end of OL Phase) and Week 36 (Week 12 of RW Phase)

    Blood pressure was measured by 24-hour ABPM.

  5. Change in Body Weight During the RW Phase

    Time frame: Week 22 (end of OL Phase) and Week 36 (Week 12 of RW Phase)

  6. Number of Patients With Any Increase or Modification in Diabetes Medication During the RW Phase

    Time frame: Week 22 (end of OL Phase) and up to Week 36 (Week 12 of RW Phase)

Other outcomes

  1. Change in Cushing Quality of Life (QoL) Normalized Total Score During the RW Phase

    Time frame: Week 22 (end of OL Phase) and Week 36 (Week 12 of RW Phase)

    The Cushing QoL patient questionnaire, which evaluates the health-related QoL in patients with Cushing syndrome, comprises 12 questions, each with 5 possible answers. The total score ranges from 12-60, with a higher score indicating improvement in QoL. The Cushing QoL instrument addresses known problem areas associated with Cushing syndrome including trouble sleeping, wound healing/bruising, irritability/mood swings/anger, self-confidence, physical changes, ability to participate in activities, interactions with friends and family, memory issues, and future health concerns.

  2. Percent Change in Tissue Fat Mass During the RW Phase

    Time frame: Week 22 (end of OL Phase) and Week 36 (Week 12 of RW Phase)

    Tissue fat mass was measured by dual energy X-ray absorptiometry (DXA) scan. Reported are change in in absolute tissue fat mass and change in percent tissue fat mass.

  3. Number of Patients Who Worsened, as Assessed by the Global Clinical Response, During the RW Phase

    Time frame: Week 22 (end of OL Phase) and up to Week 36 (Week 12 of RW Phase)

    The Global Clinical Response assessment measures the patient's signs and symptoms of endogenous hypercortisolism in 7 clinical categories: 1) glucose parameters, 2) blood pressure parameters, 3) body composition parameters, 4) clinical appearance, 5) strength parameters, 6) psychiatric health/cognitive function parameters, and 7) quality of life using the Cushing QoL score. The overall response based on the totality of signs and symptoms is rated as +1 for improved, 0 for unchanged, and -1 for worsened. Each patient's final score is the median of ratings given by 3 members of the Data Review Board.

  4. Change in Percent Tissue Fat Mass During the OL Phase

    Time frame: Baseline and Week 22 (end of OL Phase)

    Tissue fat mass was measured by DXA scan.

  5. Change in Cushing QoL Normalized Total Score During the OL Phase

    Time frame: Baseline and Week 22 (end of OL Phase)

    The Cushing QoL patient questionnaire, which evaluates the health-related QoL in patients with Cushing syndrome, comprises 12 questions, each with 5 possible answers. The total score ranges from 12-60, with a higher score indicating improvement in QoL. The Cushing QoL instrument addresses known problem areas associated with Cushing syndrome including trouble sleeping, wound healing/bruising, irritability/mood swings/anger, self-confidence, physical changes, ability to participate in activities, interactions with friends and family, memory issues, and future health concerns.

  6. Change in Beck Depression Inventory-II (BDI-II) Score During the OL Phase

    Time frame: Baseline and Week 22 (end of OL Phase)

    The BDI-II is a 21-question self-report inventory that measures depression. Each answer is scored with values of 0 to 3. The total score ranges from 0 to 63. Scores of 0 to 13 indicate minimal depression, 14 to 19; mild depression; 20 to 28; moderate depression; 29 to 63; severe depression.

  7. Mean Change From Baseline in Body Weight During the OL Phase

    Time frame: Baseline and Week 22 (end of OL Phase)

  8. Change in 2-hour Plasma Glucose During the OL Phase

    Time frame: Baseline and Week 22 (end of OL Phase)

    Plasma glucose was measured using the 2-hour oGTT.

  9. Change in Hemoglobin HbA1c During the OL Phase

    Time frame: Baseline and Week 22 (end of OL Phase)

  10. Change in SBP and DBP During the OL Phase

    Time frame: Baseline and Week 22 (end of OL Phase)

    Blood pressure was measured by 24-hour ABPM.

Sponsors and collaborators

Lead sponsor

Corcept Therapeutics

Industry

Registry information

Official study title

Glucocorticoid Receptor Antagonism in the Treatment of Cushing Syndrome (GRACE): A Phase 3, Double-Blind, Placebo-Controlled, Randomized-Withdrawal Study of the Efficacy and Safety of Relacorilant

Acronym: GRACE

Important dates

Study start
2018
Primary completion
2024
Study completion
2024
First posted
Oct 5, 2018
Registry last updated
Jul 16, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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