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

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ClinicalTrials.gov Identifier: NCT03697109
Recruitment Status : Recruiting
First Posted : October 5, 2018
Last Update Posted : May 13, 2019
Sponsor:
Information provided by (Responsible Party):
Corcept Therapeutics

Brief Summary:
This is a Phase 3, double-blind, placebo-controlled, randomized-withdrawal study to assess the safety and efficacy of relacorilant in patients with endogenous Cushing syndrome and concurrent 1) Type 2 diabetes mellitus/impaired glucose tolerance and/or 2) uncontrolled hypertension

Condition or disease Intervention/treatment Phase
Cushing Syndrome Drug: Relacorilant Other: Placebo Phase 3

Detailed Description:
This Phase 3 study involves two phases, an open-label (OL) phase and a randomized-withdrawal (RW) phase. Patients will dose-escalate in 100 mg increments to a target dose of 400 mg orally once daily during the open-label phase. Patients will remain on open-label treatment until week 22 at which time they will be evaluated for the randomized-withdrawal phase based on pre-defined 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 randomization will end treatment and may be eligible to roll over into an extension safety study. Patients who complete the randomized-withdrawal phase of the study may also be eligible to roll over into an extension study.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 130 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : October 16, 2018
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : January 2021


Arm Intervention/treatment
Experimental: Relacorilant (open-label phase)
The dose of relacorilant will be increased sequentially from 100 mg orally once daily to a target dose of 400 mg once daily.
Drug: Relacorilant
Relacorilant is supplied as 100 mg capsules for oral dosing.
Other Name: CORT125134

Experimental: Relacorilant (randomized-withdrawal phase)
Patients who meet any of the response criteria will advance to the randomized-withdrawal phase of the study and receive the same highest dose as in the open-label phase.
Drug: Relacorilant
Relacorilant is supplied as 100 mg capsules for oral dosing.
Other Name: CORT125134

Placebo Comparator: Placebo (randomized-withdrawal phase)
Placebo matched to study drug
Other: Placebo
Placebo matched to study drug




Primary Outcome Measures :
  1. In patients with diabetes mellitus/impaired glucose tolerance (DM/IGT), the mean change from Week OL22 to Week RW12 or Early Termination (ET) in the 2-hour oGTT glucose (mg/dL) as compared between relacorilant and placebo [ Time Frame: Week OL22 to Week RW12 ]
  2. In patients with hypertension, the proportion of patients with 1) an increase in systolic or diastolic blood pressure of at least 5 mmHg or 2) any increase in antihypertensive medication from OL22 to RW12/ET as compared between relacorilant and placebo [ Time Frame: Week OL22 to Week RW12 ]
  3. In all patients, assessment of safety based on treatment-emergent adverse events (TEAEs) as graded by CTCAE v5.0. [ Time Frame: Screening through Post Treatment Follow-up (up to 48 weeks) ]

Secondary Outcome Measures :
  1. In patients with DM/IGT, the proportion of patients who meet any of the DM/IGT response criteria at the end of the OL phase (Week OL22). [ Time Frame: Open Label Phase (Baseline to Week OL22) ]

    - The DM/IGT response criteria for the Open-Label Phase (assessed at Week OL22) are:

    • HbA1c has decreased by ≥0.5% from Baseline
    • The 2-hour oGTT glucose is normalized (<140 mg/dL) or decreased by ≥50 mg/dL from Baseline
    • Total daily insulin dose has decreased by ≥25% or daily sulfonylurea dose has decreased from Baseline by ≥50% and HbA1c is unchanged or decreased compared with Baseline

  2. In patients with hypertension, the proportion of patients who meet any of the hypertension response criteria at the end of the OL phase (Week OL22) [ Time Frame: Open Label Phase (Baseline to Week OL22) ]

    - The hypertension response criteria for the Open-Label Phase (assessed at Week OL22) are:

    • ≥5 mm Hg decrease in SBP and/or DBP from Baseline without worsening of either, based on 24-hour ABPM
    • A reduction in the number or dose of BP medications, and SBP and DBP by ABPM are no worse than at Baseline.

  3. The mean change from Baseline to Week OL22 in Cushing Quality-of-Life (QoL) score [ Time Frame: Open Label Phase (Baseline to Week OL22) ]
    The Cushing Quality of Life (QoL) patient questionnaire, which evaluates the health-related QoL in patients with Cushing syndrome (Webb et al. 2008), will be administered to all patients. It comprises 12 questions, each with 5 possible answers. The total score ranges from 12‒60. 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. Lower values reflect lower quality of life.

  4. Proportion of patients who worsened, as assessed by the Global Clinical Response, from Week OL22 to Week RW12/ET [ Time Frame: Week OL22 to Week RW12 ]

    Global Clinical Response will be scored in 7 categories: glucose, blood pressure, body composition, clinical appearance, strength, psychiatric health/ cognitive function, Cushing QoL score.

    An independent Data Review Board (DRB) will review the 7 categories of clinical parameters above to evaluate whether a patient's signs and symptoms of Cushing syndrome have changed and will rate each patient's overall response based on the totality of signs and symptoms as +1 (improved), 0 (unchanged), or −1 (worsened) at every visit after Baseline. Each patient's final score will be the median of the 3 ratings




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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03697109


Contacts
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Contact: Clinical Trial Lead 650-327-3270 CorceptStudy455@corcept.com

Locations
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United States, Colorado
Site 9 Recruiting
Aurora, Colorado, United States, 80045
United States, Florida
Site 10 Recruiting
Miami, Florida, United States, 33136
United States, Georgia
Site 14 Recruiting
Atlanta, Georgia, United States, 30318
United States, Indiana
Site 7 Recruiting
Indianapolis, Indiana, United States, 46202
United States, Louisiana
Site 2 Recruiting
Metairie, Louisiana, United States, 70006
United States, Mississippi
Site 4 Recruiting
Jackson, Mississippi, United States, 39202
United States, Missouri
Site 13 Recruiting
Saint Louis, Missouri, United States, 63110
United States, New York
Site 8 Recruiting
Albany, New York, United States, 12206
Site 6 Recruiting
Jamaica, New York, United States, 11432
United States, North Carolina
Site 1 Recruiting
Wilmington, North Carolina, United States, 28401
United States, Oklahoma
Site 11 Recruiting
Oklahoma City, Oklahoma, United States, 73104
United States, South Carolina
Site 5 Recruiting
Summerville, South Carolina, United States, 29485
United States, Texas
Site 3 Recruiting
El Paso, Texas, United States, 79935
Italy
Site 12 Recruiting
Napoli, Italy, 80131
Sponsors and Collaborators
Corcept Therapeutics
Investigators
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Study Director: Andreas Moraitis, MD Corcept Therapeutics

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Responsible Party: Corcept Therapeutics
ClinicalTrials.gov Identifier: NCT03697109     History of Changes
Other Study ID Numbers: CORT125134-455
First Posted: October 5, 2018    Key Record Dates
Last Update Posted: May 13, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Corcept Therapeutics:
Cushing syndrome
Cushing disease
Hypercortisolemia
Cushingoid
Type 2 Diabetes
Impaired Glucose Intolerance
Hypertension
Adrenocorticotropic hormone
Primary Pigmented Nodular Adrenal Disease
Moon Facies
Dorsocervical Fat Pad
Adrenal Adenoma
Adrenal Autonomy
Cortisol
Cushing

Additional relevant MeSH terms:
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Syndrome
Cushing Syndrome
Disease
Pathologic Processes
Adrenocortical Hyperfunction
Adrenal Gland Diseases
Endocrine System Diseases