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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03697109
Recruitment Status : Recruiting
First Posted : October 5, 2018
Last Update Posted : November 22, 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 efficacy, safety and pharmacokinetics (PK) of relacorilant in patients with endogenous Cushing syndrome and concurrent type 2 diabetes mellitus/impaired glucose tolerance and/or 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 : March 2021
Estimated Study Completion Date : March 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 in area under the curve for glucose from Week OL22 to Week RW12 as compared between relacorilant and placebo [ Time Frame: Week Open label 22 (OL22) to Week Randomized withdraw 12 (RW12) ]
  2. In patients with hypertension, the proportion of patients with a loss of response with respect to hypertension from visit OL22 to RW12 [ Time Frame: Week OL22 to Week RW12 ]
    Based on 24hour ABPM defined as 1) an increase in systolic and/or diastolic blood pressure of at least 5 mmHg or 2) any increase or modification in antihypertensive medication from Week OL22 to Week RW12/Early Termination as compared between relacorilant and placebo

  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 (HbA1c at Baseline >6.5%), the mean change from Visit OL22 to RW12 in HbA1c as compared between relacorilant and placebo. [ Time Frame: Open Label week 22 (OL22) to Randomized Withdraw week 12 (RW12) ]
  2. In patients with IGT at Baseline, the mean change from Visit OL22 to RW12 in the 2 hour glucose value of the oGTT [ Time Frame: Week OL22 to week RW12 ]
  3. In patients with hypertension the mean change in SBP or DBP as compared between relacorilant and placebo [ Time Frame: Week OL22 to week RW12 ]
  4. The mean change in body weight, body fat measured with DXA scan and Cushing Quality-of-Life (QoL) score as compared between relacorilant and placebo [ Time Frame: Week OL22 to week RW12 ]
    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.

  5. For patients in either subgroup (DM/IGT or hypertension) the proportion of patients with any increase or modification in diabetes or antihypertensive medication as compared between relacorilant and placebo [ Time Frame: Week OL22 to week RW12 ]
  6. Proportion of patients who worsened, as assessed by the Global Clinical Response, from Week OL22 to Week RW12/ET as compared between relacorilant and placebo [ 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


  7. Mean change in QoL, body fat composition as determined by DXA, Beck Depression inventory-II (BDI-II) and body weight from Baseline to visit OL22 or end of treatment (ET) [ Time Frame: Baseline to week OL22 or End of Treatment (ET) ]
  8. In patients with IGT, the mean change in 2-hour oGTT glucose from Baseline to Visit OL22/ET [ Time Frame: Baseline to week OL22 or ET ]
  9. In patients with DM (HbA1c ≥6.5% at Baseline), the mean change in HbA1c from Baseline to Visit OL22/ET [ Time Frame: Baseline to week OL22 or ET ]
  10. In patients with uncontrolled hypertension the mean change in SBP or DBP from Baseline to visit OL22/ET [ Time Frame: Baseline to week OL22 or ET ]
    Blood pressure will be measured by 24 hour ABPM readings



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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
Show Show 43 study locations
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    
Other Study ID Numbers: CORT125134-455
First Posted: October 5, 2018    Key Record Dates
Last Update Posted: November 22, 2019
Last Verified: November 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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Cushing Syndrome
Syndrome
Disease
Pathologic Processes
Adrenocortical Hyperfunction
Adrenal Gland Diseases
Endocrine System Diseases