A Phase 3 Study of the Efficacy and Safety of Relacorilant

Sponsor:

Collaborators:

Information provided by (Responsible Party):

，

Tracking Information

First Submitted Date ^ICMJE

September 27, 2018

First Posted Date ^ICMJE

October 5, 2018

Last Update Posted Date

October 5, 2018

Actual Study Start Date ^ICMJE

October 2018

Estimated Primary Completion Date

January 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

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 ]

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 ]

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) ]

Original Primary Outcome Measures ^ICMJE

Same as current

Current Secondary Outcome Measures ^ICMJE

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
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.
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.
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

Descriptive Information

Brief Title ^ICMJE

A Phase 3 Study of the Efficacy and Safety of Relacorilant

Official Title ^ICMJE

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

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

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.

Study Type ^ICMJE

Interventional

Study Phase

Phase 3

Study Design ^ICMJE

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Masking: Interventional
Masking Description:
Primary Purpose: Treatment

Condition ^ICMJE

Intervention ^ICMJE

Drug: Relacorilant
Relacorilant is supplied as 100 mg capsules for oral dosing.
Other: Placebo
Placebo matched to study drug

Study Arms

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

Recruitment Information

Recruitment Status ^ICMJE

Not yet recruiting

Estimated Enrollment ^ICMJE

130

Original Estimated Enrollment ^ICMJE

Same as current

Estimated Study Completion Date

January 2021

Estimated Primary Completion Date

January 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

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

Sex/Gender

Sexes Eligible for Study:

All

Ages

18 Years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Listed Location Countries ^ICMJE

United States

Removed Location Countries

Administrative Information

Has Data Monitoring Committee

Yes

U.S. FDA-regulated Product

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

IPD Sharing Statement

Plan to Share IPD:

Undecided

Responsible Party

，

Study Sponsor ^ICMJE

Corcept Therapeutics

Collaborators ^ICMJE

Investigators ^ICMJE

Study Director: Andreas Moraitis, MD Corcept Therapeutics

PRS Account

Verification Date

October 2018

^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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