A Study of the Efficacy and Safety of Relacorilant in Patients With Endogenous Cushing Syndrome
- Registration Number
- NCT03697109
- Lead Sponsor
- 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 (DM/IGT) and/or uncontrolled hypertension (HTN).
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 152
-
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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Relacorilant (OL Phase) Relacorilant Patients will receive relacorilant increased sequentially from 100 mg once daily to a maximum dose of 400 mg once daily. Relacorilant (RW Phase) Relacorilant Patients who meet any of the response criteria will advance to the RW Phase of the study and receive the same dose of relacorilant as the last dose administered in the OL Phase. Placebo (RW Phase) Placebo Patients who meet any of the response criteria will advance to the RW Phase of the study and receive placebo matched to study drug.
- Primary Outcome Measures
Name Time Method Number of Patients With Loss of Response With Respect to Hypertension During the RW Phase. 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.
Number of Patients With 1 or More Treatment-emergent Adverse Events (TEAEs) as Graded by CTCAE v5.0. OL Phase: Up to 22 weeks; RW Phase: up to 18 weeks after completion of the OL Phase
- Secondary Outcome Measures
Name Time Method Change in Body Weight During the RW Phase Week 22 (end of OL Phase) and Week 36 (Week 12 of RW Phase) Number of Patients With Any Increase or Modification in Diabetes Medication During the RW Phase Week 22 (end of OL Phase) and up to Week 36 (Week 12 of RW Phase) Change in Area Under the Concentration-time Curve of Blood Glucose (AUCglucose) During the RW Phase 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) Change in Hemoglobin HbA1c During the RW Phase Week 22 (end of OL Phase) and Week 36 (Week 12 of RW Phase) Change in 2-hour Plasma Glucose During the RW Phase 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).
Change in SBP and DBP During the RW Phase Week 22 (end of OL Phase) and Week 36 (Week 12 of RW Phase) Blood pressure was measured by 24-hour ABPM.
Trial Locations
- Locations (64)
Site 21
🇺🇸Phoenix, Arizona, United States
Site 36
🇺🇸Los Angeles, California, United States
Site 68
🇺🇸Torrance, California, United States
Site 10
🇺🇸Miami, Florida, United States
Site 14
🇺🇸Atlanta, Georgia, United States
Site 41
🇺🇸Chicago, Illinois, United States
Site 7
🇺🇸Indianapolis, Indiana, United States
Site 58
🇨🇦Montréal, Canada
Site 54
🇩🇪München, Germany
Site 49
🇩🇪Würzburg, Germany
Site 30
🇮🇱Jerusalem, Israel
Site 29
🇮🇱Kfar Saba, Israel
Site 28
🇮🇱Petach Tikva, Israel
Site 69
🇮🇱Tel Aviv, Israel
Site 43
🇮🇹Ancona, Italy
Site 15
🇮🇹Messina, Italy
Site 26
🇮🇹Milano, Italy
Site 12
🇮🇹Napoli, Italy
Site 38
🇮🇹Orbassano, Italy
Site 67
🇮🇹Padova, Italy
Site 40
🇮🇹Roma, Italy
Site 16
🇮🇹Roma, Italy
Site 34
🇳🇱Rotterdam, Netherlands
Site 77
🇵🇱Bialystok, Poland
Site 37
🇵🇱Chrzanów, Poland
Site 59
🇵🇱Kraków, Poland
Site 33
🇵🇱Lublin, Poland
Site 66
🇷🇴Bucharest, Romania
Site 63
🇷🇴Bucharest, Romania
Site 64
🇷🇴Bucharest, Romania
Site 73
🇷🇴Iaşi, Romania
Site 75
🇪🇸Alicante, Spain
Site 25
🇪🇸Girona, Spain
Site 24
🇪🇸Madrid, Spain
Site 22
🇪🇸Málaga, Spain
Site 23
🇪🇸Sevilla, Spain
Site 2
🇺🇸Metairie, Louisiana, United States
Site 45
🇺🇸Baltimore, Maryland, United States
Site 46
🇺🇸Boston, Massachusetts, United States
Site 20
🇺🇸Ann Arbor, Michigan, United States
Site 4
🇺🇸Jackson, Mississippi, United States
Site 13
🇺🇸Saint Louis, Missouri, United States
Site 53
🇺🇸Omaha, Nebraska, United States
Site 72
🇺🇸Reno, Nevada, United States
Site 8
🇺🇸Albany, New York, United States
Site 6
🇺🇸Jamaica, New York, United States
Site 57
🇺🇸New York, New York, United States
Site 35
🇺🇸New York, New York, United States
Site 39
🇺🇸New York, New York, United States
Site 1
🇺🇸Wilmington, North Carolina, United States
Site 17
🇺🇸Columbus, Ohio, United States
Site 11
🇺🇸Oklahoma City, Oklahoma, United States
Site 62
🇺🇸Philadelphia, Pennsylvania, United States
Site 19
🇺🇸Pittsburgh, Pennsylvania, United States
Site 71
🇺🇸Pittsburgh, Pennsylvania, United States
Site 5
🇺🇸Summerville, South Carolina, United States
Site 51
🇺🇸Dallas, Texas, United States
Site 3
🇺🇸El Paso, Texas, United States
Site 65
🇺🇸Houston, Texas, United States
Site 56
🇺🇸Shavano Park, Texas, United States
Site 31
🇺🇸Everett, Washington, United States
Site 47
🇦🇹Vienna, Austria
Site 27
🇧🇬Sofia, Bulgaria
Site 70
🇨🇦Halifax, Nova Scotia, Canada