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
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 152
- 试验地点
- 64
- 主要终点
- Number of Patients With Loss of Response With Respect to Hypertension During the RW Phase.
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Relacorilant (OL Phase)
Patients will receive relacorilant increased sequentially from 100 mg once daily to a maximum dose of 400 mg once daily.
干预措施: Relacorilant (Drug)
Relacorilant (RW Phase)
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.
干预措施: Relacorilant (Drug)
Placebo (RW Phase)
Patients who meet any of the response criteria will advance to the RW Phase of the study and receive placebo matched to study drug.
干预措施: Placebo (Other)
结局指标
主要结局
Number of Patients With Loss of Response With Respect to Hypertension During the RW Phase.
时间窗: 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.
时间窗: OL Phase: Up to 22 weeks; RW Phase: up to 18 weeks after completion of the OL Phase
次要结局
- 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))
- Change in SBP and DBP During the RW Phase(Week 22 (end of OL Phase) and Week 36 (Week 12 of RW Phase))