Glucocorticoid Receptor Antagonism in the Treatment of Hypercortisolism in Patients With Cortisol-Secreting Adrenal Adenomas or Hyperplasia (GRADIENT): A Phase 3, Randomized, Double-Blind, Placebo-Controlled 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
- 137
- 试验地点
- 45
- 主要终点
- Change in Average 24-hour SBP
研究概览
简要总结
This is a Phase 3, randomized, double-blind, placebo-controlled study to assess the efficacy, and safety of relacorilant to treat hypercortisolism in patients with cortisol-secreting adrenal adenoma or hyperplasia associated with diabetes mellitus/ impaired glucose tolerance (DM/IGT) and/or uncontrolled systolic hypertension (HTN).
详细描述
The primary outcome measures of the study are 1) to assess the efficacy of relacorilant based on blood pressure control at Week 22 compared with placebo, and 2) to assess the safety of relacorilant based on adverse events. Patients will be randomized in a 1:1 ratio to treatment with relacorilant (active drug) or placebo. Patients will receive relacorilant or placebo for 22 weeks. Patients who complete 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
- •Shows lack of cortisol suppression on dexamethasone suppression test
- •Suppressed or low early-morning adrenocorticotropic hormone (ACTH) levels
- •A radiologically confirmed adrenal lesion
- •Has IGT or DM
- •Has uncontrolled HTN
排除标准
- •Has severe, uncontrolled HTN
- •Has poorly controlled DM
- •Has DM Type 1
- •Has significantly abnormal liver test results or severe renal insufficiency
- •Has uncontrolled, clinically significant hypothyroidism or hyperthyroidism
研究组 & 干预措施
Relacorilant
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
Patients will receive relacorilant increased sequentially from 100 mg once daily to a maximum dose of 400 mg once daily.
干预措施: Placebo (Other)
Placebo
Patients will receive placebo matched to study drug once daily.
干预措施: Placebo (Other)
结局指标
主要结局
Change in Average 24-hour SBP
时间窗: Baseline and Week 22
Blood pressure was measured by 24-hour ABPM. The 24-hour average SBP is reported.
Number of Patients With 1 or More Treatment-emergent Adverse Events (TEAEs) as Graded by CTCAE v5.0.
时间窗: Baseline and up to Week 26
次要结局
- Change in Area Under the Concentration-time Curve of Blood Glucose (AUCglucose)(Before and at time intervals up to 2 hours post glucose drink at Baseline and Week 22)
- Change in Average Diastolic Blood Pressure (DBP)(Baseline and Week 22)
- Change in Average Heart Rate (HR)(Baseline and Week 22)
- Change in Average Daytime and Nighttime SBP(Baseline and Week 22)
- Change in Hemoglobin HbA1c for Patients With HbA1c ≥5.7% at Baseline(Baseline and Week 22)
- Change in HbA1c for Patients With HbA1c ≥6.5% at Baseline(Baseline and Week 22)
- Number of Patients With DM Who Achieved 2-hour oGTT Glucose <140 mg/dL(2 hours post glucose drink at Week 22)
- Number of Patients With IGT Who Achieved 2-hour oGTT Glucose <140 mg/dL(2 hours post glucose drink at Week 22)
- Number of Patients With Any Dose Decrease in Antihypertensive Medication(Baseline and Week 22)
- Number of Patients With Any Dose Decrease in Diabetes Medication(Baseline and Week 22)
- Number of Patients With Any Dose Increase or Switch in Antihypertensive Medication(Baseline and Week 22)
- Number of Patients With Any Dose Increase or Switch in Diabetes Medication(Baseline and Week 22)
- Number of Patients With HbA1c ≥6.5% at Baseline Who Achieved HbA1c <6.5%(Baseline and Week 22)
- Number of Patients With Normalization of the 24-hour Average SBP (<130 mm Hg)(Baseline and Week 22)
- Number of Patients With a Reduction in 24-hour Average SBP by ≥5 mm Hg(Baseline and Week 22)