A Phase III, Multi-center, Randomized, Double-blind, 48 Week Study With an Initial 12 Week Placebo-controlled Period to Evaluate the Safety and Efficacy of Osilodrostat in Patients With Cushing's Disease
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 73
- 试验地点
- 7
- 主要终点
- Percentage of Randomized Participants With a Complete Response
研究概览
简要总结
The purpose of this study was to confirm efficacy and safety of osilodrostat for the treatment of patients with Cushing's disease who are candidates for medical therapy.
详细描述
The study LCI699C2302 (LINC-4) is a multi-center, randomized, double-blind study to evaluate the safety and efficacy of osilodrostat in patients with Cushing's disease.
Enrolled patients were initially randomized to either osilodrostat or placebo, in a 2:1 ratio, for a 12-week double-blind period (Period 1). Randomization was stratified by history of pituitary radiation. After Week 12, all patients received open-label osilodrostat until the end of the Core phase at Week 48 (Period 2).
After Week 48, patients could join an optional 48 week extension period.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
osilodrostat Placebo Group
Participants in this arm were randomized to receive osilodrostat placebo followed after Week 12 by open-label osilodrostat at the starting dose (with a dose titration)
干预措施: osilodrostat Placebo (Drug)
osilodrostat Group
Participants in this arm were randomized to receive the study drug, osilodrostat followed after Week 12 by open-label osilodrostat at the starting dose (with a second dose titration)
干预措施: osilodrostat (Drug)
结局指标
主要结局
Percentage of Randomized Participants With a Complete Response
时间窗: at Week 12
A complete responder at week 12 is defined as a participant who had a mean urine free cortisol ≤ upper limit of normal (mUFC ≤ ULN) at Week 12. Participants who had a missing mUFC assessment at Week 12 were counted as non-responders for the primary endpoint.
次要结局
- Percentage of Participants With mUFC ≤ ULN at Week 36(At Week 36)
- Change From Baseline in mUFC(Baseline, weeks 2,5,8,12,14,17,20,23,26,29,32,36,40,48,60,72,84,96)
- Time-to-first Control of mUFC - Number (%) of Participants With mUFC <=ULN(up to 12 weeks)
- Change From Baseline in Bone Mineral Density (BMD) by Dual-energy X-ray Absorptiometry (DXA) Scan at the Femoral Neck, Hip and Spinal Cord - QC Corrected(Baseline, week 48)
- Change in Triglyceride(Baseline, weeks 12, 36, and 48)
- Change in Supine Systolic Blood Pressure(Baseline, weeks 12, 36, and 48)
- Change in Standing Diastolic Blood Pressure(Baseline, weeks 12, 36, and 48)
- Change in Supine Diastolic Blood Pressure(Baseline, weeks 12, 36, and 48)
- Change in Weight(Baseline, weeks 12, 36, and 48)
- Change in Waist Circumference(Baseline, weeks 12, 36, and 48)
- Change From Baseline to Week 12, Week 36, and Week 48 in Clinical Signs of Cushing's Disease(baseline, Week 12, Week 36 and Week 48)
- Time-to-first Control of mUFC - Median Time to First Controlled mUFC Response(up to 12 weeks)
- Time-to-first Control of mUFC - % Event Probability Estimates(up to 12 weeks)
- Time-to-escape During Osilodrostat Treatment From Collection of Normal mUFC (≤ ULN) to the First mUFC > 1.3 x ULN - % Event Probability Estimates(week 26 and week 36)
- Change in Fasting Plasma Glucose(Baseline, weeks 12, 36, and 48)
- Time-to-escape During Osilodrostat Treatment From Collection of Normal mUFC (≤ ULN) to the First mUFC > 1.3 x ULN - Number (%) of Participants(up to 48 weeks)
- Change From Baseline in Bone Mineral Density (BMD) T-score by Dual-energy X-ray Absorptiometry (DXA) Scan at the Femoral Neck, Hip and Spinal Cord - QC Corrected(Baseline, week 48)
- Change in Hemoglobin A1C(Baseline, weeks 12, 36, and 48)
- Time-to-escape During Osilodrostat Treatment From Collection of Normal mUFC (≤ ULN) to the First mUFC > 1.3 x ULN - Median Time to Escape From Normal mUFC(from week 26 to week 48)
- Change in HDL Cholesterol(Baseline, weeks 12, 36, and 48)
- Change From Baseline in Standardized Health Related Quality of Life Score, Using Cushing Disease-specific Quality of Life Patient Reported Outcome (PRO) Assessment(Baseline to Week 12 and 48, Week 12 to Week 36, Week 36 to Week 48.)
- Patients With a Complete Response (mUFC ≤ ULN) or a Partial Response (mUFC Decrease ≥ 50% From Baseline and >ULN) at Week 12, 36 and 48(baseline, week 12, 36 and 48)
- Change in LDL Cholesterol(Baseline, weeks 12, 36, and 48)
- Change From Baseline in EQ-5D-5L Utility Index(Baseline to Week 12 and 48, Week 12 to Week 36, Week 36 to Week 48.)
- Change From Baseline in EQ-5D VAS(Baseline to Week 12 and 48, Week 12 to Week 36, Week 36 to Week 48.)
- Change From Baseline in Beck Depression Inventory-II - Total Score Derived(Baseline to Week 12 and 48, Week 12 to Week 36, Week 36 to Week 48.)
- Change From Baseline in Serum Cortisol(Baseline, Week 12, Week 36, Week 48)
- Change From Baseline in Late Night Saliva Cortisol(Baseline, Week 12, Week 36, Week 48)
- Change From Baseline in Morning Saliva Cortisol(Baseline, Week 12, Week 36, Week 48)
- Change From Baseline in Hair Cortisol Levels(Baseline, Week 26, Week 48)
- Plasma Osilodrostat Concentrations (ng/mL)(pre-dose and 1-2hrs post dose at weeks 1, 2, 5, 8, 12, 14, 20, 26)
- Change in Cholesterol(Baseline, weeks 12, 36, and 48)
- Change in Standing Systolic Blood Pressure(Baseline, weeks 12, 36, and 48)
- Change From Baseline in Standardized Psychosocial Issues Score, Using Cushing Disease-specific Quality of Life Patient Reported Outcome (PRO) Assessment(Baseline to Week 12 and 48, Week 12 to Week 36, Week 36 to Week 48.)
- Change From Baseline in Standardized Physical Problems Score, Using Cushing Disease-specific Quality of Life Patient Reported Outcome (PRO) Assessment(Baseline to Week 12 and 48, Week 12 to Week 36, Week 36 to Week 48.)