A Phase 3, Multi-center, Double-blind, Placebo-controlled, Parallel-arm Trial to Determine Long-term Safety and Efficacy of Oral Tolvaptan Tablets Regimens in Adult Subjects With Autosomal Dominant Polycystic Kidney Disease
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,445
- 试验地点
- 133
- 主要终点
- Percentage Change Per Year in Total Kidney Volume From Baseline to Month 36
研究概览
简要总结
This study's purpose is to evaluate the long-term safety and efficacy of tolvaptan versus placebo in patients with ADPKD.
详细描述
This study evaluated whether or not tolvaptan is potentially beneficial, while maintaining an adequate safety profile, by reducing the rate of total kidney volume increase, while impacting the onset, severity, and progression of other important consequences of ADPKD.
During the 3-week titration phase, tolvaptan or placebo was titrated in weekly intervals from lowest to highest tolerated levels given in split-dose regimens of 45/15 mg, 60/30 mg and 90/30 mg orally upon awakening and approximately 9 hours later. As soon as a subject could not tolerate a given dose, the titration phase was over and the maintenance phase began at the dose level tolerated. The maintenance phase lasted to Month 36. Subjects were able to titrate down at any point during the study. Subjects were able to titrate up during the maintenance phase with Medical Monitor approval.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Legal adult age and able to give Informed Consent.
- •Adult subjects with a diagnosis of ADPKD. A diagnosis of ADPKD (age 18 or 20-50) required several cysts in each kidney (3 if by sonography, 5 if by CT or MRI) in those with a family history of ADPKD and 10 cysts (by any radiologic method) in each kidney and exclusion of other cystic kidney diseases if there was no family history.
- •Willingness to comply with reproductive precautions, if female.
- •Estimated creatinine clearance ≥ 60 mL/min. Estimated from serum creatinine during screening using Cockcroft-Gault with correction for gender and race, where possible.
- •Rapidly progressive kidney growth (total volume ≥ 750 cc) by magnetic resonance imaging (MRI) at randomization.
排除标准
- •Prior exposure to tolvaptan or other experimental PKD therapies.
- •Currently taking medication for purpose of affecting PKD cysts.
- •Women who are breast feeding and females of childbearing potential who are not using acceptable contraceptive methods.
- •In the opinion of the study investigator or sponsor may present a safety risk or confound study objectives.
- •Patients who are unlikely to adequately comply with study procedures.
- •Patients having contraindications to MRI.
- •Patients taking medications or having any illnesses likely to affect ADPKD outcomes.
研究组 & 干预措施
Tolvaptan
Participants received the highest tolerated split-dose regimen (upon awakening and 9 hours later) of tolvaptan 45/15 mg, 60/30 mg, or 90/30 mg orally for 36 months.
干预措施: Tolvaptan (Drug)
Placebo
Participants received placebo (upon awakening and 9 hours later) orally for 36 months.
干预措施: Placebo (Drug)
结局指标
主要结局
Percentage Change Per Year in Total Kidney Volume From Baseline to Month 36
时间窗: Baseline to Month 36
Kidney volume was assessed in T1-weighted magnetic resonance images collected at each study site and sent to a central reviewing facility. At the central reviewing facility, blinded radiologists used proprietary software to measure the volume of both kidneys.
次要结局
- Number of ADPKD Clinical Progression Events Per 100 Follow-up Years From Baseline to Month 36(Baseline to Month 36)
- Change in Renal Function Per Year From Week 3 to Month 36(Week 3 to Month 36)
- Area Under the Concentration-time Curve of Change in Renal Pain From Baseline to Month 36(At screening, Baseline, Day 1, every 4 months up to month 36/early tremination (ET), follow-up visit 1 and 2)
- Change in Mean Arterial Blood Pressure Per Year in Non-hypertensive Participants From Baseline to Month 36(Baseline to Month 36)
- Number of Hypertensive Events Per 100 Follow-up Years in Non-hypertensive Participants From Baseline to Month 36(Baseline to Month 36)
- Percentage of Participants With a Clinically Sustained Decrease of Blood Pressure Leading to a Sustained Reduction in Antihypertensive Therapy From Baseline to Month 36(Baseline to Month 36)