Multi-center, Open-label, Extension Study to Evaluate the Long-term Efficacy and Safety of Oral Tolvaptan Tablet Regimens in Subjects With Autosomal Dominant Polycystic Kidney Disease (ADPKD)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,083
- 试验地点
- 1
- 主要终点
- Percent Change From the Baseline in Total Kidney Volume (TKV) for Study 156-04-251 Participants Enrolled in This Study (156-08-271)
研究概览
简要总结
To demonstrate whether tolvaptan modifies ADPKD progression as measured by changes from Baseline (from Study 156-04-251) in total kidney volume (TKV) and renal function.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants who had successfully completed a Phase 1, 2, or 3 tolvaptan ADPKD or renal impairment study, with a confirmed diagnosis of ADPKD from prior studies [either 156-04-251 (NCT00428948) or 156-04-250 (NCT00413777), 156-06-260, 156-09-284 (NCT01336972), 156-09-285 (NCT01210560), and 156-09-290 (NCT01451827)].
排除标准
- •Participants unable to provide written informed consent.
- •Participants (men or women) would not adhere to the reproductive precautions as outlined in the Informed Consent Form.
- •Participants (women only) with a positive urine pregnancy test.
- •Participants who were pregnant or breast-feeding.
- •Participants unable to take oral medications.
- •Participants who had allergic reactions to tolvaptan or chemically related structures such as benzazepines (benzazepril, conivaptan, fenoldopam mesylate, or mirtazapine).
- •Participants with disorders in thirst recognition or an inability to access fluids.
- •Participants with critical electrolyte imbalances, as determined by the investigator
- •Participants with or at risk of significant hypovolemia, as determined by investigator.
- •Participants with significant anemia, as determined by investigator.
- •Participants with a history of substance abuse (within the last 3 years).
- •Participants who were taking other experimental (that is, non-marketed) therapies or were participating in another clinical drug or device study; participating in the off-drug follow-up period of another ADPKD trial with tolvaptan was permitted.
- •Participants unable to complete magnetic resonance imaging (MRI) assessments (for example, participants with ferro-magnetic prostheses, aneurysm clips, severe claustrophobia).
- •Participants who had taken a vasopressin antagonist (outside of previous participation in a tolvaptan study).
- •Participants unable to comply with anti-hypertensive or other important medical therapy.
- •Participants with advanced diabetes.
- •Participants who were taking medications or had an illness that could confound endpoint assessments (including taking approved therapies for the purpose of affecting polycystic kidney disease [PKD] cysts).
研究组 & 干预措施
Tolvaptan
Participants received a daily split-dose of tolvaptan titrated to the maximally tolerated dose, starting daily tolvaptan dose of 45 milligrams (mg) in the morning [AM]/15 mg in the evening [PM] titrated to 60 mg [AM]/30 mg [PM], then 90 mg [AM]/30 mg [PM] based on tolerability were given orally twice daily until the last participant originating from prior studies (either 156-04-251 or 156-04-250, 156-06-260, 156-09-284, 156-09-285, and 156-09-290) who was eligible for efficacy analysis completed the Month 24.
干预措施: Tolvaptan (Drug)
结局指标
主要结局
Percent Change From the Baseline in Total Kidney Volume (TKV) for Study 156-04-251 Participants Enrolled in This Study (156-08-271)
时间窗: Study Baseline (Prior to Day 1 in Study 156-04-251) to Month 24 in this study (Study 156-08-271)
Total kidney volume is a measure of disease progression in the ADPKD participants. 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, radiologists used proprietary software to measure the volume of both kidneys in participants continuing from previous study (156-04-251) at Month 24 of this study (156-08-271) comparing change in TKV for the early-treated (those previously treated with tolvaptan) to delayed-treated (those previously treated with placebo). The percent change in the volume of both kidneys combined was analysed using mixed-effect model repeated measures (MMRM) analysis and reported. This outcome measure was analyzed only in the participants enrolled from the previous study - 156-04-251, as pre-specified in the protocol.
次要结局
- Change From the Baseline in Estimated Glomerular Filtration Rate (eGFR) as Assessed by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) for Study 156-04-251 Participants Enrolled in This Study (156-08-271)(Study Baseline (Prior to Day 1 in Study 156-04-251) to Month 24 in this study (Study 156-08-271))
- Annualized Slope of eGFR (CKD-EPI) for Study 156-04-251 Participants Enrolled in Study 156-08-271(Study Baseline (Prior to Day 1 in Study 156-08-271) to Month 24 (Study 156-08-271))
- Annualized Slope of Renal Function (eGFRCKD-EPI) for Study 156-04-251 Placebo Participants Enrolled in Study 156-08-271(Tolvaptan, Delayed Treated: Baseline to Month 24 in Study 156-08-271; Placebo: Baseline to Month 36 in Study 156-04-251)
- Annualized Slope of Total Kidney Volume (TKV) for Study 156-04-251 Participants Enrolled in Study 156-08-271(Study Baseline (Prior to Day 1 in Study 156-08-271) to Month 24 in this study (Study 156-08-271))
- Annualized TKV Slope for Study 156-04-251 Placebo Participants Enrolled in Study 156-08-271(Tolvaptan, Delayed Treated: Baseline to Month 24 in Study 156-08-271; Placebo: Baseline to Month 36 in Study 156-04-251)