A Phase 3b, Multi-center, Randomized-withdrawal, Placebo-controlled, Double-blind, Parallel-group Trial to Compare the Efficacy and Safety of Tolvaptan (45 to 120 mg/Day, Split-dose) in Subjects With Chronic Kidney Disease Between Late Stage 2 to Early Stage 4 Due to Autosomal Dominant Polycystic Kidney Disease
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,370
- 主要终点
- The Mean Annualized Change in eGFR From Pretreatment Baseline to Post-treatment Follow-up.
研究概览
简要总结
The purpose of the study is to determine whether tolvaptan is effective and safe for the treatment of late-stage chronic kidney disease due to autosomal dominant polycystic kidney disease (ADPKD)
详细描述
The protocol will extend the understanding of the efficacy and safety of tolvaptan treatment in ADPKD patients with late stage 2 to early stage 4 CKD (chronic kidney disease).
This trial will compare the efficacy of tolvaptan treatment in reducing the annualized change in estimated glomerular filtration rate (eGFR) from pre-treatment baseline to post-treatment follow-up, as compared with placebo, in subjects who tolerate tolvaptan during an initial run-in period. The change in eGFR, calculated by the Chronic Kidney Disease-Epidemiology (CKD-EPI) formula, will provide kidney function data that are complementary to the data demonstrating the benefits previously observed primarily in ADPKD subjects with earlier stages of disease.
Also, it will compare the efficacy of tolvaptan treatment in reducing the decline of annualized eGFR slope, as compared with placebo, in this type of subjects. Finally, it will compare the overall and hepatic safety profile of tolvaptan with placebo and to compare incidence of ADPKD complications (outcomes) during the trial
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female subjects with eGFR between 25-65 mL/min/1.73m2 (if aged 18 to55) or eGFR between 25-44 mL/min/1.73m2 (if aged 56 to <66)
- •Tolvaptan naïve
- •Diagnosis of ADPKD by modified pei-Ravine criteria 1) 3 cysts per kidney by sonography or 5 cysts by CT or MRI with family history of ADPKD or 2) 10 cysts per kidney by any radiologic method and exclusion of other cystic kidney diseases if without family history
排除标准
- •Women of childbearing potential who do not agree to practice 2 different methods of birth control or remain abstinent during the trial and for 30 days after the last dose of Investigational medicinal product (IMP)
- •Women who are breast-feeding and/or who have a positive pregnancy test prior to receiving IMP
- •Need for chronic diuretic use
- •Hepatic impairment or liver function abnormalities other than that expected for ADPKD with typical cystic liver disease
- •Advanced diabetes, evidence of additional significant renal disease, renal cancer, single kidney, recent renal surgery or acute kidney injury
- •Contraindications to required trial assessments
- •Medical history or medical findings inconsistent with safety or compliance with trial assessments
研究组 & 干预措施
Tolvaptan
Tolvaptan (OPC-41061)
干预措施: Tolvaptan (OPC-41061) (Drug)
Placebo
Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
The Mean Annualized Change in eGFR From Pretreatment Baseline to Post-treatment Follow-up.
时间窗: Pretreatment baseline to post-treatment follow-up (up to 61 weeks).
The mean annualized change in eGFR was calculated using the Chronic Kidney Disease-Epidemiology (CKD-EPI) formula from pretreatment baseline to post-treatment follow-up, annualized (divided) by each subject's trial duration. The baseline for the primary endpoint was defined as the average of up to 3 eGFR values observed during the screening and placebo run-in periods.
次要结局
- Mean Annualized Slope of eGFR Change(Pretreatment baseline to post-treatment follow-up (up to 61 weeks).)