A 26-Wk, Phase 3, Open Label (OL) Study With a 12-Wk, Placebo-Controlled, Randomized Withdrawal Period and an OL Safety Extension to Evaluate the Safety and Efficacy of Tenapanor to Treat Hyperphosphatemia in CKD Patients on Dialysis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Ardelyx
- 入组人数
- 1,559
- 试验地点
- 2
- 主要终点
- Change in Serum Phosphorus Levels During Placebo Controlled Randomized Withdrawal Period in the Responder Population
研究概览
简要总结
This Phase 3, 26-week, open label study with a 12-week, placebo-controlled, randomized withdrawal period followed by an open label long term safety extension will evaluate the safety and efficacy of tenapanor to treat hyperphosphatemia in end-stage renal disease (ESRD) on hemodialysis and peritoneal dialysis.
详细描述
The study consists of a screening visit, a phosphate binder-free washout period of up to 4 weeks, a 26-week treatment period, an up to 12-week placebo-controlled, randomized withdrawal period, during which patients are randomized 1:1 to either remain on their tenapanor treatment or placebo, followed by an open label safety extension period for a total treatment period of up to 52 weeks. An active control group, for safety analysis only, will receive sevelamer carbonate, open label, for the entire 52-week study period
Depending on increase in serum phosphate (s-P) levels, subjects can be randomized 2 or 3 weeks after being taken off their phosphate lowering medication.
Subjects who qualify to enroll in the study will be randomized 3:1 to either receive tenapanor at a dose of 30 mg bid or sevelamer carbonate.
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
- •Females must be non-pregnant, non-lactating, and either be post-menopausal for at least 12 months, have documentation of irreversible surgical sterilization, or confirm the use of one of the acceptable contraceptive methods
- •Males must agree to avoid fathering a child and agree to use an appropriate method of contraception
- •Chronic maintenance hemodialysis 3x a week for at least 3 months
- •Chronic maintenance peritoneal dialysis for a minimum of 6 months
- •Kt/V ≥ 1.2 at most recent measurement prior to screening
- •Prescribed and taking at least 3 doses of phosphate binder per day
- •Serum phosphorus levels should be between 4.0 and 8.0 mg/dL at screening
- •Unchanged dose of vitamin D or calcimimetics for the last 4 weeks prior to screening
- •For enrollment in the study after at least 2 weeks of wash-out, subjects must have serum phosphorus levels of at least 6.0 mg/dL but not more than 10.0 mg/dL and have had an increase of at least 1.5 mg/dL versus pre-wash out value after 2 or 3 weeks wash-out of phosphate binders
排除标准
- •Severe hyperphosphatemia defined as serum phosphorus greater than 10.0 mg/dL on phosphate-binders at any time point during clinical routine monitoring for the 3 preceding months before screening visit
- •Serum/plasma parathyroid hormone >1200 pg/mL
- •Clinical signs of hypovolemia at enrollment
- •History of IBD or IBS-D
- •Scheduled for living donor kidney transplant, change to peritoneal dialysis, home HD or plans to relocate to another center during the study period
- •Positive serology with evidence of significant hepatic impairment or WBC elevation according to the Investigator
- •Life expectancy <6 months
- •Previous exposure to tenapanor
研究组 & 干预措施
Tenapanor 10 mg, 20 mg, 30 mg BID
During the 26-week open label part, all enrolled subjects will receive 30 mg BID doses of tenapanor. Investigators may decrease or increase the dose in 10 mg increments to a minimum of 10 g BIDor a maximum of 30 mg BID
干预措施: Tenapanor (Drug)
Placebo
Placebo
干预措施: Placebo (Drug)
Sevelamer Carbonate
Subjects randomized into the active control group, for safety analysis, will receive sevelamer carbonate, open label, for the entire 52-week study period. Sevelamer carbonate will be dosed based on package insert instructions (standard of care)
干预措施: Sevelamer Carbonate (Drug)
结局指标
主要结局
Change in Serum Phosphorus Levels During Placebo Controlled Randomized Withdrawal Period in the Responder Population
时间窗: 12 weeks (randomized withdrawal period)
Patients with at least a 1.2 mg/dL decrease in serum phosphorus during the first 26 weeks of the study were defined as the responder population.
次要结局
- Serum Phosphorus From Baseline(26 weeks (open label treatment period))
- Change in Serum Phosphorus Levels During Placebo Controlled Randomized Withdrawal Period in the ITT Population(12 weeks (randomized withdrawal period))