An 8-week, Multicenter, Randomized, Double-Blind, Parallel Group Study With a 4-week, Placebo-Controlled, Randomized Withdrawal Period to Evaluate the Efficacy, Safety, and Tolerability of Tenapanor to Treat Hyperphosphatemia in End-Stage Renal Disease Patients on Hemodialysis (ESRD-HD)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Ardelyx
- 入组人数
- 219
- 试验地点
- 32
- 主要终点
- Placebo Adjusted Change in Serum Phosphate During Randomized Withdrawal Period From Pooled Tenapanor Arms
研究概览
简要总结
This phase 3, 8-week, randomized, double-blind, parallel group, multi-center study with a 4-week, placebo-controlled, randomized withdrawal period will evaluate the efficacy, safety and tolerability of Tenapanor to treat hyperphosphatemia in end-stage renal disease patients on hemodialysis (ESRD-HD). Subjects who qualify are randomized into the study will either receive 3 mg BID, 10 mg BID, or a titration regimen of tenapanor.
详细描述
The study consists of a screening visit, a wash out period of up to 3 weeks, when existing phosphate lowering medication is withheld, an 8-week treatment period, in which all groups receive tenapanor, and a 4-week placebo-controlled, randomized withdrawal period, during which patients are re-randomized 1:1 to either remain on their current tenapanor treatment or placebo.
Depending on the increase in serum phosphate levels, subjects can be randomized 1,2, or 3 weeks after being taken off their phosphate lowering medication.
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
- •18 to 80 years old
- •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/week for at least 3 months
- •Kt/V ≥ 1.3 at most recent measurement prior to screening
- •Prescribed and taking at least 3 doses of phosphate binder per day
- •Serum phosphate levels should be between 4.0 and 7.0 mg/dL (inclusive) at screening
- •For randomization in the study, after 1 week wash-out of phosphate binders, subjects must have serum phosphate level of at least 9 mg/dL but below 10 mg/dL and have had an increase of at least 1.5 mg/dL versus pre-wash out value
- •For randomization in the study, after 2 or 3 weeks wash-out of phosphate binders, subjects must have serum phosphate level of at least 6 mg/dL but below 10 mg/dL and have had an increase of at least 1.5 mg/dL versus pre-wash out value
排除标准
- •Severe hyperphosphatemia defined as >10 mg/dL on Phosphate-binders at any time point during clinical routine monitoring for the 3 preceding months before screening
- •Serum parathyroid hormone >1200 pg/mL
- •Persistent metabolic acidosis defined as serum carbon dioxide <18 mmol/L from two consecutive measurements during screening and washout periods
- •Clinical signs of hypovolemia at randomization
- •History of inflammatory bowel disease (IBD) or diarrhea predominant irritable bowel syndrome (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
- •Diarrhea or loose stools during the week before randomization defined as BSFS ≥ 6 and frequency ≥ 3 for 2 or more days
- •Any evidence of or treatment of malignancy within one year, excluding non-melanomatous malignancies of the skin
- •Positive serology with evidence of significant hepatic impairment or WBC elevation according to the Investigator
- •Life expectancy < 6 months
研究组 & 干预措施
10mg BID
Tenapanor, 10mg BID (20mg total)
干预措施: Tenapanor (Drug)
3mg BID
Tenapanor, 3mg BID (6mg total)
干预措施: Tenapanor (Drug)
Dose Titration
Tenapanor, patients start at 30mg BID and can down titrate weekly to 20, 15, 10, and 3mg BID, sequentially based on a GI tolerability question
干预措施: Tenapanor (Drug)
Placebo
Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Placebo Adjusted Change in Serum Phosphate During Randomized Withdrawal Period From Pooled Tenapanor Arms
时间窗: 4 weeks
Serum phosphorus difference between placebo and tenapanor in the change from the end of the 8 week treatment period to the end of the randomized withdrawal period in Efficacy Analysis Set. The efficacy analysis was pre-defined to be a pooled analysis of all tenapanor treated patients with a minimum of a 1.2 mg/dL decrease in serum phosphorus during the 8-week treatment period
次要结局
- Change in Serum Phosphate During 8-Week Treatment Period(Baseline and 8 weeks)