A Phase 1b Study, to Assess the Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of Repeated Doses of DS-2330b Alone and When Co-administered With Sevelamer in Patients on Chronic Hemodialysis
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 3
- 主要终点
- Part A, Period 1: Time to maximum concentration (Tmax) of DS-2330a
研究概览
简要总结
This three-part study will be performed with participants on chronic hemodialysis.
- Part A will assess plasma pharmacokinetics of DS2330a (free form of DS2330b) after a single dose of powder in bottle (PIB) or tablet formulations of DS2330b
- Part B will test the safety, tolerability, and effects on serum phosphate (Pi) of 14-day repeated oral doses of DS-2330b PIB when given alone and when given along with sevelamer carbonate three times a day
- Part C is optional, and will test the effects on serum phosphate (Pi) of 14-day repeated oral doses of DS-2330b tablets when given with sevelamer carbonate
After screening, participants should expect the study to last about 21 days for Part A, and 46 days for Parts B and C.
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
- Double (Participant, Investigator)
盲法说明
Masking description is for Part B only - Parts A and C are Open Label, so have no masking
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
- •Has a body mass index (BMI) of 18 kg/m^2 to 40 kg/m^2 (inclusive)
- •Is on prescribed maintenance hemodialysis (three times a week) for at least 3 months before Screening with adequacy demonstrated by a dialysis clearance within 3 months before the first dose of the investigational medicinal product
- •Has permanent vascular access [arteriovenous (A-V) fistula or graft]
- •Is willing to comply with protocol-specified methods for family planning
- •For Parts B and C only:
- •Has protocol-specified acceptable serum Pi levels at Screening and in serum Pi after up to 3 weeks of washout from all Pi binders
- •Has protocol-specified acceptable serum Ca^2+ level and intact parathyroid hormone (iPTH) level at screening
排除标准
- •Is employed by the clinic or the sponsor
- •Has family relationship with another study participant
- •Has any history, current condition, or drug use that per protocol or in the opinion of the investigator might compromise:
- •safety of the participant or their children
- •safety of study staff
- •analysis of study results
- •For Parts B and C only:
- •Is not able to take sevelamer carbonate
- •Has had partial or total parathyroidectomy within the last six months
研究组 & 干预措施
Part A: DS-2330b PIB, then Tablet
On a non-dialysis day, participants are given a single 250 mg dose of DS-2330b PIB [Treatment A1] right after breakfast. At least 3 days will be allowed to let the first dose wash out. Then on a non-dialysis day the participants are given a single 250 mg dose of DS-2330b in tablet form [Treatment A2] right after breakfast.
干预措施: DS-2330b PIB (Drug)
Part A: DS-2330b PIB, then Tablet
On a non-dialysis day, participants are given a single 250 mg dose of DS-2330b PIB [Treatment A1] right after breakfast. At least 3 days will be allowed to let the first dose wash out. Then on a non-dialysis day the participants are given a single 250 mg dose of DS-2330b in tablet form [Treatment A2] right after breakfast.
干预措施: DS-2330b Tablet (Drug)
Part A: DS-2330b Tablet, then PIB
On a non-dialysis day, participants are given a single 250 mg dose of DS-2330b in tablet form [Treatment A2] right after breakfast. At least 3 days will be allowed to let the first dose wash out. Then on a non-dialysis day the participants are given a single 250 mg dose of DS-2330b PIB [Treatment A1] right after breakfast.
干预措施: DS-2330b PIB (Drug)
Part A: DS-2330b Tablet, then PIB
On a non-dialysis day, participants are given a single 250 mg dose of DS-2330b in tablet form [Treatment A2] right after breakfast. At least 3 days will be allowed to let the first dose wash out. Then on a non-dialysis day the participants are given a single 250 mg dose of DS-2330b PIB [Treatment A1] right after breakfast.
干预措施: DS-2330b Tablet (Drug)
Part B: Placebo
Participants are given placebo three times daily [Treatment B1]
干预措施: Placebo (Drug)
Part B: DS-2330b PIB
Participants are given 400 mg of DS-2330b PIB three times daily [Treatment B2]
干预措施: DS-2330b PIB (Drug)
Part B: DS-2330b PIB + Sevelamer
Participants are given 400 mg of DS-2330b PIB along with 1.6 grams of sevelamer three times daily [Treatment B3]
干预措施: DS-2330b PIB (Drug)
Part B: DS-2330b PIB + Sevelamer
Participants are given 400 mg of DS-2330b PIB along with 1.6 grams of sevelamer three times daily [Treatment B3]
干预措施: Sevelamer (Drug)
Part B: Placebo + Sevelamer
Participants are given placebo along with 1.6 grams of sevelamer three times daily [Treatment B4]
干预措施: Placebo (Drug)
Part B: Placebo + Sevelamer
Participants are given placebo along with 1.6 grams of sevelamer three times daily [Treatment B4]
干预措施: Sevelamer (Drug)
Part C: DS-2330b Tablet + Sevelamer
Participants are given one 250 mg dose of DS-2330b in tablet form along with 1.6 grams of sevelamer three times daily [Treatment C]
干预措施: Sevelamer (Drug)
Part C: DS-2330b Tablet + Sevelamer
Participants are given one 250 mg dose of DS-2330b in tablet form along with 1.6 grams of sevelamer three times daily [Treatment C]
干预措施: DS-2330b Tablet (Drug)
结局指标
主要结局
Part A, Period 1: Time to maximum concentration (Tmax) of DS-2330a
时间窗: Period 1, Pre-dose to 48 hours post-dose
Part A, Period 2: Tmax of DS-2330a
时间窗: Period 2, Pre-dose to 48 hours post-dose
Part A, Period 1: Maximum concentration (Cmax) of DS-2330a
时间窗: Period 1, Pre-dose to 48 hours post-dose
Part A, Period 1: Area under the drug concentration curve (AUC) for DS-2330a over 24 hours (AUC-24)
时间窗: Period 1, Pre-dose to 24 hours post-dose
All Parts: Number of trial participants with treatment-emergent adverse events (TEAEs)
时间窗: through trial completion (about 15 months)
TEAEs are adverse events (side effects) associated with taking an investigational product, whether or not they were caused by the investigational product. Clinically significant changes in physical exam findings, vital signs, electrocardiograms, clinical lab tests and thyroid function are recorded as TEAEs.
Part A, Period 2: Cmax of DS-2330a
时间窗: Period 2, Pre-dose to 48 hours post-dose
Parts B and C: Serum phosphate (Pi) levels before hemodialysis
时间窗: within 15 days
Part A, Period 2: AUC for DS-2330a for DS-2330a over 24 hours (AUC-24)
时间窗: Period 2, Pre-dose to 24 hours post-dose
Part A, Period 1: AUC at the last observable concentration (AUClast) and to infinity (AUCinf) for DS-2330a
时间窗: Period 1, Pre-dose to 48 hours post-dose
Categories (with the same unit of measure ng\*hr/mL): AUClast, AUCinf
Part A, Period 2: AUClast and AUCinf for DS-2330a
时间窗: Period 2, Pre-dose to 48 hours post-dose
Categories (with the same unit of measure ng\*hr/mL): AUClast, AUCinf
次要结局
- Parts B and C: Tmax of DS-2330a(within 24 hours, Day 13)
- Parts B and C: AUCinf for DS-2330a(Day 13)
- Parts B and C: Cmax of DS-2330a(within 24 hours on Day 13)
- Parts B and C: AUC-24 for DS-2330a(Day 13)
- Parts B and C: Minimum concentration (Ctrough) of DS-2330a(within 11 days)
- Part B: Dialysis clearance of DS-2330a(on Day 11)