A Single Center, Open Label, Multiple-Dose Oral Oseltamivir Suspension Study in End-Stage-Renal Disease (ESRD) Patients on Hemodialysis (HD) and Continuous Ambulatory Peritoneal Dialysis (CAPD)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 24
- 主要终点
- Maximum Plasma Concentration (Cmax) of Oseltamivir in HD Participants During Days 1 to 5
研究概览
简要总结
This study is designed to assess the pharmacokinetics (PK) and safety of oseltamivir and its metabolite oseltamivir carboxylate in participants undergoing routine HD and CAPD for end-stage renal disease (ESRD). Participants will receive 6.5 and 6 weeks of the marketed oral oseltamivir suspension dosed according to the HD or CAPD schedule, respectively.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Adults greater than or equal to (>/=) 18 years of age
- •ESRD defined as no residual renal function or a creatinine clearance (CrCl) less than (<) 10 milliliters per minute (mL/min)
- •Well established HD or CAPD therapy over a period of 3 months with stable CrCl < 10 mL/min
- •Body mass index (BMI) 18 to 34 kilograms per meter-squared (kg/m^2)
- •Use of contraception among women of childbearing potential
排除标准
- •Clinical significant comorbid disease or terminal illness
- •Known human immunodeficiency virus (HIV) or hepatitis B or C
- •History of drug or alcohol abuse within the prior year
- •Donation or loss of >/= 400 milliliters (mL) of blood in the 3 months prior to Screening
- •Participation in a clinical study with an investigational drug in the 3 months prior to study drug
- •Pregnant or lactating women
研究组 & 干预措施
Regimen A: Oseltamivir with HD
Participants will receive 30 milligrams (mg) of oseltamivir via oral suspension approximately 1 hour after alternating HD sessions. Sessions will occur three times per week within the 6.5-week study period, and participants will receive a total of 9 doses of oseltamivir.
干预措施: Oseltamivir (Drug)
Regimen B: Oseltamivir with CAPD
Participants will receive 30 mg of oseltamivir via oral suspension once weekly after dialysis exchange. CAPD sessions will occur four times every 24 hours, and participants will receive a total of 6 doses of oseltamivir within the 6-week study period.
干预措施: Oseltamivir (Drug)
结局指标
主要结局
Maximum Plasma Concentration (Cmax) of Oseltamivir in HD Participants During Days 1 to 5
时间窗: Blood samples 0, 1, 2, 4, 8, 12, 20, 32, 42, 48, 49, 90 hours from Day 1 (D1) dose
Plasma samples were obtained up to 90 hours post-dose during the first dose analysis (Days 1 to 5), and the maximum observed concentration was recorded. The Cmax was averaged among all participants and expressed in nanograms per milliliter (ng/mL).
Cmax of Oseltamivir in HD Participants During Days 38 to 43
时间窗: Blood samples 0, 1, 2, 4, 8, 12, 20, 32, 42, 48, 49, 90 hours from Day 38 (D38) dose
Plasma samples were obtained up to 90 hours post-dose during the second dose analysis (Days 38 to 43), and the maximum observed concentration was recorded. The Cmax was averaged among all participants and expressed in ng/mL.
Cmax of Metabolite Oseltamivir Carboxylate in HD Participants During Days 1 to 5
时间窗: Blood samples 0, 1, 2, 4, 8, 12, 20, 32, 42, 48, 49, 90 hours from D1 dose
Plasma samples were obtained up to 90 hours post-dose during the first dose analysis (Days 1 to 5), and the maximum observed concentration was recorded. The Cmax was averaged among all participants and expressed in ng/mL.
Cmax of Metabolite Oseltamivir Carboxylate in HD Participants During Days 38 to 43
时间窗: Blood samples 0, 1, 2, 4, 8, 12, 20, 32, 42, 48, 49, 90 hours from D38 dose
Plasma samples were obtained up to 90 hours post-dose during the second dose analysis (Days 38 to 43), and the maximum observed concentration was recorded. The Cmax was averaged among all participants and expressed in ng/mL.
Area Under the Concentration-Time Curve (AUC) of Oseltamivir in HD Participants During Days 1 to 5
时间窗: Blood samples 0, 1, 2, 4, 8, 12, 20, 32, 42, 48, 49, 90 hours from D1 dose
Plasma samples were obtained up to 90 hours post-dose during the first dose analysis (Days 1 to 5), and the AUC was determined from 0 to 12 hours (AUC12) and up to the last measurable concentration (AUClast). Values were averaged among all participants and expressed in nanograms by hours per milliliter (ng\*h/mL).
AUC of Oseltamivir in HD Participants During Days 38 to 43
时间窗: Blood samples 0, 1, 2, 4, 8, 12, 20, 32, 42, 48, 49, 90 hours from D38 dose
Plasma samples were obtained up to 90 hours post-dose during the second dose analysis (Days 38 to 43), and the AUC12 and AUClast were determined. Values were averaged among all participants and expressed in ng\*h/mL.
AUC of Metabolite Oseltamivir Carboxylate in HD Participants During Days 1 to 5
时间窗: Blood samples 0, 1, 2, 4, 8, 12, 20, 32, 42, 48, 49, 90 hours from D1 dose
Plasma samples were obtained up to 90 hours post-dose during the first dose analysis (Days 1 to 5), and the AUC was determined from 0 to 42 hours (AUC42) and up to the last measurable concentration (AUClast). Values were averaged among all participants and expressed in ng\*h/mL.
AUC of Metabolite Oseltamivir Carboxylate in HD Participants During Days 38 to 43
时间窗: Blood samples 0, 1, 2, 4, 8, 12, 20, 32, 42, 48, 49, 90 hours from D38 dose
Plasma samples were obtained up to 90 hours post-dose during the second dose analysis (Days 38 to 43), and the AUC42 and AUClast were determined. Values were averaged among all participants and expressed in ng\*h/mL.
Cmax of Oseltamivir in CAPD Participants During Days 1 to 6
时间窗: Blood samples 0, 1, 2, 4, 8, 12, 24, 48, 72, 120 hours from D1 dose
Plasma samples were obtained up to 120 hours post-dose during the first dose analysis (Days 1 to 6), and the maximum observed concentration was recorded. The Cmax was averaged among all participants and expressed in ng/mL.
Cmax of Oseltamivir in CAPD Participants During Days 36 to 43
时间窗: Blood samples 0, 1, 2, 4, 8, 12, 24, 48, 72, 120, 168 hours from Day 36 (D36) dose
Plasma samples were obtained up to 168 hours post-dose during the second dose analysis (Days 36 to 43), and the maximum observed concentration was recorded. The Cmax was averaged among all participants and expressed in ng/mL.
Cmax of Metabolite Oseltamivir Carboxylate in CAPD Participants During Days 1 to 6
时间窗: Blood samples 0, 1, 2, 4, 8, 12, 24, 48, 72, 120 hours from D1 dose
Plasma samples were obtained up to 120 hours post-dose during the first dose analysis (Days 1 to 6), and the maximum observed concentration was recorded. The Cmax was averaged among all participants and expressed in ng/mL.
Cmax of Metabolite Oseltamivir Carboxylate in CAPD Participants During Days 36 to 43
时间窗: Blood samples 0, 1, 2, 4, 8, 12, 24, 48, 72, 120, 168 hours from D36 dose
Plasma samples were obtained up to 168 hours post-dose during the second dose analysis (Days 36 to 43), and the maximum observed concentration was recorded. The Cmax was averaged among all participants and expressed in ng/mL.
AUC of Oseltamivir in CAPD Participants During Days 1 to 6
时间窗: Blood samples 0, 1, 2, 4, 8, 12, 24, 48, 72, 120 hours from D1 dose
Plasma samples were obtained up to 120 hours post-dose during the first dose analysis (Days 1 to 6), and the AUC12 and AUClast were determined. Values were averaged among all participants and expressed in ng\*h/mL.
AUC of Oseltamivir in CAPD Participants During Days 36 to 43
时间窗: Blood samples 0, 1, 2, 4, 8, 12, 24, 48, 72, 120, 168 hours from D36 dose
Plasma samples were obtained up to 168 hours post-dose during the second dose analysis (Days 36 to 43), and the AUC12 and AUClast were determined. Values were averaged among all participants and expressed in ng\*h/mL.
AUC of Metabolite Oseltamivir Carboxylate in CAPD Participants During Days 1 to 6
时间窗: Blood samples 0, 1, 2, 4, 8, 12, 24, 48, 72, 120 hours from D1 dose
Plasma samples were obtained up to 120 hours post-dose during the first dose analysis (Days 1 to 6), and the AUC was determined from 0 to 48 hours (AUC48) and up to the last measurable concentration (AUClast). Values were averaged among all participants and expressed in ng\*h/mL.
AUC of Metabolite Oseltamivir Carboxylate in CAPD Participants During Days 36 to 43
时间窗: Blood samples 0, 1, 2, 4, 8, 12, 24, 48, 72, 120, 168 hours from D36 dose
Plasma samples were obtained up to 168 hours post-dose during the second dose analysis (Days 36 to 43), and the AUC48 and AUClast were determined. Values were averaged among all participants and expressed in ng\*h/mL.
次要结局
- Percentage of Oseltamivir Dose Eliminated by Dialysis as Metabolite Oseltamivir Carboxylate in CAPD Participants(Dialysate samples 0 to 48 hours from D1 dose)
- Plasma Concentration of Oseltamivir by Timepoint in HD Participants(Blood samples 0, 1, 2, 4, 8, 12, 20, 32, 42, 48, 49 hours from D1 and D38 dose AND at 90 hours from D1 dose AND at 114 hours from D38 dose)
- Plasma Concentration of Metabolite Oseltamivir Carboxylate by Timepoint in HD Participants(Blood samples 0, 1, 2, 4, 8, 12, 20, 32, 42, 48, 49 hours from D1 and D38 dose AND at 90 hours from D1 dose AND at 114 hours from D38 dose)
- Time to Maximum Plasma Concentration (Tmax) of Oseltamivir in HD Participants(Blood samples 0, 1, 2, 4, 8, 12, 20, 32, 42, 48, 49, 90 hours from D1 and D38 dose)
- Tmax of Metabolite Oseltamivir Carboxylate in HD Participants(Blood samples 0, 1, 2, 4, 8, 12, 20, 32, 42, 48, 49, 90 hours from D1 and D38 dose)
- Oral Plasma Clearance (CL/F) of Oseltamivir in HD Participants(Blood samples 0, 1, 2, 4, 8, 12 hours from D1 and D38 dose)
- CL/F of Metabolite Oseltamivir Carboxylate in HD Participants(Blood samples 0, 1, 2, 4, 8, 12, 20, 32, 42 hours from D1 and D38 dose)
- Renal Clearance (CLr) of Oseltamivir in HD Participants(Blood samples 0, 1, 2, 4, 8, 12 hours from D1 dose; urine samples 0 to 12 hours from D1 dose)
- CLr of Metabolite Oseltamivir Carboxylate in HD Participants(Blood samples 0, 1, 2, 4, 8, 12, 20, 32, 42 hours from D1 dose; urine samples 0 to 42 hours from D1 dose)
- Dialysis Clearance (CLd) of Metabolite Oseltamivir Carboxylate in HD Participants(Blood samples 0, 1, 2, 4, 8, 12, 20, 32, 42, 48, 49, 90 hours from from D1 and D38 dose; dialyzer samples 1, 2, 4, 5 hours from start of dialysis on Days 3 and 40)
- Percentage of Oseltamivir Dose Excreted as Unchanged Drug in HD Participants(Urine samples 0 to 42 hours from D1 dose)
- Percentage of Oseltamivir Dose Excreted as Metabolite Oseltamivir Carboxylate in HD Participants(Urine samples 0 to 42 hours from D1 dose)
- Plasma Concentration of Metabolite Oseltamivir Carboxylate in Arterial and Venous Blood by Timepoint in HD Participants(Dialyzer samples 1, 2, 4, 5 hours from start of dialysis on Days 3 and 40)
- Plasma Concentration of Oseltamivir by Timepoint in CAPD Participants(Blood samples 0, 1, 2, 4, 8, 12, 24, 48, 72, 120 hours from D1 and D36 dose AND at 168 hours from D36 dose)
- Plasma Concentration of Metabolite Oseltamivir Carboxylate by Timepoint in CAPD Participants(Blood samples 0, 1, 2, 4, 8, 12, 24, 48, 72, 120 hours from D1 and D36 dose AND at 168 hours from D36 dose)
- Tmax of Oseltamivir in CAPD Participants(Blood samples 0, 1, 2, 4, 8, 12, 24, 48, 72, 120 hours from D1 and D36 dose AND at 168 hours from D36 dose)
- Tmax of Metabolite Oseltamivir Carboxylate in CAPD Participants(Blood samples 0, 1, 2, 4, 8, 12, 24, 48, 72, 120 hours from D1 and D36 dose AND at 168 hours from D36 dose)
- Elimination Rate Constant of Metabolite Oseltamivir Carboxylate in CAPD Participants(Blood samples 0, 1, 2, 4, 8, 12, 24, 48, 72, 120 hours from D1 and D36 dose AND at 168 hours from D36 dose; urine samples 0 to 48 hours from D1 dose; dialysate samples 0 to 48 hours from D1 dose)
- Terminal Elimination Half-Life of Metabolite Oseltamivir Carboxylate in CAPD Participants(Blood samples 0, 1, 2, 4, 8, 12, 24, 48, 72, 120 hours from D1 and D36 dose AND at 168 hours from D36 dose; urine samples 0 to 48 hours from D1 dose; dialysate samples 0 to 48 hours from D1 dose)
- CL/F of Oseltamivir in CAPD Participants(Blood samples 0, 1, 2, 4, 8, 12 hours from D1 and D36 dose)
- CL/F of Metabolite Oseltamivir Carboxylate in CAPD Participants(Blood samples 0, 1, 2, 4, 8, 12, 24, 48 hours from D1 and D36 dose)
- CLr of Oseltamivir in CAPD Participants(Blood samples 0, 1, 2, 4, 8, 12 hours from D1 dose; urine samples 0 to 12 hours from D1 dose)
- CLr of Metabolite Oseltamivir Carboxylate in CAPD Participants(Blood samples 0, 1, 2, 4, 8, 12, 24, 48 hours from D1 dose; urine samples 0 to 48 hours from D1 dose)
- CLd of Metabolite Oseltamivir Carboxylate in CAPD Participants(Blood samples 0, 1, 2, 4, 8, 12, 24, 48, 72, 120 hours from D1 dose; dialysate samples 0 to 48 hours from D1 dose)
- Percentage of Oseltamivir Dose Renally Excreted as Unchanged Drug in CAPD Participants(Urine samples 0 to 48 hours from D1 dose)
- Percentage of Oseltamivir Dose Renally Excreted as Metabolite Oseltamivir Carboxylate in CAPD Participants(Urine samples 0 to 48 hours from D1 dose)
- Percentage of Oseltamivir Dose Eliminated by Dialysis as Unchanged Drug in CAPD Participants(Dialysate samples 0 to 48 hours from D1 dose)