An Open Label, Prospective, Single Oral Dose Study Evaluating the Pharmacokinetics, Safety, and Tolerability of Oseltamivir in Adult Subjects on Peritoneal Dialysis (PD) Using a Rapid Cycle Regimen to Simulate APD and in Adult Subjects With Creatinine Clearance From 10 to 30 mL/Min Not on Dialysis
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 16
- 主要终点
- Cmax of Oseltamivir and Oseltamivir Carboxylate
研究概览
简要总结
This open-label, prospective, single dose study will evaluate the pharmacokinetics and safety of Tamiflu (oseltamivir) in volunteers on dialysis and in volunteers with a creatinine clearance from 10 to 30 mL/min. Volunteers will receive a single oral dose of Tamiflu.
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
- 19 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Adult volunteers, aged 19 to 90 years
- •Medically stable with no hospitalization for a significant disease in the 3 months before study start
- •Volunteers on dialysis
- •A documented and well-established dialysis therapy
- •Volunteers with reduced creatinine clearance
- •Creatinine clearance from 10 to 30 mL/min
- •Stable renal function
排除标准
- •Clinically significant and unstable disease (e.g., cardiac, hepatic, pulmonary)
- •Medical history of concurrent medical condition that would compromise participation in the study
- •Hypotensive episodes or symptoms of fainting, dizziness or lightheadedness in the 4 weeks before screening
- •Uncontrolled hypotension or hypertension
- •Infection with hepatitis B, hepatitis C or human immunodeficiency virus
研究组 & 干预措施
Volunteers on dialysis
干预措施: Tamiflu (oseltamivir) (Drug)
Volunteers with reduced creatinine clearance
干预措施: Tamiflu (oseltamivir) (Drug)
结局指标
主要结局
Cmax of Oseltamivir and Oseltamivir Carboxylate
时间窗: Pre-dose; 0.5, 1.33, 2, 2.5, 3, 4, 5, 6.67, 8, 10, 12, 14, 16, 20, 24, 28, 32, 48, 72, 96, 120, 144, and 168 hrs post-dose
The Plasma Concentration (Cmax) is defined as maximum observed analyte concentration. Oseltamivir carboxylate is a clinically active metabolite of oseltamivir.
Tmax and T1/2 of Oseltamivir and Oseltamivir Carboxylate
时间窗: Pre-dose; 0.5, 1.33, 2, 2.5, 3, 4, 5, 6.67, 8, 10, 12, 14, 16, 20, 24, 28, 32, 48, 72, 96, 120, 144, and 168 hrs post-dose
The Time of observed maximum plasma concentration (Tmax) is defined as actual sampling time to reach maximum observed analyte concentration. The Elimination Half-Life Period (T1/2) is the time measured for the plasma concentration to decrease by 1 half to its original concentration. Oseltamivir carboxylate is a clinically active metabolite of oseltamivir.
AUC120, AUC168 and AUCinf of Oseltamivir and Oseltamivir Carboxylate for 75 mg Dose
时间窗: Pre-dose; 0.5, 1.33, 2, 2.5, 3, 4, 5, 6.67, 8, 10, 12, 14, 16, 20, 24, 28, 32, 48, 72, 96, 120, 144, and 168 hrs post-dose
AUC120 is defined as the area under the plasma concentration-time curve from time zero through 120 hours post-dose, AUC168 is defined as the area under the plasma concentration-time curve from time zero through 168 hours post-dose, and AUCinf is defined as the area under the plasma concentration-time curve from time zero extrapolated to infinity. Oseltamivir carboxylate is a clinically active metabolite of oseltamivir.
AUCinf of Oseltamivir and Oseltamivir Carboxylate for 30 mg Dose
时间窗: Pre-dose; 0.5, 1.33, 2, 2.5, 3, 4, 5, 6.67, 8, 10, 12, 14, 16, 20, 24, 28, 32, 48, 72, 96, 120, 144, and 168 hrs post-dose
AUCinf is defined as the area under the plasma concentration-time curve from time zero extrapolated to infinity. Oseltamivir carboxylate is a clinically active metabolite of oseltamivir.
Renal Clearance (CLR) of Oseltamivir and Oseltamivir Carboxylate
时间窗: Pre-dose; 0.5, 1.33, 2, 2.5, 3, 4, 5, 6.67, 8, 10, 12, 14, 16, 20, 24, 28, 32, 48, 72, 96, 120, 144, and 168 hrs post-dose for blood; pre-dose and 0-24, 24-48, 48-72, 72-96, 96-120, 120-144, and 144-168 hrs post-dose for urine.
CLR is calculated as the cumulative amount of drug excreted into urine from 0 to time t hours (Ae0-tlast) / area under the concentration-time curve from time zero through the last quantifiable concentration time (AUC0-t).
Total Dialysate Clearance for Automated Peritoneal Dialysis (CLDAPD) of Oseltamivir and Oseltamivir Carboxylate for 75 mg Dose
时间窗: CCPD: pre-dose (0)-2.67, 2.67-5.33, 5.33-8; CAPD: 8-16, 16-24; CCPD: 24-26.67, 26.67-29.33, 29.33-32; CAPD: 32-40, 40-48 hrs post-dose for urine; CCPD and CAPD:0.5, 1.33, 2, 2.5, 3, 4, 5, 6.67, 8, 10, 12, 14, 16, 20, 24, 28, 32, 48 hrs post-dose for blood
CLDAPD is the total dialysate clearance for automated peritoneal dialysis, attributable to both continuous cycler-assisted peritoneal dialysis (CCPD) and continuous ambulatory peritoneal dialysis (CAPD), which was calculated with the recovery method over the dense blood sampling collection interval from 0 to 48 hours post-dose. CLDAPD = the amount excreted into dialysate from 0 to 48 hours (Aed\[0-48\])/ plasma area under the concentration-time curve from time zero through 48 hours (AUC\[0-48\]) CLDCCPD = mean of CLDCCPD from the 2 CCPD sessions, calculated as CLDCCPD = (Aed\[0-8\]/AUC\[0-8\] + Aed\[24-32\]/AUC\[24-32\]) / 2 CLDCAPD = mean of CLDCAPD from the 3 CAPD sessions, calculated as CLDCAPD = (Aed\[8-16\]/AUC\[8-16\] + Aed\[16-24\]/AUC\[16-24\] + Aed\[32-48\]/AUC\[32-48\]) / 3
C120h, C168h and Clast of Oseltamivir and Oseltamivir Carboxylate for 75 mg Dose
时间窗: Pre-dose; 0.5, 1.33, 2, 2.5, 3, 4, 5, 6.67, 8, 10, 12, 14, 16, 20, 24, 28, 32, 48, 72, 96, 120, 144, and 168 hrs post-dose
C120h is defined as the plasma concentration at 120 hours post-dose. C168h is defined as the plasma concentration at 168 hours post-dose. Clast is defined as the plasma concentration corresponding to the time of the last measureable (positive) plasma concentration. Oseltamivir carboxylate is a clinically active metabolite of oseltamivir.
次要结局
- Number of Participants With Abnormal Shifts in Vital Signs(Days 1 (post-dose), 2, 3, 4, 5, 6, 7, 8; and Follow-up visit (Days 15 to 22))
- Number of Participants With Any Adverse Event (AEs) and Any Serious Adverse Events (SAEs)(Approximately 7 weeks)
- Number of Participants With Change From Baseline in Marked Abnormality in Electrocardiogram (ECG) Parameters at Follow-up Visit(From Baseline (Day -1) to Follow-up visit (Days 15 to 22))
- Number of Participants With Marked Abnormality in Laboratory Measurements(Approximately 7 weeks)