A Single Dose Study of Tamiflu in Volunteers in Dialysis And in Volunteers With Reduced Creatinine Clearance

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.

Time frame: 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

Population: PK population was used for this outcome measure. Only 9 participants were included, who did not significantly violate the inclusion/exclusion criteria, deviate significantly from protocol or with unavailable or incomplete data which influence PK analysis. Numbers of participants analyzed for the indicated drug/metabolite were denoted by n.

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.

Time frame: 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

Population: PK population was used for this outcome measure. Only 9 participants were included, who did not significantly violate the inclusion/exclusion criteria, deviate significantly from protocol or with unavailable or incomplete data which influence PK analysis. Numbers of participants analyzed for the indicated drug/metabolite were denoted by n.

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.

Time frame: 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

Population: PK population was used for this outcome measure. Only 9 participants were included, who did not significantly violate the inclusion/exclusion criteria, deviate significantly from protocol or with unavailable or incomplete data which influence PK analysis.

The Plasma Concentration (Cmax) is defined as maximum observed analyte concentration. Oseltamivir carboxylate is a clinically active metabolite of oseltamivir.

Time frame: 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

Population: PK population was used for this outcome measure. Only 9 participants were included, who did not significantly violate the inclusion/exclusion criteria, deviate significantly from protocol or with unavailable or incomplete data which influence PK analysis. Numbers of participants analyzed for the indicated drug/metabolite were denoted by n.

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).

Time frame: 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.

Population: PK population was used for this outcome measure. Only 9 participants were included, who did not significantly violate the inclusion/exclusion criteria, deviate significantly from protocol or with unavailable or incomplete data which influence PK analysis. Numbers of participants analyzed for the indicated drug/metabolite were denoted by n.

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.

Time frame: 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

Population: PK population was used for this outcome measure. Only 9 participants were included, who did not significantly violate the inclusion/exclusion criteria, deviate significantly from protocol or with unavailable or incomplete data which influence PK analysis. Numbers of participants analyzed for the indicated drug/metabolite were denoted by n.

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

Time frame: 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

Population: Pharmacokinetic (PK) population: Only 9 participants were included for this analysis as they did not significantly violate the inclusion or exclusion criteria, deviate significantly from the protocol or if data was unavailable or incomplete which influence the PK analysis were excluded from the PK analysis population.

Vital signs included pulse rate, systolic blood pressure (SBP), diastolic blood pressure (DBP), and body temperature. Vital sign with abnormal shifts from normal at baseline to high or low at post-baseline time points were recorded. Blood pressure was recorded in millimeter of mercury (mmHg), and temperature in degrees Celsius. Low blood pressure defined as \<=70 mmHg (SBP) and \<=40 mmHg (DBP); high blood pressure defined as \>=140 mmHg (SBP) and \>=90 mmHg (DBP); low temperature defined as \<=36.5 degrees Celsius and high temperature defined as \>=37.5 degrees Celsius.

Time frame: Days 1 (post-dose), 2, 3, 4, 5, 6, 7, 8; and Follow-up visit (Days 15 to 22)

Population: Safety population: All participants who received the study drug, whether prematurely withdrawn from the study or not, were included.

An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with the intervention. An SAE is any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or results in a congenital anomaly/birth defect.

Time frame: Approximately 7 weeks

Population: Safety population: All participants who received the study drug, whether prematurely withdrawn from the study or not, were included.

ECG parameter included QT interval, QTcB interval and QTcF interval (all intervals are measured in millisecond \[msec\]). Marked abnormality in ECG is predefined for QT, QTcB, and QTcF interval as \<=30, \>30-60, and \>60 msec increase from baseline.

Time frame: From Baseline (Day -1) to Follow-up visit (Days 15 to 22)

Population: Safety population: All participants who received the study drug, whether prematurely withdrawn from the study or not, were included.

Laboratory analysis included: hematology (hemoglobin, hematocrit, reticulocyte, red blood cell, platelet and white blood cell count, mean corpuscular volume, mean corpuscular hemoglobin), prothrombin and activated partial thromboplastin time, biochemistry (sodium, potassium, bicarbonate, phosphate, chloride, calcium, urea, serum creatinine, bilirubin, cholesterol, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase \[ALT\], gamma-glutamyl transferase, protein, albumin, amylase, creatinine, lipase), random glucose, and urinalysis. Laboratory test result values falling outside of the marked abnormality range that also represent a defined change from baseline were considered as marked laboratory abnormalities. A marked reference range for sodium is 130-150 millimole (mmol)/L, chloride is 95-115 mmol/L, phosphate is 0.75-1.60 mmol/L, calcium is 2-2.90 mmol/L, glucose is 2.8-11.10 mmol/L, bicarbonate is 18-28 mmol/L, and ALT is 0-110 Unit/L.

Time frame: Approximately 7 weeks

Population: Safety population: All participants who received the study drug, whether prematurely withdrawn from the study or not, were included.