End Stage Renal Disease
Conditions
Brief summary
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.
Interventions
DRUGOseltamivir
Oseltamivir will be given as marketed oral suspension, 30 mg after HD or CAPD treatment.
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Plasma Concentration (Cmax) of Oseltamivir in HD Participants During Days 1 to 5 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 1 to 6 | 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 | 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 36 to 43 | 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 | 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 | 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 | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Plasma samples were obtained up to 120 hours post-dose during the first dose analysis (Days 1 to 6) and up to 168 hours post-dose during the second dose analysis (Days 36 to 43). Urine and dialysate samples were also obtained up to 48 hours post-dose during the first dose analysis. The elimination rate constant was calculated as \[natural log (ln)(2) divided by the half-life\] and expressed as inverse hours (1/h). |
| 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 | Plasma samples were obtained up to 120 hours post-dose during the first dose analysis (Days 1 to 6) and up to 168 hours post-dose during the second dose analysis (Days 36 to 43). Urine and dialysate samples were also obtained up to 48 hours post-dose during the first dose analysis. The time required for the concentration to decrease by one-half was recorded and averaged among all participants and expressed in hours. |
| CL/F of Oseltamivir in CAPD Participants | Blood samples 0, 1, 2, 4, 8, 12 hours from D1 and D36 dose | Plasma samples up to 12 hours post-dose during the first (Days 1 to 6) and second (Days 36 to 43) dose analyses were used to calculate apparent clearance adjusted for oral bioavailability. The CL/F with each dose was averaged among all participants and expressed in L/h. |
| 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 | Plasma samples up to 48 hours post-dose during the first (Days 1 to 6) and second (Days 36 to 43) dose analyses were used to calculate apparent clearance adjusted for oral bioavailability. The CL/F with each dose was averaged among all participants and expressed in L/h. |
| 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 | Plasma and urine samples up to 12 hours post-dose during the first dose analysis (Days 1 to 6) were used to calculate CLr, computed as \[amount of drug excreted divided by the AUC12\]. The CLr was averaged among all participants and expressed in L/h. |
| 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 | Plasma and urine samples up to 48 hours post-dose during the first dose analysis (Days 1 to 6) were used to calculate CLr, computed as \[amount of metabolite excreted divided by the AUC48\]. The CLr was averaged among all participants and expressed in L/h. |
| 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 | Plasma samples up to 120 hours and dialysate samples up to 48 hours post-dose during the first dose analysis (Days 1 to 6) were used to calculate CLd, computed as \[amount of metabolite recovered in dialysate divided by the AUC over the dialysis interval\]. The CLd was averaged among all participants and expressed in L/h. |
| Percentage of Oseltamivir Dose Renally Excreted as Unchanged Drug in CAPD Participants | Urine samples 0 to 48 hours from D1 dose | Urine samples up to 48 hours post-dose during the first dose analysis (Days 1 to 6) were used to calculate renal excretion, computed as \[amount of drug in urine divided by the oral oseltamivir dose\] multiplied by 100. The value was averaged among all participants and expressed as a percent of the oseltamivir dose administered. |
| Percentage of Oseltamivir Dose Renally Excreted as Metabolite Oseltamivir Carboxylate in CAPD Participants | Urine samples 0 to 48 hours from D1 dose | Urine samples up to 48 hours post-dose during the first dose analysis (Days 1 to 6) were used to calculate renal excretion, computed as \[amount of metabolite in urine divided by the oral oseltamivir dose\] multiplied by 100. The value was averaged among all participants and expressed as a percent of the oseltamivir dose administered. |
| Percentage of Oseltamivir Dose Eliminated by Dialysis as Unchanged Drug in CAPD Participants | Dialysate samples 0 to 48 hours from D1 dose | Dialysate samples up to 48 hours post-dose during the first dose analysis (Days 1 to 6) were used to calculate dialysis elimination, computed as \[amount of drug in dialysate divided by the oral oseltamivir dose\] multiplied by 100. The value was averaged among all participants and expressed as a percent of the oseltamivir dose administered. |
| 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 samples were obtained up to 90 hours post-dose during the first dose analysis (Days 1 to 5) and up to 114 hours post-dose during the second dose analysis (Days 38 to 43). The concentration at each collection time was recorded and averaged among all participants and expressed in ng/mL. |
| Percentage of Oseltamivir Dose Eliminated by Dialysis as Metabolite Oseltamivir Carboxylate in CAPD Participants | Dialysate samples 0 to 48 hours from D1 dose | Dialysate samples up to 48 hours post-dose during the first dose analysis (Days 1 to 6) were used to calculate dialysis elimination, computed as \[amount of metabolite in dialysate divided by the oral oseltamivir dose\] multiplied by 100. The value was averaged among all participants and expressed as a percent of the oseltamivir dose administered. |
| 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 | Plasma samples were obtained up to 90 hours post-dose during the first dose analysis (Days 1 to 5) and up to 114 hours post-dose during the second dose analysis (Days 38 to 43). The concentration at each collection time was recorded and averaged among all participants and expressed in ng/mL. |
| 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 | Plasma samples were obtained up to 90 hours post-dose during the first (Days 1 to 5) and second (Days 38 to 43) dose analyses, and the observed time of maximum concentration was recorded. The Tmax following each dose was averaged among all participants and expressed in hours. |
| 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 | Plasma samples were obtained up to 90 hours post-dose during the first (Days 1 to 5) and second (Days 38 to 43) dose analyses, and the observed time of maximum concentration was recorded. The Tmax following each dose was averaged among all participants and expressed in hours. |
| Oral Plasma Clearance (CL/F) of Oseltamivir in HD Participants | Blood samples 0, 1, 2, 4, 8, 12 hours from D1 and D38 dose | Plasma samples up to 12 hours post-dose during the first (Days 1 to 5) and second (Days 38 to 43) dose analyses were used to calculate apparent clearance adjusted for oral bioavailability. The CL/F with each dose was averaged among all participants and expressed in liters per hour (L/h). |
| 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 | Plasma samples up to 42 hours post-dose during the first (Days 1 to 5) and second (Days 38 to 43) dose analyses were used to calculate apparent clearance adjusted for oral bioavailability. The CL/F with each dose was averaged among all participants and expressed in L/h. |
| 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 | Plasma and urine samples up to 12 hours post-dose during the first dose analysis (Days 1 to 5) were used to calculate CLr, computed as \[amount of drug excreted divided by the AUC12\]. The CLr was averaged among all participants and expressed in L/h. |
| 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 | Plasma and urine samples up to 42 hours post-dose during the first dose analysis (Days 1 to 5) were used to calculate CLr, computed as \[amount of metabolite excreted divided by the AUC42\]. The CLr was averaged among all participants and expressed in L/h. |
| 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 | Plasma samples up to 90 hours post-dose during the first (Days 1 to 5) and second (Days 38 to 43) dose analyses, in addition to dialyzer samples obtained on Days 3 and 40, were used to calculate CLd, computed as \[amount of metabolite recovered in dialysate divided by the AUC over the dialysis interval\]. The CLd with each dose was averaged among all participants and expressed in L/h. |
| Percentage of Oseltamivir Dose Excreted as Unchanged Drug in HD Participants | Urine samples 0 to 42 hours from D1 dose | Urine samples up to 42 hours post-dose during the first dose analysis (Days 1 to 5) were used to calculate drug excretion, computed as \[amount of drug excreted divided by the oral oseltamivir dose\] multiplied by 100. The value was averaged among all participants and expressed as a percent of the oseltamivir dose administered. |
| Percentage of Oseltamivir Dose Excreted as Metabolite Oseltamivir Carboxylate in HD Participants | Urine samples 0 to 42 hours from D1 dose | Urine samples up to 42 hours post-dose during the first dose analysis (Days 1 to 5) were used to calculate metabolite excretion, computed as \[amount of metabolite excreted divided by the oral oseltamivir dose\] multiplied by 100. The value was averaged among all participants and expressed as a percent of the oseltamivir dose administered. |
| 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 | Dialyzer samples were obtained up to 5 hours from the start of dialysis on Days 3 and 40 (corresponding to HD sessions 2 and 18). Arterial concentrations were estimated using the inflow to the dialyzer, and venous concentrations were estimated using the outflow from the dialyzer. The concentration at each collection time was recorded and averaged among all participants and expressed in ng/mL. |
| 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 samples were obtained up to 120 hours post-dose during the first dose analysis (Days 1 to 6) and up to 168 hours post-dose during the second dose analysis (Days 36 to 43). The concentration at each collection time was recorded and averaged among all participants and expressed in ng/mL. |
| 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 | Plasma samples were obtained up to 120 post-dose during the first dose analysis (Days 1 to 6) and up to 168 hours post-dose during the second dose analysis (Days 36 to 43). The concentration at each collection time was recorded and averaged among all participants and expressed in ng/mL. |
| 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 | Plasma samples were obtained up to 120 hours post-dose during the first dose analysis (Days 1 to 6) and up to 168 hours post-dose during the second dose analysis (Days 36 to 43), and the observed time of maximum concentration was recorded. The Tmax following each dose was averaged among all participants and expressed in hours. |
| 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 | Plasma samples were obtained up to 120 hours post-dose during the first dose analysis (Days 1 to 6) and up to 168 hours post-dose during the second dose analysis (Days 36 to 43), and the observed time of maximum concentration was recorded. The Tmax following each dose was averaged among all participants and expressed in hours. |
Countries
New Zealand
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Oseltamivir With HD Participants on HD received 9 doses of 30-mg oseltamivir oral suspension, given 1 hour after completion of alternating HD sessions. All HD participants were planned to receive 19 routine HD sessions (three per week) during the 6.5-week study period. | 12 |
| Oseltamivir With CAPD Participants on CAPD received 6 doses of 30-mg oseltamivir oral suspension, given once weekly after dialysis exchange. All CAPD participants underwent routine CAPD sessions (four exchanges per 24 hours) during the 6-week study period. | 12 |
| Total | 24 |
Baseline characteristics
| Characteristic | Oseltamivir With HD | Oseltamivir With CAPD | Total |
|---|---|---|---|
| Age, Continuous | 48.00 years STANDARD_DEVIATION 13.23 | 54.42 years STANDARD_DEVIATION 14.3 | 51.21 years STANDARD_DEVIATION 13.87 |
| Sex: Female, Male Female | 1 Participants | 7 Participants | 8 Participants |
| Sex: Female, Male Male | 11 Participants | 5 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 8 / 12 | 10 / 12 |
| serious Total, serious adverse events | 1 / 12 | 2 / 12 |
Outcome results
Primary
Area Under the Concentration-Time Curve (AUC) of Oseltamivir in HD Participants During Days 1 to 5
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).
Time frame: Blood samples 0, 1, 2, 4, 8, 12, 20, 32, 42, 48, 49, 90 hours from D1 dose
Population: PK Analysis Population (First Dose Subpopulation).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oseltamivir With HD | Area Under the Concentration-Time Curve (AUC) of Oseltamivir in HD Participants During Days 1 to 5 | AUC12 | 63.9 ng*h/mL | Standard Deviation 24.6 |
| Oseltamivir With HD | Area Under the Concentration-Time Curve (AUC) of Oseltamivir in HD Participants During Days 1 to 5 | AUClast | 62.1 ng*h/mL | Standard Deviation 26.8 |
Primary
AUC of Metabolite Oseltamivir Carboxylate in CAPD Participants During Days 1 to 6
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.
Time frame: Blood samples 0, 1, 2, 4, 8, 12, 24, 48, 72, 120 hours from D1 dose
Population: PK Analysis Population (First Dose Subpopulation).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oseltamivir With HD | AUC of Metabolite Oseltamivir Carboxylate in CAPD Participants During Days 1 to 6 | AUC48 | 33400 ng*h/mL | Standard Deviation 9700 |
| Oseltamivir With HD | AUC of Metabolite Oseltamivir Carboxylate in CAPD Participants During Days 1 to 6 | AUClast | 56800 ng*h/mL | Standard Deviation 18300 |
Primary
AUC of Metabolite Oseltamivir Carboxylate in CAPD Participants During Days 36 to 43
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.
Time frame: Blood samples 0, 1, 2, 4, 8, 12, 24, 48, 72, 120, 168 hours from D36 dose
Population: PK Analysis Population (Second Dose Subpopulation).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oseltamivir With HD | AUC of Metabolite Oseltamivir Carboxylate in CAPD Participants During Days 36 to 43 | AUC48 | 32400 ng*h/mL | Standard Deviation 8210 |
| Oseltamivir With HD | AUC of Metabolite Oseltamivir Carboxylate in CAPD Participants During Days 36 to 43 | AUClast | 60800 ng*h/mL | Standard Deviation 18800 |
Primary
AUC of Metabolite Oseltamivir Carboxylate in HD Participants During Days 1 to 5
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.
Time frame: Blood samples 0, 1, 2, 4, 8, 12, 20, 32, 42, 48, 49, 90 hours from D1 dose
Population: PK Analysis Population (First Dose Subpopulation).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oseltamivir With HD | AUC of Metabolite Oseltamivir Carboxylate in HD Participants During Days 1 to 5 | AUC42 | 31600 ng*h/mL | Standard Deviation 14100 |
| Oseltamivir With HD | AUC of Metabolite Oseltamivir Carboxylate in HD Participants During Days 1 to 5 | AUClast | 44400 ng*h/mL | Standard Deviation 19000 |
Primary
AUC of Metabolite Oseltamivir Carboxylate in HD Participants During Days 38 to 43
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.
Time frame: Blood samples 0, 1, 2, 4, 8, 12, 20, 32, 42, 48, 49, 90 hours from D38 dose
Population: PK Analysis Population (Second Dose Subpopulation).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oseltamivir With HD | AUC of Metabolite Oseltamivir Carboxylate in HD Participants During Days 38 to 43 | AUC42 | 38200 ng*h/mL | Standard Deviation 11500 |
| Oseltamivir With HD | AUC of Metabolite Oseltamivir Carboxylate in HD Participants During Days 38 to 43 | AUClast | 60400 ng*h/mL | Standard Deviation 16700 |
Primary
AUC of Oseltamivir in CAPD Participants During Days 1 to 6
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.
Time frame: Blood samples 0, 1, 2, 4, 8, 12, 24, 48, 72, 120 hours from D1 dose
Population: PK Analysis Population (First Dose Subpopulation).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oseltamivir With HD | AUC of Oseltamivir in CAPD Participants During Days 1 to 6 | AUC12 | 85.6 ng*h/mL | Standard Deviation 40.7 |
| Oseltamivir With HD | AUC of Oseltamivir in CAPD Participants During Days 1 to 6 | AUClast | 78.5 ng*h/mL | Standard Deviation 41.8 |
Primary
AUC of Oseltamivir in CAPD Participants During Days 36 to 43
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.
Time frame: Blood samples 0, 1, 2, 4, 8, 12, 24, 48, 72, 120, 168 hours from D36 dose
Population: PK Analysis Population (Second Dose Subpopulation).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oseltamivir With HD | AUC of Oseltamivir in CAPD Participants During Days 36 to 43 | AUClast | 67.7 ng*h/mL | Standard Deviation 27.7 |
| Oseltamivir With HD | AUC of Oseltamivir in CAPD Participants During Days 36 to 43 | AUC12 | 72.4 ng*h/mL | Standard Deviation 28.3 |
Primary
AUC of Oseltamivir in HD Participants During Days 38 to 43
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.
Time frame: Blood samples 0, 1, 2, 4, 8, 12, 20, 32, 42, 48, 49, 90 hours from D38 dose
Population: PK Analysis Population (Second Dose Subpopulation).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oseltamivir With HD | AUC of Oseltamivir in HD Participants During Days 38 to 43 | AUC12 | 68.5 ng*h/mL | Standard Deviation 19.5 |
| Oseltamivir With HD | AUC of Oseltamivir in HD Participants During Days 38 to 43 | AUClast | 65.6 ng*h/mL | Standard Deviation 20.1 |
Primary
Cmax of Metabolite Oseltamivir Carboxylate in CAPD Participants During Days 1 to 6
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.
Time frame: Blood samples 0, 1, 2, 4, 8, 12, 24, 48, 72, 120 hours from D1 dose
Population: PK Analysis Population (First Dose Subpopulation).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oseltamivir With HD | Cmax of Metabolite Oseltamivir Carboxylate in CAPD Participants During Days 1 to 6 | 885 ng/mL | Standard Deviation 244 |
Primary
Cmax of Metabolite Oseltamivir Carboxylate in CAPD Participants During Days 36 to 43
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.
Time frame: Blood samples 0, 1, 2, 4, 8, 12, 24, 48, 72, 120, 168 hours from D36 dose
Population: PK Analysis Population (Second Dose Subpopulation).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oseltamivir With HD | Cmax of Metabolite Oseltamivir Carboxylate in CAPD Participants During Days 36 to 43 | 849 ng/mL | Standard Deviation 200 |
Primary
Cmax of Metabolite Oseltamivir Carboxylate in HD Participants During Days 1 to 5
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.
Time frame: Blood samples 0, 1, 2, 4, 8, 12, 20, 32, 42, 48, 49, 90 hours from D1 dose
Population: PK Analysis Population (First Dose Subpopulation).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oseltamivir With HD | Cmax of Metabolite Oseltamivir Carboxylate in HD Participants During Days 1 to 5 | 943 ng/mL | Standard Deviation 393 |
Primary
Cmax of Metabolite Oseltamivir Carboxylate in HD Participants During Days 38 to 43
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.
Time frame: Blood samples 0, 1, 2, 4, 8, 12, 20, 32, 42, 48, 49, 90 hours from D38 dose
Population: PK Analysis Population (Second Dose Subpopulation).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oseltamivir With HD | Cmax of Metabolite Oseltamivir Carboxylate in HD Participants During Days 38 to 43 | 1120 ng/mL | Standard Deviation 320 |
Primary
Cmax of Oseltamivir in CAPD Participants During Days 1 to 6
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.
Time frame: Blood samples 0, 1, 2, 4, 8, 12, 24, 48, 72, 120 hours from D1 dose
Population: PK Analysis Population (First Dose Subpopulation).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oseltamivir With HD | Cmax of Oseltamivir in CAPD Participants During Days 1 to 6 | 32.0 ng/mL | Standard Deviation 20.4 |
Primary
Cmax of Oseltamivir in CAPD Participants During Days 36 to 43
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.
Time frame: Blood samples 0, 1, 2, 4, 8, 12, 24, 48, 72, 120, 168 hours from Day 36 (D36) dose
Population: PK Analysis Population (Second Dose Subpopulation).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oseltamivir With HD | Cmax of Oseltamivir in CAPD Participants During Days 36 to 43 | 27.7 ng/mL | Standard Deviation 15.9 |
Primary
Cmax of Oseltamivir in HD Participants During Days 38 to 43
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.
Time frame: Blood samples 0, 1, 2, 4, 8, 12, 20, 32, 42, 48, 49, 90 hours from Day 38 (D38) dose
Population: PK Analysis Population (Second Dose Subpopulation): All participants who completed treatment and provided evaluable data during the second dose assessment period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oseltamivir With HD | Cmax of Oseltamivir in HD Participants During Days 38 to 43 | 22.6 ng/mL | Standard Deviation 9.69 |
Primary
Maximum Plasma Concentration (Cmax) of Oseltamivir in HD Participants During Days 1 to 5
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).
Time frame: Blood samples 0, 1, 2, 4, 8, 12, 20, 32, 42, 48, 49, 90 hours from Day 1 (D1) dose
Population: Pharmacokinetic (PK) Analysis Population (First Dose Subpopulation): All participants who completed treatment and provided evaluable data during the first dose assessment period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oseltamivir With HD | Maximum Plasma Concentration (Cmax) of Oseltamivir in HD Participants During Days 1 to 5 | 20.2 ng/mL | Standard Deviation 12.3 |
Secondary
CLd of Metabolite Oseltamivir Carboxylate in CAPD Participants
Plasma samples up to 120 hours and dialysate samples up to 48 hours post-dose during the first dose analysis (Days 1 to 6) were used to calculate CLd, computed as \[amount of metabolite recovered in dialysate divided by the AUC over the dialysis interval\]. The CLd was averaged among all participants and expressed in L/h.
Time frame: 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
Population: PK Analysis Population (First Dose Subpopulation).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oseltamivir With HD | CLd of Metabolite Oseltamivir Carboxylate in CAPD Participants | 0.425 L/h | Standard Deviation 0.0456 |
Secondary
CL/F of Metabolite Oseltamivir Carboxylate in CAPD Participants
Plasma samples up to 48 hours post-dose during the first (Days 1 to 6) and second (Days 36 to 43) dose analyses were used to calculate apparent clearance adjusted for oral bioavailability. The CL/F with each dose was averaged among all participants and expressed in L/h.
Time frame: Blood samples 0, 1, 2, 4, 8, 12, 24, 48 hours from D1 and D36 dose
Population: PK Analysis Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oseltamivir With HD | CL/F of Metabolite Oseltamivir Carboxylate in CAPD Participants | Days 1 to 6 | 0.882 L/h | Standard Deviation 0.25 |
| Oseltamivir With HD | CL/F of Metabolite Oseltamivir Carboxylate in CAPD Participants | Days 36 to 43 | 0.898 L/h | Standard Deviation 0.246 |
Secondary
CL/F of Metabolite Oseltamivir Carboxylate in HD Participants
Plasma samples up to 42 hours post-dose during the first (Days 1 to 5) and second (Days 38 to 43) dose analyses were used to calculate apparent clearance adjusted for oral bioavailability. The CL/F with each dose was averaged among all participants and expressed in L/h.
Time frame: Blood samples 0, 1, 2, 4, 8, 12, 20, 32, 42 hours from D1 and D38 dose
Population: PK Analysis Population; n = number of participants included in the specific dose analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oseltamivir With HD | CL/F of Metabolite Oseltamivir Carboxylate in HD Participants | Days 1 to 5 (n=12) | 1.20 L/h | Standard Deviation 1.05 |
| Oseltamivir With HD | CL/F of Metabolite Oseltamivir Carboxylate in HD Participants | Days 38 to 43 (n=11) | 0.779 L/h | Standard Deviation 0.239 |
Secondary
CL/F of Oseltamivir in CAPD Participants
Plasma samples up to 12 hours post-dose during the first (Days 1 to 6) and second (Days 36 to 43) dose analyses were used to calculate apparent clearance adjusted for oral bioavailability. The CL/F with each dose was averaged among all participants and expressed in L/h.
Time frame: Blood samples 0, 1, 2, 4, 8, 12 hours from D1 and D36 dose
Population: PK Analysis Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oseltamivir With HD | CL/F of Oseltamivir in CAPD Participants | Days 1 to 6 | 424 L/h | Standard Deviation 183 |
| Oseltamivir With HD | CL/F of Oseltamivir in CAPD Participants | Days 36 to 43 | 485 L/h | Standard Deviation 215 |
Secondary
CLr of Metabolite Oseltamivir Carboxylate in CAPD Participants
Plasma and urine samples up to 48 hours post-dose during the first dose analysis (Days 1 to 6) were used to calculate CLr, computed as \[amount of metabolite excreted divided by the AUC48\]. The CLr was averaged among all participants and expressed in L/h.
Time frame: Blood samples 0, 1, 2, 4, 8, 12, 24, 48 hours from D1 dose; urine samples 0 to 48 hours from D1 dose
Population: PK Analysis Population (First Dose Subpopulation).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oseltamivir With HD | CLr of Metabolite Oseltamivir Carboxylate in CAPD Participants | 0.0665 L/h | Standard Deviation 0.114 |
Secondary
CLr of Metabolite Oseltamivir Carboxylate in HD Participants
Plasma and urine samples up to 42 hours post-dose during the first dose analysis (Days 1 to 5) were used to calculate CLr, computed as \[amount of metabolite excreted divided by the AUC42\]. The CLr was averaged among all participants and expressed in L/h.
Time frame: Blood samples 0, 1, 2, 4, 8, 12, 20, 32, 42 hours from D1 dose; urine samples 0 to 42 hours from D1 dose
Population: PK Analysis Population (First Dose Subpopulation).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oseltamivir With HD | CLr of Metabolite Oseltamivir Carboxylate in HD Participants | 0.0203 L/h | Standard Deviation 0.0568 |
Secondary
CLr of Oseltamivir in CAPD Participants
Plasma and urine samples up to 12 hours post-dose during the first dose analysis (Days 1 to 6) were used to calculate CLr, computed as \[amount of drug excreted divided by the AUC12\]. The CLr was averaged among all participants and expressed in L/h.
Time frame: Blood samples 0, 1, 2, 4, 8, 12 hours from D1 dose; urine samples 0 to 12 hours from D1 dose
Population: PK Analysis Population (First Dose Subpopulation).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oseltamivir With HD | CLr of Oseltamivir in CAPD Participants | 0.146 L/h | Standard Deviation 0.25 |
Secondary
Dialysis Clearance (CLd) of Metabolite Oseltamivir Carboxylate in HD Participants
Plasma samples up to 90 hours post-dose during the first (Days 1 to 5) and second (Days 38 to 43) dose analyses, in addition to dialyzer samples obtained on Days 3 and 40, were used to calculate CLd, computed as \[amount of metabolite recovered in dialysate divided by the AUC over the dialysis interval\]. The CLd with each dose was averaged among all participants and expressed in L/h.
Time frame: 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
Population: PK Analysis Population; n = number of participants included in the specific dose analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oseltamivir With HD | Dialysis Clearance (CLd) of Metabolite Oseltamivir Carboxylate in HD Participants | Days 1 to 5 (n=12) | 7.42 L/h | Standard Deviation 0.447 |
| Oseltamivir With HD | Dialysis Clearance (CLd) of Metabolite Oseltamivir Carboxylate in HD Participants | Days 38 to 43 (n=11) | 8.43 L/h | Standard Deviation 3.02 |
Secondary
Elimination Rate Constant of Metabolite Oseltamivir Carboxylate in CAPD Participants
Plasma samples were obtained up to 120 hours post-dose during the first dose analysis (Days 1 to 6) and up to 168 hours post-dose during the second dose analysis (Days 36 to 43). Urine and dialysate samples were also obtained up to 48 hours post-dose during the first dose analysis. The elimination rate constant was calculated as \[natural log (ln)(2) divided by the half-life\] and expressed as inverse hours (1/h).
Time frame: 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
Population: PK Analysis Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oseltamivir With HD | Elimination Rate Constant of Metabolite Oseltamivir Carboxylate in CAPD Participants | Days 1 to 6 | 0.0211 1/h | Standard Deviation 0.00578 |
| Oseltamivir With HD | Elimination Rate Constant of Metabolite Oseltamivir Carboxylate in CAPD Participants | Days 36 to 43 | 0.0200 1/h | Standard Deviation 0.00488 |
Secondary
Oral Plasma Clearance (CL/F) of Oseltamivir in HD Participants
Plasma samples up to 12 hours post-dose during the first (Days 1 to 5) and second (Days 38 to 43) dose analyses were used to calculate apparent clearance adjusted for oral bioavailability. The CL/F with each dose was averaged among all participants and expressed in liters per hour (L/h).
Time frame: Blood samples 0, 1, 2, 4, 8, 12 hours from D1 and D38 dose
Population: PK Analysis Population; n = number of participants included in the specific dose analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oseltamivir With HD | Oral Plasma Clearance (CL/F) of Oseltamivir in HD Participants | Days 1 to 5 (n=12) | 677 L/h | Standard Deviation 727 |
| Oseltamivir With HD | Oral Plasma Clearance (CL/F) of Oseltamivir in HD Participants | Days 38 to 43 (n=11) | 474 L/h | Standard Deviation 141 |
Secondary
Percentage of Oseltamivir Dose Eliminated by Dialysis as Metabolite Oseltamivir Carboxylate in CAPD Participants
Dialysate samples up to 48 hours post-dose during the first dose analysis (Days 1 to 6) were used to calculate dialysis elimination, computed as \[amount of metabolite in dialysate divided by the oral oseltamivir dose\] multiplied by 100. The value was averaged among all participants and expressed as a percent of the oseltamivir dose administered.
Time frame: Dialysate samples 0 to 48 hours from D1 dose
Population: PK Analysis Population (First Dose Subpopulation).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oseltamivir With HD | Percentage of Oseltamivir Dose Eliminated by Dialysis as Metabolite Oseltamivir Carboxylate in CAPD Participants | 32.6 percentage of oseltamivir dose | Standard Deviation 8.77 |
Secondary
Percentage of Oseltamivir Dose Eliminated by Dialysis as Unchanged Drug in CAPD Participants
Dialysate samples up to 48 hours post-dose during the first dose analysis (Days 1 to 6) were used to calculate dialysis elimination, computed as \[amount of drug in dialysate divided by the oral oseltamivir dose\] multiplied by 100. The value was averaged among all participants and expressed as a percent of the oseltamivir dose administered.
Time frame: Dialysate samples 0 to 48 hours from D1 dose
Population: PK Analysis Population (First Dose Subpopulation).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oseltamivir With HD | Percentage of Oseltamivir Dose Eliminated by Dialysis as Unchanged Drug in CAPD Participants | 0.00367 percentage of oseltamivir dose | Standard Deviation 0.0127 |
Secondary
Percentage of Oseltamivir Dose Excreted as Metabolite Oseltamivir Carboxylate in HD Participants
Urine samples up to 42 hours post-dose during the first dose analysis (Days 1 to 5) were used to calculate metabolite excretion, computed as \[amount of metabolite excreted divided by the oral oseltamivir dose\] multiplied by 100. The value was averaged among all participants and expressed as a percent of the oseltamivir dose administered.
Time frame: Urine samples 0 to 42 hours from D1 dose
Population: PK Analysis Population (First Dose Subpopulation).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oseltamivir With HD | Percentage of Oseltamivir Dose Excreted as Metabolite Oseltamivir Carboxylate in HD Participants | 1.86 percentage of osteltamivir dose | Standard Deviation 4.66 |
Secondary
Percentage of Oseltamivir Dose Excreted as Unchanged Drug in HD Participants
Urine samples up to 42 hours post-dose during the first dose analysis (Days 1 to 5) were used to calculate drug excretion, computed as \[amount of drug excreted divided by the oral oseltamivir dose\] multiplied by 100. The value was averaged among all participants and expressed as a percent of the oseltamivir dose administered.
Time frame: Urine samples 0 to 42 hours from D1 dose
Population: PK Analysis Population (First Dose Subpopulation).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oseltamivir With HD | Percentage of Oseltamivir Dose Excreted as Unchanged Drug in HD Participants | 0.00982 percentage of oseltamivir dose | Standard Deviation 0.0221 |
Secondary
Percentage of Oseltamivir Dose Renally Excreted as Metabolite Oseltamivir Carboxylate in CAPD Participants
Urine samples up to 48 hours post-dose during the first dose analysis (Days 1 to 6) were used to calculate renal excretion, computed as \[amount of metabolite in urine divided by the oral oseltamivir dose\] multiplied by 100. The value was averaged among all participants and expressed as a percent of the oseltamivir dose administered.
Time frame: Urine samples 0 to 48 hours from D1 dose
Population: PK Analysis Population (First Dose Subpopulation).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oseltamivir With HD | Percentage of Oseltamivir Dose Renally Excreted as Metabolite Oseltamivir Carboxylate in CAPD Participants | 6.44 percentage of oseltamivir dose | Standard Deviation 10.8 |
Secondary
Percentage of Oseltamivir Dose Renally Excreted as Unchanged Drug in CAPD Participants
Urine samples up to 48 hours post-dose during the first dose analysis (Days 1 to 6) were used to calculate renal excretion, computed as \[amount of drug in urine divided by the oral oseltamivir dose\] multiplied by 100. The value was averaged among all participants and expressed as a percent of the oseltamivir dose administered.
Time frame: Urine samples 0 to 48 hours from D1 dose
Population: PK Analysis Population (First Dose Subpopulation).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oseltamivir With HD | Percentage of Oseltamivir Dose Renally Excreted as Unchanged Drug in CAPD Participants | 0.0290 percentage of oseltamivir dose | Standard Deviation 0.049 |
Secondary
Plasma Concentration of Metabolite Oseltamivir Carboxylate by Timepoint in CAPD Participants
Plasma samples were obtained up to 120 post-dose during the first dose analysis (Days 1 to 6) and up to 168 hours post-dose during the second dose analysis (Days 36 to 43). The concentration at each collection time was recorded and averaged among all participants and expressed in ng/mL.
Time frame: 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
Population: PK Analysis Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oseltamivir With HD | Plasma Concentration of Metabolite Oseltamivir Carboxylate by Timepoint in CAPD Participants | 0 hours from D1 dose | 0.0 ng/mL | Standard Deviation 0 |
| Oseltamivir With HD | Plasma Concentration of Metabolite Oseltamivir Carboxylate by Timepoint in CAPD Participants | 1 hour from D1 dose | 20.3 ng/mL | Standard Deviation 19.9 |
| Oseltamivir With HD | Plasma Concentration of Metabolite Oseltamivir Carboxylate by Timepoint in CAPD Participants | 2 hours from D1 dose | 121 ng/mL | Standard Deviation 72.7 |
| Oseltamivir With HD | Plasma Concentration of Metabolite Oseltamivir Carboxylate by Timepoint in CAPD Participants | 4 hours from D1 dose | 381 ng/mL | Standard Deviation 171 |
| Oseltamivir With HD | Plasma Concentration of Metabolite Oseltamivir Carboxylate by Timepoint in CAPD Participants | 8 hours from D1 dose | 691 ng/mL | Standard Deviation 217 |
| Oseltamivir With HD | Plasma Concentration of Metabolite Oseltamivir Carboxylate by Timepoint in CAPD Participants | 12 hours from D1 dose | 812 ng/mL | Standard Deviation 251 |
| Oseltamivir With HD | Plasma Concentration of Metabolite Oseltamivir Carboxylate by Timepoint in CAPD Participants | 24 hours from D1 dose | 879 ng/mL | Standard Deviation 245 |
| Oseltamivir With HD | Plasma Concentration of Metabolite Oseltamivir Carboxylate by Timepoint in CAPD Participants | 48 hours from D1 dose | 580 ng/mL | Standard Deviation 193 |
| Oseltamivir With HD | Plasma Concentration of Metabolite Oseltamivir Carboxylate by Timepoint in CAPD Participants | 72 hours from D1 dose | 360 ng/mL | Standard Deviation 148 |
| Oseltamivir With HD | Plasma Concentration of Metabolite Oseltamivir Carboxylate by Timepoint in CAPD Participants | 120 hours from D1 dose | 147 ng/mL | Standard Deviation 80.9 |
| Oseltamivir With HD | Plasma Concentration of Metabolite Oseltamivir Carboxylate by Timepoint in CAPD Participants | 0 hours from D36 dose | 69.2 ng/mL | Standard Deviation 40.1 |
| Oseltamivir With HD | Plasma Concentration of Metabolite Oseltamivir Carboxylate by Timepoint in CAPD Participants | 1 hour from D36 dose | 97.0 ng/mL | Standard Deviation 52.3 |
| Oseltamivir With HD | Plasma Concentration of Metabolite Oseltamivir Carboxylate by Timepoint in CAPD Participants | 2 hours from D36 dose | 184 ng/mL | Standard Deviation 84.7 |
| Oseltamivir With HD | Plasma Concentration of Metabolite Oseltamivir Carboxylate by Timepoint in CAPD Participants | 4 hours from D36 dose | 403 ng/mL | Standard Deviation 149 |
| Oseltamivir With HD | Plasma Concentration of Metabolite Oseltamivir Carboxylate by Timepoint in CAPD Participants | 8 hours from D36 dose | 663 ng/mL | Standard Deviation 179 |
| Oseltamivir With HD | Plasma Concentration of Metabolite Oseltamivir Carboxylate by Timepoint in CAPD Participants | 12 hours from D36 dose | 802 ng/mL | Standard Deviation 200 |
| Oseltamivir With HD | Plasma Concentration of Metabolite Oseltamivir Carboxylate by Timepoint in CAPD Participants | 24 hours from D36 dose | 831 ng/mL | Standard Deviation 201 |
| Oseltamivir With HD | Plasma Concentration of Metabolite Oseltamivir Carboxylate by Timepoint in CAPD Participants | 48 hours from D36 dose | 563 ng/mL | Standard Deviation 172 |
| Oseltamivir With HD | Plasma Concentration of Metabolite Oseltamivir Carboxylate by Timepoint in CAPD Participants | 72 hours from D36 dose | 362 ng/mL | Standard Deviation 138 |
| Oseltamivir With HD | Plasma Concentration of Metabolite Oseltamivir Carboxylate by Timepoint in CAPD Participants | 120 hours from D36 dose | 149 ng/mL | Standard Deviation 71.6 |
| Oseltamivir With HD | Plasma Concentration of Metabolite Oseltamivir Carboxylate by Timepoint in CAPD Participants | 168 hours from D36 dose | 63.0 ng/mL | Standard Deviation 38.1 |
Secondary
Plasma Concentration of Metabolite Oseltamivir Carboxylate by Timepoint in HD Participants
Plasma samples were obtained up to 90 hours post-dose during the first dose analysis (Days 1 to 5) and up to 114 hours post-dose during the second dose analysis (Days 38 to 43). The concentration at each collection time was recorded and averaged among all participants and expressed in ng/mL.
Time frame: 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
Population: PK Analysis Population; n = number of participants included at specified timepoints in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oseltamivir With HD | Plasma Concentration of Metabolite Oseltamivir Carboxylate by Timepoint in HD Participants | 0 hours from D1 dose (n=12) | 0.908 ng/mL | Standard Deviation 3.15 |
| Oseltamivir With HD | Plasma Concentration of Metabolite Oseltamivir Carboxylate by Timepoint in HD Participants | 1 hour from D1 dose (n=12) | 25.7 ng/mL | Standard Deviation 24.5 |
| Oseltamivir With HD | Plasma Concentration of Metabolite Oseltamivir Carboxylate by Timepoint in HD Participants | 2 hours from D1 dose (n=12) | 107 ng/mL | Standard Deviation 83.7 |
| Oseltamivir With HD | Plasma Concentration of Metabolite Oseltamivir Carboxylate by Timepoint in HD Participants | 4 hours from D1 dose (n=12) | 276 ng/mL | Standard Deviation 181 |
| Oseltamivir With HD | Plasma Concentration of Metabolite Oseltamivir Carboxylate by Timepoint in HD Participants | 8 hours from D1 dose (n=12) | 589 ng/mL | Standard Deviation 321 |
| Oseltamivir With HD | Plasma Concentration of Metabolite Oseltamivir Carboxylate by Timepoint in HD Participants | 12 hours from D1 dose (n=12) | 772 ng/mL | Standard Deviation 363 |
| Oseltamivir With HD | Plasma Concentration of Metabolite Oseltamivir Carboxylate by Timepoint in HD Participants | 20 hours from D1 dose (n=12) | 908 ng/mL | Standard Deviation 383 |
| Oseltamivir With HD | Plasma Concentration of Metabolite Oseltamivir Carboxylate by Timepoint in HD Participants | 32 hours from D1 dose (n=12) | 926 ng/mL | Standard Deviation 399 |
| Oseltamivir With HD | Plasma Concentration of Metabolite Oseltamivir Carboxylate by Timepoint in HD Participants | 42 hours from D1 dose (n=12) | 877 ng/mL | Standard Deviation 393 |
| Oseltamivir With HD | Plasma Concentration of Metabolite Oseltamivir Carboxylate by Timepoint in HD Participants | 48 hours from D1 dose (n=12) | 212 ng/mL | Standard Deviation 78.6 |
| Oseltamivir With HD | Plasma Concentration of Metabolite Oseltamivir Carboxylate by Timepoint in HD Participants | 49 hours from D1 dose (n=12) | 233 ng/mL | Standard Deviation 88.2 |
| Oseltamivir With HD | Plasma Concentration of Metabolite Oseltamivir Carboxylate by Timepoint in HD Participants | 90 hours from D1 dose (n=12) | 240 ng/mL | Standard Deviation 123 |
| Oseltamivir With HD | Plasma Concentration of Metabolite Oseltamivir Carboxylate by Timepoint in HD Participants | 0 hours from D38 dose (n=11) | 59.0 ng/mL | Standard Deviation 32.1 |
| Oseltamivir With HD | Plasma Concentration of Metabolite Oseltamivir Carboxylate by Timepoint in HD Participants | 1 hour from D38 dose (n=11) | 95.0 ng/mL | Standard Deviation 32.8 |
| Oseltamivir With HD | Plasma Concentration of Metabolite Oseltamivir Carboxylate by Timepoint in HD Participants | 2 hours from D38 dose (n=11) | 200 ng/mL | Standard Deviation 58.7 |
| Oseltamivir With HD | Plasma Concentration of Metabolite Oseltamivir Carboxylate by Timepoint in HD Participants | 4 hours from D38 dose (n=11) | 413 ng/mL | Standard Deviation 137 |
| Oseltamivir With HD | Plasma Concentration of Metabolite Oseltamivir Carboxylate by Timepoint in HD Participants | 8 hours from D38 dose (n=11) | 745 ng/mL | Standard Deviation 239 |
| Oseltamivir With HD | Plasma Concentration of Metabolite Oseltamivir Carboxylate by Timepoint in HD Participants | 12 hours from D38 dose (n=11) | 933 ng/mL | Standard Deviation 295 |
| Oseltamivir With HD | Plasma Concentration of Metabolite Oseltamivir Carboxylate by Timepoint in HD Participants | 20 hours from D38 dose (n=11) | 1090 ng/mL | Standard Deviation 327 |
| Oseltamivir With HD | Plasma Concentration of Metabolite Oseltamivir Carboxylate by Timepoint in HD Participants | 32 hours from D38 dose (n=11) | 1080 ng/mL | Standard Deviation 328 |
| Oseltamivir With HD | Plasma Concentration of Metabolite Oseltamivir Carboxylate by Timepoint in HD Participants | 42 hours from D38 dose (n=11) | 1050 ng/mL | Standard Deviation 340 |
| Oseltamivir With HD | Plasma Concentration of Metabolite Oseltamivir Carboxylate by Timepoint in HD Participants | 48 hours from D38 dose (n=11) | 263 ng/mL | Standard Deviation 61.4 |
| Oseltamivir With HD | Plasma Concentration of Metabolite Oseltamivir Carboxylate by Timepoint in HD Participants | 49 hours from D38 dose (n=11) | 279 ng/mL | Standard Deviation 66.4 |
| Oseltamivir With HD | Plasma Concentration of Metabolite Oseltamivir Carboxylate by Timepoint in HD Participants | 114 hours from D38 dose (n=11) | 283 ng/mL | Standard Deviation 112 |
Secondary
Plasma Concentration of Metabolite Oseltamivir Carboxylate in Arterial and Venous Blood by Timepoint in HD Participants
Dialyzer samples were obtained up to 5 hours from the start of dialysis on Days 3 and 40 (corresponding to HD sessions 2 and 18). Arterial concentrations were estimated using the inflow to the dialyzer, and venous concentrations were estimated using the outflow from the dialyzer. The concentration at each collection time was recorded and averaged among all participants and expressed in ng/mL.
Time frame: Dialyzer samples 1, 2, 4, 5 hours from start of dialysis on Days 3 and 40
Population: PK Analysis Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oseltamivir With HD | Plasma Concentration of Metabolite Oseltamivir Carboxylate in Arterial and Venous Blood by Timepoint in HD Participants | Arterial: 1 hour (Day 3) | 570 ng/mL | Standard Deviation 229 |
| Oseltamivir With HD | Plasma Concentration of Metabolite Oseltamivir Carboxylate in Arterial and Venous Blood by Timepoint in HD Participants | Arterial: 2 hours (Day 3) | 412 ng/mL | Standard Deviation 157 |
| Oseltamivir With HD | Plasma Concentration of Metabolite Oseltamivir Carboxylate in Arterial and Venous Blood by Timepoint in HD Participants | Arterial: 4 hours (Day 3) | 227 ng/mL | Standard Deviation 82.2 |
| Oseltamivir With HD | Plasma Concentration of Metabolite Oseltamivir Carboxylate in Arterial and Venous Blood by Timepoint in HD Participants | Arterial: 5 hours (Day 3) | 171 ng/mL | Standard Deviation 61.8 |
| Oseltamivir With HD | Plasma Concentration of Metabolite Oseltamivir Carboxylate in Arterial and Venous Blood by Timepoint in HD Participants | Venous: 1 hour (Day 3) | 284 ng/mL | Standard Deviation 121 |
| Oseltamivir With HD | Plasma Concentration of Metabolite Oseltamivir Carboxylate in Arterial and Venous Blood by Timepoint in HD Participants | Venous: 2 hours (Day 3) | 202 ng/mL | Standard Deviation 74.4 |
| Oseltamivir With HD | Plasma Concentration of Metabolite Oseltamivir Carboxylate in Arterial and Venous Blood by Timepoint in HD Participants | Venous: 4 hours (Day 3) | 127 ng/mL | Standard Deviation 69.1 |
| Oseltamivir With HD | Plasma Concentration of Metabolite Oseltamivir Carboxylate in Arterial and Venous Blood by Timepoint in HD Participants | Venous: 5 hours (Day 3) | 84.3 ng/mL | Standard Deviation 29.6 |
| Oseltamivir With HD | Plasma Concentration of Metabolite Oseltamivir Carboxylate in Arterial and Venous Blood by Timepoint in HD Participants | Arterial: 1 hour (Day 40) | 666 ng/mL | Standard Deviation 179 |
| Oseltamivir With HD | Plasma Concentration of Metabolite Oseltamivir Carboxylate in Arterial and Venous Blood by Timepoint in HD Participants | Arterial: 2 hours (Day 40) | 496 ng/mL | Standard Deviation 125 |
| Oseltamivir With HD | Plasma Concentration of Metabolite Oseltamivir Carboxylate in Arterial and Venous Blood by Timepoint in HD Participants | Arterial: 4 hours (Day 40) | 281 ng/mL | Standard Deviation 58.8 |
| Oseltamivir With HD | Plasma Concentration of Metabolite Oseltamivir Carboxylate in Arterial and Venous Blood by Timepoint in HD Participants | Arterial: 5 hours (Day 40) | 218 ng/mL | Standard Deviation 45.6 |
| Oseltamivir With HD | Plasma Concentration of Metabolite Oseltamivir Carboxylate in Arterial and Venous Blood by Timepoint in HD Participants | Venous: 1 hour (Day 40) | 317 ng/mL | Standard Deviation 103 |
| Oseltamivir With HD | Plasma Concentration of Metabolite Oseltamivir Carboxylate in Arterial and Venous Blood by Timepoint in HD Participants | Venous: 2 hours (Day 40) | 229 ng/mL | Standard Deviation 69.6 |
| Oseltamivir With HD | Plasma Concentration of Metabolite Oseltamivir Carboxylate in Arterial and Venous Blood by Timepoint in HD Participants | Venous: 4 hours (Day 40) | 128 ng/mL | Standard Deviation 37.3 |
| Oseltamivir With HD | Plasma Concentration of Metabolite Oseltamivir Carboxylate in Arterial and Venous Blood by Timepoint in HD Participants | Venous: 5 hours (Day 40) | 95.4 ng/mL | Standard Deviation 27.7 |
Secondary
Plasma Concentration of Oseltamivir by Timepoint in CAPD Participants
Plasma samples were obtained up to 120 hours post-dose during the first dose analysis (Days 1 to 6) and up to 168 hours post-dose during the second dose analysis (Days 36 to 43). The concentration at each collection time was recorded and averaged among all participants and expressed in ng/mL.
Time frame: 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
Population: PK Analysis Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oseltamivir With HD | Plasma Concentration of Oseltamivir by Timepoint in CAPD Participants | 0 hours from D1 dose | 0.0 ng/mL | Standard Deviation 0 |
| Oseltamivir With HD | Plasma Concentration of Oseltamivir by Timepoint in CAPD Participants | 1 hour from D1 dose | 27.8 ng/mL | Standard Deviation 21.9 |
| Oseltamivir With HD | Plasma Concentration of Oseltamivir by Timepoint in CAPD Participants | 2 hours from D1 dose | 22.6 ng/mL | Standard Deviation 12.6 |
| Oseltamivir With HD | Plasma Concentration of Oseltamivir by Timepoint in CAPD Participants | 4 hours from D1 dose | 6.98 ng/mL | Standard Deviation 2.7 |
| Oseltamivir With HD | Plasma Concentration of Oseltamivir by Timepoint in CAPD Participants | 8 hours from D1 dose | 0.630 ng/mL | Standard Deviation 0.833 |
| Oseltamivir With HD | Plasma Concentration of Oseltamivir by Timepoint in CAPD Participants | 12 hours from D1 dose | 0.100 ng/mL | Standard Deviation 0.346 |
| Oseltamivir With HD | Plasma Concentration of Oseltamivir by Timepoint in CAPD Participants | 24 hours from D1 dose | 0.0 ng/mL | Standard Deviation 0 |
| Oseltamivir With HD | Plasma Concentration of Oseltamivir by Timepoint in CAPD Participants | 48 hours from D1 dose | 0.0 ng/mL | Standard Deviation 0 |
| Oseltamivir With HD | Plasma Concentration of Oseltamivir by Timepoint in CAPD Participants | 72 hours from D1 dose | 0.0 ng/mL | Standard Deviation 0 |
| Oseltamivir With HD | Plasma Concentration of Oseltamivir by Timepoint in CAPD Participants | 120 hours from D1 dose | 0.0 ng/mL | Standard Deviation 0 |
| Oseltamivir With HD | Plasma Concentration of Oseltamivir by Timepoint in CAPD Participants | 0 hours from D36 dose | 0.0 ng/mL | Standard Deviation 0 |
| Oseltamivir With HD | Plasma Concentration of Oseltamivir by Timepoint in CAPD Participants | 1 hour from D36 dose | 24.8 ng/mL | Standard Deviation 16.8 |
| Oseltamivir With HD | Plasma Concentration of Oseltamivir by Timepoint in CAPD Participants | 2 hours from D36 dose | 18.0 ng/mL | Standard Deviation 8.88 |
| Oseltamivir With HD | Plasma Concentration of Oseltamivir by Timepoint in CAPD Participants | 4 hours from D36 dose | 5.78 ng/mL | Standard Deviation 2.09 |
| Oseltamivir With HD | Plasma Concentration of Oseltamivir by Timepoint in CAPD Participants | 8 hours from D36 dose | 0.754 ng/mL | Standard Deviation 0.705 |
| Oseltamivir With HD | Plasma Concentration of Oseltamivir by Timepoint in CAPD Participants | 12 hours from D36 dose | 0.103 ng/mL | Standard Deviation 0.358 |
| Oseltamivir With HD | Plasma Concentration of Oseltamivir by Timepoint in CAPD Participants | 24 hours from D36 dose | 0.0 ng/mL | Standard Deviation 0 |
| Oseltamivir With HD | Plasma Concentration of Oseltamivir by Timepoint in CAPD Participants | 48 hours from D36 dose | 0.0 ng/mL | Standard Deviation 0 |
| Oseltamivir With HD | Plasma Concentration of Oseltamivir by Timepoint in CAPD Participants | 72 hours from D36 dose | 0.0 ng/mL | Standard Deviation 0 |
| Oseltamivir With HD | Plasma Concentration of Oseltamivir by Timepoint in CAPD Participants | 120 hours from D36 dose | 0.0 ng/mL | Standard Deviation 0 |
| Oseltamivir With HD | Plasma Concentration of Oseltamivir by Timepoint in CAPD Participants | 168 hours from D36 dose | 0.0 ng/mL | Standard Deviation 0 |
Secondary
Plasma Concentration of Oseltamivir by Timepoint in HD Participants
Plasma samples were obtained up to 90 hours post-dose during the first dose analysis (Days 1 to 5) and up to 114 hours post-dose during the second dose analysis (Days 38 to 43). The concentration at each collection time was recorded and averaged among all participants and expressed in ng/mL.
Time frame: 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
Population: PK Analysis Population; number (n) equals (=) number of participants included at specified timepoints in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oseltamivir With HD | Plasma Concentration of Oseltamivir by Timepoint in HD Participants | 0 hours from D1 dose (n=12) | 0 ng/mL | Standard Deviation 0 |
| Oseltamivir With HD | Plasma Concentration of Oseltamivir by Timepoint in HD Participants | 1 hour from D1 dose (n=12) | 18.0 ng/mL | Standard Deviation 14.2 |
| Oseltamivir With HD | Plasma Concentration of Oseltamivir by Timepoint in HD Participants | 2 hours from D1 dose (n=12) | 12.5 ng/mL | Standard Deviation 6.58 |
| Oseltamivir With HD | Plasma Concentration of Oseltamivir by Timepoint in HD Participants | 4 hours from D1 dose (n=12) | 6.06 ng/mL | Standard Deviation 2.37 |
| Oseltamivir With HD | Plasma Concentration of Oseltamivir by Timepoint in HD Participants | 8 hours from D1 dose (n=12) | 1.93 ng/mL | Standard Deviation 1.64 |
| Oseltamivir With HD | Plasma Concentration of Oseltamivir by Timepoint in HD Participants | 12 hours from D1 dose (n=12) | 0.513 ng/mL | Standard Deviation 0.783 |
| Oseltamivir With HD | Plasma Concentration of Oseltamivir by Timepoint in HD Participants | 20 hours from D1 dose (n=12) | 0.104 ng/mL | Standard Deviation 0.361 |
| Oseltamivir With HD | Plasma Concentration of Oseltamivir by Timepoint in HD Participants | 32 hours from D1 dose (n=12) | 0.0 ng/mL | Standard Deviation 0 |
| Oseltamivir With HD | Plasma Concentration of Oseltamivir by Timepoint in HD Participants | 42 hours from D1 dose (n=12) | 0.0 ng/mL | Standard Deviation 0 |
| Oseltamivir With HD | Plasma Concentration of Oseltamivir by Timepoint in HD Participants | 48 hours from D1 dose (n=12) | 0.0 ng/mL | Standard Deviation 0 |
| Oseltamivir With HD | Plasma Concentration of Oseltamivir by Timepoint in HD Participants | 49 hours from D1 dose (n=12) | 0.0 ng/mL | Standard Deviation 0 |
| Oseltamivir With HD | Plasma Concentration of Oseltamivir by Timepoint in HD Participants | 90 hours from D1 dose (n=12) | 0.0 ng/mL | Standard Deviation 0 |
| Oseltamivir With HD | Plasma Concentration of Oseltamivir by Timepoint in HD Participants | 0 hours from D38 dose (n=11) | 0.413 ng/mL | Standard Deviation 0.938 |
| Oseltamivir With HD | Plasma Concentration of Oseltamivir by Timepoint in HD Participants | 1 hour from D38 dose (n=11) | 21.5 ng/mL | Standard Deviation 9.96 |
| Oseltamivir With HD | Plasma Concentration of Oseltamivir by Timepoint in HD Participants | 2 hours from D38 dose (n=11) | 15.4 ng/mL | Standard Deviation 5.98 |
| Oseltamivir With HD | Plasma Concentration of Oseltamivir by Timepoint in HD Participants | 4 hours from D38 dose (n=11) | 6.07 ng/mL | Standard Deviation 2.8 |
| Oseltamivir With HD | Plasma Concentration of Oseltamivir by Timepoint in HD Participants | 8 hours from D38 dose (n=11) | 1.30 ng/mL | Standard Deviation 0.801 |
| Oseltamivir With HD | Plasma Concentration of Oseltamivir by Timepoint in HD Participants | 12 hours from D38 dose (n=11) | 0.193 ng/mL | Standard Deviation 0.429 |
| Oseltamivir With HD | Plasma Concentration of Oseltamivir by Timepoint in HD Participants | 20 hours from D38 dose (n=11) | 0.0 ng/mL | Standard Deviation 0 |
| Oseltamivir With HD | Plasma Concentration of Oseltamivir by Timepoint in HD Participants | 32 hours from D38 dose (n=11) | 0.0 ng/mL | Standard Deviation 0 |
| Oseltamivir With HD | Plasma Concentration of Oseltamivir by Timepoint in HD Participants | 42 hours from D38 dose (n=11) | 0.0 ng/mL | Standard Deviation 0 |
| Oseltamivir With HD | Plasma Concentration of Oseltamivir by Timepoint in HD Participants | 48 hours from D38 dose (n=11) | 0.0 ng/mL | Standard Deviation 0 |
| Oseltamivir With HD | Plasma Concentration of Oseltamivir by Timepoint in HD Participants | 49 hours from D38 dose (n=11) | 0.0 ng/mL | Standard Deviation 0 |
| Oseltamivir With HD | Plasma Concentration of Oseltamivir by Timepoint in HD Participants | 114 hours from D38 dose (n=11) | 0.0 ng/mL | Standard Deviation 0 |
Secondary
Renal Clearance (CLr) of Oseltamivir in HD Participants
Plasma and urine samples up to 12 hours post-dose during the first dose analysis (Days 1 to 5) were used to calculate CLr, computed as \[amount of drug excreted divided by the AUC12\]. The CLr was averaged among all participants and expressed in L/h.
Time frame: Blood samples 0, 1, 2, 4, 8, 12 hours from D1 dose; urine samples 0 to 12 hours from D1 dose
Population: PK Analysis Population (First Dose Subpopulation).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oseltamivir With HD | Renal Clearance (CLr) of Oseltamivir in HD Participants | 0.0521 L/h | Standard Deviation 0.133 |
Secondary
Terminal Elimination Half-Life of Metabolite Oseltamivir Carboxylate in CAPD Participants
Plasma samples were obtained up to 120 hours post-dose during the first dose analysis (Days 1 to 6) and up to 168 hours post-dose during the second dose analysis (Days 36 to 43). Urine and dialysate samples were also obtained up to 48 hours post-dose during the first dose analysis. The time required for the concentration to decrease by one-half was recorded and averaged among all participants and expressed in hours.
Time frame: 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
Population: PK Analysis Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oseltamivir With HD | Terminal Elimination Half-Life of Metabolite Oseltamivir Carboxylate in CAPD Participants | Days 1 to 6 | 34.8 hours | Standard Deviation 8.39 |
| Oseltamivir With HD | Terminal Elimination Half-Life of Metabolite Oseltamivir Carboxylate in CAPD Participants | Days 36 to 43 | 36.3 hours | Standard Deviation 7.53 |
Secondary
Time to Maximum Plasma Concentration (Tmax) of Oseltamivir in HD Participants
Plasma samples were obtained up to 90 hours post-dose during the first (Days 1 to 5) and second (Days 38 to 43) dose analyses, and the observed time of maximum concentration was recorded. The Tmax following each dose was averaged among all participants and expressed in hours.
Time frame: Blood samples 0, 1, 2, 4, 8, 12, 20, 32, 42, 48, 49, 90 hours from D1 and D38 dose
Population: PK Analysis Population; n = number of participants included in the specific dose analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oseltamivir With HD | Time to Maximum Plasma Concentration (Tmax) of Oseltamivir in HD Participants | Days 1 to 5 (n=12) | 1.75 hours | Standard Deviation 1.14 |
| Oseltamivir With HD | Time to Maximum Plasma Concentration (Tmax) of Oseltamivir in HD Participants | Days 38 to 43 (n=11) | 1.18 hours | Standard Deviation 0.4 |
Secondary
Tmax of Metabolite Oseltamivir Carboxylate in CAPD Participants
Plasma samples were obtained up to 120 hours post-dose during the first dose analysis (Days 1 to 6) and up to 168 hours post-dose during the second dose analysis (Days 36 to 43), and the observed time of maximum concentration was recorded. The Tmax following each dose was averaged among all participants and expressed in hours.
Time frame: 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
Population: PK Analysis Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oseltamivir With HD | Tmax of Metabolite Oseltamivir Carboxylate in CAPD Participants | Days 1 to 6 | 20.0 hours | Standard Deviation 5.91 |
| Oseltamivir With HD | Tmax of Metabolite Oseltamivir Carboxylate in CAPD Participants | Days 36 to 43 | 19.0 hours | Standard Deviation 6.18 |
Secondary
Tmax of Metabolite Oseltamivir Carboxylate in HD Participants
Plasma samples were obtained up to 90 hours post-dose during the first (Days 1 to 5) and second (Days 38 to 43) dose analyses, and the observed time of maximum concentration was recorded. The Tmax following each dose was averaged among all participants and expressed in hours.
Time frame: Blood samples 0, 1, 2, 4, 8, 12, 20, 32, 42, 48, 49, 90 hours from D1 and D38 dose
Population: PK Analysis Population; n = number of participants included in the specific dose analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oseltamivir With HD | Tmax of Metabolite Oseltamivir Carboxylate in HD Participants | Days 1 to 5 (n=12) | 29.7 hours | Standard Deviation 8 |
| Oseltamivir With HD | Tmax of Metabolite Oseltamivir Carboxylate in HD Participants | Days 38 to 43 (n=11) | 29.2 hours | Standard Deviation 9.61 |
Secondary
Tmax of Oseltamivir in CAPD Participants
Plasma samples were obtained up to 120 hours post-dose during the first dose analysis (Days 1 to 6) and up to 168 hours post-dose during the second dose analysis (Days 36 to 43), and the observed time of maximum concentration was recorded. The Tmax following each dose was averaged among all participants and expressed in hours.
Time frame: 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
Population: PK Analysis Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oseltamivir With HD | Tmax of Oseltamivir in CAPD Participants | Days 1 to 6 | 1.50 hours | Standard Deviation 0.52 |
| Oseltamivir With HD | Tmax of Oseltamivir in CAPD Participants | Days 36 to 43 | 1.28 hours | Standard Deviation 0.047 |