Back to resultsA Multiple-Dose Study of Oral Oseltamivir in Participants on Hemodialysis (HD) and Continuous Ambulatory Peritoneal Dialysis (CAPD)
Primary Purpose
End Stage Renal Disease
Status
Completed
Phase
Phase 1
Locations
New Zealand
Study Type
Interventional
Intervention
Oseltamivir
Sponsored by
About this trial
This is an interventional treatment trial for End Stage Renal Disease
Eligibility Criteria
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Regimen A: Oseltamivir with HD
Regimen B: Oseltamivir with CAPD
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
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).
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.
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.
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.
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).
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Secondary Outcome Measures
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.
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 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.
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.
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).
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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).
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02617784
Brief Title
A Multiple-Dose Study of Oral Oseltamivir in Participants on Hemodialysis (HD) and Continuous Ambulatory Peritoneal Dialysis (CAPD)
Official Title
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)
Study Type
Interventional
2. Study Status
Record Verification Date
January 2016
Overall Recruitment Status
Completed
Study Start Date
October 2001 (undefined)
Primary Completion Date
June 2002 (Actual)
Study Completion Date
June 2002 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche
4. Oversight
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
End Stage Renal Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
24 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Regimen A: Oseltamivir with HD
Arm Type
Experimental
Arm Description
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.
Arm Title
Regimen B: Oseltamivir with CAPD
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Oseltamivir
Other Intervention Name(s)
Tamiflu
Intervention Description
Oseltamivir will be given as marketed oral suspension, 30 mg after HD or CAPD treatment.
Primary Outcome Measure Information:
Title
Maximum Plasma Concentration (Cmax) of Oseltamivir in HD Participants During Days 1 to 5
Description
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
Title
Cmax of Oseltamivir in HD Participants During Days 38 to 43
Description
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
Title
Cmax of Metabolite Oseltamivir Carboxylate in HD Participants During Days 1 to 5
Description
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
Title
Cmax of Metabolite Oseltamivir Carboxylate in HD Participants During Days 38 to 43
Description
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
Title
Area Under the Concentration-Time Curve (AUC) of Oseltamivir in HD Participants During Days 1 to 5
Description
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
Title
AUC of Oseltamivir in HD Participants During Days 38 to 43
Description
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
Title
AUC of Metabolite Oseltamivir Carboxylate in HD Participants During Days 1 to 5
Description
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
Title
AUC of Metabolite Oseltamivir Carboxylate in HD Participants During Days 38 to 43
Description
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
Title
Cmax of Oseltamivir in CAPD Participants During Days 1 to 6
Description
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
Title
Cmax of Oseltamivir in CAPD Participants During Days 36 to 43
Description
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
Title
Cmax of Metabolite Oseltamivir Carboxylate in CAPD Participants During Days 1 to 6
Description
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
Title
Cmax of Metabolite Oseltamivir Carboxylate in CAPD Participants During Days 36 to 43
Description
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
Title
AUC of Oseltamivir in CAPD Participants During Days 1 to 6
Description
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
Title
AUC of Oseltamivir in CAPD Participants During Days 36 to 43
Description
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
Title
AUC of Metabolite Oseltamivir Carboxylate in CAPD Participants During Days 1 to 6
Description
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
Title
AUC of Metabolite Oseltamivir Carboxylate in CAPD Participants During Days 36 to 43
Description
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
Secondary Outcome Measure Information:
Title
Plasma Concentration of Oseltamivir by Timepoint in HD Participants
Description
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
Title
Plasma Concentration of Metabolite Oseltamivir Carboxylate by Timepoint in HD Participants
Description
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
Title
Time to Maximum Plasma Concentration (Tmax) of Oseltamivir in HD Participants
Description
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
Title
Tmax of Metabolite Oseltamivir Carboxylate in HD Participants
Description
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
Title
Oral Plasma Clearance (CL/F) of Oseltamivir in HD Participants
Description
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
Title
CL/F of Metabolite Oseltamivir Carboxylate in HD Participants
Description
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
Title
Renal Clearance (CLr) of Oseltamivir in HD Participants
Description
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
Title
CLr of Metabolite Oseltamivir Carboxylate in HD Participants
Description
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
Title
Dialysis Clearance (CLd) of Metabolite Oseltamivir Carboxylate in HD Participants
Description
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
Title
Percentage of Oseltamivir Dose Excreted as Unchanged Drug in HD Participants
Description
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
Title
Percentage of Oseltamivir Dose Excreted as Metabolite Oseltamivir Carboxylate in HD Participants
Description
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
Title
Plasma Concentration of Metabolite Oseltamivir Carboxylate in Arterial and Venous Blood by Timepoint in HD Participants
Description
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
Title
Plasma Concentration of Oseltamivir by Timepoint in CAPD Participants
Description
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
Title
Plasma Concentration of Metabolite Oseltamivir Carboxylate by Timepoint in CAPD Participants
Description
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
Title
Tmax of Oseltamivir in CAPD Participants
Description
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
Title
Tmax of Metabolite Oseltamivir Carboxylate in CAPD Participants
Description
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
Title
Elimination Rate Constant of Metabolite Oseltamivir Carboxylate in CAPD Participants
Description
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
Title
Terminal Elimination Half-Life of Metabolite Oseltamivir Carboxylate in CAPD Participants
Description
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
Title
CL/F of Oseltamivir in CAPD Participants
Description
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
Title
CL/F of Metabolite Oseltamivir Carboxylate in CAPD Participants
Description
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
Title
CLr of Oseltamivir in CAPD Participants
Description
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
Title
CLr of Metabolite Oseltamivir Carboxylate in CAPD Participants
Description
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
Title
CLd of Metabolite Oseltamivir Carboxylate in CAPD Participants
Description
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
Title
Percentage of Oseltamivir Dose Renally Excreted as Unchanged Drug in CAPD Participants
Description
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
Title
Percentage of Oseltamivir Dose Renally Excreted as Metabolite Oseltamivir Carboxylate in CAPD Participants
Description
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
Title
Percentage of Oseltamivir Dose Eliminated by Dialysis as Unchanged Drug in CAPD Participants
Description
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
Title
Percentage of Oseltamivir Dose Eliminated by Dialysis as Metabolite Oseltamivir Carboxylate in CAPD Participants
Description
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
City
Christchurch
ZIP/Postal Code
8011
Country
New Zealand
12. IPD Sharing Statement
Learn more about this trial
A Multiple-Dose Study of Oral Oseltamivir in Participants on Hemodialysis (HD) and Continuous Ambulatory Peritoneal Dialysis (CAPD)
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