A Multiple-Dose Study of Oral Oseltamivir in Participants on Hemodialysis (HD) and Continuous Ambulatory Peritoneal Dialysis (CAPD)

End Stage Renal Disease Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02617784
• Other study ID #: NP16472
• Status: Completed
• Phase: Phase 1
• First received: November 27, 2015
• Last updated: January 17, 2016
• Start date: October 2001
• Est. completion date: June 2002

Study information

• Verified date: January 2016
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: New Zealand: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: June 2002
• Est. primary completion date: June 2002
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• End Stage Renal Disease
• Kidney Diseases
• Kidney Failure, Chronic

Intervention

Drug:
• Oseltamivir
Oseltamivir will be given as marketed oral suspension, 30 mg after HD or CAPD treatment.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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).	Blood samples 0, 1, 2, 4, 8, 12, 20, 32, 42, 48, 49, 90 hours from Day 1 (D1) dose	No
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.	Blood samples 0, 1, 2, 4, 8, 12, 20, 32, 42, 48, 49, 90 hours from Day 38 (D38) dose	No
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.	Blood samples 0, 1, 2, 4, 8, 12, 20, 32, 42, 48, 49, 90 hours from D1 dose	No
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.	Blood samples 0, 1, 2, 4, 8, 12, 20, 32, 42, 48, 49, 90 hours from D38 dose	No
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).	Blood samples 0, 1, 2, 4, 8, 12, 20, 32, 42, 48, 49, 90 hours from D1 dose	No
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.	Blood samples 0, 1, 2, 4, 8, 12, 20, 32, 42, 48, 49, 90 hours from D38 dose	No
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.	Blood samples 0, 1, 2, 4, 8, 12, 20, 32, 42, 48, 49, 90 hours from D1 dose	No
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.	Blood samples 0, 1, 2, 4, 8, 12, 20, 32, 42, 48, 49, 90 hours from D38 dose	No
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.	Blood samples 0, 1, 2, 4, 8, 12, 24, 48, 72, 120 hours from D1 dose	No
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.	Blood samples 0, 1, 2, 4, 8, 12, 24, 48, 72, 120, 168 hours from Day 36 (D36) dose	No
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.	Blood samples 0, 1, 2, 4, 8, 12, 24, 48, 72, 120 hours from D1 dose	No
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.	Blood samples 0, 1, 2, 4, 8, 12, 24, 48, 72, 120, 168 hours from D36 dose	No
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.	Blood samples 0, 1, 2, 4, 8, 12, 24, 48, 72, 120 hours from D1 dose	No
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.	Blood samples 0, 1, 2, 4, 8, 12, 24, 48, 72, 120, 168 hours from D36 dose	No
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.	Blood samples 0, 1, 2, 4, 8, 12, 24, 48, 72, 120 hours from D1 dose	No
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.	Blood samples 0, 1, 2, 4, 8, 12, 24, 48, 72, 120, 168 hours from D36 dose	No
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.	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	No
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.	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	No
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.	Blood samples 0, 1, 2, 4, 8, 12, 20, 32, 42, 48, 49, 90 hours from D1 and D38 dose	No
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.	Blood samples 0, 1, 2, 4, 8, 12, 20, 32, 42, 48, 49, 90 hours from D1 and D38 dose	No
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).	Blood samples 0, 1, 2, 4, 8, 12 hours from D1 and D38 dose	No
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.	Blood samples 0, 1, 2, 4, 8, 12, 20, 32, 42 hours from D1 and D38 dose	No
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.	Blood samples 0, 1, 2, 4, 8, 12 hours from D1 dose; urine samples 0 to 12 hours from D1 dose	No
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.	Blood samples 0, 1, 2, 4, 8, 12, 20, 32, 42 hours from D1 dose; urine samples 0 to 42 hours from D1 dose	No
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.	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	No
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.	Urine samples 0 to 42 hours from D1 dose	No
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.	Urine samples 0 to 42 hours from D1 dose	No
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.	Dialyzer samples 1, 2, 4, 5 hours from start of dialysis on Days 3 and 40	No
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.	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	No
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.	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	No
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.	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	No
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.	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	No
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).	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	No
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.	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	No
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.	Blood samples 0, 1, 2, 4, 8, 12 hours from D1 and D36 dose	No
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.	Blood samples 0, 1, 2, 4, 8, 12, 24, 48 hours from D1 and D36 dose	No
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.	Blood samples 0, 1, 2, 4, 8, 12 hours from D1 dose; urine samples 0 to 12 hours from D1 dose	No
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.	Blood samples 0, 1, 2, 4, 8, 12, 24, 48 hours from D1 dose; urine samples 0 to 48 hours from D1 dose	No
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.	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	No
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.	Urine samples 0 to 48 hours from D1 dose	No
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.	Urine samples 0 to 48 hours from D1 dose	No
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.	Dialysate samples 0 to 48 hours from D1 dose	No
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.	Dialysate samples 0 to 48 hours from D1 dose	No