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

NCT02617784 | Completed Phase 1 Results

• 1 other identifier: NP16472
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

End Stage Renal Disease

Outcome Measures

Primary Outcomes (16)

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

Secondary Outcomes (27)

• 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 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

• 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

• 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

• Oral Plasma Clearance (CL/F) of Oseltamivir in HD Participants

  Blood samples 0, 1, 2, 4, 8, 12 hours from D1 and D38 dose

Study Arms (2)

Regimen A: Oseltamivir with HD

EXPERIMENTAL

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.

Drug: Oseltamivir

Regimen B: Oseltamivir with CAPD

EXPERIMENTAL

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.

Drug: Oseltamivir

Interventions

Oseltamivir DRUG

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

Also known as: Tamiflu

Regimen A: Oseltamivir with HD; Regimen B: Oseltamivir with CAPD

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (1)

Unknown Facility

Christchurch, 8011, New Zealand

Location

MeSH Terms

Conditions

Kidney Failure, Chronic

Interventions

Oseltamivir

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Acetamides; Amides; Organic Chemicals; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-LaRoche

genentech@druginfo.com

800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 27, 2015
• First Posted: December 1, 2015
• Study Start: October 1, 2001
• Primary Completion: June 1, 2002
• Study Completion: June 1, 2002
• Last Updated: February 15, 2016
• Results First Posted: February 15, 2016

Record last verified: 2016-01

Locations

NZ (1)