A Study to Investigate the Safety, Tolerability, and Pharmacokinetics (PK) of Oseltamivir and Its Carboxylate Metabolite, RO0640802 in Healthy Participants

May 18, 2016 updated by: Hoffmann-La Roche

A Multiple-Center, Randomized, Double-blind, Multiple-Dose, Placebo-Controlled, Parallel-Group Study to Investigate the Safety, Tolerability, and Pharmacokinetics of RO0640796 (Oseltamivir) and Its Carboxylate Metabolite, RO0640802, Following Intravenous Administrations in Healthy Subjects

This multi-center, randomized, double-blind, multiple-dose, placebo-controlled, parallel-group study will assess the safety and PK of oseltamivir (Tamiflu) and its carboxylate metabolite, RO0640802 in healthy participants. Participants will be randomized to receive 100 milligrams (mg) oseltamivir, 200 mg oseltamivir, or placebo, all administered intravenously twice daily (BID). The anticipated time on study treatment is 5 days.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

99

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Arkansas
      • Little Rock, Arkansas, United States, 72204
    • Texas
      • Austin, Texas, United States, 78744

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 45 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Participants with Body Mass Index (BMI) 18-34 kilograms per meter square (kg/m^2), inclusive
  • Male participants who are willing to use barrier contraception for the duration of the study and for 3 months following the end of treatment
  • Female participants who are of non-child bearing potential
  • Female participants who are of child bearing potential utilizing two effective methods of contraception for the duration of the study and for 3 months following the end of treatment

Exclusion Criteria:

  • Evidence of clinically significant disease or disorder (for example, renal, cardiac, bronchopulmonary)
  • Any other condition or disease which would place the participant at undue risk, or interfere with the assessment, or with the ability of the participant to complete the study
  • Clinically significant orthostatic hypotension present at screening or history of clinically significant hypotensive episodes or symptoms of fainting, dizziness, or lightheadedness.
  • Participants with abnormal electrocardiogram (ECG), bradycardia or mean QTc at screening
  • Positive result for Hepatitis B, Hepatitis C, human immunodeficiency virus (HIV) 1 or 2 at screening
  • Renal impairment
  • Transplant recipients
  • A known clinically relevant history of allergy or hypersensitivity
  • Any clinically relevant abnormal laboratory test results
  • A clinically relevant history of abuse of alcohol or other drugs of abuse
  • Any major illness within 30 days prior to the screening examination
  • Smoking of more than 10 cigarettes a day or an equivalent amount of tobacco in the form of cigars or pipe
  • Participation in a clinical study with an investigational drug within 3 months prior to Day 1
  • Donation/loss of more than 500 milliliters (mL) of blood within 3 months prior to Day 1
  • Positive pregnancy test at screening or Day -1 and lactating women

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Oseltamivir 100 mg
Participants will receive 100 mg oseltamivir intravenous BID for 5 days.
Oseltamivir will be administered at 100 or 200 mg intravenous BID for 5 days.
Other Names:
  • Tamiflu, RO0640796
Experimental: Oseltamivir 200 mg
Participants will receive 200 mg oseltamivir intravenous BID for 5 days.
Oseltamivir will be administered at 100 or 200 mg intravenous BID for 5 days.
Other Names:
  • Tamiflu, RO0640796
Placebo Comparator: Placebo
Participants will receive oseltamivir matched placebo intravenous BID for 5 days.
Oseltamivir matched placebo will be administered intravenous for 5 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Area Under the Plasma Concentration-Time Curve From Time 0 to 12 Hour (AUC0-12h) of Oseltamivir and RO0640802 at Steady State
Time Frame: Predose (0 hour), 1, 2, 3, 3.5, 4, 5, 6, 8, 10, 12 hours post dose on Day 5
AUC is a measure of the plasma concentration of the drug over time. AUC is presented in nanogram times (*) hour per milliliter (ng*hour/mL). RO0640802 is the pharmacologically active carboxylate metabolite of oseltamivir.
Predose (0 hour), 1, 2, 3, 3.5, 4, 5, 6, 8, 10, 12 hours post dose on Day 5
Maximum Plasma Concentration (Cmax) of Oseltamivir and RO0640802 at Steady State
Time Frame: Predose (0 hour), 1, 2, 3, 3.5, 4, 5, 6, 8, 10, 12 hours post dose on Day 5
Cmax is the maximum observed plasma concentration, presented in nanogram per milliliter (ng/mL). RO0640802 is the pharmacologically active carboxylate metabolite of oseltamivir.
Predose (0 hour), 1, 2, 3, 3.5, 4, 5, 6, 8, 10, 12 hours post dose on Day 5

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUC0-inf) of Oseltamivir and RO0640802
Time Frame: Predose (0 hour), 1, 2, 3, 3.5, 4, 5, 6, 8, 10, 12 hours post dose on Day 1
AUC is a measure of the plasma concentration of the drug over time. RO0640802 is the pharmacologically active carboxylate metabolite of oseltamivir.
Predose (0 hour), 1, 2, 3, 3.5, 4, 5, 6, 8, 10, 12 hours post dose on Day 1
Area Under the Plasma Concentration-Time Curve From Time 0 to Last Measurable Concentration (AUC0-last) of Oseltamivir and RO0640802
Time Frame: Predose (0 hour), 1, 2, 3, 3.5, 4, 5, 6, 8, 10, 12 hours post dose on Day 1 and Day 5
AUC is a measure of the plasma concentration of the drug over time. RO0640802 is the pharmacologically active carboxylate metabolite of oseltamivir.
Predose (0 hour), 1, 2, 3, 3.5, 4, 5, 6, 8, 10, 12 hours post dose on Day 1 and Day 5
Cmax of Oseltamivir and RO0640802
Time Frame: Predose (0 hour), 1, 2, 3, 3.5, 4, 5, 6, 8, 10, 12 hours post dose on Day 1
Cmax is the maximum observed plasma concentration. RO0640802 is the pharmacologically active carboxylate metabolite of oseltamivir.
Predose (0 hour), 1, 2, 3, 3.5, 4, 5, 6, 8, 10, 12 hours post dose on Day 1
Time to Reach Maximum Plasma Concentration (Tmax) of Oseltamivir and RO0640802
Time Frame: Predose (0 hour), 1, 2, 3, 3.5, 4, 5, 6, 8, 10, 12 hours post dose on Day 1 and Day 5
Tmax is time of observed maximum plasma concentration. RO0640802 is the pharmacologically active carboxylate metabolite of oseltamivir.
Predose (0 hour), 1, 2, 3, 3.5, 4, 5, 6, 8, 10, 12 hours post dose on Day 1 and Day 5
Half-Life (t1/2) of Oseltamivir and RO0640802
Time Frame: Predose (0 hour), 1, 2, 3, 3.5, 4, 5, 6, 8, 10, 12 hours post dose on Day 1 and Day 5
t1/2 is the time measured for the plasma concentration to decrease by one half. RO0640802 is the pharmacologically active carboxylate metabolite of oseltamivir.
Predose (0 hour), 1, 2, 3, 3.5, 4, 5, 6, 8, 10, 12 hours post dose on Day 1 and Day 5
Volume of Distribution (Vd) of Oseltamivir and RO0640802
Time Frame: Predose (0 hour), 1, 2, 3, 3.5, 4, 5, 6, 8, 10, 12 hours post dose on Day 1 and Day 5
Vd is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. RO0640802 is the pharmacologically active carboxylate metabolite of oseltamivir.
Predose (0 hour), 1, 2, 3, 3.5, 4, 5, 6, 8, 10, 12 hours post dose on Day 1 and Day 5
Clearance (CL) of Oseltamivir and RO0640802
Time Frame: Predose (0 hour), 1, 2, 3, 3.5, 4, 5, 6, 8, 10, 12 hours post dose on Day 1 and Day 5
CL is a quantitative measure of the rate at which a drug substance is removed from the body. RO0640802 is the pharmacologically active carboxylate metabolite of oseltamivir.
Predose (0 hour), 1, 2, 3, 3.5, 4, 5, 6, 8, 10, 12 hours post dose on Day 1 and Day 5
Minimum Plasma Concentration (Cmin) of RO0640802
Time Frame: 12-hour post dose on Day 1, 5 and predose on Day 2, 3, 4, 5
Collection of the 12-hour post-dose sample took place prior to administration of the second daily dose of drug. RO0640802 is the pharmacologically active carboxylate metabolite of oseltamivir.
12-hour post dose on Day 1, 5 and predose on Day 2, 3, 4, 5

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2009

Primary Completion (Actual)

May 1, 2010

Study Completion (Actual)

May 1, 2010

Study Registration Dates

First Submitted

March 20, 2016

First Submitted That Met QC Criteria

March 20, 2016

First Posted (Estimate)

March 24, 2016

Study Record Updates

Last Update Posted (Estimate)

June 27, 2016

Last Update Submitted That Met QC Criteria

May 18, 2016

Last Verified

May 1, 2016

More Information

Terms related to this study

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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