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

Phase 1

Completed

• Conditions: Healthy Volunteer
• Interventions: Drug: Placebo; Drug: Oseltamivir

• Registration Number: NCT02717754
• Lead Sponsor: Hoffmann-La Roche

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2009-12
• Primary Completion: 2010-05
• Study Completion: 2010-05
• Study First Submitted: 2016-03-20
• Study First Submitted QC: 2016-03-20
• Study First Posted: 2016-03-24
• Status Verified: 2016-05
• Results First Submitted: 2016-05-18
• Results First Submitted QC: 2016-05-18
• Last Update Submitted: 2016-05-18
• Results First Posted: 2016-06-27
• Last Update Posted: 2016-06-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 99

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Participants will receive oseltamivir matched placebo intravenous BID for 5 days.
Oseltamivir 100 mg	Oseltamivir	Participants will receive 100 mg oseltamivir intravenous BID for 5 days.
Oseltamivir 200 mg	Oseltamivir	Participants will receive 200 mg oseltamivir intravenous BID for 5 days.

Primary Outcome Measures

Name	Time	Method
Area Under the Plasma Concentration-Time Curve From Time 0 to 12 Hour (AUC0-12h) of Oseltamivir and RO0640802 at Steady State	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.
Maximum Plasma Concentration (Cmax) of Oseltamivir and RO0640802 at Steady State	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.

Secondary Outcome Measures

Name	Time	Method
Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUC0-inf) of Oseltamivir and RO0640802	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.
Volume of Distribution (Vd) of Oseltamivir and RO0640802	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.
Minimum Plasma Concentration (Cmin) of RO0640802	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.
Area Under the Plasma Concentration-Time Curve From Time 0 to Last Measurable Concentration (AUC0-last) of Oseltamivir and RO0640802	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.
Cmax of Oseltamivir and RO0640802	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.
Time to Reach Maximum Plasma Concentration (Tmax) of Oseltamivir and RO0640802	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.
Clearance (CL) of Oseltamivir and RO0640802	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.
Half-Life (t1/2) of Oseltamivir and RO0640802	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.