Clinical trial NCT02717754: A Study to Investigate the Safety, Tolerability, and Pharmacokinetics (PK) of Oseltamivir and Its Carboxylate Metabolite, RO0640802 in Healthy Participants
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2016-03-24
Enrollment: 99
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL

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.


Eligibility criteria: 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

Primary outcomes:
measure: Area Under the Plasma Concentration-Time Curve From Time 0 to 12 Hour (AUC0-12h) of Oseltamivir and RO0640802 at Steady State
timeFrame: Predose (0 hour), 1, 2, 3, 3.5, 4, 5, 6, 8, 10, 12 hours post dose on Day 5
measure: Maximum Plasma Concentration (Cmax) of Oseltamivir and RO0640802 at Steady State
timeFrame: Predose (0 hour), 1, 2, 3, 3.5, 4, 5, 6, 8, 10, 12 hours post dose on Day 5
Secondary outcomes:
measure: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUC0-inf) of Oseltamivir and RO0640802
timeFrame: Predose (0 hour), 1, 2, 3, 3.5, 4, 5, 6, 8, 10, 12 hours post dose on Day 1
measure: Area Under the Plasma Concentration-Time Curve From Time 0 to Last Measurable Concentration (AUC0-last) of Oseltamivir and RO0640802
timeFrame: Predose (0 hour), 1, 2, 3, 3.5, 4, 5, 6, 8, 10, 12 hours post dose on Day 1 and Day 5
measure: Cmax of Oseltamivir and RO0640802
timeFrame: Predose (0 hour), 1, 2, 3, 3.5, 4, 5, 6, 8, 10, 12 hours post dose on Day 1
measure: Time to Reach Maximum Plasma Concentration (Tmax) of Oseltamivir and RO0640802
timeFrame: Predose (0 hour), 1, 2, 3, 3.5, 4, 5, 6, 8, 10, 12 hours post dose on Day 1 and Day 5
measure: Half-Life (t1/2) of Oseltamivir and RO0640802
timeFrame: Predose (0 hour), 1, 2, 3, 3.5, 4, 5, 6, 8, 10, 12 hours post dose on Day 1 and Day 5
measure: Volume of Distribution (Vd) of Oseltamivir and RO0640802
timeFrame: Predose (0 hour), 1, 2, 3, 3.5, 4, 5, 6, 8, 10, 12 hours post dose on Day 1 and Day 5
measure: Clearance (CL) of Oseltamivir and RO0640802
timeFrame: Predose (0 hour), 1, 2, 3, 3.5, 4, 5, 6, 8, 10, 12 hours post dose on Day 1 and Day 5
measure: Minimum Plasma Concentration (Cmin) of RO0640802
timeFrame: 12-hour post dose on Day 1, 5 and predose on Day 2, 3, 4, 5
Other outcomes:
Locations:
city: Little Rock
country: United States
state: Arkansas
city: Austin
country: United States
state: Texas
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: