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

Healthy Volunteer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02717754
• Other study ID #: NP25140
• Status: Completed
• Phase: Phase 1
• First received: March 20, 2016
• Last updated: March 20, 2016
• Start date: December 2009
• Est. completion date: June 2010

Study information

• Verified date: March 2016
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: Country:USA
• Study type: Interventional

Clinical Trial 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 volunteers. Volunteers 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.

Description:

Evaluation of multiple-dose PK of Oseltamivir and metabolite RO640802

Recruitment information / eligibility

• Status: Completed
• Enrollment: 99
• Est. completion date: June 2010
• Est. primary completion date: June 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

• Volunteers with Body Mass Index (BMI) 18-34 kilograms per meter square (kg/m^2), inclusive

• Male volunteers who are willing to use barrier contraception for the duration of the study and for 3 months following the end of treatment

• Female volunteers who are of non-child bearing potential

• Female volunteers 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 (e.g., renal, cardiac, bronchopulmonary)

• Any other condition or disease which would place the volunteer at undue risk, or interfere with the assessment, or with the ability of the volunteer 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.

• Volunteers 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

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator)

Related Conditions & MeSH terms

• Healthy Volunteer

Intervention

Drug:
• Oseltamivir
Oseltamivir will be administered at 100 or 200 mg IV BID for 5 days.
• Placebo
Oseltamivir matched placebo will be administered IV for 5 days.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area Under the Plasma Concentration-Time Curve From Time 0 to 12 Hours (AUC0-12h) of Oseltamivir RO0640802 at Steady State		Predose (0 hour), 1, 2, 3, 3.5, 4, 5, 6, 8, 10, 12 hour post dose on Day 5 of treatment	No
Primary	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 hour post dose on Day 5 of treatment	No
Secondary	Number of participants with adverse events		Approximately 2 weeks	No
Secondary	AUC0-12h of Oseltamivir and RO0640802		Predose (0 hour), 1, 2, 3, 3.5, 4, 5, 6, 8, 10, 12 hour post dose on Day 1	No
Secondary	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 hour post dose on Day 1 and Day 5 and predose (0 hour) on Days 2, 3, 4	No
Secondary	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 hour post dose on Day 1 and Day 5 and predose (0 hour) on Days 2, 3, 4	No
Secondary	Cmax of Oseltamivir and RO0640802		Predose (0 hour), 1, 2, 3, 3.5, 4, 5, 6, 8, 10, 12 hour post dose on Day 1	No
Secondary	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 hour post dose on Day 1 and Day 5 and predose (0 hour) on Days 2, 3, 4	No
Secondary	Half-Life (t1/2) of Oseltamivir and ROo640802		Predose (0 hour), 1, 2, 3, 3.5, 4, 5, 6, 8, 10, 12 hour post dose on Day 1 and Day 5 and predose (0 hour) on Days 2, 3, 4	No
Secondary	Plasma concentration at 12 hour post dose (C12) of Oseltamivir and RO0640802		12 hours post-dose on Days 1 and 5	No
Secondary	Volume of Distribution (Vd) of Oseltamivir and RO0640802		Predose (0 hour), 1, 2, 3, 3.5, 4, 5, 6, 8, 10, 12 hour post dose on Day 1 and Day 5 and predose (0 hour) on Days 2, 3, 4	No
Secondary	Clearance (CL) of Oseltamivir and RO0640802		Predose (0 hour), 1, 2, 3, 3.5, 4, 5, 6, 8, 10, 12 hour post dose on Day 1 and Day 5 and predose (0 hour) on Days 2, 3, 4	No