A Study to Assess the Drug-Drug Interaction Between VX-787 and Oseltamivir

Study Overview
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Brief Summary
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The purpose of this study is to investigate the drug-drug interaction between VX-787 and oseltamivir, when co-administered at steady-state in healthy participants. In addition the safety, tolerability and pharmacokinetics (the study of the way a drug enters and leaves the blood and tissues over time) of VX-787 will be assessed.

Detailed Description
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This study consists of 2 parts. Part 1 is an open-label (a medical research study in which participants and researchers are told which treatments the participants are receiving), randomized (treatment group assigned by chance), 3-way crossover (a method used to switch participants from one treatment group to another in a clinical trial) study to estimate drug-drug interaction between VX-787 and oseltamivir. It consists of 3 phases: a Screening phase, a Treatment phase and a Follow-up phase. Treatment phase will include 3 treatment sessions, each of the participant will receive Treatment A (VX-787, 600 milligram [mg] 2 times a day on Day 1 to 4, followed by a single dose of VX 787, 600 mg on Day 5); Treatment B (Oseltamivir, 75 mg 2 times a day on Day 1 to 4, followed by a single dose of oseltamivir 75 mg on Day 5) and Treatment C (VX-787, 600 mg 2 times a day + oseltamivir, 75 mg 2 times a day on Day 1 to 4, followed by a single dose of VX-787, 600 mg + a single dose of oseltamivir, 75 mg on Day 5). Each treatment session will be separated by a wash-out period of 5 days. The order each participant will receive treatments A, B and C will be decided at randomization. Part 2 is double-blind (a medical research study in which neither the researchers nor the participants know what treatment the subjects is receiving), randomized, placebo-controlled. It consists of 3 phases: a Screening phase, a Treatment phase and a Follow-up phase. In Treatment phase participants will be randomly assigned VX-787, 600 mg or placebo 2 times a day, on Day 1 to 9, followed by a single dose of VX-787 600 mg or placebo in the morning on Day 10. Pharmacokinetic parameters will be assessed primarily. Participants' safety will be monitored throughout the study.

Official Title
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A Phase 1, Randomized, 3-way Crossover, Open-label Study to Assess the Drug-drug Interaction Between VX-787 and Tamiflu®, Followed by a Double-blind, Randomized, Placebo-controlled Study to Collect Safety, Tolerability and Pharmacokinetics of VX-787, in Healthy Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: VX-787
* Drug: Oseltamivir
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female participants must be of non-childbearing potential: postmenopausal for at least 2 years (amenorrheal for at least 3 years and a serum follicle stimulating hormone [FSH] level greater than [>] 40 international unit per liter [IU/L]), or surgically sterile (have had a total hysterectomy, bilateral oophorectomy, or bilateral tubal ligation/bilateral tubal clips without reversal operation), or otherwise incapable of becoming pregnant Participants must be non-smoking or smoking no more than 10 cigarettes, or 2 cigars, or 2 pipes per day for at least 3 months prior to screening Participants must have a Body Mass Index (BMI: weight in kg divided by the square of height in meters) of 18.0 to 30.0 kilogram per meter square [kg/m^2] Participants must be willing/able to adhere to the prohibitions and restrictions specified in the protocol and study procedures Participants must be healthy on the basis of a medical evaluation that reveals the absence of any clinically significant abnormality and includes a physical examination, medical history, vital signs and the results of blood biochemistry, blood coagulation and hematology test and a urinalysis performed at screening Exclusion Criteria: Participants with a past history of heart arrhythmias (for example, extrasystoli, tachycardia at rest), history of risk factors for Torsade de Pointes syndrome (for example, hypokalemia, family history of long QT Syndrome) Participants with a history or evidence of use of alcohol, barbiturates, amphetamines, recreational or narcotic drug use within the past 1 year, which in the Investigator's opinion would compromise participant's safety and/or compliance with the study procedures Participants with current hepatitis A infection (confirmed by hepatitis A antibody immunoglobulin M [IgM]), or hepatitis B infection (confirmed by hepatitis B surface antigen [HBsAg]), or hepatitis C infection (confirmed by hepatitis C virus [HCV] antibody), or human immunodeficiency virus type 1 (HIV-1) or HIV-2 infection at study screening Participants having a positive urine drug test or alcohol breath test at study screening. Urine will be tested for the presence of amphetamines, benzodiazepines, cocaine, cannabinoids, opioids, methadone and barbiturates Participants with known allergies, hypersensitivity, or intolerance to VX-787, oseltamivir, or excipients of the drug products used

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1<br>Participants will receive in random order Treatment A (VX-787, 600 mg tablet 2 times a day on Day 1 to 4, followed by VX 787, 600 mg tablet on Day 5); Treatment B (Oseltamivir, 75 mg capsule 2 times a day on Day 1 to 4, followed by oseltamivir 75 mg capsule in the morning on Day 5) or Treatment C (VX-787, 600 mg tablet, 2 times a day orally + oseltamivir, 75 mg capsule, 2 times a day on Day 1 to 4, followed by a single dose of VX-787, 600 mg + oseltamivir, 75 mg capsule on Day 5). Each participant will receive all three treatments (Treatment A, B and C) in a random sequence. | Drug: VX-787<br>* Participants will receive VX-787, 600 mg either two times a day or once a day in either of the Part.<br>Drug: Oseltamivir<br>* Participants will receive Oseltamivir 75 mg either two times a day or once a day in either of the Part.<br>|
| Experimental: Part 2 VX-787<br>Participants will receive VX-787, 600 mg, tablet 2 times a day, orally on Day 1 to Day 9, followed by single dose of VX-787, 600 mg on Day 10. | Drug: VX-787<br>* Participants will receive VX-787, 600 mg either two times a day or once a day in either of the Part.<br>|
| Experimental: Part 2 Placebo<br>Participants will receive placebo matching to VX-787, 2 times a day, orally on Day 1 to Day 9, followed by single dose of matching placebo on Day 10. | Other: Placebo<br>* Participants will receive placebo matching to VX-787 either two times a day or or once a day.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess the drug-drug interaction between VX-787 600 mg bid coadministered with oseltamivir 75 mg bid at steady-state in healthy participants | Based on the individual plasma concentration-time data, using the actual sampling times the following PK parameters will be derived: Ctrough, Cmin, Cmax, tmax, AUC12h, Cavg, FI Ratio Cmax,test/refrence (ref), Ratio Cmin,test/ref and ratio AUC12h, test/ref | Day 5 | 
| Evaluate the safety and tolerability of a VX-787 600 mg bid regimen during 10 days in healthy participants | Safety and tolerability will be evaluated throughout the study from signing of the ICF onwards until the last study-related activity. The study will include the following evaluations of safety and tolerability: Adverse Events, Clinical Laboratory Test, Electrocardiograms, Vital Signs, Physical Exams. | Days 1-10 | 
| Assessment of Pharmacokinetics of VX-787 | Pharmacokinetic parameters will include assessment of Ctrough, Cmin, Cmax, tmax, AUC12h, Cavg, FI Ratio Cmax,test/ref, ratio Cmin,test/ref and ratio AUC12h,test/ref. | Days 1-10 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Investigate the short-term safety and tolerability of the concomitant use of VX-787 and oseltamivir in healthy participants | Safety and tolerability will be evaluated throughout the study from signing of the ICF onwards until the last study-related activity. The study will include the following evaluations of safety and tolerability: Adverse Events, Clinical Laboratory Test, Electrocardiograms, Vital Signs, Physical Exams | Days 1-5 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Oseltamivir, VX-787