Drug-Drug Interaction Study of VX-770 and VX-809 in Healthy Subjects

Study Overview
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Brief Summary
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The purpose of this study is to assess the pharmacokinetics and safety of VX-809 and VX-770 alone and in combination in healthy subjects.

Detailed Description
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This is a Phase 1, randomized, double-blind, placebo-controlled, multiple-dose study of orally administered VX-809 and VX-770 in healthy subjects. This study will evaluate safety and tolerability of VX-809 and VX-770 alone and in combination. Subjects will be randomized to receive study drug or placebo during three 14-day treatment periods separated by 14-day washout periods. In Treatment Period 1, subjects randomized to study drug will receive VX-809 every 24 hours. In Treatment Period 2, subjects randomized to study drug will receive VX-770 every 12 hours. In Treatment Period 3, subjects will receive VX-809 every 24 hours and VX-770 every 12 hours. Subjects randomized to placebo will receive placebo during all treatment periods. Enrollment is planned at 1 clinical site (Lenexa, Kansas). Up to 72 subjects will be enrolled. The study will be separated into 3 dose escalation cohorts. Cohort 1 and Cohort 2 will enroll 24 subjects. Cohort 3 is optional and may be conducted after a review of safety and pharmacokinetic data by Vertex.

Official Title
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A Phase 1, Randomized, Double-Blind, Placebo Controlled, Multiple-Dose, Dose-Escalation, Drug-Drug Interaction Study of VX-809 and VX-770 in Healthy Subjects

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Drug: VX-809
* Drug: VX-770
* Drug: VX-809 placebo
* Drug: VX-770 placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subject between 18 and 55 years of age, inclusive Body mass index (BMI) between 18.5 and 30.0 kg/m2, inclusive Subjects of child bearing potential and who are sexually active must meet the contraception requirements Female subject must have a negative serum pregnancy test at screening and Day -1 Exclusion Criteria: History of any illness that, in the opinion of the investigator might confound the results of the study or pose an additional risk in administering study drug to the subject Participated in a clinical study involving administration of either an investigational or a marketed drug within 30 days or 5 terminal half-lives (whichever is longer) before the Screening visit Subject who has received VX-770 or VX-809 in a previous clinical study

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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Arm<br>Subjects randomized to study drug will take VX-809 for 14 days followed by a 14 day washout. Next subjects will take VX-770 for 14 days followed by a 14 day washout. Lastly, subjects will take both VX-809 and VX-770 for 14 days. | Drug: VX-809<br>* capsule, taken once daily<br>Drug: VX-770<br>* tablet, taken once every 12 hours<br>|
| Placebo Comparator: Placebo Arm<br>Subjects randomized to placebo will take VX-809 placebo for 14 days followed by a 14 day washout. Next subjects will take VX-770 placebo for 14 days followed by a 14 day washout. Lastly, subjects will take both VX-809 and VX-770 placebo for 14 days. | Drug: VX-809 placebo<br>* capsule, taken once daily<br>Drug: VX-770 placebo<br>* tablet, taken once every 12 hours<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK parameters (including concentration, exposure and half-life) of VX-809 and its metabolite in plasma in the presence and absence of VX 770 | Blood samples drawn during the study will be analyzed to measure the PK parameters, such as concentration, exposure and half-life of VX-809 and its metabolite. | 70 days | 
| PK parameters (including concentration, exposure and half-life) of VX-770 and its metabolites in plasma in the presence and absence of VX 809 | Blood samples drawn during the study will be analyzed to measure the PK parameters, such as concentration, exposure and half-life of VX-770 and its metabolites. | 70 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability as measured by adverse events (AEs) and clinically significant changes in laboratory values (clinical chemistry, hematology, coagulation, and urinalysis), electrocardiograms, and vital signs |  | 70 days |