A Study Evaluating Safety and Pharmacokinetics of VX-440 in Combination With Tezacaftor/Ivacaftor in Healthy Adult Subjects

Study Overview
=================
Brief Summary
-----------------
This study evaluated the safety and pharmacokinetics of multiple ascending doses of VX-440 in combination with tezacaftor/ivacaftor (TEZ/IVA) (triple combination [TC]) administered for 13 days to healthy male and female subjects

Official Title
-----------------
A Phase 1, Randomized, Double Blind, Placebo Controlled, Multiple Dose Escalation Study Evaluating Safety and Pharmacokinetics of VX-440 in Combination With VX-661/Ivacaftor in Healthy Adult Subjects

Conditions
-----------------
Cystic Fibrosis

Intervention / Treatment
-----------------
* Drug: VX-440
* Drug: TEZ
* Drug: IVA
* Drug: Matched Placebos


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Female subjects of non-childbearing potential only. Body mass index (BMI) of 18.0 to 31.0 kg/m2, inclusive, and a total body weight >50 kg. Normal pulmonary function measurements, defined as forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) both ≥80% of their predicted value at screening. Exclusion Criteria: For female subjects: Pregnant or nursing subjects. Glucose-6-phosphate dehydrogenase (G6PD) deficiency. History of hemolysis. Total bilirubin level >2 × ULN at Screening. Other protocol defined Inclusion/Exclusion criteria applied.

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort C1<br> | Drug: VX-440<br>* VX-440 was administered in TC with TEZ and IVA.<br>Drug: TEZ<br>* TEZ was administered as part of a fixed-dose combination (FDC) tablet (TEZ/IVA)<br>* Other names: VX-661;Drug: IVA<br>* IVA was administered as part of a FDC tablet (TEZ/IVA) and as a mono tablet<br>* Other names: VX-770;|
| Placebo Comparator: Cohort C1: Triple Placebo<br> | Drug: Matched Placebos<br>* Placebos matched to VX-440, TEZ, and IVA.<br>|
| Experimental: Cohort C2<br> | Drug: VX-440<br>* VX-440 was administered in TC with TEZ and IVA.<br>Drug: TEZ<br>* TEZ was administered as part of a fixed-dose combination (FDC) tablet (TEZ/IVA)<br>* Other names: VX-661;Drug: IVA<br>* IVA was administered as part of a FDC tablet (TEZ/IVA) and as a mono tablet<br>* Other names: VX-770;|
| Placebo Comparator: Cohort C2: Triple Placebo<br> | Drug: Matched Placebos<br>* Placebos matched to VX-440, TEZ, and IVA.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability were based on the number and assessment of adverse events (AEs) and serious adverse events (SAEs) |  | from baseline through safety follow-up visit (up to 29 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum observed concentration (Cmax) of VX-440, TEZ and its metabolites (M1-TEZ and M2-TEZ), and IVA and its metabolites (M1-IVA and M6-IVA) |  | from Day 1 through Day 18 | 
| Area under the concentration versus time curve during a dosing interval (AUCtau) of VX-440, TEZ and its metabolites (M1-TEZ and M2-TEZ), and IVA and its metabolites (M1-IVA and M6-IVA) |  | from Day 1 through Day 18 | 
| Observed pre-dose concentration (Ctrough) of VX-440, TEZ and its metabolites (M1-TEZ and M2-TEZ), and IVA and its metabolites (M1-IVA and M6-IVA) |  | from Day 1 through Day 18 |