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A Study Evaluating the Safety of VX-152 Combination Therapy in Adults With Cystic Fibrosis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02951195
Recruitment Status : Completed
First Posted : November 1, 2016
Results First Posted : January 28, 2021
Last Update Posted : January 28, 2021
Sponsor:
Information provided by (Responsible Party):
Vertex Pharmaceuticals Incorporated

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Cystic Fibrosis
Interventions Drug: VX-152
Drug: TEZ/IVA
Drug: IVA
Drug: Placebo
Enrollment 80
Recruitment Details  
Pre-assignment Details A total of 80 participants were enrolled in the study (34 participants in Part 1 and 46 participants in Part 2). Out of 46 participants enrolled in Part 2, 4 participants discontinued during the run-in period and were not randomized in the treatment period. Therefore, results are presented for 76 participants in this study.
Arm/Group Title Part 1: Placebo Part 1 Cohort 1A: TC Part 1 Cohort 1B: TC Part 1 Cohort 1C: TC Part 2 Cohort 2A: TEZ/IVA Part 2 Cohort 2A: TC Part 2 Cohort 2B: TEZ/IVA Part 2 Cohort 2B: TC
Hide Arm/Group Description Participants received placebo matched to VX-152/TEZ/IVA triple combination (TC) for 2 weeks. Participants received VX-152 100 milligram (mg) every 12 hours (q12h)/TEZ 100 mg once daily (qd)/IVA 150 mg q12h TC for 2 weeks. Participants received VX-152 200 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 2 weeks. Participants received VX-152 300 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 2 weeks. Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received placebo matched to VX-152 and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period. Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-152 200 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 2 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period. Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received placebo matched to VX-152 and TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period. Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-152 300 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 4 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period.
Period Title: Overall Study
Started 8 6 10 10 4 10 7 21
Completed 8 6 10 10 4 10 7 21
Not Completed 0 0 0 0 0 0 0 0
Arm/Group Title Part 1: Placebo Part 1 Cohort 1A: TC Part 1 Cohort 1B: TC Part 1 Cohort 1C: TC Part 2 Cohort 2A: TEZ/IVA Part 2 Cohort 2A: TC Part 2 Cohort 2B: TEZ/IVA Part 2 Cohort 2B: TC Total
Hide Arm/Group Description Participants received placebo matched to VX-152/TEZ/IVA TC for 2 weeks. Participants received VX-152 100 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 2 weeks. Participants received VX-152 200 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 2 weeks. Participants received VX-152 300 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 2 weeks. Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received placebo matched to VX-152 and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period. Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-152 200 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 2 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period. Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received placebo matched to VX-152 and TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period. Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-152 300 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 4 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period. Total of all reporting groups
Overall Number of Baseline Participants 8 6 10 10 4 10 7 21 76
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 6 participants 10 participants 10 participants 4 participants 10 participants 7 participants 21 participants 76 participants
<18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
>=18 and <65 years
8
 100.0%
6
 100.0%
10
 100.0%
10
 100.0%
4
 100.0%
10
 100.0%
7
 100.0%
21
 100.0%
76
 100.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 6 participants 10 participants 10 participants 4 participants 10 participants 7 participants 21 participants 76 participants
Female
4
  50.0%
2
  33.3%
4
  40.0%
3
  30.0%
2
  50.0%
6
  60.0%
4
  57.1%
14
  66.7%
39
  51.3%
Male
4
  50.0%
4
  66.7%
6
  60.0%
7
  70.0%
2
  50.0%
4
  40.0%
3
  42.9%
7
  33.3%
37
  48.7%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 6 participants 10 participants 10 participants 4 participants 10 participants 7 participants 21 participants 76 participants
Hispanic or Latino
2
  25.0%
0
   0.0%
0
   0.0%
1
  10.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
3
   3.9%
Not Hispanic or Latino
6
  75.0%
6
 100.0%
10
 100.0%
9
  90.0%
4
 100.0%
10
 100.0%
7
 100.0%
21
 100.0%
73
  96.1%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 6 participants 10 participants 10 participants 4 participants 10 participants 7 participants 21 participants 76 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
White
7
  87.5%
5
  83.3%
10
 100.0%
10
 100.0%
4
 100.0%
10
 100.0%
7
 100.0%
21
 100.0%
74
  97.4%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
1
  12.5%
1
  16.7%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
2
   2.6%
Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 6 participants 10 participants 10 participants 4 participants 10 participants 7 participants 21 participants 76 participants
<40 percent
1
  12.5%
0
   0.0%
2
  20.0%
1
  10.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
4
   5.3%
≥40 to <70 percent
5
  62.5%
6
 100.0%
7
  70.0%
4
  40.0%
3
  75.0%
10
 100.0%
5
  71.4%
18
  85.7%
58
  76.3%
≥70 to ≤90 percent
2
  25.0%
0
   0.0%
1
  10.0%
5
  50.0%
1
  25.0%
0
   0.0%
2
  28.6%
3
  14.3%
14
  18.4%
>90 percent
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
[1]
Measure Description: FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
1.Primary Outcome
Title Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Hide Description [Not Specified]
Time Frame Day 1 Through Safety Follow-up Visit (Up to Day 43 for Part 1 and Day 71 for Part 2)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Set included all participants who received at least 1 dose of study drug in the treatment period.
Arm/Group Title Part 1: Placebo Part 1 Cohort 1A: TC Part 1 Cohort 1B: TC Part 1 Cohort 1C: TC Part 2 Cohort 2A: TEZ/IVA Part 2 Cohort 2A: TC Part 2 Cohort 2B: TEZ/IVA Part 2 Cohort 2B: TC
Hide Arm/Group Description:
Participants received placebo matched to VX-152/TEZ/IVA TC for 2 weeks.
Participants received VX-152 100 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 2 weeks.
Participants received VX-152 200 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 2 weeks.
Participants received VX-152 300 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 2 weeks.
Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received placebo matched to VX-152 and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period.
Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-152 200 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 2 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period.
Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received placebo matched to VX-152 and TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period.
Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-152 300 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 4 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period.
Overall Number of Participants Analyzed 8 6 10 10 4 10 7 21
Measure Type: Number
Unit of Measure: participants
Participants with TEAEs 8 3 7 10 3 6 5 19
Participants with SAEs 2 0 0 1 0 0 0 0
2.Primary Outcome
Title Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 15 for Part 1 and Part 2 Cohort 2A
Hide Description FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Time Frame From Baseline at Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) included all randomized participants with the intended cystic fibrosis transmembrane conductance regulator protein (CFTR) allele mutation who received at least 1 dose of study drug in the treatment period. As pre-specified in analysis plan, only Part 1 and Part 2 Cohort 2A arms were assessed for this outcome measure.
Arm/Group Title Part 1: Placebo Part 1 Cohort 1A: TC Part 1 Cohort 1B: TC Part 1 Cohort 1C: TC Part 2 Cohort 2A: TEZ/IVA Part 2 Cohort 2A: TC
Hide Arm/Group Description:
Participants received placebo matched to VX-152/TEZ/IVA TC for 2 weeks.
Participants received VX-152 100 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 2 weeks.
Participants received VX-152 200 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 2 weeks.
Participants received VX-152 300 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 2 weeks.
Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received placebo matched to VX-152 and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period.
Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-152 200 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 2 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period.
Overall Number of Participants Analyzed 8 6 10 10 4 10
Least Squares Mean (95% Confidence Interval)
Unit of Measure: percentage points
-0.8
(-4.8 to 3.3)
5.7
(1.0 to 10.3)
9.7
(6.1 to 13.3)
8.0
(4.0 to 12.0)
-1.0
(-9.9 to 7.8)
7.3
(1.9 to 12.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: Placebo, Part 1 Cohort 1A: TC
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0207
Comments [Not Specified]
Method Mixed-effects Model for Repeated Measure
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 6.4
Confidence Interval (2-Sided) 95%
0.3 to 12.6
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1: Placebo, Part 1 Cohort 1B: TC
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments [Not Specified]
Method Mixed-effects Model for Repeated Measure
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 10.5
Confidence Interval (2-Sided) 95%
5.0 to 15.9
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part 1: Placebo, Part 1 Cohort 1C: TC
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0019
Comments [Not Specified]
Method Mixed-effects Model for Repeated Measure
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 8.8
Confidence Interval (2-Sided) 95%
3.0 to 14.5
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Part 2 Cohort 2A: TEZ/IVA, Part 2 Cohort 2A: TC
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0540
Comments [Not Specified]
Method Mixed-effects Model for Repeated Measure
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 8.3
Confidence Interval (2-Sided) 95%
-2.1 to 18.7
Estimation Comments [Not Specified]
3.Primary Outcome
Title Absolute Change in ppFEV1 Through Day 29 for Part 2 Cohort 2B
Hide Description FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Time Frame From Baseline Through Day 29
Hide Outcome Measure Data
Hide Analysis Population Description
FAS. As pre-specified in analysis plan, only Part 2 Cohort 2B arms were assessed for this outcome measure.
Arm/Group Title Part 2 Cohort 2B: TEZ/IVA Part 2 Cohort 2B: TC
Hide Arm/Group Description:
Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received placebo matched to VX-152 and TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period.
Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-152 300 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 4 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period.
Overall Number of Participants Analyzed 7 21
Least Squares Mean (95% Confidence Interval)
Unit of Measure: percentage points
-2.2
(-6.6 to 2.1)
6.5
(4.0 to 9.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 2 Cohort 2B: TEZ/IVA, Part 2 Cohort 2B: TC
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0007
Comments [Not Specified]
Method Mixed-effects Model for Repeated Measure
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 8.7
Confidence Interval (2-Sided) 95%
3.7 to 13.8
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Absolute Change in Sweat Chloride Concentrations at Day 15 for Part 1 and Part 2 Cohort 2A
Hide Description Sweat samples were collected using an approved collection device.
Time Frame From Baseline at Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
FAS. As pre-specified in analysis plan, only Part 1 and Part 2 Cohort 2A arms were assessed for this outcome measure.
Arm/Group Title Part 1: Placebo Part 1 Cohort 1A: TC Part 1 Cohort 1B: TC Part 1 Cohort 1C: TC Part 2 Cohort 2A: TEZ/IVA Part 2 Cohort 2A: TC
Hide Arm/Group Description:
Participants received placebo matched to VX-152/TEZ/IVA TC for 2 weeks.
Participants received VX-152 100 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 2 weeks.
Participants received VX-152 200 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 2 weeks.
Participants received VX-152 300 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 2 weeks.
Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received placebo matched to VX-152 and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period.
Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-152 200 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 2 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period.
Overall Number of Participants Analyzed 8 6 10 10 4 10
Least Squares Mean (95% Confidence Interval)
Unit of Measure: millimole per liter (mmol/L)
-0.1
(-8.4 to 8.3)
-19.5
(-29.1 to -10.0)
-13.6
(-21.4 to -5.8)
-27.5
(-35.0 to -20.1)
3.5
(-9.2 to 16.2)
-21.3
(-29.5 to -13.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: Placebo, Part 1 Cohort 1A: TC
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0018
Comments [Not Specified]
Method Mixed-effects Model for Repeated Measure
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares (LS) Mean Difference
Estimated Value -19.5
Confidence Interval (2-Sided) 95%
-32.2 to -6.8
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1: Placebo, Part 1 Cohort 1B: TC
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0106
Comments [Not Specified]
Method Mixed-effects Model for Repeated Measure
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -13.6
Confidence Interval (2-Sided) 95%
-25.0 to -2.1
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part 1: Placebo, Part 1 Cohort 1C: TC
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed-effects Model for Repeated Measure
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -27.5
Confidence Interval (2-Sided) 95%
-38.6 to -16.3
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Part 2 Cohort 2A: TEZ/IVA, Part 2 Cohort 2A: TC
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0017
Comments [Not Specified]
Method Mixed-effects Model for Repeated Measure
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -24.8
Confidence Interval (2-Sided) 95%
-40.0 to -9.7
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Absolute Change in Sweat Chloride Concentrations Through Day 29 for Part 2 Cohort 2B
Hide Description Sweat samples were collected using an approved collection device.
Time Frame From Baseline Through Day 29
Hide Outcome Measure Data
Hide Analysis Population Description
FAS. As pre-specified in analysis plan, only Part 2 Cohort 2B arms were assessed for this outcome measure.
Arm/Group Title Part 2 Cohort 2B: TEZ/IVA Part 2 Cohort 2B: TC
Hide Arm/Group Description:
Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received placebo matched to VX-152 and TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period.
Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-152 300 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 4 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period.
Overall Number of Participants Analyzed 7 21
Least Squares Mean (95% Confidence Interval)
Unit of Measure: mmol/L
1.6
(-6.8 to 10.0)
-22.3
(-27.3 to -17.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 2 Cohort 2B: TEZ/IVA, Part 2 Cohort 2B: TC
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed-effects Model for Repeated Measure
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -23.9
Confidence Interval (2-Sided) 95%
-33.7 to -14.1
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Relative Change in ppFEV1 at Day 15 for Part 1 and Part 2 Cohort 2A
Hide Description FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Time Frame From Baseline at Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
FAS. As pre-specified in analysis plan, only Part 1 and Part 2 Cohort 2A arms were assessed for this outcome measure.
Arm/Group Title Part 1: Placebo Part 1 Cohort 1A: TC Part 1 Cohort 1B: TC Part 1 Cohort 1C: TC Part 2 Cohort 2A: TEZ/IVA Part 2 Cohort 2A: TC
Hide Arm/Group Description:
Participants received placebo matched to VX-152/TEZ/IVA for 2 weeks.
Participants received VX-152 100 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 2 weeks.
Participants received VX-152 200 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 2 weeks.
Participants received VX-152 300 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 2 weeks.
Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received placebo matched to VX-152 and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period.
Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-152 200 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 2 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period.
Overall Number of Participants Analyzed 8 6 10 10 4 10
Least Squares Mean (95% Confidence Interval)
Unit of Measure: percent change
-2.3
(-9.8 to 5.3)
10.3
(1.6 to 19.0)
19.0
(12.3 to 25.8)
14.8
(7.3 to 22.4)
-1.4
(-17.1 to 14.4)
13.2
(3.7 to 22.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: Placebo, Part 1 Cohort 1A: TC
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0166
Comments [Not Specified]
Method Mixed-effects Model for Repeated Measure
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 12.5
Confidence Interval (2-Sided) 95%
1.1 to 24.0
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1: Placebo, Part 1 Cohort 1B: TC
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed-effects Model for Repeated Measure
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 21.3
Confidence Interval (2-Sided) 95%
11.2 to 31.4
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part 1: Placebo, Part 1 Cohort 1C: TC
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0013
Comments [Not Specified]
Method Mixed-effects Model for Repeated Measure
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 17.1
Confidence Interval (2-Sided) 95%
6.3 to 27.8
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Part 2 Cohort 2A: TEZ/IVA, Part 2 Cohort 2A: TC
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0563
Comments [Not Specified]
Method Mixed-effects Model for Repeated Measure
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 14.5
Confidence Interval (2-Sided) 95%
-3.8 to 32.9
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Relative Change in ppFEV1 Through Day 29 for Part 2 Cohort 2B
Hide Description FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Time Frame From Baseline Through Day 29
Hide Outcome Measure Data
Hide Analysis Population Description
FAS. As pre-specified in analysis plan, only Part 2 Cohort 2B arms were assessed for this outcome measure.
Arm/Group Title Part 2 Cohort 2B: TEZ/IVA Part 2 Cohort 2B: TC
Hide Arm/Group Description:
Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received placebo matched to VX-152 and TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period.
Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-152 300 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 4 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period.
Overall Number of Participants Analyzed 7 21
Least Squares Mean (95% Confidence Interval)
Unit of Measure: percent change
-2.0
(-9.2 to 5.1)
11.5
(7.4 to 15.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 2 Cohort 2B: TEZ/IVA, Part 2 Cohort 2B: TC
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0012
Comments [Not Specified]
Method Mixed-effects Model for Repeated Measure
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 13.6
Confidence Interval (2-Sided) 95%
5.3 to 21.9
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Day 15 for Part 1 and Part 2 Cohort 2A
Hide Description The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.
Time Frame From Baseline at Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
FAS. As pre-specified in analysis plan, only Part 1 and Part 2 Cohort 2A arms were assessed for this outcome measure.
Arm/Group Title Part 1: Placebo Part 1 Cohort 1A: TC Part 1 Cohort 1B: TC Part 1 Cohort 1C: TC Part 2 Cohort 2A: TEZ/IVA Part 2 Cohort 2A: TC
Hide Arm/Group Description:
Participants received placebo matched to VX-152/TEZ/IVA for 2 weeks.
Participants received VX-152 100 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 2 weeks.
Participants received VX-152 200 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 2 weeks.
Participants received VX-152 300 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 2 weeks.
Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received placebo matched to VX-152 and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period.
Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-152 200 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 2 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period.
Overall Number of Participants Analyzed 8 6 10 10 4 10
Least Squares Mean (95% Confidence Interval)
Unit of Measure: units on a scale
-7.6
(-18.6 to 3.4)
6.6
(-6.0 to 19.1)
21.8
(12.1 to 31.6)
18.6
(8.8 to 28.5)
5.8
(-8.0 to 19.6)
10.6
(1.9 to 19.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: Placebo, Part 1 Cohort 1A: TC
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0476
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 14.1
Confidence Interval (2-Sided) 95%
-2.6 to 30.9
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1: Placebo, Part 1 Cohort 1B: TC
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 29.4
Confidence Interval (2-Sided) 95%
14.8 to 44.0
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part 1: Placebo, Part 1 Cohort 1C: TC
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0006
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 26.2
Confidence Interval (2-Sided) 95%
11.3 to 41.1
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Part 2 Cohort 2A: TEZ/IVA, Part 2 Cohort 2A: TC
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2714
Comments [Not Specified]
Method Mixed-effects Model for Repeated Measure
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 4.8
Confidence Interval (2-Sided) 95%
-11.6 to 21.2
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Absolute Change From Baseline in CFQ-R Respiratory Domain Score at Day 29 for Part 2 Cohort 2B
Hide Description The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.
Time Frame From Baseline at Day 29
Hide Outcome Measure Data
Hide Analysis Population Description
FAS. As pre-specified in analysis plan, only Part 2 Cohort 2B arms were assessed for this outcome measure.
Arm/Group Title Part 2 Cohort 2B: TEZ/IVA Part 2 Cohort 2B: TC
Hide Arm/Group Description:
Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received placebo matched to VX-152 and TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period.
Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-152 300 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 4 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period.
Overall Number of Participants Analyzed 7 21
Least Squares Mean (95% Confidence Interval)
Unit of Measure: units on a scale
4.8
(-3.7 to 13.3)
16.1
(11.2 to 21.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 2 Cohort 2B: TEZ/IVA, Part 2 Cohort 2B: TC
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0138
Comments [Not Specified]
Method Mixed-effects Model for Repeated Measure
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 11.3
Confidence Interval (2-Sided) 95%
1.3 to 21.2
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA
Hide Description [Not Specified]
Time Frame Pre-dose at Day 8, Day 15 and Day 29
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic Set (PK) included all participants who received at least 1 dose of study drug in treatment period. Here "Number Analyzed" signifies those participants who were evaluable at specified time points. Day 29 assessments were planned for Part 2: Cohort 2B groups only. VX-152 Ctrough category was not applicable to Part 2: TEZ/IVA groups.
Arm/Group Title Part 1 Cohort 1A: TC Part 1 Cohort 1B: TC Part 1 Cohort 1C: TC Part 2 Cohort 2A: TEZ/IVA Part 2 Cohort 2A: TC Part 2 Cohort 2B: TEZ/IVA Part 2 Cohort 2B: TC
Hide Arm/Group Description:
Participants received VX-152 100 mg q12h/TEZ 100 qd/IVA 150 mg q12h TC for 2 weeks.
Participants received VX-152 200 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 2 weeks.
Participants received VX-152 300 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 2 weeks.
Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received placebo matched to VX-152 and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period.
Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-152 200 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 2 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period.
Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received placebo matched to VX-152 and TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period.
Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-152 300 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 4 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period.
Overall Number of Participants Analyzed 6 10 10 4 10 7 21
Mean (Standard Deviation)
Unit of Measure: nanogram per milliliter (ng/mL)
Day 8: VX-152 Number Analyzed 6 participants 10 participants 10 participants 0 participants 10 participants 0 participants 21 participants
167  (65.4) 240  (370) 538  (576) 355  (287) 463  (730)
Day 15: VX-152 Number Analyzed 6 participants 10 participants 10 participants 0 participants 9 participants 0 participants 20 participants
173  (72.1) 278  (212) 804  (812) 554  (429) 560  (657)
Day 29: VX-152 Number Analyzed 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants 17 participants
698  (1040)
Day 8: TEZ Number Analyzed 6 participants 10 participants 10 participants 4 participants 10 participants 7 participants 21 participants
2610  (1400) 1500  (1140) 1680  (996) 1900  (1730) 1830  (693) 2010  (669) 1460  (1470)
Day 15: TEZ Number Analyzed 6 participants 10 participants 10 participants 4 participants 9 participants 7 participants 20 participants
2450  (2000) 1220  (545) 1180  (495) 1120  (135) 1620  (1030) 1970  (1040) 1050  (543)
Day 29: TEZ Number Analyzed 0 participants 0 participants 0 participants 0 participants 0 participants 6 participants 17 participants
2470  (1060) 1190  (422)
Day 8: M1-TEZ Number Analyzed 6 participants 10 participants 10 participants 4 participants 10 participants 7 participants 21 participants
4520  (1090) 3060  (1480) 3490  (1640) 3760  (1100) 4900  (1050) 4980  (1450) 4150  (1280)
Day 15: M1-TEZ Number Analyzed 6 participants 10 participants 9 participants 4 participants 9 participants 7 participants 20 participants
4680  (1020) 2890  (898) 3310  (1220) 3430  (824) 4270  (1280) 4420  (1810) 3650  (1320)
Day 29: M1-TEZ Number Analyzed 0 participants 0 participants 0 participants 0 participants 0 participants 6 participants 17 participants
4280  (1650) 3680  (742)
Day 8: IVA Number Analyzed 6 participants 10 participants 10 participants 4 participants 10 participants 7 participants 21 participants
779  (442) 522  (401) 545  (234) 702  (425) 610  (262) 953  (360) 434  (251)
Day 15: IVA Number Analyzed 6 participants 10 participants 10 participants 4 participants 9 participants 7 participants 20 participants
841  (588) 535  (310) 467  (236) 441  (300) 645  (373) 863  (488) 389  (222)
Day 29: IVA Number Analyzed 0 participants 0 participants 0 participants 0 participants 0 participants 6 participants 17 participants
1010  (446) 468  (279)
Day 8: M1-IVA Number Analyzed 6 participants 10 participants 10 participants 4 participants 10 participants 7 participants 21 participants
1590  (1050) 1040  (947) 1330  (747) 1660  (1200) 1470  (671) 1810  (665) 1170  (551)
Day 15: M1-IVA Number Analyzed 6 participants 10 participants 9 participants 4 participants 9 participants 7 participants 20 participants
1230  (326) 1200  (848) 1140  (550) 1030  (762) 1510  (891) 1620  (760) 1100  (598)
Day 29: M1-IVA Number Analyzed 0 participants 0 participants 0 participants 0 participants 0 participants 6 participants 17 participants
1890  (659) 1240  (705)
Time Frame Day 1 Through Safety Follow-up Visit (Up to Day 43 for Part 1 and Day 71 for Part 2)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Part 1: Placebo Part 1 Cohort 1A: TC Part 1 Cohort 1B: TC Part 1 Cohort 1C: TC Part 2 Cohort 2A: TEZ/IVA Part 2 Cohort 2A: TC Part 2 Cohort 2B: TEZ/IVA Part 2 Cohort 2B: TC
Hide Arm/Group Description Participants received placebo matched to VX-152/TEZ/IVA TC for 2 weeks. Participants received VX-152 100 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 2 weeks. Participants received VX-152 200 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 2 weeks. Participants received VX-152 300 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 2 weeks. Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received placebo matched to VX-152 and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period. Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-152 200 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 2 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period. Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received placebo matched to VX-152 and TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period. Following run-in period on TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-152 300 mg q12h/TEZ 100 mg qd/IVA 150 mg q12h TC for 4 weeks in treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 2 weeks in washout period.
All-Cause Mortality
Part 1: Placebo Part 1 Cohort 1A: TC Part 1 Cohort 1B: TC Part 1 Cohort 1C: TC Part 2 Cohort 2A: TEZ/IVA Part 2 Cohort 2A: TC Part 2 Cohort 2B: TEZ/IVA Part 2 Cohort 2B: TC
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/8 (0.00%)   0/6 (0.00%)   0/10 (0.00%)   0/10 (0.00%)   0/4 (0.00%)   0/10 (0.00%)   0/7 (0.00%)   0/21 (0.00%) 
Hide Serious Adverse Events
Part 1: Placebo Part 1 Cohort 1A: TC Part 1 Cohort 1B: TC Part 1 Cohort 1C: TC Part 2 Cohort 2A: TEZ/IVA Part 2 Cohort 2A: TC Part 2 Cohort 2B: TEZ/IVA Part 2 Cohort 2B: TC
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/8 (25.00%)   0/6 (0.00%)   0/10 (0.00%)   1/10 (10.00%)   0/4 (0.00%)   0/10 (0.00%)   0/7 (0.00%)   0/21 (0.00%) 
Infections and infestations                 
Infective pulmonary exacerbation of cystic fibrosis  1  1/8 (12.50%)  0/6 (0.00%)  0/10 (0.00%)  1/10 (10.00%)  0/4 (0.00%)  0/10 (0.00%)  0/7 (0.00%)  0/21 (0.00%) 
Viral infection  1  1/8 (12.50%)  0/6 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/10 (0.00%)  0/7 (0.00%)  0/21 (0.00%) 
1
Term from vocabulary, MedDRA 20.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Part 1: Placebo Part 1 Cohort 1A: TC Part 1 Cohort 1B: TC Part 1 Cohort 1C: TC Part 2 Cohort 2A: TEZ/IVA Part 2 Cohort 2A: TC Part 2 Cohort 2B: TEZ/IVA Part 2 Cohort 2B: TC
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   8/8 (100.00%)   3/6 (50.00%)   7/10 (70.00%)   9/10 (90.00%)   3/4 (75.00%)   6/10 (60.00%)   5/7 (71.43%)   18/21 (85.71%) 
Blood and lymphatic system disorders                 
Anaemia  1  0/8 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  1/10 (10.00%)  0/4 (0.00%)  0/10 (0.00%)  0/7 (0.00%)  0/21 (0.00%) 
Lymphadenopathy  1  1/8 (12.50%)  0/6 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/10 (0.00%)  0/7 (0.00%)  0/21 (0.00%) 
Ear and labyrinth disorders                 
Ear discomfort  1  1/8 (12.50%)  0/6 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/10 (0.00%)  0/7 (0.00%)  0/21 (0.00%) 
Eye disorders                 
Eye swelling  1  0/8 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  1/10 (10.00%)  0/7 (0.00%)  0/21 (0.00%) 
Gastrointestinal disorders                 
Abdominal discomfort  1  0/8 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  1/10 (10.00%)  0/4 (0.00%)  0/10 (0.00%)  0/7 (0.00%)  0/21 (0.00%) 
Abdominal distension  1  0/8 (0.00%)  1/6 (16.67%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/10 (0.00%)  0/7 (0.00%)  1/21 (4.76%) 
Abdominal pain  1  0/8 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/10 (0.00%)  0/7 (0.00%)  2/21 (9.52%) 
Colitis  1  1/8 (12.50%)  0/6 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/10 (0.00%)  0/7 (0.00%)  0/21 (0.00%) 
Constipation  1  0/8 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/10 (0.00%)  0/7 (0.00%)  2/21 (9.52%) 
Diarrhoea  1  0/8 (0.00%)  2/6 (33.33%)  2/10 (20.00%)  1/10 (10.00%)  0/4 (0.00%)  0/10 (0.00%)  0/7 (0.00%)  3/21 (14.29%) 
Dyspepsia  1  0/8 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  1/10 (10.00%)  0/4 (0.00%)  0/10 (0.00%)  0/7 (0.00%)  0/21 (0.00%) 
Faeces soft  1  0/8 (0.00%)  0/6 (0.00%)  1/10 (10.00%)  0/10 (0.00%)  0/4 (0.00%)  0/10 (0.00%)  0/7 (0.00%)  0/21 (0.00%) 
Flatulence  1  0/8 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  1/10 (10.00%)  0/4 (0.00%)  0/10 (0.00%)  0/7 (0.00%)  2/21 (9.52%) 
Nausea  1  1/8 (12.50%)  0/6 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  1/4 (25.00%)  0/10 (0.00%)  0/7 (0.00%)  2/21 (9.52%) 
Post-tussive vomiting  1  0/8 (0.00%)  0/6 (0.00%)  1/10 (10.00%)  0/10 (0.00%)  0/4 (0.00%)  0/10 (0.00%)  0/7 (0.00%)  0/21 (0.00%) 
Vomiting  1  1/8 (12.50%)  0/6 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/10 (0.00%)  1/7 (14.29%)  0/21 (0.00%) 
General disorders                 
Chest discomfort  1  0/8 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/10 (0.00%)  1/7 (14.29%)  0/21 (0.00%) 
Fatigue  1  0/8 (0.00%)  1/6 (16.67%)  2/10 (20.00%)  1/10 (10.00%)  0/4 (0.00%)  1/10 (10.00%)  0/7 (0.00%)  2/21 (9.52%) 
Pyrexia  1  0/8 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/10 (0.00%)  0/7 (0.00%)  2/21 (9.52%) 
Thirst  1  0/8 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  1/10 (10.00%)  0/4 (0.00%)  0/10 (0.00%)  0/7 (0.00%)  0/21 (0.00%) 
Vessel puncture site haemorrhage  1  1/8 (12.50%)  0/6 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/10 (0.00%)  0/7 (0.00%)  0/21 (0.00%) 
Immune system disorders                 
Seasonal allergy  1  0/8 (0.00%)  0/6 (0.00%)  1/10 (10.00%)  0/10 (0.00%)  0/4 (0.00%)  0/10 (0.00%)  0/7 (0.00%)  0/21 (0.00%) 
Infections and infestations                 
Chronic sinusitis  1  0/8 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  1/10 (10.00%)  0/4 (0.00%)  0/10 (0.00%)  0/7 (0.00%)  0/21 (0.00%) 
Gastroenteritis  1  0/8 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  1/4 (25.00%)  0/10 (0.00%)  0/7 (0.00%)  0/21 (0.00%) 
Infective pulmonary exacerbation of cystic fibrosis  1  3/8 (37.50%)  0/6 (0.00%)  1/10 (10.00%)  0/10 (0.00%)  0/4 (0.00%)  1/10 (10.00%)  3/7 (42.86%)  5/21 (23.81%) 
Nasopharyngitis  1  0/8 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  1/10 (10.00%)  1/7 (14.29%)  0/21 (0.00%) 
Pneumonia  1  0/8 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  1/10 (10.00%)  0/7 (0.00%)  0/21 (0.00%) 
Upper respiratory tract infection  1  1/8 (12.50%)  0/6 (0.00%)  1/10 (10.00%)  0/10 (0.00%)  0/4 (0.00%)  0/10 (0.00%)  0/7 (0.00%)  1/21 (4.76%) 
Viral upper respiratory tract infection  1  1/8 (12.50%)  0/6 (0.00%)  0/10 (0.00%)  1/10 (10.00%)  0/4 (0.00%)  0/10 (0.00%)  0/7 (0.00%)  1/21 (4.76%) 
Injury, poisoning and procedural complications                 
Incision site pain  1  0/8 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  1/10 (10.00%)  0/7 (0.00%)  0/21 (0.00%) 
Muscle strain  1  0/8 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  1/4 (25.00%)  0/10 (0.00%)  0/7 (0.00%)  0/21 (0.00%) 
Procedural dizziness  1  0/8 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  1/10 (10.00%)  0/4 (0.00%)  0/10 (0.00%)  0/7 (0.00%)  0/21 (0.00%) 
Procedural haemorrhage  1  0/8 (0.00%)  0/6 (0.00%)  1/10 (10.00%)  0/10 (0.00%)  0/4 (0.00%)  0/10 (0.00%)  0/7 (0.00%)  0/21 (0.00%) 
Investigations                 
Alanine aminotransferase increased  1  0/8 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  1/10 (10.00%)  0/4 (0.00%)  0/10 (0.00%)  0/7 (0.00%)  1/21 (4.76%) 
Aspartate aminotransferase increased  1  1/8 (12.50%)  0/6 (0.00%)  0/10 (0.00%)  1/10 (10.00%)  0/4 (0.00%)  0/10 (0.00%)  0/7 (0.00%)  1/21 (4.76%) 
Blood alkaline phosphatase increased  1  1/8 (12.50%)  0/6 (0.00%)  0/10 (0.00%)  1/10 (10.00%)  0/4 (0.00%)  0/10 (0.00%)  0/7 (0.00%)  0/21 (0.00%) 
Blood bilirubin increased  1  0/8 (0.00%)  0/6 (0.00%)  1/10 (10.00%)  0/10 (0.00%)  0/4 (0.00%)  0/10 (0.00%)  0/7 (0.00%)  1/21 (4.76%) 
Gamma-glutamyltransferase increased  1  1/8 (12.50%)  0/6 (0.00%)  0/10 (0.00%)  1/10 (10.00%)  0/4 (0.00%)  0/10 (0.00%)  0/7 (0.00%)  0/21 (0.00%) 
Platelet count increased  1  0/8 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  1/10 (10.00%)  0/4 (0.00%)  0/10 (0.00%)  0/7 (0.00%)  0/21 (0.00%) 
Weight decreased  1  0/8 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  1/4 (25.00%)  0/10 (0.00%)  0/7 (0.00%)  0/21 (0.00%) 
Metabolism and nutrition disorders                 
Hypoglycaemia  1  0/8 (0.00%)  1/6 (16.67%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/10 (0.00%)  0/7 (0.00%)  0/21 (0.00%) 
Musculoskeletal and connective tissue disorders                 
Arthralgia  1  0/8 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  1/4 (25.00%)  0/10 (0.00%)  0/7 (0.00%)  0/21 (0.00%) 
Musculoskeletal chest pain  1  0/8 (0.00%)  1/6 (16.67%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/10 (0.00%)  0/7 (0.00%)  0/21 (0.00%) 
Tendon pain  1  0/8 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  1/4 (25.00%)  0/10 (0.00%)  0/7 (0.00%)  0/21 (0.00%) 
Nervous system disorders                 
Dizziness  1  1/8 (12.50%)  1/6 (16.67%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/10 (0.00%)  0/7 (0.00%)  0/21 (0.00%) 
Dysgeusia  1  0/8 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  1/10 (10.00%)  0/4 (0.00%)  0/10 (0.00%)  0/7 (0.00%)  0/21 (0.00%) 
Headache  1  0/8 (0.00%)  1/6 (16.67%)  1/10 (10.00%)  3/10 (30.00%)  1/4 (25.00%)  0/10 (0.00%)  0/7 (0.00%)  4/21 (19.05%) 
Migraine  1  1/8 (12.50%)  0/6 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/10 (0.00%)  0/7 (0.00%)  1/21 (4.76%) 
Sinus headache  1  0/8 (0.00%)  0/6 (0.00%)  1/10 (10.00%)  1/10 (10.00%)  0/4 (0.00%)  0/10 (0.00%)  0/7 (0.00%)  0/21 (0.00%) 
Psychiatric disorders                 
Anxiety  1  1/8 (12.50%)  0/6 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/10 (0.00%)  0/7 (0.00%)  0/21 (0.00%) 
Insomnia  1  0/8 (0.00%)  0/6 (0.00%)  1/10 (10.00%)  0/10 (0.00%)  0/4 (0.00%)  0/10 (0.00%)  0/7 (0.00%)  1/21 (4.76%) 
Renal and urinary disorders                 
Chromaturia  1  0/8 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  1/10 (10.00%)  0/4 (0.00%)  0/10 (0.00%)  0/7 (0.00%)  4/21 (19.05%) 
Reproductive system and breast disorders                 
Breast discomfort  1  0/8 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  1/10 (10.00%)  0/4 (0.00%)  0/10 (0.00%)  0/7 (0.00%)  0/21 (0.00%) 
Breast tenderness  1  0/8 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  1/10 (10.00%)  0/4 (0.00%)  0/10 (0.00%)  0/7 (0.00%)  1/21 (4.76%) 
Respiratory, thoracic and mediastinal disorders                 
Bronchospasm  1  0/8 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  1/10 (10.00%)  0/7 (0.00%)  0/21 (0.00%) 
Cough  1  1/8 (12.50%)  0/6 (0.00%)  3/10 (30.00%)  1/10 (10.00%)  1/4 (25.00%)  1/10 (10.00%)  0/7 (0.00%)  6/21 (28.57%) 
Dysphonia  1  1/8 (12.50%)  0/6 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/10 (0.00%)  0/7 (0.00%)  0/21 (0.00%) 
Dyspnoea  1  1/8 (12.50%)  0/6 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  1/4 (25.00%)  0/10 (0.00%)  1/7 (14.29%)  2/21 (9.52%) 
Dyspnoea exertional  1  0/8 (0.00%)  0/6 (0.00%)  1/10 (10.00%)  0/10 (0.00%)  0/4 (0.00%)  0/10 (0.00%)  0/7 (0.00%)  0/21 (0.00%) 
Haemoptysis  1  0/8 (0.00%)  1/6 (16.67%)  0/10 (0.00%)  1/10 (10.00%)  1/4 (25.00%)  1/10 (10.00%)  0/7 (0.00%)  2/21 (9.52%) 
Increased viscosity of bronchial secretion  1  0/8 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/10 (0.00%)  0/7 (0.00%)  2/21 (9.52%) 
Lower respiratory tract congestion  1  0/8 (0.00%)  1/6 (16.67%)  1/10 (10.00%)  1/10 (10.00%)  1/4 (25.00%)  0/10 (0.00%)  1/7 (14.29%)  0/21 (0.00%) 
Nasal congestion  1  1/8 (12.50%)  0/6 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/10 (0.00%)  0/7 (0.00%)  1/21 (4.76%) 
Oropharyngeal pain  1  1/8 (12.50%)  0/6 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/10 (0.00%)  0/7 (0.00%)  2/21 (9.52%) 
Pleuritic pain  1  0/8 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/10 (0.00%)  0/7 (0.00%)  2/21 (9.52%) 
Productive cough  1  0/8 (0.00%)  2/6 (33.33%)  2/10 (20.00%)  2/10 (20.00%)  0/4 (0.00%)  0/10 (0.00%)  0/7 (0.00%)  3/21 (14.29%) 
Pulmonary pain  1  0/8 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  1/10 (10.00%)  0/4 (0.00%)  0/10 (0.00%)  0/7 (0.00%)  0/21 (0.00%) 
Respiration abnormal  1  0/8 (0.00%)  0/6 (0.00%)  1/10 (10.00%)  2/10 (20.00%)  0/4 (0.00%)  0/10 (0.00%)  0/7 (0.00%)  2/21 (9.52%) 
Respiratory tract congestion  1  0/8 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  1/10 (10.00%)  0/4 (0.00%)  0/10 (0.00%)  0/7 (0.00%)  0/21 (0.00%) 
Rhinorrhoea  1  0/8 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  1/4 (25.00%)  0/10 (0.00%)  0/7 (0.00%)  0/21 (0.00%) 
Sinus congestion  1  2/8 (25.00%)  0/6 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/10 (0.00%)  0/7 (0.00%)  1/21 (4.76%) 
Sputum discoloured  1  0/8 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  1/10 (10.00%)  0/7 (0.00%)  1/21 (4.76%) 
Sputum increased  1  1/8 (12.50%)  1/6 (16.67%)  2/10 (20.00%)  1/10 (10.00%)  0/4 (0.00%)  1/10 (10.00%)  1/7 (14.29%)  6/21 (28.57%) 
Upper respiratory tract congestion  1  0/8 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  1/4 (25.00%)  0/10 (0.00%)  0/7 (0.00%)  0/21 (0.00%) 
Wheezing  1  0/8 (0.00%)  0/6 (0.00%)  1/10 (10.00%)  1/10 (10.00%)  1/4 (25.00%)  0/10 (0.00%)  1/7 (14.29%)  0/21 (0.00%) 
Skin and subcutaneous tissue disorders                 
Acne  1  0/8 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/10 (0.00%)  0/7 (0.00%)  2/21 (9.52%) 
Erythema  1  0/8 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  1/4 (25.00%)  0/10 (0.00%)  0/7 (0.00%)  0/21 (0.00%) 
Night sweats  1  0/8 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  1/10 (10.00%)  0/7 (0.00%)  0/21 (0.00%) 
Rash  1  0/8 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  0/4 (0.00%)  0/10 (0.00%)  0/7 (0.00%)  2/21 (9.52%) 
1
Term from vocabulary, MedDRA 20.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
 
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Monitor
Organization: Vertex Pharmaceuticals Incorporated
Phone: 617-341-6777
EMail: medicalinfo@vrtx.com
Layout table for additonal information
Responsible Party: Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier: NCT02951195    
Other Study ID Numbers: VX16-152-102
First Submitted: October 26, 2016
First Posted: November 1, 2016
Results First Submitted: January 7, 2021
Results First Posted: January 28, 2021
Last Update Posted: January 28, 2021