Trial Outcomes & Findings for A Phase 3 Study to Evaluate the Efficacy and Safety of Ivacaftor and VX-661 in Combination With Ivacaftor in Subjects Aged 12 Years and Older With Cystic Fibrosis, Heterozygous for the F508del-cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Mutation (NCT NCT02392234)
NCT ID: NCT02392234
Last Updated: 2018-06-12
Results Overview
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
248 participants
Primary outcome timeframe
Baseline, Week 4 and Week 8 of each treatment period
Results posted on
2018-06-12
Participant Flow
A total of 248 participants were enrolled. Out of which, 246 received at least 1 dose of study drug were included in safety set and 244 participants who carried intended cystic fibrosis transmembrane conductance regulator (CFTR) mutations were included in Full analysis set.
Participants were randomized to 1 of 6 treatment sequences, each of which included 2 treatment periods and 2 of 3 potential treatments (placebo, VX-661/ivacaftor \[IVA\], IVA). Treatment periods were separated by an 8 week wash-out period.
Participant milestones
| Measure |
First VX-661/IVA, Then IVA
VX-661 100 milligram (mg) plus IVA 150 mg fixed dose combination (FDC) tablet and placebo matched to IVA in the morning, IVA 150 mg tablet in the evening for 8 weeks in treatment period 1 followed by IVA 150 mg tablet and placebo matched to VX-661 plus IVA FDC tablet in the morning, IVA 150 mg tablet in the evening for 8 weeks in treatment period 2. Each treatment period was separated by a minimum 8 weeks of washout period.
|
First VX-661/IVA, Then Placebo
VX-661 100 mg plus IVA 150 mg FDC tablet and placebo matched to IVA in the morning, IVA 150 mg tablet in the evening for 8 weeks in treatment period 1 followed by placebo matched to VX-661 plus IVA FDC tablet and placebo matched to IVA tablet in the morning, placebo matched to IVA tablet in the evening for 8 weeks in treatment period 2. Each treatment period was separated by a minimum 8 weeks of washout period.
|
First IVA, Then Placebo
IVA 150 mg tablet and placebo matched to VX-661 plus IVA FDC tablet in the morning, IVA 150 mg tablet in the evening for 8 weeks in treatment period 1 followed by placebo matched to VX-661 plus IVA FDC tablet and placebo matched to IVA tablet in the morning, placebo matched to IVA tablet in the evening for 8 weeks in treatment period 2. Each treatment period was separated by a minimum 8 weeks of washout period.
|
First IVA, Then VX- 661/IVA
IVA 150 mg tablet and placebo matched to VX-661 plus IVA FDC tablet in the morning, IVA 150 mg tablet in the evening for 8 weeks in treatment period 1 followed by VX-661 100 mg plus IVA 150 mg FDC tablet and placebo matched to IVA tablet in the morning, IVA 150 mg tablet in the evening for 8 weeks in treatment period 2. Each treatment period was separated by a minimum 8 weeks of washout period.
|
First Placebo, Then VX- 661/IVA
Placebo matched to VX-661 plus IVA FDC tablet and placebo matched to IVA tablet in the morning, placebo matched to IVA tablet in the evening for 8 weeks in treatment period 1 followed by VX-661 100 mg plus IVA 150 mg FDC tablet and placebo matched to IVA tablet in the morning, IVA 150 mg tablet in the evening for 8 weeks in treatment period 2. Each treatment period was separated by a minimum 8 weeks of washout period.
|
First Placebo, Then IVA
Placebo matched to VX-661 plus IVA FDC tablet and placebo matched to IVA tablet in the morning, placebo matched to IVA tablet in the evening for 8 weeks in treatment period 1 followed by IVA 150 mg tablet and placebo matched to VX-661 plus IVA FDC tablet in the morning, IVA 150 mg tablet in the evening for 8 weeks in treatment period 2. Each treatment period was separated by a minimum 8 weeks of washout period.
|
|---|---|---|---|---|---|---|
|
Treatment Period 1 (8 Weeks)
STARTED
|
41
|
43
|
40
|
42
|
41
|
41
|
|
Treatment Period 1 (8 Weeks)
Treated
|
41
|
43
|
39
|
42
|
40
|
41
|
|
Treatment Period 1 (8 Weeks)
COMPLETED
|
38
|
43
|
38
|
41
|
37
|
38
|
|
Treatment Period 1 (8 Weeks)
NOT COMPLETED
|
3
|
0
|
2
|
1
|
4
|
3
|
|
Treatment Period 2 (8 Weeks)
STARTED
|
38
|
43
|
38
|
41
|
37
|
38
|
|
Treatment Period 2 (8 Weeks)
COMPLETED
|
37
|
43
|
38
|
41
|
37
|
38
|
|
Treatment Period 2 (8 Weeks)
NOT COMPLETED
|
1
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
First VX-661/IVA, Then IVA
VX-661 100 milligram (mg) plus IVA 150 mg fixed dose combination (FDC) tablet and placebo matched to IVA in the morning, IVA 150 mg tablet in the evening for 8 weeks in treatment period 1 followed by IVA 150 mg tablet and placebo matched to VX-661 plus IVA FDC tablet in the morning, IVA 150 mg tablet in the evening for 8 weeks in treatment period 2. Each treatment period was separated by a minimum 8 weeks of washout period.
|
First VX-661/IVA, Then Placebo
VX-661 100 mg plus IVA 150 mg FDC tablet and placebo matched to IVA in the morning, IVA 150 mg tablet in the evening for 8 weeks in treatment period 1 followed by placebo matched to VX-661 plus IVA FDC tablet and placebo matched to IVA tablet in the morning, placebo matched to IVA tablet in the evening for 8 weeks in treatment period 2. Each treatment period was separated by a minimum 8 weeks of washout period.
|
First IVA, Then Placebo
IVA 150 mg tablet and placebo matched to VX-661 plus IVA FDC tablet in the morning, IVA 150 mg tablet in the evening for 8 weeks in treatment period 1 followed by placebo matched to VX-661 plus IVA FDC tablet and placebo matched to IVA tablet in the morning, placebo matched to IVA tablet in the evening for 8 weeks in treatment period 2. Each treatment period was separated by a minimum 8 weeks of washout period.
|
First IVA, Then VX- 661/IVA
IVA 150 mg tablet and placebo matched to VX-661 plus IVA FDC tablet in the morning, IVA 150 mg tablet in the evening for 8 weeks in treatment period 1 followed by VX-661 100 mg plus IVA 150 mg FDC tablet and placebo matched to IVA tablet in the morning, IVA 150 mg tablet in the evening for 8 weeks in treatment period 2. Each treatment period was separated by a minimum 8 weeks of washout period.
|
First Placebo, Then VX- 661/IVA
Placebo matched to VX-661 plus IVA FDC tablet and placebo matched to IVA tablet in the morning, placebo matched to IVA tablet in the evening for 8 weeks in treatment period 1 followed by VX-661 100 mg plus IVA 150 mg FDC tablet and placebo matched to IVA tablet in the morning, IVA 150 mg tablet in the evening for 8 weeks in treatment period 2. Each treatment period was separated by a minimum 8 weeks of washout period.
|
First Placebo, Then IVA
Placebo matched to VX-661 plus IVA FDC tablet and placebo matched to IVA tablet in the morning, placebo matched to IVA tablet in the evening for 8 weeks in treatment period 1 followed by IVA 150 mg tablet and placebo matched to VX-661 plus IVA FDC tablet in the morning, IVA 150 mg tablet in the evening for 8 weeks in treatment period 2. Each treatment period was separated by a minimum 8 weeks of washout period.
|
|---|---|---|---|---|---|---|
|
Treatment Period 1 (8 Weeks)
Adverse Event
|
1
|
0
|
1
|
0
|
1
|
1
|
|
Treatment Period 1 (8 Weeks)
Withdrawal by Subject
|
0
|
0
|
0
|
0
|
2
|
0
|
|
Treatment Period 1 (8 Weeks)
Lost to Follow-up
|
0
|
0
|
0
|
0
|
0
|
1
|
|
Treatment Period 1 (8 Weeks)
Pregnancy
|
1
|
0
|
0
|
1
|
0
|
0
|
|
Treatment Period 1 (8 Weeks)
Noncompliance
|
0
|
0
|
0
|
0
|
0
|
1
|
|
Treatment Period 1 (8 Weeks)
Other
|
1
|
0
|
0
|
0
|
0
|
0
|
|
Treatment Period 1 (8 Weeks)
Randomized but not treated
|
0
|
0
|
1
|
0
|
1
|
0
|
|
Treatment Period 2 (8 Weeks)
Adverse Event
|
1
|
0
|
0
|
0
|
0
|
0
|
Baseline Characteristics
A Phase 3 Study to Evaluate the Efficacy and Safety of Ivacaftor and VX-661 in Combination With Ivacaftor in Subjects Aged 12 Years and Older With Cystic Fibrosis, Heterozygous for the F508del-cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Mutation
Baseline characteristics by cohort
| Measure |
First VX- 661/IVA, Then IVA
n=41 Participants
VX-661 100 mg plus IVA 150 mg FDC tablet and placebo matched to IVA in the morning, IVA 150 mg tablet in the evening for 8 weeks in treatment period 1 followed by IVA 150 mg tablet and placebo matched to VX-661 plus IVA FDC tablet in the morning, IVA 150 mg tablet in the evening for 8 weeks in treatment period 2. Each treatment period was separated by a minimum 8 weeks of washout period.
|
First VX-661/IVA, Then Placebo
n=43 Participants
VX-661 100 mg plus IVA 150 mg FDC tablet and placebo matched to IVA in the morning, IVA 150 mg tablet in the evening for 8 weeks in treatment period 1 followed by placebo matched to VX-661 plus IVA FDC tablet and placebo matched to IVA tablet in the morning, placebo matched to IVA tablet in the evening for 8 weeks in treatment period 2. Each treatment period was separated by a minimum 8 weeks of washout period.
|
First IVA, Then Placebo
n=40 Participants
IVA 150 mg tablet and placebo matched to VX-661 plus IVA FDC tablet in the morning, IVA 150 mg tablet in the evening for 8 weeks in treatment period 1 followed by placebo matched to VX-661 plus IVA FDC tablet and placebo matched to IVA tablet in the morning, placebo matched to IVA tablet in the evening for 8 weeks in treatment period 2. Each treatment period was separated by a minimum 8 weeks of washout period.
|
First IVA, Then VX- 661/IVA
n=42 Participants
IVA 150 mg tablet and placebo matched to VX-661 plus IVA FDC tablet in the morning, IVA 150 mg tablet in the evening for 8 weeks in treatment period 1 followed by VX-661 100 mg plus IVA 150 mg FDC tablet and placebo matched to IVA tablet in the morning, IVA 150 mg tablet in the evening for 8 weeks in treatment period 2. Each treatment period was separated by a minimum 8 weeks of washout period.
|
First Placebo, Then VX- 661/IVA
n=41 Participants
Placebo matched to VX-661 plus IVA FDC tablet and placebo matched to IVA tablet in the morning, placebo matched to IVA tablet in the evening for 8 weeks in treatment period 1 followed by VX-661 100 mg plus IVA 150 mg FDC tablet and placebo matched to IVA tablet in the morning, IVA 150 mg tablet in the evening for 8 weeks in treatment period 2. Each treatment period was separated by a minimum 8 weeks of washout period.
|
First Placebo, Then IVA
n=41 Participants
Placebo matched to VX-661 plus IVA FDC tablet and placebo matched to IVA tablet in the morning, placebo matched to IVA tablet in the evening for 8 weeks in treatment period 1 followed by IVA 150 mg tablet and placebo matched to VX-661 plus IVA FDC tablet in the morning, IVA 150 mg tablet in the evening for 8 weeks in treatment period 2. Each treatment period was separated by a minimum 8 weeks of washout period.
|
Total
n=248 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
5 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
5 Participants
n=21 Participants
|
6 Participants
n=8 Participants
|
34 Participants
n=8 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
36 Participants
n=5 Participants
|
37 Participants
n=7 Participants
|
33 Participants
n=5 Participants
|
37 Participants
n=4 Participants
|
34 Participants
n=21 Participants
|
35 Participants
n=8 Participants
|
212 Participants
n=8 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
2 Participants
n=8 Participants
|
|
Sex: Female, Male
Female
|
23 Participants
n=5 Participants
|
25 Participants
n=7 Participants
|
19 Participants
n=5 Participants
|
21 Participants
n=4 Participants
|
23 Participants
n=21 Participants
|
23 Participants
n=8 Participants
|
134 Participants
n=8 Participants
|
|
Sex: Female, Male
Male
|
18 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
21 Participants
n=5 Participants
|
21 Participants
n=4 Participants
|
18 Participants
n=21 Participants
|
18 Participants
n=8 Participants
|
114 Participants
n=8 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
2 Participants
n=8 Participants
|
9 Participants
n=8 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
40 Participants
n=5 Participants
|
43 Participants
n=7 Participants
|
39 Participants
n=5 Participants
|
39 Participants
n=4 Participants
|
37 Participants
n=21 Participants
|
39 Participants
n=8 Participants
|
237 Participants
n=8 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
2 Participants
n=8 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
1 Participants
n=8 Participants
|
1 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
1 Participants
n=8 Participants
|
3 Participants
n=8 Participants
|
|
Race (NIH/OMB)
White
|
39 Participants
n=5 Participants
|
42 Participants
n=7 Participants
|
40 Participants
n=5 Participants
|
42 Participants
n=4 Participants
|
39 Participants
n=21 Participants
|
39 Participants
n=8 Participants
|
241 Participants
n=8 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
3 Participants
n=8 Participants
|
PRIMARY outcome
Timeframe: Baseline, Week 4 and Week 8 of each treatment periodPopulation: Full Analysis Set (FAS) included all randomized participants who carry the protocol specified cystic fibrosis transmembrane conductance regulator gene (CFTR) mutations and had received at least 1 dose of study drug. Here 'Overall Number of participants analyzed' signifies those participants who had evaluable data for this outcome measure.
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Outcome measures
| Measure |
Placebo
n=160 Participants
Placebo matched to VX-661/Ivacaftor (IVA) fixed dose combination (FDC) tablet and placebo matched to IVA tablet in the morning, placebo matched to IVA tablet in the evening for 8 weeks in treatment period 1 and 2.
|
Ivacaftor
n=156 Participants
IVA 150 milligram (mg) tablet and placebo matched to VX-661/IVA FDC tablet in the morning, IVA 150 mg tablet in the evening for 8 weeks in treatment period 1 and 2.
|
VX-661/IVA
n=159 Participants
VX-661 100 mg/IVA 150 mg FDC tablet and placebo matched to IVA in the morning, IVA 150 mg tablet in the evening for 8 weeks in treatment period 1 and 2.
|
|---|---|---|---|
|
Absolute Change From Study Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Average of Week 4 and Week 8
|
-0.3 percentage of predicted FEV1
Interval -1.2 to 0.6
|
4.4 percentage of predicted FEV1
Interval 3.5 to 5.3
|
6.5 percentage of predicted FEV1
Interval 5.6 to 7.3
|
SECONDARY outcome
Timeframe: Baseline, Week 4 and Week 8 of each treatment periodPopulation: FAS was used. Here 'Overall Number of participants analyzed' signifies those participants who had evaluable data for this outcome measure.
The CFQ-R assessed respiratory symptoms on a scale with scores ranging from 0 to 100; where higher scores indicated fewer symptoms and better health-related quality of life.
Outcome measures
| Measure |
Placebo
n=160 Participants
Placebo matched to VX-661/Ivacaftor (IVA) fixed dose combination (FDC) tablet and placebo matched to IVA tablet in the morning, placebo matched to IVA tablet in the evening for 8 weeks in treatment period 1 and 2.
|
Ivacaftor
n=156 Participants
IVA 150 milligram (mg) tablet and placebo matched to VX-661/IVA FDC tablet in the morning, IVA 150 mg tablet in the evening for 8 weeks in treatment period 1 and 2.
|
VX-661/IVA
n=161 Participants
VX-661 100 mg/IVA 150 mg FDC tablet and placebo matched to IVA in the morning, IVA 150 mg tablet in the evening for 8 weeks in treatment period 1 and 2.
|
|---|---|---|---|
|
Absolute Change From Study Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Average of Week 4 and Week 8
|
-1.0 units on a scale
Interval -2.9 to 1.0
|
8.7 units on a scale
Interval 6.8 to 10.7
|
10.1 units on a scale
Interval 8.2 to 12.1
|
SECONDARY outcome
Timeframe: Day 1 up to Week 28Population: Safety Set included all participants who received at least 1 dose of study drug.
Outcome measures
| Measure |
Placebo
n=162 Participants
Placebo matched to VX-661/Ivacaftor (IVA) fixed dose combination (FDC) tablet and placebo matched to IVA tablet in the morning, placebo matched to IVA tablet in the evening for 8 weeks in treatment period 1 and 2.
|
Ivacaftor
n=157 Participants
IVA 150 milligram (mg) tablet and placebo matched to VX-661/IVA FDC tablet in the morning, IVA 150 mg tablet in the evening for 8 weeks in treatment period 1 and 2.
|
VX-661/IVA
n=162 Participants
VX-661 100 mg/IVA 150 mg FDC tablet and placebo matched to IVA in the morning, IVA 150 mg tablet in the evening for 8 weeks in treatment period 1 and 2.
|
|---|---|---|---|
|
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Participants with any AEs
|
126 participants
|
114 participants
|
117 participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Participants with SAEs
|
14 participants
|
10 participants
|
8 participants
|
SECONDARY outcome
Timeframe: Baseline, Week 4 and Week 8 of each treatment periodPopulation: FAS was used. Here 'Overall Number of participants analyzed' signifies those participants who had evaluable data for this outcome measure.
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Outcome measures
| Measure |
Placebo
n=160 Participants
Placebo matched to VX-661/Ivacaftor (IVA) fixed dose combination (FDC) tablet and placebo matched to IVA tablet in the morning, placebo matched to IVA tablet in the evening for 8 weeks in treatment period 1 and 2.
|
Ivacaftor
n=156 Participants
IVA 150 milligram (mg) tablet and placebo matched to VX-661/IVA FDC tablet in the morning, IVA 150 mg tablet in the evening for 8 weeks in treatment period 1 and 2.
|
VX-661/IVA
n=159 Participants
VX-661 100 mg/IVA 150 mg FDC tablet and placebo matched to IVA in the morning, IVA 150 mg tablet in the evening for 8 weeks in treatment period 1 and 2.
|
|---|---|---|---|
|
Relative Change From Study Baseline in ppFEV1 at Average of Week 4 and Week 8
|
-0.2 percent change
Interval -1.7 to 1.4
|
7.9 percent change
Interval 6.4 to 9.4
|
11.2 percent change
Interval 9.7 to 12.7
|
SECONDARY outcome
Timeframe: Baseline, Week 4 and Week 8 of each treatment periodPopulation: FAS was used. Here 'Overall Number of participants analyzed' signifies those participants who had evaluable data for this outcome measure.
Outcome measures
| Measure |
Placebo
n=151 Participants
Placebo matched to VX-661/Ivacaftor (IVA) fixed dose combination (FDC) tablet and placebo matched to IVA tablet in the morning, placebo matched to IVA tablet in the evening for 8 weeks in treatment period 1 and 2.
|
Ivacaftor
n=153 Participants
IVA 150 milligram (mg) tablet and placebo matched to VX-661/IVA FDC tablet in the morning, IVA 150 mg tablet in the evening for 8 weeks in treatment period 1 and 2.
|
VX-661/IVA
n=151 Participants
VX-661 100 mg/IVA 150 mg FDC tablet and placebo matched to IVA in the morning, IVA 150 mg tablet in the evening for 8 weeks in treatment period 1 and 2.
|
|---|---|---|---|
|
Absolute Change From Study Baseline in Sweat Chloride at Average of Week 4 and Week 8
|
-0.4 millimoles per liter (mmol/L)
Interval -2.3 to 1.5
|
-4.9 millimoles per liter (mmol/L)
Interval -6.7 to -3.0
|
-9.9 millimoles per liter (mmol/L)
Interval -11.8 to -8.0
|
SECONDARY outcome
Timeframe: Pre-morning dose on Week 8 of each treatment periodPopulation: Pharmacokinetic (PK) set included all randomized participants who received any amount of study drug and had a PK assessment.
Outcome measures
| Measure |
Placebo
n=161 Participants
Placebo matched to VX-661/Ivacaftor (IVA) fixed dose combination (FDC) tablet and placebo matched to IVA tablet in the morning, placebo matched to IVA tablet in the evening for 8 weeks in treatment period 1 and 2.
|
Ivacaftor
IVA 150 milligram (mg) tablet and placebo matched to VX-661/IVA FDC tablet in the morning, IVA 150 mg tablet in the evening for 8 weeks in treatment period 1 and 2.
|
VX-661/IVA
VX-661 100 mg/IVA 150 mg FDC tablet and placebo matched to IVA in the morning, IVA 150 mg tablet in the evening for 8 weeks in treatment period 1 and 2.
|
|---|---|---|---|
|
Trough Plasma Concentrations (Ctrough) of VX-661, VX-661 Metabolites (M1 VX-661), IVA and IVA Metabolite (M1 IVA) After Administration of VX-661/IVA Combination Therapy
M1 IVA
|
2010 nanogram per milliliter (ng/mL)
Standard Deviation 1050
|
—
|
—
|
|
Trough Plasma Concentrations (Ctrough) of VX-661, VX-661 Metabolites (M1 VX-661), IVA and IVA Metabolite (M1 IVA) After Administration of VX-661/IVA Combination Therapy
VX-661
|
2370 nanogram per milliliter (ng/mL)
Standard Deviation 1330
|
—
|
—
|
|
Trough Plasma Concentrations (Ctrough) of VX-661, VX-661 Metabolites (M1 VX-661), IVA and IVA Metabolite (M1 IVA) After Administration of VX-661/IVA Combination Therapy
M1 VX-661
|
5230 nanogram per milliliter (ng/mL)
Standard Deviation 1940
|
—
|
—
|
|
Trough Plasma Concentrations (Ctrough) of VX-661, VX-661 Metabolites (M1 VX-661), IVA and IVA Metabolite (M1 IVA) After Administration of VX-661/IVA Combination Therapy
IVA
|
909 nanogram per milliliter (ng/mL)
Standard Deviation 530
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-morning dose on Week 8 of each treatment periodPopulation: PK set was used. Here 'Overall Number of participants analyzed' signifies those participants who had evaluable data for this outcome measure.
Outcome measures
| Measure |
Placebo
n=155 Participants
Placebo matched to VX-661/Ivacaftor (IVA) fixed dose combination (FDC) tablet and placebo matched to IVA tablet in the morning, placebo matched to IVA tablet in the evening for 8 weeks in treatment period 1 and 2.
|
Ivacaftor
IVA 150 milligram (mg) tablet and placebo matched to VX-661/IVA FDC tablet in the morning, IVA 150 mg tablet in the evening for 8 weeks in treatment period 1 and 2.
|
VX-661/IVA
VX-661 100 mg/IVA 150 mg FDC tablet and placebo matched to IVA in the morning, IVA 150 mg tablet in the evening for 8 weeks in treatment period 1 and 2.
|
|---|---|---|---|
|
Ctrough of IVA and IVA Metabolite (M1 IVA) After Administration of IVA Monotherapy
IVA
|
696 ng/mL
Standard Deviation 435
|
—
|
—
|
|
Ctrough of IVA and IVA Metabolite (M1 IVA) After Administration of IVA Monotherapy
M1 IVA
|
1550 ng/mL
Standard Deviation 808
|
—
|
—
|
Adverse Events
Placebo
Serious events: 14 serious events
Other events: 87 other events
Deaths: 0 deaths
Ivacaftor
Serious events: 10 serious events
Other events: 54 other events
Deaths: 0 deaths
VX-661/IVA
Serious events: 8 serious events
Other events: 80 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo
n=162 participants at risk
Placebo matched to VX-661/Ivacaftor (IVA) fixed dose combination (FDC) tablet and placebo matched to IVA tablet in the morning, placebo matched to IVA tablet in the evening for 8 weeks in treatment period 1 and 2.
|
Ivacaftor
n=157 participants at risk
IVA 150 milligram (mg) tablet and placebo matched to VX-661/IVA FDC tablet in the morning, IVA 150 mg tablet in the evening for 8 weeks in treatment period 1 and 2.
|
VX-661/IVA
n=162 participants at risk
VX-661 100 mg/IVA 150 mg FDC tablet and placebo matched to IVA in the morning, IVA 150 mg tablet in the evening for 8 weeks in treatment period 1 and 2.
|
|---|---|---|---|
|
Infections and infestations
Infective pulmonary exacerbation of cystic fibrosis
|
4.9%
8/162 • Day 1 up to Week 28
|
3.8%
6/157 • Day 1 up to Week 28
|
2.5%
4/162 • Day 1 up to Week 28
|
|
Infections and infestations
Influenza
|
0.00%
0/162 • Day 1 up to Week 28
|
0.00%
0/157 • Day 1 up to Week 28
|
0.62%
1/162 • Day 1 up to Week 28
|
|
Infections and infestations
Pneumonia
|
1.2%
2/162 • Day 1 up to Week 28
|
0.00%
0/157 • Day 1 up to Week 28
|
0.00%
0/162 • Day 1 up to Week 28
|
|
Injury, poisoning and procedural complications
Ankle fracture
|
0.00%
0/162 • Day 1 up to Week 28
|
0.00%
0/157 • Day 1 up to Week 28
|
0.62%
1/162 • Day 1 up to Week 28
|
|
Nervous system disorders
Headache
|
0.00%
0/162 • Day 1 up to Week 28
|
0.00%
0/157 • Day 1 up to Week 28
|
0.62%
1/162 • Day 1 up to Week 28
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.62%
1/162 • Day 1 up to Week 28
|
0.00%
0/157 • Day 1 up to Week 28
|
0.62%
1/162 • Day 1 up to Week 28
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
|
0.62%
1/162 • Day 1 up to Week 28
|
0.00%
0/157 • Day 1 up to Week 28
|
0.00%
0/162 • Day 1 up to Week 28
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
1.2%
2/162 • Day 1 up to Week 28
|
0.64%
1/157 • Day 1 up to Week 28
|
0.00%
0/162 • Day 1 up to Week 28
|
|
Gastrointestinal disorders
Abdominal pain
|
1.2%
2/162 • Day 1 up to Week 28
|
0.00%
0/157 • Day 1 up to Week 28
|
0.00%
0/162 • Day 1 up to Week 28
|
|
Gastrointestinal disorders
Distal intestinal obstruction syndrome
|
0.00%
0/162 • Day 1 up to Week 28
|
0.64%
1/157 • Day 1 up to Week 28
|
0.00%
0/162 • Day 1 up to Week 28
|
|
Gastrointestinal disorders
Pancreatitis
|
0.00%
0/162 • Day 1 up to Week 28
|
0.64%
1/157 • Day 1 up to Week 28
|
0.00%
0/162 • Day 1 up to Week 28
|
|
Investigations
Blood creatine phosphokinase increased
|
0.00%
0/162 • Day 1 up to Week 28
|
1.3%
2/157 • Day 1 up to Week 28
|
0.00%
0/162 • Day 1 up to Week 28
|
|
Investigations
Pulmonary function test decreased
|
0.62%
1/162 • Day 1 up to Week 28
|
0.00%
0/157 • Day 1 up to Week 28
|
0.00%
0/162 • Day 1 up to Week 28
|
|
Psychiatric disorders
Mental status changes
|
0.62%
1/162 • Day 1 up to Week 28
|
0.00%
0/157 • Day 1 up to Week 28
|
0.00%
0/162 • Day 1 up to Week 28
|
|
Renal and urinary disorders
Urethral stenosis
|
0.62%
1/162 • Day 1 up to Week 28
|
0.00%
0/157 • Day 1 up to Week 28
|
0.00%
0/162 • Day 1 up to Week 28
|
|
Skin and subcutaneous tissue disorders
Acute febrile neutrophilic dermatosis
|
0.62%
1/162 • Day 1 up to Week 28
|
0.00%
0/157 • Day 1 up to Week 28
|
0.00%
0/162 • Day 1 up to Week 28
|
Other adverse events
| Measure |
Placebo
n=162 participants at risk
Placebo matched to VX-661/Ivacaftor (IVA) fixed dose combination (FDC) tablet and placebo matched to IVA tablet in the morning, placebo matched to IVA tablet in the evening for 8 weeks in treatment period 1 and 2.
|
Ivacaftor
n=157 participants at risk
IVA 150 milligram (mg) tablet and placebo matched to VX-661/IVA FDC tablet in the morning, IVA 150 mg tablet in the evening for 8 weeks in treatment period 1 and 2.
|
VX-661/IVA
n=162 participants at risk
VX-661 100 mg/IVA 150 mg FDC tablet and placebo matched to IVA in the morning, IVA 150 mg tablet in the evening for 8 weeks in treatment period 1 and 2.
|
|---|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
18.5%
30/162 • Day 1 up to Week 28
|
10.8%
17/157 • Day 1 up to Week 28
|
14.2%
23/162 • Day 1 up to Week 28
|
|
Respiratory, thoracic and mediastinal disorders
Sputum increased
|
6.8%
11/162 • Day 1 up to Week 28
|
7.6%
12/157 • Day 1 up to Week 28
|
8.6%
14/162 • Day 1 up to Week 28
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
7.4%
12/162 • Day 1 up to Week 28
|
10.8%
17/157 • Day 1 up to Week 28
|
7.4%
12/162 • Day 1 up to Week 28
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
6.8%
11/162 • Day 1 up to Week 28
|
1.9%
3/157 • Day 1 up to Week 28
|
5.6%
9/162 • Day 1 up to Week 28
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
5.6%
9/162 • Day 1 up to Week 28
|
4.5%
7/157 • Day 1 up to Week 28
|
5.6%
9/162 • Day 1 up to Week 28
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
5.6%
9/162 • Day 1 up to Week 28
|
1.9%
3/157 • Day 1 up to Week 28
|
3.7%
6/162 • Day 1 up to Week 28
|
|
Infections and infestations
Infective pulmonary exacerbation of cystic fibrosis
|
15.4%
25/162 • Day 1 up to Week 28
|
8.9%
14/157 • Day 1 up to Week 28
|
11.7%
19/162 • Day 1 up to Week 28
|
|
Infections and infestations
Nasopharyngitis
|
3.1%
5/162 • Day 1 up to Week 28
|
3.8%
6/157 • Day 1 up to Week 28
|
8.0%
13/162 • Day 1 up to Week 28
|
|
Gastrointestinal disorders
Diarrhoea
|
6.2%
10/162 • Day 1 up to Week 28
|
3.2%
5/157 • Day 1 up to Week 28
|
8.0%
13/162 • Day 1 up to Week 28
|
|
Gastrointestinal disorders
Nausea
|
6.2%
10/162 • Day 1 up to Week 28
|
1.9%
3/157 • Day 1 up to Week 28
|
5.6%
9/162 • Day 1 up to Week 28
|
|
Nervous system disorders
Headache
|
8.0%
13/162 • Day 1 up to Week 28
|
7.0%
11/157 • Day 1 up to Week 28
|
11.1%
18/162 • Day 1 up to Week 28
|
|
General disorders
Fatigue
|
9.9%
16/162 • Day 1 up to Week 28
|
4.5%
7/157 • Day 1 up to Week 28
|
7.4%
12/162 • Day 1 up to Week 28
|
|
General disorders
Pyrexia
|
7.4%
12/162 • Day 1 up to Week 28
|
1.3%
2/157 • Day 1 up to Week 28
|
4.9%
8/162 • Day 1 up to Week 28
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee PI is free to publish results of the study after (1) the first multi-center publication, (2) if the sponsor elects not to publish the results, or (3) 18 months after close of the study, whichever occurs first. Proposed publications are to be submitted to the sponsor for review and comment for a period of at least 45 days (which may be extended under certain circumstances related to protection of intellectual property); the sponsor cannot require changes to the proposed publications.
- Publication restrictions are in place
Restriction type: OTHER