Trial Outcomes & Findings for A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of VX-661 in Combination With Ivacaftor (NCT NCT02347657)
NCT ID: NCT02347657
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
510 participants
Primary outcome timeframe
Day 1, Through Week 24
Results posted on
2018-06-12
Participant Flow
The study was conducted across 91 sites in 12 countries.
A total of 510 participants were randomized and 509 participants were treated in the study.
Participant milestones
| Measure |
Placebo
Placebo matched to VX-661 plus Ivacaftor (IVA, VX-770) fixed dose combination (FDC) tablet administered orally in the morning and placebo matched to IVA tablet administered orally in the evening up to Week 24.
|
VX-661/IVA
VX-661 100 milligram (mg) plus IVA 150 mg FDC tablet administered orally in the morning and IVA 150 mg tablet administered orally in the evening up to Week 24.
|
|---|---|---|
|
Overall Study
STARTED
|
259
|
251
|
|
Overall Study
Treated
|
258
|
251
|
|
Overall Study
COMPLETED
|
241
|
236
|
|
Overall Study
NOT COMPLETED
|
18
|
15
|
Reasons for withdrawal
| Measure |
Placebo
Placebo matched to VX-661 plus Ivacaftor (IVA, VX-770) fixed dose combination (FDC) tablet administered orally in the morning and placebo matched to IVA tablet administered orally in the evening up to Week 24.
|
VX-661/IVA
VX-661 100 milligram (mg) plus IVA 150 mg FDC tablet administered orally in the morning and IVA 150 mg tablet administered orally in the evening up to Week 24.
|
|---|---|---|
|
Overall Study
Physician Decision
|
0
|
1
|
|
Overall Study
Adverse Event
|
8
|
4
|
|
Overall Study
Withdrawal by Subject
|
6
|
7
|
|
Overall Study
Randomized but not treated
|
1
|
0
|
|
Overall Study
Other
|
3
|
3
|
Baseline Characteristics
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of VX-661 in Combination With Ivacaftor
Baseline characteristics by cohort
| Measure |
Placebo
n=256 Participants
Placebo matched to VX-661 plus IVA FDC tablet administered orally in the morning and placebo matched to IVA tablet administered orally in the evening up to Week 24.
|
VX-661/IVA
n=248 Participants
VX-661 100 mg plus IVA 150 mg FDC tablet administered orally in the morning and IVA 150 mg tablet administered orally in the evening up to Week 24.
|
Total
n=504 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
25.7 years
STANDARD_DEVIATION 9.5 • n=99 Participants
|
26.9 years
STANDARD_DEVIATION 11.2 • n=107 Participants
|
26.3 years
STANDARD_DEVIATION 10.4 • n=206 Participants
|
|
Sex: Female, Male
Female
|
125 Participants
n=99 Participants
|
121 Participants
n=107 Participants
|
246 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
131 Participants
n=99 Participants
|
127 Participants
n=107 Participants
|
258 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
3 Participants
n=99 Participants
|
9 Participants
n=107 Participants
|
12 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
250 Participants
n=99 Participants
|
234 Participants
n=107 Participants
|
484 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
3 Participants
n=99 Participants
|
5 Participants
n=107 Participants
|
8 Participants
n=206 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Race (NIH/OMB)
White
|
254 Participants
n=99 Participants
|
245 Participants
n=107 Participants
|
499 Participants
n=206 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Day 1, Through Week 24Population: FAS included all randomized participants who carry the intended CFTR allele mutation and have received at least 1 dose of study drug. Here 'Number of participants analyzed' signifies those participants who were evaluable 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=256 Participants
Placebo matched to VX-661 plus IVA FDC tablet administered orally in the morning and placebo matched to IVA tablet administered orally in the evening up to Week 24.
|
VX-661/IVA
n=245 Participants
VX-661 100 mg plus IVA 150 mg FDC tablet administered orally in the morning and IVA 150 mg tablet administered orally in the evening up to Week 24.
|
|---|---|---|
|
Absolute Change From Baseline (Day 1) in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) Through Week 24
|
-0.6 Percentage of predicted FEV1
Interval -1.3 to 0.0
|
3.4 Percentage of predicted FEV1
Interval 2.7 to 4.0
|
SECONDARY outcome
Timeframe: Day 1, Through Week 24Population: FAS included all randomized participants who carry the intended CFTR allele mutation and have received at least 1 dose of study drug. Here 'Number of participants analyzed' signifies those participants who were evaluable 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=256 Participants
Placebo matched to VX-661 plus IVA FDC tablet administered orally in the morning and placebo matched to IVA tablet administered orally in the evening up to Week 24.
|
VX-661/IVA
n=245 Participants
VX-661 100 mg plus IVA 150 mg FDC tablet administered orally in the morning and IVA 150 mg tablet administered orally in the evening up to Week 24.
|
|---|---|---|
|
Relative Change From Baseline (Day 1) in ppFEV1 Through Week 24
|
-0.5 percent change
Interval -1.7 to 0.6
|
6.3 percent change
Interval 5.1 to 7.4
|
SECONDARY outcome
Timeframe: Day 1 through Week 24Population: FAS included all randomized participants who carry the intended CFTR allele mutation and have received at least 1 dose of study drug.
Pulmonary exacerbation was defined as a new event or change in antibiotic therapy for greater than or equal to 4 sinopulmonary signs/symptoms. Pulmonary exacerbation events per year (48 weeks) were reported.
Outcome measures
| Measure |
Placebo
n=256 Participants
Placebo matched to VX-661 plus IVA FDC tablet administered orally in the morning and placebo matched to IVA tablet administered orally in the evening up to Week 24.
|
VX-661/IVA
n=248 Participants
VX-661 100 mg plus IVA 150 mg FDC tablet administered orally in the morning and IVA 150 mg tablet administered orally in the evening up to Week 24.
|
|---|---|---|
|
Number of Pulmonary Exacerbations Per Year
|
0.99 pulmonary exacerbation events per year
|
0.64 pulmonary exacerbation events per year
|
SECONDARY outcome
Timeframe: Day 1, Week 24Population: FAS included all randomized participants who carry the intended CFTR allele mutation and have received at least 1 dose of study drug. Here 'Number of participants analyzed' signifies those participants who were evaluable for this outcome measure.
BMI was defined as weight in kilograms (kg) divided by height in square meter (m\^2).
Outcome measures
| Measure |
Placebo
n=245 Participants
Placebo matched to VX-661 plus IVA FDC tablet administered orally in the morning and placebo matched to IVA tablet administered orally in the evening up to Week 24.
|
VX-661/IVA
n=237 Participants
VX-661 100 mg plus IVA 150 mg FDC tablet administered orally in the morning and IVA 150 mg tablet administered orally in the evening up to Week 24.
|
|---|---|---|
|
Absolute Change From Baseline (Day 1) Body Mass Index (BMI) at Week 24
|
0.12 kilogram per square meter (kg/m^2)
Interval 0.03 to 0.22
|
0.18 kilogram per square meter (kg/m^2)
Interval 0.08 to 0.28
|
SECONDARY outcome
Timeframe: Day 1, Through Week 24Population: FAS included all randomized participants who carry the intended CFTR allele mutation and have received at least 1 dose of study drug. Here 'Number of participants analyzed' signifies those participants who were evaluable for this outcome measure.
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.
Outcome measures
| Measure |
Placebo
n=256 Participants
Placebo matched to VX-661 plus IVA FDC tablet administered orally in the morning and placebo matched to IVA tablet administered orally in the evening up to Week 24.
|
VX-661/IVA
n=246 Participants
VX-661 100 mg plus IVA 150 mg FDC tablet administered orally in the morning and IVA 150 mg tablet administered orally in the evening up to Week 24.
|
|---|---|---|
|
Absolute Change From Baseline (Day 1) in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 24
|
-0.1 units on a scale
Interval -1.6 to 1.4
|
5.0 units on a scale
Interval 3.5 to 6.5
|
SECONDARY outcome
Timeframe: Day 1 up to Week 28Population: Safety Set included all participants who received at least 1 dose of the study drug.
AE: any untoward medical occurrence in a participant during the study; the event does not necessarily have a causal relationship with the treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after the informed consent form is signed. AE includes serious as well as non-serious AEs. SAE (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, inpatient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. Any AE that increased in severity or newly developed at or after initial dosing of study drug to Week 28 was considered treatment-emergent.
Outcome measures
| Measure |
Placebo
n=258 Participants
Placebo matched to VX-661 plus IVA FDC tablet administered orally in the morning and placebo matched to IVA tablet administered orally in the evening up to Week 24.
|
VX-661/IVA
n=251 Participants
VX-661 100 mg plus IVA 150 mg FDC tablet administered orally in the morning and IVA 150 mg tablet administered orally in the evening up to Week 24.
|
|---|---|---|
|
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Participants with AEs
|
245 Participants
|
227 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Participants with SAEs
|
47 Participants
|
31 Participants
|
SECONDARY outcome
Timeframe: Day 1 through Week 24Population: FAS included all randomized participants who carry the intended CFTR allele mutation and have received at least 1 dose of study drug.
Pulmonary exacerbation was defined as a new event or change in antibiotic therapy for greater than or equal to 4 sinopulmonary signs/symptoms. Time to event data was not collected and instead, Number of Subjects with first event were collected and are reported. Time-to-first pulmonary exacerbation was planned to be estimated using Kaplan-Meier (KM) estimates. However, due to less than 50% of events, time-to-first event data was not estimated. Instead, number of participants with at least one pulmonary exacerbation event were collected and are reported.
Outcome measures
| Measure |
Placebo
n=256 Participants
Placebo matched to VX-661 plus IVA FDC tablet administered orally in the morning and placebo matched to IVA tablet administered orally in the evening up to Week 24.
|
VX-661/IVA
n=248 Participants
VX-661 100 mg plus IVA 150 mg FDC tablet administered orally in the morning and IVA 150 mg tablet administered orally in the evening up to Week 24.
|
|---|---|---|
|
Number of Participants With at Least One Pulmonary Exacerbation Pulmonary Exacerbation Through Week 24
|
88 Participants
|
62 Participants
|
SECONDARY outcome
Timeframe: Day 1, Through Week 24Population: FAS included all randomized participants who carry the intended CFTR allele mutation and have received at least 1 dose of study drug. Here 'Number of participants analyzed' signifies those participants who were evaluable for this outcome measure.
Sweat samples were collected using an approved collection device.
Outcome measures
| Measure |
Placebo
n=242 Participants
Placebo matched to VX-661 plus IVA FDC tablet administered orally in the morning and placebo matched to IVA tablet administered orally in the evening up to Week 24.
|
VX-661/IVA
n=240 Participants
VX-661 100 mg plus IVA 150 mg FDC tablet administered orally in the morning and IVA 150 mg tablet administered orally in the evening up to Week 24.
|
|---|---|---|
|
Absolute Change From Baseline (Day 1) in Sweat Chloride Through Week 24
|
0.2 millimole per liter (mmol/L)
Interval -0.8 to 1.2
|
-9.9 millimole per liter (mmol/L)
Interval -10.9 to -8.9
|
SECONDARY outcome
Timeframe: Day 1, Week 24Population: Analysis population included all randomized participants who received at least 1 dose of study drug and were \<20 years of age at the time of screening. Here 'Number of participants analyzed' signifies those participants who were evaluable for this outcome measure.
BMI was defined as weight in kg divided by height in m\^2. z-score is a statistical measure to describe whether a mean was above or below the standard. BMI, adjusted for age and sex, was analyzed as BMI-for-age z-score (BMI z-score).
Outcome measures
| Measure |
Placebo
n=74 Participants
Placebo matched to VX-661 plus IVA FDC tablet administered orally in the morning and placebo matched to IVA tablet administered orally in the evening up to Week 24.
|
VX-661/IVA
n=76 Participants
VX-661 100 mg plus IVA 150 mg FDC tablet administered orally in the morning and IVA 150 mg tablet administered orally in the evening up to Week 24.
|
|---|---|---|
|
Absolute Change From Baseline (Day 1) in BMI Z-score at Week 24 in Participants Less Than (<) 20 Years Old at the Time of Screening)
|
-0.02 z-score
Interval -0.1 to 0.06
|
-0.06 z-score
Interval -0.14 to 0.02
|
SECONDARY outcome
Timeframe: Day 1, Week 24Population: FAS included all randomized participants who carry the intended CFTR allele mutation and have received at least 1 dose of study drug. Here 'Number of participants analyzed' signifies those participants who were evaluable for this outcome measure.
Outcome measures
| Measure |
Placebo
n=245 Participants
Placebo matched to VX-661 plus IVA FDC tablet administered orally in the morning and placebo matched to IVA tablet administered orally in the evening up to Week 24.
|
VX-661/IVA
n=237 Participants
VX-661 100 mg plus IVA 150 mg FDC tablet administered orally in the morning and IVA 150 mg tablet administered orally in the evening up to Week 24.
|
|---|---|---|
|
Absolute Change From Baseline (Day 1) in Body Weight at Week 24
|
0.6 kg
Interval 0.3 to 0.9
|
0.7 kg
Interval 0.4 to 1.0
|
SECONDARY outcome
Timeframe: Pre-morning dose on Week 16Population: Pharmacokinetic (PK) set included all randomized participants who received any amount of study drug and had a PK assessment. Here 'Number of participants analyzed' signifies those participants who were evaluable for this outcome measure.
This outcome was not planned to be assessed in Placebo arm.
Outcome measures
| Measure |
Placebo
n=233 Participants
Placebo matched to VX-661 plus IVA FDC tablet administered orally in the morning and placebo matched to IVA tablet administered orally in the evening up to Week 24.
|
VX-661/IVA
VX-661 100 mg plus IVA 150 mg FDC tablet administered orally in the morning and IVA 150 mg tablet administered orally in the evening up to Week 24.
|
|---|---|---|
|
Trough Plasma Concentrations (Ctrough) of VX-661, VX-661 Metabolites (M1 VX-661 and M2-VX-661), Ivacaftor (IVA) and IVA Metabolite (M1-IVA)
M1 VX-661
|
4730 nanogram per milliliter (ng/mL)
Standard Deviation 1730
|
—
|
|
Trough Plasma Concentrations (Ctrough) of VX-661, VX-661 Metabolites (M1 VX-661 and M2-VX-661), Ivacaftor (IVA) and IVA Metabolite (M1-IVA)
VX-661
|
1890 nanogram per milliliter (ng/mL)
Standard Deviation 1150
|
—
|
|
Trough Plasma Concentrations (Ctrough) of VX-661, VX-661 Metabolites (M1 VX-661 and M2-VX-661), Ivacaftor (IVA) and IVA Metabolite (M1-IVA)
M2 VX-661
|
4830 nanogram per milliliter (ng/mL)
Standard Deviation 2750
|
—
|
|
Trough Plasma Concentrations (Ctrough) of VX-661, VX-661 Metabolites (M1 VX-661 and M2-VX-661), Ivacaftor (IVA) and IVA Metabolite (M1-IVA)
IVA
|
815 nanogram per milliliter (ng/mL)
Standard Deviation 572
|
—
|
|
Trough Plasma Concentrations (Ctrough) of VX-661, VX-661 Metabolites (M1 VX-661 and M2-VX-661), Ivacaftor (IVA) and IVA Metabolite (M1-IVA)
M1 IVA
|
1590 nanogram per milliliter (ng/mL)
Standard Deviation 961
|
—
|
Adverse Events
Placebo
Serious events: 47 serious events
Other events: 243 other events
Deaths: 0 deaths
VX-661/IVA
Serious events: 31 serious events
Other events: 227 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo
n=258 participants at risk
Placebo matched to VX-661 plus IVA FDC tablet administered orally in the morning and placebo matched to IVA tablet administered orally in the evening up to Week 24.
|
VX-661/IVA
n=251 participants at risk
VX-661 100 mg plus IVA 150 mg FDC tablet administered orally in the morning and IVA 150 mg tablet administered orally in the evening up to Week 24.
|
|---|---|---|
|
Nervous system disorders
Benign intracranial hypertension
|
0.00%
0/258 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
0.40%
1/251 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
|
Nervous system disorders
Generalised tonic-clonic seizure
|
0.00%
0/258 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
0.40%
1/251 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
|
Nervous system disorders
Migraine
|
0.00%
0/258 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
0.40%
1/251 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
|
Infections and infestations
Infective pulmonary exacerbation of cystic fibrosis
|
12.4%
32/258 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
9.2%
23/251 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
|
Infections and infestations
Pneumonia
|
0.39%
1/258 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
0.80%
2/251 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
|
Infections and infestations
Clostridium difficile colitis
|
0.00%
0/258 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
0.40%
1/251 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
|
Infections and infestations
Lung abscess
|
0.00%
0/258 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
0.40%
1/251 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
|
Infections and infestations
Respiratory tract infection viral
|
0.00%
0/258 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
0.40%
1/251 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
|
Infections and infestations
Acarodermatitis
|
0.39%
1/258 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
0.00%
0/251 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
|
Infections and infestations
Bronchitis
|
0.39%
1/258 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
0.00%
0/251 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
|
Infections and infestations
Bronchopulmonary aspergillosis allergic
|
0.39%
1/258 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
0.00%
0/251 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
|
Infections and infestations
Gastroenteritis viral
|
0.39%
1/258 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
0.00%
0/251 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
|
Infections and infestations
Influenza
|
0.39%
1/258 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
0.00%
0/251 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
|
Nervous system disorders
Headache
|
0.39%
1/258 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
0.00%
0/251 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
1.2%
3/258 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
1.2%
3/251 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.39%
1/258 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
0.00%
0/251 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Paranasal cyst
|
0.39%
1/258 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
0.00%
0/251 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
|
Gastrointestinal disorders
Inguinal hernia
|
0.00%
0/258 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
0.40%
1/251 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
|
Gastrointestinal disorders
Coeliac disease
|
0.39%
1/258 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
0.00%
0/251 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
|
Gastrointestinal disorders
Constipation
|
0.78%
2/258 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
0.00%
0/251 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
|
Gastrointestinal disorders
Faecaloma
|
0.39%
1/258 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
0.00%
0/251 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
|
Gastrointestinal disorders
Gastric ulcer
|
0.39%
1/258 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
0.00%
0/251 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
|
Gastrointestinal disorders
Gastritis
|
0.39%
1/258 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
0.00%
0/251 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
|
Gastrointestinal disorders
Pancreatitis acute
|
0.39%
1/258 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
0.00%
0/251 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
|
Investigations
Blood creatine phosphokinase increased
|
0.39%
1/258 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
0.40%
1/251 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
|
Investigations
Blood glucose abnormal
|
0.39%
1/258 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
0.00%
0/251 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
|
Investigations
Electrocardiogram ST segment elevation
|
0.39%
1/258 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
0.00%
0/251 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
|
Investigations
Pulmonary function test decreased
|
0.39%
1/258 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
0.00%
0/251 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
0.00%
0/258 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
0.40%
1/251 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
|
Blood and lymphatic system disorders
Haemolytic anaemia
|
0.39%
1/258 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
0.00%
0/251 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
|
General disorders
Chest discomfort
|
0.39%
1/258 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
0.00%
0/251 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
|
General disorders
Fatigue
|
0.39%
1/258 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
0.00%
0/251 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
|
Injury, poisoning and procedural complications
Alcohol poisoning
|
0.39%
1/258 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
0.00%
0/251 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
|
Injury, poisoning and procedural complications
Toxicity to various agents
|
0.39%
1/258 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
0.00%
0/251 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
|
Injury, poisoning and procedural complications
Wrist fracture
|
0.39%
1/258 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
0.00%
0/251 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
|
Renal and urinary disorders
Acute kidney injury
|
0.78%
2/258 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
0.00%
0/251 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
Other adverse events
| Measure |
Placebo
n=258 participants at risk
Placebo matched to VX-661 plus IVA FDC tablet administered orally in the morning and placebo matched to IVA tablet administered orally in the evening up to Week 24.
|
VX-661/IVA
n=251 participants at risk
VX-661 100 mg plus IVA 150 mg FDC tablet administered orally in the morning and IVA 150 mg tablet administered orally in the evening up to Week 24.
|
|---|---|---|
|
Infections and infestations
Infective pulmonary exacerbation of cystic fibrosis
|
29.1%
75/258 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
22.7%
57/251 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
|
Infections and infestations
Nasopharyngitis
|
15.1%
39/258 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
16.7%
42/251 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
|
Infections and infestations
Rhinitis
|
5.4%
14/258 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
4.0%
10/251 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
32.2%
83/258 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
26.3%
66/251 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Sputum increased
|
16.3%
42/258 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
14.3%
36/251 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
12.8%
33/258 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
9.6%
24/251 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
11.2%
29/258 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
8.8%
22/251 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
7.0%
18/258 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
6.4%
16/251 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
6.2%
16/258 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
3.2%
8/251 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
|
Gastrointestinal disorders
Abdominal pain
|
8.5%
22/258 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
9.2%
23/251 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
|
Gastrointestinal disorders
Nausea
|
7.0%
18/258 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
9.2%
23/251 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
|
Gastrointestinal disorders
Diarrhoea
|
8.9%
23/258 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
6.8%
17/251 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
|
Gastrointestinal disorders
Vomiting
|
5.8%
15/258 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
5.2%
13/251 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
6.6%
17/258 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
4.0%
10/251 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
|
Gastrointestinal disorders
Constipation
|
5.4%
14/258 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
2.8%
7/251 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
|
General disorders
Pyrexia
|
12.4%
32/258 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
11.2%
28/251 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
|
General disorders
Fatigue
|
11.6%
30/258 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
6.4%
16/251 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
|
Nervous system disorders
Headache
|
14.0%
36/258 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
17.5%
44/251 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
|
Investigations
Alanine aminotransferase increased
|
5.0%
13/258 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
3.2%
8/251 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
|
Investigations
Bacterial test positive
|
6.2%
16/258 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
3.2%
8/251 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
|
Skin and subcutaneous tissue disorders
Rash
|
5.0%
13/258 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
1.6%
4/251 • Day 1 up to Week 28
Safety Set included all participants who received at least 1 dose of the study drug.
|
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