Trial Outcomes & Findings for Study of Ivacaftor in Cystic Fibrosis Subjects Aged 12 Years and Older With the G551D Mutation (NCT NCT00909532)

NCT ID: NCT00909532

Last Updated: 2013-01-18

Results Overview

Spirometry (as measured by FEV1) is a standardized assessment to evaluate lung function that is the most widely used endpoint in cystic fibrosis studies.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 167 participants
• Primary outcome timeframe: baseline through 24 weeks
• Results posted on: 2013-01-18

Participant Flow

The study started on 10 June 2009 (signing of first informed consent). After obtaining consent and assent (where applicable), screening evaluations were completed during a period of 2 to 5 weeks (Day -35 to Day -15) before the first dose of study drug.

A total of 167 subjects were randomized; 161 subjects received at least 1 dose of the study drug. A 2-week run-in period was included to establish the baseline assessments on Day 1 after ensuring that subjects were properly taking their cystic fibrosis (CF) medication regimens.

Participant milestones

Measure	Placebo Oral tablet every 12 hours (q12h) for up to 48 weeks.	150 mg Ivacaftor q12h Oral tablet of 150 mg of ivacaftor q12h for up to 48 weeks.
Overall Study STARTED	78	83
Overall Study Completed Treatment Period, Week 24	71	80
Overall Study COMPLETED	68	77
Overall Study NOT COMPLETED	10	6

Reasons for withdrawal

Measure	Placebo Oral tablet every 12 hours (q12h) for up to 48 weeks.	150 mg Ivacaftor q12h Oral tablet of 150 mg of ivacaftor q12h for up to 48 weeks.
Overall Study Adverse Event	4	1
Overall Study Pregnancy	0	1
Overall Study Prohibited Medication	2	1
Overall Study Withdrawal of Consent	1	1
Overall Study Noncompliance with Study Requirements	0	2
Overall Study Physician Decision	1	0
Overall Study Wrong Genotype	1	0
Overall Study Increased Lab Draws, Difficult Lab Stick	1	0

Baseline Characteristics

Study of Ivacaftor in Cystic Fibrosis Subjects Aged 12 Years and Older With the G551D Mutation

Baseline characteristics by cohort

Measure	Placebo n=78 Participants Oral tablet every 12 hours (q12h) for up to 48 weeks.	150 mg Ivacaftor q12h n=83 Participants Oral tablet of 150 mg of ivacaftor q12h for up to 48 weeks.	Total n=161 Participants Total of all reporting groups
Age, Categorical <=18 years	17 Participants n=5 Participants	19 Participants n=7 Participants	36 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	61 Participants n=5 Participants	64 Participants n=7 Participants	125 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age Continuous	24.7 years STANDARD_DEVIATION 9.21 • n=5 Participants	26.2 years STANDARD_DEVIATION 9.85 • n=7 Participants	25.5 years STANDARD_DEVIATION 9.54 • n=5 Participants
Sex: Female, Male Female	40 Participants n=5 Participants	44 Participants n=7 Participants	84 Participants n=5 Participants
Sex: Female, Male Male	38 Participants n=5 Participants	39 Participants n=7 Participants	77 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	77 Participants n=5 Participants	81 Participants n=7 Participants	158 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized White	77 participants n=5 Participants	81 participants n=7 Participants	158 participants n=5 Participants
Race/Ethnicity, Customized Not Allowed to Ask Per Local Regulations	1 participants n=5 Participants	2 participants n=7 Participants	3 participants n=5 Participants
Region of Enrollment North America	50 participants n=5 Participants	50 participants n=7 Participants	100 participants n=5 Participants
Region of Enrollment Europe	19 participants n=5 Participants	23 participants n=7 Participants	42 participants n=5 Participants
Region of Enrollment Australia	9 participants n=5 Participants	10 participants n=7 Participants	19 participants n=5 Participants
Percent Predicted Forced Expiratory Volume in 1 Second (FEV1), Continuous	63.7 percentage STANDARD_DEVIATION 16.83 • n=5 Participants	63.5 percentage STANDARD_DEVIATION 16.14 • n=7 Participants	63.6 percentage STANDARD_DEVIATION 16.43 • n=5 Participants
Percent Predicted FEV1, Categorical < 70% predicted FEV1	45 participants n=5 Participants	49 participants n=7 Participants	94 participants n=5 Participants
Percent Predicted FEV1, Categorical ≥ 70% predicted FEV1	33 participants n=5 Participants	34 participants n=7 Participants	67 participants n=5 Participants
Weight	61.2 kilograms STANDARD_DEVIATION 13.93 • n=5 Participants	61.7 kilograms STANDARD_DEVIATION 14.26 • n=7 Participants	61.5 kilograms STANDARD_DEVIATION 14.06 • n=5 Participants
Body Mass Index	21.9 kilograms per square meter STANDARD_DEVIATION 3.49 • n=5 Participants	21.7 kilograms per square meter STANDARD_DEVIATION 3.65 • n=7 Participants	21.8 kilograms per square meter STANDARD_DEVIATION 3.56 • n=5 Participants
Sweat Chloride	100.1 millimoles per liter STANDARD_DEVIATION 10.63 • n=5 Participants	100.4 millimoles per liter STANDARD_DEVIATION 10.00 • n=7 Participants	100.2 millimoles per liter STANDARD_DEVIATION 10.28 • n=5 Participants

PRIMARY outcome

Timeframe: baseline through 24 weeks

Population: All randomized subjects who received at least 1 dose of study drug (ivacaftor or placebo) and had available assessments during the time frame.

Spirometry (as measured by FEV1) is a standardized assessment to evaluate lung function that is the most widely used endpoint in cystic fibrosis studies.

Outcome measures

Measure	Placebo n=78 Participants Oral tablet every 12 hours (q12h) for up to 48 weeks.	150 mg Ivacaftor q12h n=83 Participants Oral tablet of 150 mg of ivacaftor q12h for up to 48 weeks.
Absolute Mean Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 24	-0.2 percent of predicted volume (L) Standard Error 0.7	10.4 percent of predicted volume (L) Standard Error 0.7

SECONDARY outcome

Timeframe: baseline through 48 weeks

Population: All randomized subjects who received at least 1 dose of study drug (ivacaftor or placebo) and had available assessments during the time frame..

Spirometry (as measured by FEV1) is a standardized assessment to evaluate lung function that is the most widely used endpoint in cystic fibrosis studies.

Outcome measures

Measure	Placebo n=78 Participants Oral tablet every 12 hours (q12h) for up to 48 weeks.	150 mg Ivacaftor q12h n=83 Participants Oral tablet of 150 mg of ivacaftor q12h for up to 48 weeks.
Absolute Mean Change From Baseline in Percent Predicted FEV1 Through Week 48	-0.4 percent of predicted volume (L) Standard Error 0.7	10.1 percent of predicted volume (L) Standard Error 0.7

SECONDARY outcome

Timeframe: baseline through 24 weeks and 48 weeks

Population: All randomized subjects who received at least 1 dose of study drug (ivacaftor or placebo) and had available assessments during the time frame.

The CFQ-R is a health-related quality of life measure for subjects with cystic fibrosis. Each domain is scored from 0 (worst) to 100 (best). A difference of at least 4 points in the respiratory domain score of the CFQ-R is considered a minimal clinically important difference (MCID).

Outcome measures

Measure	Placebo n=71 Participants Oral tablet every 12 hours (q12h) for up to 48 weeks.	150 mg Ivacaftor q12h n=80 Participants Oral tablet of 150 mg of ivacaftor q12h for up to 48 weeks.
Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Score Through Week 24 and Week 48 (Respiratory Domain Score, Pooled) Change from Baseline Through Week 24	-2.1 score on a scale Standard Error 1.3	6.0 score on a scale Standard Error 1.2
Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Score Through Week 24 and Week 48 (Respiratory Domain Score, Pooled) Change from Baseline Through Week 48	-2.7 score on a scale Standard Error 1.2	6.0 score on a scale Standard Error 1.1

SECONDARY outcome

Timeframe: baseline through 24 weeks and 48 weeks

Population: All randomized subjects who received at least 1 dose of study drug (ivacaftor or placebo) and had available assessments during the time frame..

The sweat chloride (quantitative pilocarpine iontophoresis) test is a standard diagnostic tool for cystic fibrosis (CF), serving as an indicator of cystic fibrosis transmembrane conductance regulator (CFTR) activity.

Outcome measures

Measure	Placebo n=74 Participants Oral tablet every 12 hours (q12h) for up to 48 weeks.	150 mg Ivacaftor q12h n=78 Participants Oral tablet of 150 mg of ivacaftor q12h for up to 48 weeks.
Absolute Change From Baseline in Sweat Chloride Concentration Through Week 24 and Week 48 Change from Baseline Through Week 24	-0.8 millimoles per liter Standard Error 1.3	-48.7 millimoles per liter Standard Error 1.2
Absolute Change From Baseline in Sweat Chloride Concentration Through Week 24 and Week 48 Change from Baseline Through Week 48	-0.6 millimoles per liter Standard Error 1.3	-48.7 millimoles per liter Standard Error 1.2

SECONDARY outcome

Timeframe: baseline through 24 weeks and 48 weeks

Population: All randomized subjects who received at least 1 dose of study drug (ivacaftor or placebo) and had available assessments during the time frame.

Pulmonary exacerbation was defined as a change in antibiotic therapy (intravenous, inhaled, or oral) for any 4 or more of signs/symptoms such as change in sputum; new or increased hemoptysis; increased cough or dyspnea; malaise, fatigue, or lethargy; temperature above 38 degrees C; anorexia or weight loss; sinus pain/tenderness and discharge; change in physical examination of the chest; decreased pulmonary function by 10%; and radiographic changes indicative of pulmonary infection.

Outcome measures

Measure	Placebo n=78 Participants Oral tablet every 12 hours (q12h) for up to 48 weeks.	150 mg Ivacaftor q12h n=83 Participants Oral tablet of 150 mg of ivacaftor q12h for up to 48 weeks.
Time-to-first Pulmonary Exacerbation Through Week 24 and Week 48 0 to 15 Days	0.97 proportion of event-free participants Interval 0.9 to 0.99	0.98 proportion of event-free participants Interval 0.91 to 0.99
Time-to-first Pulmonary Exacerbation Through Week 24 and Week 48 16 to 56 Days	0.87 proportion of event-free participants Interval 0.77 to 0.93	0.89 proportion of event-free participants Interval 0.8 to 0.94
Time-to-first Pulmonary Exacerbation Through Week 24 and Week 48 57 to 112 Days	0.72 proportion of event-free participants Interval 0.61 to 0.81	0.83 proportion of event-free participants Interval 0.73 to 0.9
Time-to-first Pulmonary Exacerbation Through Week 24 and Week 48 113 to 168 Days	0.53 proportion of event-free participants Interval 0.41 to 0.64	0.78 proportion of event-free participants Interval 0.68 to 0.86
Time-to-first Pulmonary Exacerbation Through Week 24 and Week 48 169 to 224 Days	0.51 proportion of event-free participants Interval 0.39 to 0.61	0.75 proportion of event-free participants Interval 0.64 to 0.83
Time-to-first Pulmonary Exacerbation Through Week 24 and Week 48 225 to 280 Days	0.44 proportion of event-free participants Interval 0.32 to 0.55	0.70 proportion of event-free participants Interval 0.58 to 0.78
Time-to-first Pulmonary Exacerbation Through Week 24 and Week 48 281 to 336 Days	0.41 proportion of event-free participants Interval 0.29 to 0.52	0.67 proportion of event-free participants Interval 0.55 to 0.76

SECONDARY outcome

Timeframe: baseline to 24 weeks and 48 weeks

Population: All randomized subjects who received at least 1 dose of study drug (ivacaftor or placebo) and had available assessments during the time frame.

As malnutrition is common in patients with cystic fibrosis (CF) because of increased energy expenditures due to lung disease and fat malabsorption, body weight is an important clinical measure of nutritional status.

Outcome measures

Measure	Placebo n=78 Participants Oral tablet every 12 hours (q12h) for up to 48 weeks.	150 mg Ivacaftor q12h n=83 Participants Oral tablet of 150 mg of ivacaftor q12h for up to 48 weeks.
Absolute Change From Baseline in Weight at Week 24 and Week 48 At Week 24	0.2 kilograms Standard Error 0.4	3.0 kilograms Standard Error 0.4
Absolute Change From Baseline in Weight at Week 24 and Week 48 At Week 48	0.4 kilograms Standard Error 0.5	3.1 kilograms Standard Error 0.5

Adverse Events

Placebo

Serious events: 33 serious events

Other events: 78 other events

Deaths: 0 deaths

150 mg Ivacaftor q12h

Serious events: 20 serious events

Other events: 82 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=78 participants at risk Oral tablet every 12 hours (q12h) for up to 48 weeks.	150 mg Ivacaftor q12h n=83 participants at risk Oral tablet of 150 mg of ivacaftor q12h for up to 48 weeks.
Cardiac disorders Atrioventricular block complete	1.3% 1/78 • Number of events 1 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	0.00% 0/83 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
Congenital, familial and genetic disorders Cystic fibrosis lung	33.3% 26/78 • Number of events 37 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	13.3% 11/83 • Number of events 22 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
Gastrointestinal disorders Gastrooesophageal reflux disease	1.3% 1/78 • Number of events 1 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	0.00% 0/83 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
Gastrointestinal disorders Pancreatic pseudocyst	0.00% 0/78 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	1.2% 1/83 • Number of events 1 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
Gastrointestinal disorders Pancreatitis	0.00% 0/78 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	1.2% 1/83 • Number of events 1 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
Gastrointestinal disorders Vomiting	1.3% 1/78 • Number of events 1 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	0.00% 0/83 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
General disorders Catheter related complication	1.3% 1/78 • Number of events 1 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	0.00% 0/83 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
Immune system disorders Anaphylactic shock	0.00% 0/78 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	1.2% 1/83 • Number of events 1 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
Infections and infestations Implant site infection	1.3% 1/78 • Number of events 1 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	0.00% 0/83 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
Infections and infestations Influenza	0.00% 0/78 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	1.2% 1/83 • Number of events 1 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
Infections and infestations Lung infection pseudomonal	1.3% 1/78 • Number of events 1 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	0.00% 0/83 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
Infections and infestations Myringitis bullous	0.00% 0/78 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	1.2% 1/83 • Number of events 1 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
Infections and infestations Pneumonia	0.00% 0/78 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	1.2% 1/83 • Number of events 1 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
Infections and infestations Sinusitis	0.00% 0/78 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	1.2% 1/83 • Number of events 1 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
Investigations Hepatic enzyme increased	0.00% 0/78 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	1.2% 1/83 • Number of events 1 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
Investigations Weight decreased	0.00% 0/78 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	1.2% 1/83 • Number of events 1 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/78 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	2.4% 2/83 • Number of events 2 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/78 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	1.2% 1/83 • Number of events 1 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
Musculoskeletal and connective tissue disorders Pain in extremity	1.3% 1/78 • Number of events 1 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	0.00% 0/83 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cervix carcinoma	0.00% 0/78 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	1.2% 1/83 • Number of events 1 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
Pregnancy, puerperium and perinatal conditions Abortion spontaneous	0.00% 0/78 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	1.2% 1/83 • Number of events 1 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
Renal and urinary disorders Haematuria	0.00% 0/78 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	1.2% 1/83 • Number of events 1 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
Renal and urinary disorders IgA nephropathy	0.00% 0/78 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	1.2% 1/83 • Number of events 1 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
Renal and urinary disorders Nephrolithiasis	1.3% 1/78 • Number of events 1 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	0.00% 0/83 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
Renal and urinary disorders Renal colic	1.3% 1/78 • Number of events 1 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	0.00% 0/83 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
Reproductive system and breast disorders Testicular torsion	1.3% 1/78 • Number of events 1 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	0.00% 0/83 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/78 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	1.2% 1/83 • Number of events 1 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
Respiratory, thoracic and mediastinal disorders Hemoptysis	5.1% 4/78 • Number of events 4 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	1.2% 1/83 • Number of events 1 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
Respiratory, thoracic and mediastinal disorders Pleuritic pain	0.00% 0/78 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	1.2% 1/83 • Number of events 1 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	1.3% 1/78 • Number of events 1 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	0.00% 0/83 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
Respiratory, thoracic and mediastinal disorders Respiratory distress	1.3% 1/78 • Number of events 1 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	0.00% 0/83 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
Respiratory, thoracic and mediastinal disorders Respiratory failure	1.3% 1/78 • Number of events 1 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	0.00% 0/83 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.

Other adverse events

Measure	Placebo n=78 participants at risk Oral tablet every 12 hours (q12h) for up to 48 weeks.	150 mg Ivacaftor q12h n=83 participants at risk Oral tablet of 150 mg of ivacaftor q12h for up to 48 weeks.
Respiratory, thoracic and mediastinal disorders Cough	42.3% 33/78 • Number of events 59 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	32.5% 27/83 • Number of events 38 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	19.2% 15/78 • Number of events 23 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	20.5% 17/83 • Number of events 25 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
Respiratory, thoracic and mediastinal disorders Nasal congestion	15.4% 12/78 • Number of events 17 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	20.5% 17/83 • Number of events 22 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
Respiratory, thoracic and mediastinal disorders Haemoptysis	19.2% 15/78 • Number of events 21 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	10.8% 9/83 • Number of events 17 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
Respiratory, thoracic and mediastinal disorders Productive cough	14.1% 11/78 • Number of events 19 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	14.5% 12/83 • Number of events 15 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
Respiratory, thoracic and mediastinal disorders Rales	10.3% 8/78 • Number of events 14 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	10.8% 9/83 • Number of events 17 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
Respiratory, thoracic and mediastinal disorders Respiratory tract congestion	7.7% 6/78 • Number of events 9 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	7.2% 6/83 • Number of events 7 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
Respiratory, thoracic and mediastinal disorders Sinus congestion	5.1% 4/78 • Number of events 4 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	9.6% 8/83 • Number of events 9 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	7.7% 6/78 • Number of events 6 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	4.8% 4/83 • Number of events 4 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
Respiratory, thoracic and mediastinal disorders Paranasal sinus hypersecretion	7.7% 6/78 • Number of events 7 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	3.6% 3/83 • Number of events 3 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
Respiratory, thoracic and mediastinal disorders Wheezing	3.8% 3/78 • Number of events 3 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	6.0% 5/83 • Number of events 8 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
Respiratory, thoracic and mediastinal disorders Dyspnoea	6.4% 5/78 • Number of events 5 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	2.4% 2/83 • Number of events 2 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
Respiratory, thoracic and mediastinal disorders Pleuritic pain	2.6% 2/78 • Number of events 2 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	6.0% 5/83 • Number of events 7 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
Respiratory, thoracic and mediastinal disorders Respiration abnormal	5.1% 4/78 • Number of events 5 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	2.4% 2/83 • Number of events 2 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
Infections and infestations Upper respiratory tract infection	15.4% 12/78 • Number of events 16 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	22.9% 19/83 • Number of events 26 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
Infections and infestations Nasopharyngitis	12.8% 10/78 • Number of events 14 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	12.0% 10/83 • Number of events 13 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
Infections and infestations Sinusitis	9.0% 7/78 • Number of events 12 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	7.2% 6/83 • Number of events 8 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
Infections and infestations Rhinitis	5.1% 4/78 • Number of events 4 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	7.2% 6/83 • Number of events 6 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
Infections and infestations Viral infection	6.4% 5/78 • Number of events 5 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	2.4% 2/83 • Number of events 2 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
Gastrointestinal disorders Abdominal pain	12.8% 10/78 • Number of events 13 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	15.7% 13/83 • Number of events 14 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
Gastrointestinal disorders Nausea	11.5% 9/78 • Number of events 12 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	15.7% 13/83 • Number of events 22 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
Gastrointestinal disorders Diarrhoea	12.8% 10/78 • Number of events 12 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	13.3% 11/83 • Number of events 12 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
Gastrointestinal disorders Vomiting	12.8% 10/78 • Number of events 10 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	10.8% 9/83 • Number of events 13 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
Gastrointestinal disorders Abdominal pain upper	7.7% 6/78 • Number of events 7 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	4.8% 4/83 • Number of events 5 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
Gastrointestinal disorders Constipation	6.4% 5/78 • Number of events 5 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	1.2% 1/83 • Number of events 1 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
Investigations Pulmonary function test decreased	14.1% 11/78 • Number of events 14 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	3.6% 3/83 • Number of events 3 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
Investigations Alanine aminotransferase increased	6.4% 5/78 • Number of events 6 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	6.0% 5/83 • Number of events 9 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
Investigations C-reactive protein increased	6.4% 5/78 • Number of events 6 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	4.8% 4/83 • Number of events 4 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
Investigations Blood glucose increased	3.8% 3/78 • Number of events 3 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	6.0% 5/83 • Number of events 6 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
Investigations Aspartate aminotransferase increased	2.6% 2/78 • Number of events 2 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	6.0% 5/83 • Number of events 7 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
Investigations Bacteria sputum identified	1.3% 1/78 • Number of events 1 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	7.2% 6/83 • Number of events 7 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
Investigations Breath sounds abnormal	5.1% 4/78 • Number of events 5 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	2.4% 2/83 • Number of events 2 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
Investigations Weight decreased	5.1% 4/78 • Number of events 4 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	2.4% 2/83 • Number of events 2 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
Congenital, familial and genetic disorders Cystic fibrosis lung	50.0% 39/78 • Number of events 77 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	34.9% 29/83 • Number of events 47 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
Nervous system disorders Headache	16.7% 13/78 • Number of events 31 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	22.9% 19/83 • Number of events 39 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
Nervous system disorders Dizziness	1.3% 1/78 • Number of events 1 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	12.0% 10/83 • Number of events 11 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
Nervous system disorders Sinus headache	5.1% 4/78 • Number of events 4 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	7.2% 6/83 • Number of events 6 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
Musculoskeletal and connective tissue disorders Arthralgia	6.4% 5/78 • Number of events 5 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	8.4% 7/83 • Number of events 11 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
Musculoskeletal and connective tissue disorders Back pain	6.4% 5/78 • Number of events 7 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	6.0% 5/83 • Number of events 5 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
Skin and subcutaneous tissue disorders Rash	5.1% 4/78 • Number of events 4 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	14.5% 12/83 • Number of events 22 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
Skin and subcutaneous tissue disorders Acne	3.8% 3/78 • Number of events 3 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	7.2% 6/83 • Number of events 6 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
General disorders Pyrexia	11.5% 9/78 • Number of events 11 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	12.0% 10/83 • Number of events 13 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
General disorders Fatigue	9.0% 7/78 • Number of events 9 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	8.4% 7/83 • Number of events 8 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
Injury, poisoning and procedural complications Joint sprain	5.1% 4/78 • Number of events 5 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	0.00% 0/83 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.
Metabolism and nutrition disorders Hypoglycaemia	5.1% 4/78 • Number of events 4 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.	3.6% 3/83 • Number of events 3 • For enrolled subjects, adverse events were collected through the Follow-up Visit (4 weeks [± 7 days] after the last dose of study drug). For subjects who were screened but were not subsequently enrolled in the study, non-serious AEs were not collected, but SAEs were reported. For subjects who completed 48 weeks of study drug treatment and enrolled in the open-label extension study, adverse events were only collected through the Week 48 Visit.

Additional Information

Medical Monitor

Vertex

Phone: 617-444-6777

Email: medicalinfo@vrtx.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: GT60