Trial Outcomes & Findings for A Study to Evaluate the Efficacy and Safety of Lumacaftor in Combination With Ivacaftor in Subjects With CF, Homozygous for the F508del-CFTR Mutation (NCT NCT02514473)

NCT ID: NCT02514473

Last Updated: 2017-10-23

Results Overview

Lung clearance index (LCI) is a measure of ventilation inhomogeneity that is derived from a multiple breath washout test using Nitrogen (N2). LCI2.5 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting value.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 206 participants
• Primary outcome timeframe: Baseline, Through Week 24
• Results posted on: 2017-10-23

Participant Flow

A total of 206 participants were randomized in the study, of which 204 participants were exposed to study treatment (101 participants received 'Placebo' and 103 participants received '(lumacaftor [LUM] / ivacaftor [IVA])'.

Participant milestones

Measure	Placebo Participants received placebo matched to LUM in combination with IVA fixed-dose combination (FDC) tablets orally every 12 hours (q12h) for 24 weeks.	LUM/IVA Participants received LUM 200 milligram (mg) in combination with IVA 250 mg FDC tablets orally q12h for 24 weeks.
Overall Study STARTED	101	103
Overall Study COMPLETED	98	98
Overall Study NOT COMPLETED	3	5

Reasons for withdrawal

Measure	Placebo Participants received placebo matched to LUM in combination with IVA fixed-dose combination (FDC) tablets orally every 12 hours (q12h) for 24 weeks.	LUM/IVA Participants received LUM 200 milligram (mg) in combination with IVA 250 mg FDC tablets orally q12h for 24 weeks.
Overall Study Adverse Event	0	2
Overall Study Withdrawal by Subject	2	1
Overall Study Lost to Follow-up	0	1
Overall Study Other	1	1

Baseline Characteristics

A Study to Evaluate the Efficacy and Safety of Lumacaftor in Combination With Ivacaftor in Subjects With CF, Homozygous for the F508del-CFTR Mutation

Baseline characteristics by cohort

Measure	Placebo n=101 Participants Participants received placebo matched to LUM in combination with IVA FDC tablets orally q12h for 24 weeks.	LUM/IVA n=103 Participants Participants received LUM 200 mg in combination with IVA 250 mg FDC tablets orally q12h for 24 weeks.	Total n=204 Participants Total of all reporting groups
Age, Continuous	8.9 years STANDARD_DEVIATION 1.59 • n=5 Participants	8.7 years STANDARD_DEVIATION 1.6 • n=7 Participants	8.8 years STANDARD_DEVIATION 1.59 • n=5 Participants
Sex: Female, Male Female	58 Participants n=5 Participants	63 Participants n=7 Participants	121 Participants n=5 Participants
Sex: Female, Male Male	43 Participants n=5 Participants	40 Participants n=7 Participants	83 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Through Week 24

Population: Full Analysis Set (FAS) included all randomized participants who received any amount of study drug. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.

Lung clearance index (LCI) is a measure of ventilation inhomogeneity that is derived from a multiple breath washout test using Nitrogen (N2). LCI2.5 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting value.

Outcome measures

Measure	Placebo n=99 Participants Participants received placebo matched to LUM in combination with IVA FDC tablets orally q12h for 24 weeks.	LUM/IVA n=99 Participants Participants received LUM 200 mg in combination with IVA 250 mg FDC tablets orally q12h for 24 weeks.
Absolute Change From Baseline in Lung Clearance Index 2.5 (LCI2.5) Through Week 24	0.08 Ratio Standard Error 0.13	-1.01 Ratio Standard Error 0.13

SECONDARY outcome

Timeframe: Baseline, Day 15 and Week 4

Population: FAS. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.

Sweat samples were collected using an approved collection device. Baseline was defined as the average of the measurements at screening and on Day 1 pre-dose. Change from Baseline in sweat chloride at Day 15 and Week 4 was calculated. The average of the 2 values (Change at Day 15 and Week 4) was reported.

Outcome measures

Measure	Placebo n=94 Participants Participants received placebo matched to LUM in combination with IVA FDC tablets orally q12h for 24 weeks.	LUM/IVA n=95 Participants Participants received LUM 200 mg in combination with IVA 250 mg FDC tablets orally q12h for 24 weeks.
Average Absolute Change From Baseline in Sweat Chloride at Day 15 and Week 4	0.8 Millimole per liter (mmol/L) Standard Error 1.0	-20.0 Millimole per liter (mmol/L) Standard Error 1.0

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: FAS. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.

BMI was defined as weight in kg divided by height in square meter (m^2).

Outcome measures

Measure	Placebo n=97 Participants Participants received placebo matched to LUM in combination with IVA FDC tablets orally q12h for 24 weeks.	LUM/IVA n=98 Participants Participants received LUM 200 mg in combination with IVA 250 mg FDC tablets orally q12h for 24 weeks.
Absolute Change From Baseline in Body Mass Index (BMI) at Week 24	0.27 Kg/m^2 Standard Error 0.07	0.38 Kg/m^2 Standard Error 0.07

SECONDARY outcome

Timeframe: Baseline, Through Week 24

Population: FAS. Here, number of participants analyzed signifies 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 (for example, coughing, congestion, wheezing), score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.

Outcome measures

Measure	Placebo n=78 Participants Participants received placebo matched to LUM in combination with IVA FDC tablets orally q12h for 24 weeks.	LUM/IVA n=76 Participants Participants received LUM 200 mg in combination with IVA 250 mg FDC tablets orally q12h for 24 weeks.
Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 24	3.0 Units on a scale Standard Error 1.0	5.5 Units on a scale Standard Error 1.0

SECONDARY outcome

Timeframe: Baseline, Through Week 24

Population: FAS. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.

LCI is a measure of ventilation inhomogeneity that is derived from a multiple breath washout test using Nitrogen (N2). LCI5.0 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/20th of its starting value.

Outcome measures

Measure	Placebo n=99 Participants Participants received placebo matched to LUM in combination with IVA FDC tablets orally q12h for 24 weeks.	LUM/IVA n=99 Participants Participants received LUM 200 mg in combination with IVA 250 mg FDC tablets orally q12h for 24 weeks.
Absolute Change From Baseline in Lung Clearance Index 5.0 (LCI5.0) Through Week 24	0.08 Ratio Standard Error 0.05	-0.36 Ratio Standard Error 0.05

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: FAS. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.

Sweat samples were collected using an approved collection device.

Outcome measures

Measure	Placebo n=91 Participants Participants received placebo matched to LUM in combination with IVA FDC tablets orally q12h for 24 weeks.	LUM/IVA n=90 Participants Participants received LUM 200 mg in combination with IVA 250 mg FDC tablets orally q12h for 24 weeks.
Absolute Change From Baseline in Sweat Chloride at Week 24	3.2 mmol/L Standard Error 1.3	-21.6 mmol/L Standard Error 1.3

SECONDARY outcome

Timeframe: Baseline, Through Week 24

Population: FAS. Here, number of participants analyzed signifies 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. Wang standards were used to calculate ppFEV1 (for age, gender, race, and height).

Outcome measures

Measure	Placebo n=100 Participants Participants received placebo matched to LUM in combination with IVA FDC tablets orally q12h for 24 weeks.	LUM/IVA n=101 Participants Participants received LUM 200 mg in combination with IVA 250 mg FDC tablets orally q12h for 24 weeks.
Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) Through Week 24	-1.3 Percent predicted of FEV1 Standard Error 0.8	1.1 Percent predicted of FEV1 Standard Error 0.8

SECONDARY outcome

Timeframe: Baseline, Through Week 24

Population: FAS. Here, number of participants analyzed signifies 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. Wang standards were used to calculate ppFEV1 (for age, gender, race, and height).

Outcome measures

Measure	Placebo n=100 Participants Participants received placebo matched to LUM in combination with IVA FDC tablets orally q12h for 24 weeks.	LUM/IVA n=101 Participants Participants received LUM 200 mg in combination with IVA 250 mg FDC tablets orally q12h for 24 weeks.
Relative Change From Baseline in ppFEV1 Through Week 24	-0.9 Percent change Standard Error 1.0	2.2 Percent change Standard Error 1.0

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: FAS. Here, number of participants analyzed signifies 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 evaluate how a single data point compares to a standard. It describes 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). The BMI-for-age z-scores were calculated using National Center for Health Statistics growth charts.

Outcome measures

Measure	Placebo n=97 Participants Participants received placebo matched to LUM in combination with IVA FDC tablets orally q12h for 24 weeks.	LUM/IVA n=98 Participants Participants received LUM 200 mg in combination with IVA 250 mg FDC tablets orally q12h for 24 weeks.
Absolute Change From Baseline in BMI-for-age Z-score at Week 24	0.05 Z-score Standard Error 0.04	0.08 Z-score Standard Error 0.04

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: FAS. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.

Outcome measures

Measure	Placebo n=97 Participants Participants received placebo matched to LUM in combination with IVA FDC tablets orally q12h for 24 weeks.	LUM/IVA n=98 Participants Participants received LUM 200 mg in combination with IVA 250 mg FDC tablets orally q12h for 24 weeks.
Absolute Change From Baseline in Weight at Week 24	1.7 Kg Standard Error 0.2	2.0 Kg Standard Error 0.1

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: FAS. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.

Z-score is a statistical measure to evaluate how a single data point compares to a standard. It describes whether a mean was above or below the standard. Weight, adjusted for age and sex, was analyzed as weight-for-age z-score (weight z-score). The weight-for-age z-scores were calculated using National Center for Health Statistics growth charts.

Outcome measures

Measure	Placebo n=97 Participants Participants received placebo matched to LUM in combination with IVA FDC tablets orally q12h for 24 weeks.	LUM/IVA n=98 Participants Participants received LUM 200 mg in combination with IVA 250 mg FDC tablets orally q12h for 24 weeks.
Absolute Change From Baseline in Weight-for-age Z-score at Week 24	0.02 Z-score Standard Error 0.02	0.06 Z-score Standard Error 0.02

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: FAS. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.

Outcome measures

Measure	Placebo n=97 Participants Participants received placebo matched to LUM in combination with IVA FDC tablets orally q12h for 24 weeks.	LUM/IVA n=98 Participants Participants received LUM 200 mg in combination with IVA 250 mg FDC tablets orally q12h for 24 weeks.
Absolute Change From Baseline in Height at Week 24	2.6 Centimeter (cm) Standard Error 0.1	2.9 Centimeter (cm) Standard Error 0.1

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: FAS. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.

Z-score is a statistical measure to evaluate how a single data point compares to a standard. It describes whether a mean was above or below the standard. Height, adjusted for age and sex, was analyzed as height-for-age z-score (height z-score). The height-for-age z-scores were calculated using National Center for Health Statistics growth charts.

Outcome measures

Measure	Placebo n=97 Participants Participants received placebo matched to LUM in combination with IVA FDC tablets orally q12h for 24 weeks.	LUM/IVA n=98 Participants Participants received LUM 200 mg in combination with IVA 250 mg FDC tablets orally q12h for 24 weeks.
Absolute Change From Baseline in Height-for-age Z-score at Week 24	0.00 Z-score Standard Error 0.02	0.03 Z-score Standard Error 0.02

SECONDARY outcome

Timeframe: Baseline, Through Week 24

Population: FAS. Here, 'Number of participants analyzed' = those participants who were evaluable for this endpoint and 'Number Analyzed' = those participants who were evaluable at the specified time points for each arm, respectively.

The TSQM is a 14-item self-administered questionnaire which measures participants' experiences with their medication on four dimensions: effectiveness, side effects, convenience and global satisfaction. For each dimension, responses are added and transformed to a scale from 0 to 100, where higher scores indicate greater satisfaction.

Outcome measures

Measure	Placebo n=91 Participants Participants received placebo matched to LUM in combination with IVA FDC tablets orally q12h for 24 weeks.	LUM/IVA n=91 Participants Participants received LUM 200 mg in combination with IVA 250 mg FDC tablets orally q12h for 24 weeks.
Absolute Change From Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Domains Through Week 24 Change Through Week 24: Convenience	9.9 Units on a scale Standard Error 1.2	11.9 Units on a scale Standard Error 1.2
Absolute Change From Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Domains Through Week 24 Change Through Week 24: Effectiveness	0.6 Units on a scale Standard Error 1.5	1.7 Units on a scale Standard Error 1.5
Absolute Change From Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Domains Through Week 24 Change Through Week 24: Side Effects	0.4 Units on a scale Standard Error 0.8	-1.0 Units on a scale Standard Error 0.8
Absolute Change From Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Domains Through Week 24 Change Through Week 24: Global Score	-2.3 Units on a scale Standard Error 1.6	-1.4 Units on a scale Standard Error 1.6

SECONDARY outcome

Timeframe: Baseline through Week 24

Population: FAS.

Pulmonary exacerbation was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms. The number of events were reported.

Outcome measures

Measure	Placebo n=101 Participants Participants received placebo matched to LUM in combination with IVA FDC tablets orally q12h for 24 weeks.	LUM/IVA n=103 Participants Participants received LUM 200 mg in combination with IVA 250 mg FDC tablets orally q12h for 24 weeks.
Number of Pulmonary Exacerbation Events	18 Pulmonary exacerbation events	24 Pulmonary exacerbation events

SECONDARY outcome

Timeframe: Baseline through Week 24

Population: FAS.

Pulmonary exacerbation was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms.

Outcome measures

Measure	Placebo n=101 Participants Participants received placebo matched to LUM in combination with IVA FDC tablets orally q12h for 24 weeks.	LUM/IVA n=103 Participants Participants received LUM 200 mg in combination with IVA 250 mg FDC tablets orally q12h for 24 weeks.
Percentage of Participants With At Least 1 Pulmonary Exacerbation Event	14.9 Percentage of participants	19.4 Percentage of participants

SECONDARY outcome

Timeframe: Baseline through Week 24

Population: FAS.

Time-to-first pulmonary exacerbation was analyzed using the Kaplan-Meier estimates. Pulmonary exacerbation was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms.

Outcome measures

Measure	Placebo n=101 Participants Participants received placebo matched to LUM in combination with IVA FDC tablets orally q12h for 24 weeks.	LUM/IVA n=103 Participants Participants received LUM 200 mg in combination with IVA 250 mg FDC tablets orally q12h for 24 weeks.
Time-to-first Pulmonary Exacerbation	NA Days Median and range was not reached as less than 50% of participants had the event of interest.	NA Days Median and range was not reached as less than 50% of participants had the event of interest.

SECONDARY outcome

Timeframe: Baseline up to Week 28

Population: Safety Set included all participants who were exposed to any amount of 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=101 Participants Participants received placebo matched to LUM in combination with IVA FDC tablets orally q12h for 24 weeks.	LUM/IVA n=103 Participants Participants received LUM 200 mg in combination with IVA 250 mg FDC tablets orally q12h for 24 weeks.
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) Participants With Any Treatment-Emergent AEs	98 participants	98 participants
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) Participants With Treatment-Emergent SAEs	11 participants	13 participants

SECONDARY outcome

Timeframe: For Ctrough,ave: before morning dose on Week 4 and 24; For C3-6h,ave: 3 to 6 hours after morning dose on Day 1, 15 and Week 4

Population: Pharmacokinetic (PK) set included all randomized participants who received any amount of study drug and had a PK assessment. Here, 'Number of participants analyzed' = those participants who were evaluable for this endpoint and 'Number Analyzed' = those participants who were evaluable at the specified time points for each arm, respectively.

Ctrough,ave is average of individual pre-dose observed concentrations across Week 4 and 24. C3-6h,ave is average of individual 3 to 6 hours post-dose observed concentrations across Day 1, 15 and Week 4. This outcome was not planned to be assessed in Placebo arm.

Outcome measures

Measure	Placebo n=102 Participants Participants received placebo matched to LUM in combination with IVA FDC tablets orally q12h for 24 weeks.	LUM/IVA Participants received LUM 200 mg in combination with IVA 250 mg FDC tablets orally q12h for 24 weeks.
Average Pre-dose Concentration (Ctrough,Ave) and Average 3 to 6 Hours Post-dose Concentration (C3-6h,Ave) For Lumacaftor and Ivacaftor LUM: Ctrough,ave	10200 Nanogram per milliliter (ng/mL) Standard Deviation 4460	—
Average Pre-dose Concentration (Ctrough,Ave) and Average 3 to 6 Hours Post-dose Concentration (C3-6h,Ave) For Lumacaftor and Ivacaftor LUM: C3-6h,ave	20600 Nanogram per milliliter (ng/mL) Standard Deviation 6560	—
Average Pre-dose Concentration (Ctrough,Ave) and Average 3 to 6 Hours Post-dose Concentration (C3-6h,Ave) For Lumacaftor and Ivacaftor IVA: Ctrough,ave	107 Nanogram per milliliter (ng/mL) Standard Deviation 91.2	—
Average Pre-dose Concentration (Ctrough,Ave) and Average 3 to 6 Hours Post-dose Concentration (C3-6h,Ave) For Lumacaftor and Ivacaftor IVA: C3-6h,ave	821 Nanogram per milliliter (ng/mL) Standard Deviation 348	—

Adverse Events

Placebo

Serious events: 11 serious events

Other events: 98 other events

Deaths: 0 deaths

LUM/IVA

Serious events: 13 serious events

Other events: 98 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=101 participants at risk Participants received placebo matched to LUM in combination with IVA FDC tablets orally q12h for 24 weeks.	LUM/IVA n=103 participants at risk Participants received LUM 200 mg in combination with IVA 250 mg FDC tablets orally q12h for 24 weeks.
Vascular disorders Poor venous access	0.00% 0/101 • Baseline up to Week 28	0.97% 1/103 • Baseline up to Week 28
Injury, poisoning and procedural complications Procedural anxiety	0.00% 0/101 • Baseline up to Week 28	0.97% 1/103 • Baseline up to Week 28
Investigations Bacterial test positive	0.00% 0/101 • Baseline up to Week 28	0.97% 1/103 • Baseline up to Week 28
Investigations Alanine aminotransferase increased	0.99% 1/101 • Baseline up to Week 28	0.00% 0/103 • Baseline up to Week 28
Investigations Aspartate aminotransferase increased	0.99% 1/101 • Baseline up to Week 28	0.00% 0/103 • Baseline up to Week 28
Investigations Transaminases increased	0.99% 1/101 • Baseline up to Week 28	0.00% 0/103 • Baseline up to Week 28
Blood and lymphatic system disorders Lymphadenitis	0.99% 1/101 • Baseline up to Week 28	0.00% 0/103 • Baseline up to Week 28
Respiratory, thoracic and mediastinal disorders Obstructive airways disorder	0.00% 0/101 • Baseline up to Week 28	0.97% 1/103 • Baseline up to Week 28
General disorders Drug interaction	0.00% 0/101 • Baseline up to Week 28	0.97% 1/103 • Baseline up to Week 28
General disorders Device related thrombosis	0.99% 1/101 • Baseline up to Week 28	0.00% 0/103 • Baseline up to Week 28
Gastrointestinal disorders Constipation	0.99% 1/101 • Baseline up to Week 28	0.00% 0/103 • Baseline up to Week 28
Gastrointestinal disorders Distal intestinal obstruction syndrome	2.0% 2/101 • Baseline up to Week 28	0.00% 0/103 • Baseline up to Week 28
Infections and infestations Infective pulmonary exacerbation of cystic fibrosis	5.0% 5/101 • Baseline up to Week 28	7.8% 8/103 • Baseline up to Week 28
Infections and infestations Bronchopulmonary aspergillosis allergic	0.00% 0/101 • Baseline up to Week 28	0.97% 1/103 • Baseline up to Week 28
Infections and infestations Pneumonia	0.99% 1/101 • Baseline up to Week 28	0.97% 1/103 • Baseline up to Week 28

Other adverse events

Measure	Placebo n=101 participants at risk Participants received placebo matched to LUM in combination with IVA FDC tablets orally q12h for 24 weeks.	LUM/IVA n=103 participants at risk Participants received LUM 200 mg in combination with IVA 250 mg FDC tablets orally q12h for 24 weeks.
Investigations Alanine aminotransferase increased	7.9% 8/101 • Baseline up to Week 28	7.8% 8/103 • Baseline up to Week 28
Investigations Bacterial test positive	7.9% 8/101 • Baseline up to Week 28	6.8% 7/103 • Baseline up to Week 28
Investigations Aspartate aminotransferase increased	5.9% 6/101 • Baseline up to Week 28	5.8% 6/103 • Baseline up to Week 28
Respiratory, thoracic and mediastinal disorders Cough	46.5% 47/101 • Baseline up to Week 28	44.7% 46/103 • Baseline up to Week 28
Respiratory, thoracic and mediastinal disorders Productive cough	5.9% 6/101 • Baseline up to Week 28	17.5% 18/103 • Baseline up to Week 28
Respiratory, thoracic and mediastinal disorders Nasal congestion	7.9% 8/101 • Baseline up to Week 28	16.5% 17/103 • Baseline up to Week 28
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	9.9% 10/101 • Baseline up to Week 28	14.6% 15/103 • Baseline up to Week 28
Respiratory, thoracic and mediastinal disorders Sputum increased	2.0% 2/101 • Baseline up to Week 28	10.7% 11/103 • Baseline up to Week 28
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	5.0% 5/101 • Baseline up to Week 28	9.7% 10/103 • Baseline up to Week 28
Respiratory, thoracic and mediastinal disorders Respiration abnormal	4.0% 4/101 • Baseline up to Week 28	5.8% 6/103 • Baseline up to Week 28
Nervous system disorders Headache	8.9% 9/101 • Baseline up to Week 28	12.6% 13/103 • Baseline up to Week 28
General disorders Pyrexia	19.8% 20/101 • Baseline up to Week 28	14.6% 15/103 • Baseline up to Week 28
General disorders Fatigue	10.9% 11/101 • Baseline up to Week 28	8.7% 9/103 • Baseline up to Week 28
Gastrointestinal disorders Abdominal pain upper	6.9% 7/101 • Baseline up to Week 28	12.6% 13/103 • Baseline up to Week 28
Gastrointestinal disorders Abdominal pain	9.9% 10/101 • Baseline up to Week 28	9.7% 10/103 • Baseline up to Week 28
Gastrointestinal disorders Nausea	8.9% 9/101 • Baseline up to Week 28	9.7% 10/103 • Baseline up to Week 28
Gastrointestinal disorders Vomiting	9.9% 10/101 • Baseline up to Week 28	9.7% 10/103 • Baseline up to Week 28
Gastrointestinal disorders Diarrhoea	4.0% 4/101 • Baseline up to Week 28	5.8% 6/103 • Baseline up to Week 28
Gastrointestinal disorders Constipation	7.9% 8/101 • Baseline up to Week 28	4.9% 5/103 • Baseline up to Week 28
Skin and subcutaneous tissue disorders Rash	0.99% 1/101 • Baseline up to Week 28	5.8% 6/103 • Baseline up to Week 28
Metabolism and nutrition disorders Decreased appetite	5.9% 6/101 • Baseline up to Week 28	2.9% 3/103 • Baseline up to Week 28
Infections and infestations Infective pulmonary exacerbation of cystic fibrosis	15.8% 16/101 • Baseline up to Week 28	12.6% 13/103 • Baseline up to Week 28
Infections and infestations Upper respiratory tract infection	9.9% 10/101 • Baseline up to Week 28	12.6% 13/103 • Baseline up to Week 28
Infections and infestations Rhinitis	5.0% 5/101 • Baseline up to Week 28	5.8% 6/103 • Baseline up to Week 28
Infections and infestations Nasopharyngitis	7.9% 8/101 • Baseline up to Week 28	4.9% 5/103 • Baseline up to Week 28
Infections and infestations Viral upper respiratory tract infection	7.9% 8/101 • Baseline up to Week 28	4.9% 5/103 • Baseline up to Week 28
Infections and infestations Influenza	5.9% 6/101 • Baseline up to Week 28	3.9% 4/103 • Baseline up to Week 28

Additional Information

Medical Monitor

Vertex Pharmaceuticals Incorporated

Phone: 617-341-6777

Email: medicalinfo@vrtx.com

Results disclosure agreements

• Principal investigator is a sponsor employee Restriction Description: PI is free to publish results of the study after (1)first multi-center publication, (2)if 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