Trial Outcomes & Findings for Pilot Study Testing the Effect of Ivacaftor on Lung Function in Subjects With Cystic Fibrosis and Residual CFTR Function (NCT NCT01685801)

Last Updated: 2015-05-19

Results Overview

FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Hankinson and Wang standards were used to calculate percent predicted FEV1 (for age, gender, and height). The Hankinson standard was used for male participants 18 years and older and female participants 16 years and older. The Wang standard was used for male participants aged 12 to 17 years and for female participants aged 12 to 15 years. Data was to be reported for each cycle (Cycle 1 and Cycle 2) and as per drug treatment, for overall participants and as per genotype (residual function mutation and mRNA splice site mutation).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

24 participants

Primary outcome timeframe

Cycle 1 baseline, Cycle 1 Day 15 (for Cycle 1 reporting arms); Cycle 2 baseline, Cycle 2 Day 15 (for Cycle 2 reporting arms)

Results posted on

2015-05-19

Participant Flow

Participant milestones

Participant milestones
Measure	Ivacaftor, Placebo, Ivacaftor, Placebo (IPIP) During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 \[(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)\] and Cycle 2 \[(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)\] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all participants received ivacaftor.	Ivacaftor, Placebo, Placebo, Ivacaftor (IPPI) During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 \[(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)\] and Cycle 2 \[(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)\] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all participants received ivacaftor.	Placebo, Ivacaftor, Ivacaftor, Placebo (PIIP) During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 \[(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)\] and Cycle 2 \[(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)\] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all participants received ivacaftor.	Placebo, Ivacaftor, Placebo, Ivacaftor (PIPI) During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 \[(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)\] and Cycle 2 \[(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)\] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all participants received ivacaftor.
Cycle 1 Period 1 (2 Weeks) STARTED	5	6	7	6
Cycle 1 Period 1 (2 Weeks) COMPLETED	5	6	7	6
Cycle 1 Period 1 (2 Weeks) NOT COMPLETED	0	0	0	0
Cycle 1 Period 2 (2 Weeks) STARTED	5	6	7	6
Cycle 1 Period 2 (2 Weeks) COMPLETED	5	6	7	5
Cycle 1 Period 2 (2 Weeks) NOT COMPLETED	0	0	0	1
Washout Period 1 (4 Weeks) STARTED	5	6	7	5
Washout Period 1 (4 Weeks) COMPLETED	5	6	7	5
Washout Period 1 (4 Weeks) NOT COMPLETED	0	0	0	0
Cycle 2 Period 1 (2 Weeks) STARTED	5	6	7	5
Cycle 2 Period 1 (2 Weeks) COMPLETED	5	6	7	5
Cycle 2 Period 1 (2 Weeks) NOT COMPLETED	0	0	0	0
Cycle 2 Period 2 (2 Weeks) STARTED	5	6	7	5
Cycle 2 Period 2 (2 Weeks) COMPLETED	5	5	7	4
Cycle 2 Period 2 (2 Weeks) NOT COMPLETED	0	1	0	1
Washout Period 2 (4 Weeks) STARTED	5	5	7	4
Washout Period 2 (4 Weeks) COMPLETED	5	5	7	4
Washout Period 2 (4 Weeks) NOT COMPLETED	0	0	0	0
Open-label Period (8 Weeks) STARTED	5	5	7	4
Open-label Period (8 Weeks) COMPLETED	5	5	7	4
Open-label Period (8 Weeks) NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Ivacaftor, Placebo, Ivacaftor, Placebo (IPIP) During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 \[(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)\] and Cycle 2 \[(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)\] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all participants received ivacaftor.	Ivacaftor, Placebo, Placebo, Ivacaftor (IPPI) During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 \[(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)\] and Cycle 2 \[(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)\] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all participants received ivacaftor.	Placebo, Ivacaftor, Ivacaftor, Placebo (PIIP) During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 \[(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)\] and Cycle 2 \[(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)\] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all participants received ivacaftor.	Placebo, Ivacaftor, Placebo, Ivacaftor (PIPI) During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 \[(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)\] and Cycle 2 \[(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)\] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all participants received ivacaftor.
Cycle 1 Period 2 (2 Weeks) Adverse Event	0	0	0	1
Cycle 2 Period 2 (2 Weeks) Non-compliance with Study Drug	0	1	0	1

Baseline Characteristics

Pilot Study Testing the Effect of Ivacaftor on Lung Function in Subjects With Cystic Fibrosis and Residual CFTR Function

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	IPIP n=5 Participants Detailed reporting group description is provided in Participant Flow module.	IPPI n=6 Participants Detailed reporting group description is provided in Participant Flow module.	PIIP n=7 Participants Detailed reporting group description is provided in Participant Flow module.	PIPI n=6 Participants Detailed reporting group description is provided in Participant Flow module.	Total n=24 Participants Total of all reporting groups
Age, Continuous	44.8 years STANDARD_DEVIATION 8.04 • n=5 Participants	29.7 years STANDARD_DEVIATION 11.66 • n=7 Participants	41.4 years STANDARD_DEVIATION 13.96 • n=5 Participants	33.8 years STANDARD_DEVIATION 17.26 • n=4 Participants	37.3 years STANDARD_DEVIATION 13.86 • n=21 Participants
Age, Customized less than (<) 20 years	0 participants n=5 Participants	1 participants n=7 Participants	0 participants n=5 Participants	2 participants n=4 Participants	3 participants n=21 Participants
Age, Customized 20 - 40 years	1 participants n=5 Participants	4 participants n=7 Participants	3 participants n=5 Participants	2 participants n=4 Participants	10 participants n=21 Participants
Age, Customized greater than (>) 40 years	4 participants n=5 Participants	1 participants n=7 Participants	4 participants n=5 Participants	2 participants n=4 Participants	11 participants n=21 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	4 Participants n=7 Participants	3 Participants n=5 Participants	2 Participants n=4 Participants	12 Participants n=21 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants	4 Participants n=4 Participants	12 Participants n=21 Participants
Genotype mRNA Splice Site (Class V) Mutations	3 participants n=5 Participants	3 participants n=7 Participants	2 participants n=5 Participants	2 participants n=4 Participants	10 participants n=21 Participants
Genotype Residual Function Mutations	2 participants n=5 Participants	3 participants n=7 Participants	5 participants n=5 Participants	4 participants n=4 Participants	14 participants n=21 Participants

PRIMARY outcome

Timeframe: Cycle 1 baseline, Cycle 1 Day 15 (for Cycle 1 reporting arms); Cycle 2 baseline, Cycle 2 Day 15 (for Cycle 2 reporting arms)

Population: Full analysis set (FAS) population. Here, number of participants analyzed signifies participant evaluable for this outcome measure and "n" signifies participants who were evaluable for the specified category in each arm, respectively.

Outcome measures

Outcome measures
Measure	Cycle 1: Placebo n=24 Participants Placebo-matched-to-ivacaftor tablet orally every 12 hours for 2 weeks during either in period 1 or 2 of Cycle 1.	Cycle 1: Ivacaftor n=24 Participants Ivacaftor 150 mg tablet orally every 12 hours for 2 weeks during either in period 1 or 2 of Cycle 1.	Cycle 2: Placebo n=23 Participants Placebo-matched-to-ivacaftor tablet orally every 12 hours for 2 weeks during either in period 1 or 2 of Cycle 2.	Cycle 2: Ivacaftor n=23 Participants Ivacaftor 150 mg tablet orally every 12 hours for 2 weeks during either in period 1 or 2 of Cycle 2.
Cycle 1 and Cycle 2: Absolute Change From Cycle Baseline In Percent Predicted Forced Expiratory Volume In 1 Second (FEV1) After 2 Weeks of Treatment mRNA Splice Site(ClassV)Mutations (n=10, 10, 9, 9)	-0.5710 Percent predicted of FEV1 Standard Deviation 3.39739	0.8196 Percent predicted of FEV1 Standard Deviation 5.09161	1.7132 Percent predicted of FEV1 Standard Deviation 3.80933	2.0640 Percent predicted of FEV1 Standard Deviation 3.55493
Cycle 1 and Cycle 2: Absolute Change From Cycle Baseline In Percent Predicted Forced Expiratory Volume In 1 Second (FEV1) After 2 Weeks of Treatment Overall (n=24, 24, 23, 23)	0.5828 Percent predicted of FEV1 Standard Deviation 3.67326	2.0898 Percent predicted of FEV1 Standard Deviation 4.63833	0.8495 Percent predicted of FEV1 Standard Deviation 4.20641	3.6868 Percent predicted of FEV1 Standard Deviation 6.13466
Cycle 1 and Cycle 2: Absolute Change From Cycle Baseline In Percent Predicted Forced Expiratory Volume In 1 Second (FEV1) After 2 Weeks of Treatment Residual Function Mutations (n=14, 14, 14, 14)	1.4069 Percent predicted of FEV1 Standard Deviation 3.75842	2.9971 Percent predicted of FEV1 Standard Deviation 4.24124	0.2942 Percent predicted of FEV1 Standard Deviation 4.49056	4.7300 Percent predicted of FEV1 Standard Deviation 7.27436

SECONDARY outcome

Timeframe: Cycle 1 baseline, Cycle 1 Day 15 (for Cycle 1 reporting arms); Cycle 2 baseline, Cycle 2 Day 15 (for Cycle 2 reporting arms)

Population: FAS population. Here, number of participants analyzed signifies participant evaluable for this outcome measure and "n" signifies participants who were evaluable for the specified category in each arm, respectively.

LCI is a measure of ventilation inhomogeneity that is derived from a multiple-breath washout test. The LCI was calculated as the number of lung volume turnovers (cumulative expired volume divided by the functional residual capacity \[FRC\]) required to reduce end-tidal concentration of an inert gas to 1/40th of the starting value. Data was to be reported for each cycle (Cycle 1 and Cycle 2) and as per drug treatment. Data was to be reported for each cycle (Cycle 1 and Cycle 2) and as per drug treatment, for overall participants and as per genotype (residual function mutation and mRNA splice site mutation).

Outcome measures

Outcome measures
Measure	Cycle 1: Placebo n=23 Participants Placebo-matched-to-ivacaftor tablet orally every 12 hours for 2 weeks during either in period 1 or 2 of Cycle 1.	Cycle 1: Ivacaftor n=24 Participants Ivacaftor 150 mg tablet orally every 12 hours for 2 weeks during either in period 1 or 2 of Cycle 1.	Cycle 2: Placebo n=23 Participants Placebo-matched-to-ivacaftor tablet orally every 12 hours for 2 weeks during either in period 1 or 2 of Cycle 2.	Cycle 2: Ivacaftor n=22 Participants Ivacaftor 150 mg tablet orally every 12 hours for 2 weeks during either in period 1 or 2 of Cycle 2.
Cycle 1 and Cycle 2: Absolute Change From Cycle Baseline In Lung Clearance Index (LCI) After 2 Weeks of Treatment Overall (n=23, 24, 23, 22)	0.4596 ratio Standard Deviation 1.97774	0.2822 ratio Standard Deviation 3.54741	0.4111 ratio Standard Deviation 2.39920	0.0770 ratio Standard Deviation 1.98188
Cycle 1 and Cycle 2: Absolute Change From Cycle Baseline In Lung Clearance Index (LCI) After 2 Weeks of Treatment mRNA Splice Site(ClassV)Mutations (n=10, 10, 9, 9)	0.4321 ratio Standard Deviation 1.97140	-0.5306 ratio Standard Deviation 1.91374	1.0568 ratio Standard Deviation 2.12093	-0.3136 ratio Standard Deviation 1.89562
Cycle 1 and Cycle 2: Absolute Change From Cycle Baseline In Lung Clearance Index (LCI) After 2 Weeks of Treatment Residual Function Mutations (n=13, 14, 14, 13)	0.4808 ratio Standard Deviation 2.06279	0.8628 ratio Standard Deviation 4.34252	-0.0039 ratio Standard Deviation 2.54929	0.3475 ratio Standard Deviation 2.06990

SECONDARY outcome

Timeframe: Open-label Baseline, Open-label Day 57

FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Hankinson and Wang standards were used to calculate percent predicted FEV1 (for age, gender, and height). The Hankinson standard was used for male participants 18 years and older and female participants 16 years and older. The Wang standard was used for male participants aged 12 to 17 years and for female participants aged 12 to 15 years. Data was to be reported for overall participants and as per genotype (residual function mutation and mRNA splice site mutation).

Outcome measures

Outcome measures
Measure	Cycle 1: Placebo n=21 Participants Placebo-matched-to-ivacaftor tablet orally every 12 hours for 2 weeks during either in period 1 or 2 of Cycle 1.	Cycle 1: Ivacaftor Ivacaftor 150 mg tablet orally every 12 hours for 2 weeks during either in period 1 or 2 of Cycle 1.	Cycle 2: Placebo Placebo-matched-to-ivacaftor tablet orally every 12 hours for 2 weeks during either in period 1 or 2 of Cycle 2.	Cycle 2: Ivacaftor Ivacaftor 150 mg tablet orally every 12 hours for 2 weeks during either in period 1 or 2 of Cycle 2.
Open-label Period: Absolute Change From Open-label Baseline In Percent Predicted Forced Expiratory Volume In 1 Second (FEV1) at Day 57 Overall (n=21)	4.6815 Percent predicted of FEV1 Standard Deviation 4.17934	—	—	—
Open-label Period: Absolute Change From Open-label Baseline In Percent Predicted Forced Expiratory Volume In 1 Second (FEV1) at Day 57 mRNA Splice Site(ClassV)Mutations (n=9)	4.3072 Percent predicted of FEV1 Standard Deviation 2.93624	—	—	—
Open-label Period: Absolute Change From Open-label Baseline In Percent Predicted Forced Expiratory Volume In 1 Second (FEV1) at Day 57 Residual Function Mutations (n=12)	4.9622 Percent predicted of FEV1 Standard Deviation 5.02864	—	—	—

SECONDARY outcome

Timeframe: Open-label Baseline, Open-label Day 57

LCI is a measure of ventilation inhomogeneity that is derived from a multiple-breath washout test. The LCI was calculated as the number of lung volume turnovers (cumulative expired volume divided by the functional residual capacity \[FRC\]) required to reduce end-tidal concentration of an inert gas to 1/40th of the starting value. Data was to be reported for overall participants and as per genotype (residual function mutation and mRNA splice site mutation).

Outcome measures

Outcome measures
Measure	Cycle 1: Placebo n=21 Participants Placebo-matched-to-ivacaftor tablet orally every 12 hours for 2 weeks during either in period 1 or 2 of Cycle 1.	Cycle 1: Ivacaftor Ivacaftor 150 mg tablet orally every 12 hours for 2 weeks during either in period 1 or 2 of Cycle 1.	Cycle 2: Placebo Placebo-matched-to-ivacaftor tablet orally every 12 hours for 2 weeks during either in period 1 or 2 of Cycle 2.	Cycle 2: Ivacaftor Ivacaftor 150 mg tablet orally every 12 hours for 2 weeks during either in period 1 or 2 of Cycle 2.
Open-label Period: Absolute Change From Open-label Baseline In Lung Clearance Index (LCI) at Day 57 Overall (n=21)	-1.5687 ratio Standard Deviation 2.27137	—	—	—
Open-label Period: Absolute Change From Open-label Baseline In Lung Clearance Index (LCI) at Day 57 mRNA Splice Site(ClassV)Mutations (n=9)	-1.3459 ratio Standard Deviation 2.88447	—	—	—
Open-label Period: Absolute Change From Open-label Baseline In Lung Clearance Index (LCI) at Day 57 Residual Function Mutations (n=12)	-1.7358 ratio Standard Deviation 1.80502	—	—	—

SECONDARY outcome

Timeframe: Study Baseline, Open-label Day 57

Sweat samples were collected using an approved Macroduct (Wescor, Logan, Utah) collection device. A volume of greater than or equal to (\>=) 15 microliter was required for determination of sweat chloride. Data was to be reported for overall participants and as per genotype (residual function mutation and mRNA splice site mutation).

Outcome measures

Outcome measures
Measure	Cycle 1: Placebo n=19 Participants Placebo-matched-to-ivacaftor tablet orally every 12 hours for 2 weeks during either in period 1 or 2 of Cycle 1.	Cycle 1: Ivacaftor Ivacaftor 150 mg tablet orally every 12 hours for 2 weeks during either in period 1 or 2 of Cycle 1.	Cycle 2: Placebo Placebo-matched-to-ivacaftor tablet orally every 12 hours for 2 weeks during either in period 1 or 2 of Cycle 2.	Cycle 2: Ivacaftor Ivacaftor 150 mg tablet orally every 12 hours for 2 weeks during either in period 1 or 2 of Cycle 2.
Open-label Period: Absolute Change From Study Baseline In Sweat Chloride at Day 57 Overall (n=19)	-15.74 millimole per liter (mmol/L) Standard Deviation 14.781	—	—	—
Open-label Period: Absolute Change From Study Baseline In Sweat Chloride at Day 57 mRNA Splice Site(ClassV)Mutations (n=8)	-14.13 millimole per liter (mmol/L) Standard Deviation 8.254	—	—	—
Open-label Period: Absolute Change From Study Baseline In Sweat Chloride at Day 57 Residual Function Mutations (n=11)	-16.91 millimole per liter (mmol/L) Standard Deviation 18.493	—	—	—

SECONDARY outcome

Timeframe: Open-label Baseline, Open-label Day 57

Data was to be reported for overall participants and as per genotype (residual function mutation and mRNA splice site mutation).

Outcome measures

Outcome measures
Measure	Cycle 1: Placebo n=21 Participants Placebo-matched-to-ivacaftor tablet orally every 12 hours for 2 weeks during either in period 1 or 2 of Cycle 1.	Cycle 1: Ivacaftor Ivacaftor 150 mg tablet orally every 12 hours for 2 weeks during either in period 1 or 2 of Cycle 1.	Cycle 2: Placebo Placebo-matched-to-ivacaftor tablet orally every 12 hours for 2 weeks during either in period 1 or 2 of Cycle 2.	Cycle 2: Ivacaftor Ivacaftor 150 mg tablet orally every 12 hours for 2 weeks during either in period 1 or 2 of Cycle 2.
Open-label Period: Absolute Change From Open-label Baseline In Weight at Day 57 Overall (n=21)	1.77 kilograms (kg) Standard Deviation 1.906	—	—	—
Open-label Period: Absolute Change From Open-label Baseline In Weight at Day 57 mRNA Splice Site(ClassV)Mutations (n=9)	2.32 kilograms (kg) Standard Deviation 2.111	—	—	—
Open-label Period: Absolute Change From Open-label Baseline In Weight at Day 57 Residual Function Mutations (n=12)	1.35 kilograms (kg) Standard Deviation 1.710	—	—	—

SECONDARY outcome

Timeframe: From first dose of study drug through completion of follow-up visit (up to 26 weeks)

Population: Safety set included all participants who received at least 1 dose of study drug. Here, number of participants analyzed signifies participant evaluable for this outcome measure.

Adverse events (AEs) that started (or increased in severity) from first dose of study drug through completion of Follow-up were considered TEAEs, with exception that if an AE started during a Washout Period and was beyond 14 days from last dose date of preceding cycle, AE was considered as a "Washout Period" AE, and hence not TEAE. A TEAE was attributed to treatment in which it started or to the treatment in second cycling period of previous Crossover Period if it started during a Washout Period. SAE: medical event or condition, which falls into any of following categories, regardless of its relationship to study drug: death, life threatening adverse experience, in-patient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. Data was to be reported by drug treatment for double-blind crossover period (Cycle 1 up to Washout Period 2) and open-label period.

Outcome measures

Outcome measures
Measure	Cycle 1: Placebo n=24 Participants Placebo-matched-to-ivacaftor tablet orally every 12 hours for 2 weeks during either in period 1 or 2 of Cycle 1.	Cycle 1: Ivacaftor n=24 Participants Ivacaftor 150 mg tablet orally every 12 hours for 2 weeks during either in period 1 or 2 of Cycle 1.	Cycle 2: Placebo n=21 Participants Placebo-matched-to-ivacaftor tablet orally every 12 hours for 2 weeks during either in period 1 or 2 of Cycle 2.	Cycle 2: Ivacaftor Ivacaftor 150 mg tablet orally every 12 hours for 2 weeks during either in period 1 or 2 of Cycle 2.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) SAEs	0 participants	1 participants	0 participants	—
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) AEs	17 participants	18 participants	20 participants	—

Adverse Events

Crossover Double-blind Period: Placebo

Serious events: 0 serious events

Other events: 17 other events

Deaths: 0 deaths

Crossover Double-blind Period: Ivacaftor

Serious events: 1 serious events

Other events: 18 other events

Deaths: 0 deaths

Open-label Period: Ivacaftor

Serious events: 0 serious events

Other events: 20 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Crossover Double-blind Period: Placebo n=24 participants at risk Placebo matched to ivacaftor tablet orally every 12 hours for 2 weeks either during the double blind period 1 or 2 of cycle 1 and cycle 2.	Crossover Double-blind Period: Ivacaftor n=24 participants at risk Ivacaftor 150 mg tablet orally every 12 hours for 2 weeks either during the double blind period 1 or 2 of cycle 1 and cycle 2.	Open-label Period: Ivacaftor n=21 participants at risk Ivacaftor 150 mg tablet orally every 12 hours for 8 weeks during the open-label period after washout period 2.
Infections and infestations Infective pulmonary exacerbation of cystic fibrosis	0.00% 0/24 • From first dose of study drug through completion of follow-up visit (up to 26 weeks)	4.2% 1/24 • From first dose of study drug through completion of follow-up visit (up to 26 weeks)	0.00% 0/21 • From first dose of study drug through completion of follow-up visit (up to 26 weeks)

Other adverse events

Additional Information

Medical Monitor

Vertex Pharmaceuticals Incorporated

Phone: 617-341-6777

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee PI is free to publish results of the study after (1) the first multi-center publication, (2) if the sponsor elects not to publish the results, or (3) 18 months after close of the study, whichever occurs first. Proposed publications are to be submitted to the sponsor for review and comment for a period of at least 45 days (which may be extended under certain circumstances related to protection of intellectual property); the sponsor cannot require changes to the proposed publications.
Publication restrictions are in place

Restriction type: OTHER