Trial Outcomes & Findings for Study of Ivacaftor in Subjects With Cystic Fibrosis (CF) Who Have the R117H-CF Transmembrane Conductance Regulator (CFTR) Mutation (KONDUCT) (NCT NCT01614457)

Last Updated: 2015-02-12

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 subjects 18 years and older and female subjects 16 years and older. The Wang standard was used for male subjects aged 6 to 17 years and for female subjects aged 6 to 15 years.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

70 participants

Primary outcome timeframe

Baseline, Week 24

Results posted on

2015-02-12

Participant Flow

A total of 70 subjects were randomized, of which 1 subject discontinued the study prior to study drug administration. A total of 69 subjects started treatment.

Participant milestones

Participant milestones
Measure	Ivacaftor Ivacaftor 150 milligram (mg) tablet orally twice daily for 24 weeks.	Placebo Placebo matched to ivacaftor tablet orally twice daily for 24 weeks.
Overall Study STARTED	34	35
Overall Study COMPLETED	32	35
Overall Study NOT COMPLETED	2	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Ivacaftor Ivacaftor 150 milligram (mg) tablet orally twice daily for 24 weeks.	Placebo Placebo matched to ivacaftor tablet orally twice daily for 24 weeks.
Overall Study Non-Compliance	1	0
Overall Study Pregnancy (Self or Partner)	1	0

Baseline Characteristics

Study of Ivacaftor in Subjects With Cystic Fibrosis (CF) Who Have the R117H-CF Transmembrane Conductance Regulator (CFTR) Mutation (KONDUCT)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ivacaftor n=34 Participants Ivacaftor 150 milligram (mg) tablet orally twice daily for 24 weeks.	Placebo n=35 Participants Placebo matched to ivacaftor tablet orally twice daily for 24 weeks.	Total n=69 Participants Total of all reporting groups
Age, Continuous	29.2 years STANDARD_DEVIATION 16.57 • n=93 Participants	32.7 years STANDARD_DEVIATION 17.43 • n=4 Participants	31.0 years STANDARD_DEVIATION 16.98 • n=27 Participants
Sex: Female, Male Female	19 Participants n=93 Participants	20 Participants n=4 Participants	39 Participants n=27 Participants
Sex: Female, Male Male	15 Participants n=93 Participants	15 Participants n=4 Participants	30 Participants n=27 Participants

PRIMARY outcome

Timeframe: Baseline, Week 24

Population: Full Analysis Set (FAS) included all randomized subjects who received at least 1 dose of study drug (ivacaftor or placebo).

Outcome measures

Outcome measures
Measure	Ivacaftor n=34 Participants Ivacaftor 150 milligram (mg) tablet orally twice daily for 24 weeks.	Placebo n=35 Participants Placebo matched to ivacaftor tablet orally twice daily for 24 weeks.
Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 24	2.5724 percent predicted of FEV1 Standard Error 1.1532	0.4611 percent predicted of FEV1 Standard Error 1.1313

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: FAS included all randomized subjects who received at least 1 dose of study drug (ivacaftor or placebo).

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

Outcome measures

Outcome measures
Measure	Ivacaftor n=34 Participants Ivacaftor 150 milligram (mg) tablet orally twice daily for 24 weeks.	Placebo n=35 Participants Placebo matched to ivacaftor tablet orally twice daily for 24 weeks.
Change From Baseline in Body Mass Index (BMI) at Week 24	0.4910 kg/m^2 Standard Error 0.6653	0.2284 kg/m^2 Standard Error 0.6504

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: FAS included all randomized subjects who received at least 1 dose of study drug (ivacaftor or placebo). Here, "Number of participants analyzed" signifies those subjects who were evaluable for this measure.

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.

Outcome measures

Outcome measures
Measure	Ivacaftor n=32 Participants Ivacaftor 150 milligram (mg) tablet orally twice daily for 24 weeks.	Placebo n=35 Participants Placebo matched to ivacaftor tablet orally twice daily for 24 weeks.
Change From Baseline in Sweat Chloride Through Week 24	-26.2771 millimole per liter (mmol/L) Standard Error 1.4584	-2.3078 millimole per liter (mmol/L) Standard Error 1.3716

SECONDARY outcome

Timeframe: Baseline, Week 24

The CFQ-R is a validated subject-reported outcome measuring health-related quality of life for subjects 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

Outcome measures
Measure	Ivacaftor n=33 Participants Ivacaftor 150 milligram (mg) tablet orally twice daily for 24 weeks.	Placebo n=34 Participants Placebo matched to ivacaftor tablet orally twice daily for 24 weeks.
Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 24	7.5585 units on a scale Standard Error 2.2073	-0.8289 units on a scale Standard Error 2.1569

SECONDARY outcome

Timeframe: Day 0 to 15, Day 16 to 56, Day 57 to 112, Day 113 to 168

Population: FAS included all randomized subjects who received at least 1 dose of study drug (ivacaftor or placebo).

Number of events (pulmonary exacerbation) during the pre-specified time intervals were reported. A subject without an exacerbation before withdrawal from the study was considered censored at the time of withdrawal, and a subject without an exacerbation who completes the study period was considered censored at the end of the analysis period.

Outcome measures

Outcome measures
Measure	Ivacaftor n=34 Participants Ivacaftor 150 milligram (mg) tablet orally twice daily for 24 weeks.	Placebo n=35 Participants Placebo matched to ivacaftor tablet orally twice daily for 24 weeks.
Time to First Pulmonary Exacerbation Day 0 to 15	3 events	1 events
Time to First Pulmonary Exacerbation Day 16 to 56	4 events	2 events
Time to First Pulmonary Exacerbation Day 57 to 112	2 events	6 events
Time to First Pulmonary Exacerbation Day 113 to 168	1 events	4 events

SECONDARY outcome

Timeframe: Baseline up to follow-up (3 to 4 weeks after last dose [last dose = Week 24])

Population: Safety Set included all subjects who received at least 1 dose of study drug (ivacaftor or placebo).

AE: any untoward medical occurrence, including clinically significant clinical laboratory assessments which occurs during course of study, whether it is considered related to study drug or not. SAE: medical event or condition, which falls into any of following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, in-patient hospitalization/prolonged hospitalization, persistent/significant disability/incapacity, congenital anomaly/birth defect, important medical event.

Outcome measures

Outcome measures
Measure	Ivacaftor n=34 Participants Ivacaftor 150 milligram (mg) tablet orally twice daily for 24 weeks.	Placebo n=35 Participants Placebo matched to ivacaftor tablet orally twice daily for 24 weeks.
Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs) Subjects with any AEs	32 participants	35 participants
Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs) Subjects with SAEs	4 participants	6 participants

Adverse Events

Ivacaftor

Serious events: 4 serious events

Other events: 32 other events

Deaths: 0 deaths

Placebo

Serious events: 6 serious events

Other events: 35 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Ivacaftor n=34 participants at risk Ivacaftor 150 milligram (mg) tablet orally twice daily for 24 weeks.	Placebo n=35 participants at risk Placebo matched to ivacaftor tablet orally twice daily for 24 weeks.
Infections and infestations Infective pulmonary exacerbation of cystic fibrosis	8.8% 3/34 • Baseline up to follow-up (3 to 4 weeks after last dose [last dose = Week 24])	17.1% 6/35 • Baseline up to follow-up (3 to 4 weeks after last dose [last dose = Week 24])
Infections and infestations Cellulitis	2.9% 1/34 • Baseline up to follow-up (3 to 4 weeks after last dose [last dose = Week 24])	0.00% 0/35 • Baseline up to follow-up (3 to 4 weeks after last dose [last dose = Week 24])
Gastrointestinal disorders Constipation	2.9% 1/34 • Baseline up to follow-up (3 to 4 weeks after last dose [last dose = Week 24])	0.00% 0/35 • Baseline up to follow-up (3 to 4 weeks after last dose [last dose = Week 24])

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