Trial Outcomes & Findings for Study of Ivacaftor in Cystic Fibrosis Subjects Aged 6 to 11 Years With the G551D Mutation (NCT NCT00909727)

Last Updated: 2012-08-21

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

52 participants

Primary outcome timeframe

baseline through 24 weeks

Results posted on

2012-08-21

Participant Flow

Part A started on 05 August 2009 (signing of first informed consent). Screening evaluations were completed during Day -28 to Day -2. All subjects completing Part A were offered the opportunity to participate in Part B, which started on 12 March 2010. Screening evaluations were completed during Day -35 to Day -15 before the first dose of study drug.

Nine subjects were dosed and included in Part A. In Part B, 52 subjects were enrolled and all were randomized to ivacaftor (26 subjects) or placebo (26 subjects). 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

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	26	26
Overall Study Completed Treatment Period, Week 24	23	26
Overall Study COMPLETED	22	26
Overall Study NOT COMPLETED	4	0

Reasons for withdrawal

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	1	0
Overall Study Wrong Genotype	1	0
Overall Study Withdrawal of Consent	1	0
Overall Study Prohibited Medication	1	0

Baseline Characteristics

Study of Ivacaftor in Cystic Fibrosis Subjects Aged 6 to 11 Years With the G551D Mutation

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=26 Participants Oral tablet every 12 hours (q12h) for up to 48 weeks	150 mg Ivacaftor q12h n=26 Participants Oral tablet of 150 mg of ivacaftor q12h for up to 48 weeks	Total n=52 Participants Total of all reporting groups
Age Continuous	8.9 years STANDARD_DEVIATION 1.86 • n=5 Participants	8.9 years STANDARD_DEVIATION 2.00 • n=7 Participants	8.9 years STANDARD_DEVIATION 1.91 • n=5 Participants
Age, Customized 6 to 8 Years	13 participants n=5 Participants	12 participants n=7 Participants	25 participants n=5 Participants
Age, Customized 9 to 11 Years	12 participants n=5 Participants	11 participants n=7 Participants	23 participants n=5 Participants
Age, Customized > 11 Years	1 participants n=5 Participants	3 participants n=7 Participants	4 participants n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	17 Participants n=7 Participants	27 Participants n=5 Participants
Sex: Female, Male Male	16 Participants n=5 Participants	9 Participants n=7 Participants	25 Participants n=5 Participants
Race/Ethnicity, Customized White	23 participants n=5 Participants	22 participants n=7 Participants	45 participants n=5 Participants
Race/Ethnicity, Customized Other	1 participants n=5 Participants	2 participants n=7 Participants	3 participants n=5 Participants
Race/Ethnicity, Customized Not Allowed to Ask Per Local Regulations	2 participants n=5 Participants	2 participants n=7 Participants	4 participants n=5 Participants
Race/Ethnicity, Customized Hispanic or Latino	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	24 participants n=5 Participants	23 participants n=7 Participants	47 participants n=5 Participants
Region of Enrollment North America	15 participants n=5 Participants	12 participants n=7 Participants	27 participants n=5 Participants
Region of Enrollment Europe	5 participants n=5 Participants	6 participants n=7 Participants	11 participants n=5 Participants
Region of Enrollment Australia	6 participants n=5 Participants	8 participants n=7 Participants	14 participants n=5 Participants
Weight	30.0 kilograms STANDARD_DEVIATION 7.16 • n=5 Participants	31.8 kilograms STANDARD_DEVIATION 9.95 • n=7 Participants	30.9 kilograms STANDARD_DEVIATION 8.63 • n=5 Participants
Body Mass Index	16.8 kilograms per square meter STANDARD_DEVIATION 1.75 • n=5 Participants	17.1 kilograms per square meter STANDARD_DEVIATION 2.61 • n=7 Participants	17.0 kilograms per square meter STANDARD_DEVIATION 2.21 • n=5 Participants
Sweat Chloride	104.8 millimoles per liter STANDARD_DEVIATION 8.87 • n=5 Participants	104.3 millimoles per liter STANDARD_DEVIATION 14.54 • n=7 Participants	104.6 millimoles per liter STANDARD_DEVIATION 11.92 • n=5 Participants
Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) < 70%	8 participants n=5 Participants	4 participants n=7 Participants	12 participants n=5 Participants
Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) ≥ 70% to ≤ 90%	6 participants n=5 Participants	12 participants n=7 Participants	18 participants n=5 Participants
Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) > 90%	12 participants n=5 Participants	10 participants n=7 Participants	22 participants n=5 Participants
Percent Predicted Forced Expiratory Volume in 1 Second (FEV1)	83.7 percentage STANDARD_DEVIATION 20.37 • n=5 Participants	84.7 percentage STANDARD_DEVIATION 15.83 • n=7 Participants	84.2 percentage STANDARD_DEVIATION 18.07 • 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

Outcome measures
Measure	Placebo n=25 Participants Oral tablet every 12 hours (q12h) for up to 48 weeks	150 mg Ivacaftor q12h n=26 Participants Oral tablet of 150 mg of ivacaftor q12h for up to 48 weeks
Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 24	0.1 percent of predicted volume (L) Standard Error 2.1	12.6 percent of predicted volume (L) Standard Error 2.1

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

Outcome measures
Measure	Placebo n=25 Participants Oral tablet every 12 hours (q12h) for up to 48 weeks	150 mg Ivacaftor q12h n=26 Participants Oral tablet of 150 mg of ivacaftor q12h for up to 48 weeks
Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 48	0.7 percent of predicted volume (L) Standard Error 2.0	10.7 percent of predicted volume (L) Standard Error 1.9

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

Outcome measures
Measure	Placebo n=25 Participants Oral tablet every 12 hours (q12h) for up to 48 weeks	150 mg Ivacaftor q12h n=26 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) Through Week 24 and Week 48 (Respiratory Domain Score, Children) Change from Baseline Through Week 48	1.0 score on a scale Standard Error 2.3	6.1 score on a scale Standard Error 2.2
Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Through Week 24 and Week 48 (Respiratory Domain Score, Children) Change from Baseline Through Week 24	0.3 score on a scale Standard Error 2.6	6.3 score on a scale Standard Error 2.5

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

Outcome measures
Measure	Placebo n=23 Participants Oral tablet every 12 hours (q12h) for up to 48 weeks	150 mg Ivacaftor q12h n=23 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	-1.2 millimoles per liter Standard Error 2.6	-55.5 millimoles per liter Standard Error 2.6
Absolute Change From Baseline in Sweat Chloride Concentration Through Week 24 and Week 48 Change from Baseline Through Week 48	-2.6 millimoles per liter Standard Error 2.6	-56.0 millimoles per liter Standard Error 2.5

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

Outcome measures
Measure	Placebo n=26 Participants Oral tablet every 12 hours (q12h) for up to 48 weeks	150 mg Ivacaftor q12h n=26 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	1.8 kilograms Standard Error 0.4	3.7 kilograms Standard Error 0.4
Absolute Change From Baseline in Weight at Week 24 and Week 48 At Week 48	3.1 kilograms Standard Error 0.5	5.9 kilograms Standard Error 0.5

Adverse Events

Placebo

Serious events: 6 serious events

Other events: 25 other events

Deaths: 0 deaths

150 mg Ivacaftor q12h

Serious events: 5 serious events

Other events: 26 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=26 participants at risk Oral tablet every 12 hours (q12h) for up to 48 weeks	150 mg Ivacaftor q12h n=26 participants at risk Oral tablet of 150 mg of ivacaftor q12h for up to 48 weeks
Congenital, familial and genetic disorders Cystic fibrosis lung	11.5% 3/26 • Number of events 3 • For enrolled subjects, adverse events (AEs) were collected through the Follow-up visit in each study part. For subjects who completed 48 weeks of treatment and enrolled in the open-label extension study, AEs were only collected through the Week 48 visit.	7.7% 2/26 • Number of events 2 • For enrolled subjects, adverse events (AEs) were collected through the Follow-up visit in each study part. For subjects who completed 48 weeks of treatment and enrolled in the open-label extension study, AEs were only collected through the Week 48 visit.
Respiratory, thoracic and mediastinal disorders Productive cough	3.8% 1/26 • Number of events 1 • For enrolled subjects, adverse events (AEs) were collected through the Follow-up visit in each study part. For subjects who completed 48 weeks of treatment and enrolled in the open-label extension study, AEs were only collected through the Week 48 visit.	3.8% 1/26 • Number of events 1 • For enrolled subjects, adverse events (AEs) were collected through the Follow-up visit in each study part. For subjects who completed 48 weeks of treatment and enrolled in the open-label extension study, AEs were only collected through the Week 48 visit.
Respiratory, thoracic and mediastinal disorders Lung consolidation	3.8% 1/26 • Number of events 1 • For enrolled subjects, adverse events (AEs) were collected through the Follow-up visit in each study part. For subjects who completed 48 weeks of treatment and enrolled in the open-label extension study, AEs were only collected through the Week 48 visit.	0.00% 0/26 • For enrolled subjects, adverse events (AEs) were collected through the Follow-up visit in each study part. For subjects who completed 48 weeks of treatment and enrolled in the open-label extension study, AEs were only collected through the Week 48 visit.
Gastrointestinal disorders Abdominal pain	0.00% 0/26 • For enrolled subjects, adverse events (AEs) were collected through the Follow-up visit in each study part. For subjects who completed 48 weeks of treatment and enrolled in the open-label extension study, AEs were only collected through the Week 48 visit.	3.8% 1/26 • Number of events 1 • For enrolled subjects, adverse events (AEs) were collected through the Follow-up visit in each study part. For subjects who completed 48 weeks of treatment and enrolled in the open-label extension study, AEs were only collected through the Week 48 visit.
Gastrointestinal disorders Constipation	3.8% 1/26 • Number of events 1 • For enrolled subjects, adverse events (AEs) were collected through the Follow-up visit in each study part. For subjects who completed 48 weeks of treatment and enrolled in the open-label extension study, AEs were only collected through the Week 48 visit.	0.00% 0/26 • For enrolled subjects, adverse events (AEs) were collected through the Follow-up visit in each study part. For subjects who completed 48 weeks of treatment and enrolled in the open-label extension study, AEs were only collected through the Week 48 visit.
Investigations Hepatic enzyme increased	0.00% 0/26 • For enrolled subjects, adverse events (AEs) were collected through the Follow-up visit in each study part. For subjects who completed 48 weeks of treatment and enrolled in the open-label extension study, AEs were only collected through the Week 48 visit.	3.8% 1/26 • Number of events 1 • For enrolled subjects, adverse events (AEs) were collected through the Follow-up visit in each study part. For subjects who completed 48 weeks of treatment and enrolled in the open-label extension study, AEs were only collected through the Week 48 visit.
Investigations Pulmonary function test decreased	3.8% 1/26 • Number of events 1 • For enrolled subjects, adverse events (AEs) were collected through the Follow-up visit in each study part. For subjects who completed 48 weeks of treatment and enrolled in the open-label extension study, AEs were only collected through the Week 48 visit.	0.00% 0/26 • For enrolled subjects, adverse events (AEs) were collected through the Follow-up visit in each study part. For subjects who completed 48 weeks of treatment and enrolled in the open-label extension study, AEs were only collected through the Week 48 visit.
Psychiatric disorders Adjustment disorder	3.8% 1/26 • Number of events 1 • For enrolled subjects, adverse events (AEs) were collected through the Follow-up visit in each study part. For subjects who completed 48 weeks of treatment and enrolled in the open-label extension study, AEs were only collected through the Week 48 visit.	0.00% 0/26 • For enrolled subjects, adverse events (AEs) were collected through the Follow-up visit in each study part. For subjects who completed 48 weeks of treatment and enrolled in the open-label extension study, AEs were only collected through the Week 48 visit.
Psychiatric disorders Anxiety	3.8% 1/26 • Number of events 1 • For enrolled subjects, adverse events (AEs) were collected through the Follow-up visit in each study part. For subjects who completed 48 weeks of treatment and enrolled in the open-label extension study, AEs were only collected through the Week 48 visit.	0.00% 0/26 • For enrolled subjects, adverse events (AEs) were collected through the Follow-up visit in each study part. For subjects who completed 48 weeks of treatment and enrolled in the open-label extension study, AEs were only collected through the Week 48 visit.
Psychiatric disorders Affective disorder	3.8% 1/26 • Number of events 1 • For enrolled subjects, adverse events (AEs) were collected through the Follow-up visit in each study part. For subjects who completed 48 weeks of treatment and enrolled in the open-label extension study, AEs were only collected through the Week 48 visit.	0.00% 0/26 • For enrolled subjects, adverse events (AEs) were collected through the Follow-up visit in each study part. For subjects who completed 48 weeks of treatment and enrolled in the open-label extension study, AEs were only collected through the Week 48 visit.
Psychiatric disorders Conversion disorder	0.00% 0/26 • For enrolled subjects, adverse events (AEs) were collected through the Follow-up visit in each study part. For subjects who completed 48 weeks of treatment and enrolled in the open-label extension study, AEs were only collected through the Week 48 visit.	3.8% 1/26 • Number of events 1 • For enrolled subjects, adverse events (AEs) were collected through the Follow-up visit in each study part. For subjects who completed 48 weeks of treatment and enrolled in the open-label extension study, AEs were only collected through the Week 48 visit.
General disorders Pyrexia	0.00% 0/26 • For enrolled subjects, adverse events (AEs) were collected through the Follow-up visit in each study part. For subjects who completed 48 weeks of treatment and enrolled in the open-label extension study, AEs were only collected through the Week 48 visit.	3.8% 1/26 • Number of events 1 • For enrolled subjects, adverse events (AEs) were collected through the Follow-up visit in each study part. For subjects who completed 48 weeks of treatment and enrolled in the open-label extension study, AEs were only collected through the Week 48 visit.
Infections and infestations Pseudomonas infection	3.8% 1/26 • Number of events 1 • For enrolled subjects, adverse events (AEs) were collected through the Follow-up visit in each study part. For subjects who completed 48 weeks of treatment and enrolled in the open-label extension study, AEs were only collected through the Week 48 visit.	0.00% 0/26 • For enrolled subjects, adverse events (AEs) were collected through the Follow-up visit in each study part. For subjects who completed 48 weeks of treatment and enrolled in the open-label extension study, AEs were only collected through the Week 48 visit.
Injury, poisoning and procedural complications Muscle strain	0.00% 0/26 • For enrolled subjects, adverse events (AEs) were collected through the Follow-up visit in each study part. For subjects who completed 48 weeks of treatment and enrolled in the open-label extension study, AEs were only collected through the Week 48 visit.	3.8% 1/26 • Number of events 1 • For enrolled subjects, adverse events (AEs) were collected through the Follow-up visit in each study part. For subjects who completed 48 weeks of treatment and enrolled in the open-label extension study, AEs were only collected through the Week 48 visit.

Other adverse events

Additional Information

Medical Monitor

Vertex

Phone: 617-444-6777

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60