Study of Ivacaftor in Cystic Fibrosis Subjects Aged 12 Years and Older Homozygous for the F508del-CFTR Mutation (DISCOVER)

This study has been terminated.
(Following review of results obtained from a pre-specified 6-month analysis of Part B data the study was terminated on the basis of futility.)
Sponsor:
Collaborator:
Cystic Fibrosis Foundation Therapeutics
Information provided by (Responsible Party):
Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier:
NCT00953706
First received: August 4, 2009
Last updated: July 29, 2015
Last verified: July 2015
Results First Received: February 27, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Cystic Fibrosis
Interventions: Drug: Ivacaftor
Drug: Placebo

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Placebo – Part A Placebo matched to ivacaftor tablet orally every 12 hours (q12h) for 16 weeks during Part A (double-blind treatment period).
Ivacaftor – Part A Ivacaftor 150 milligram (mg) tablet orally q12h for 16 weeks during Part A (double-blind treatment period).
Placebo/Ivacaftor – Part B Participants who received placebo during Part A, received ivacaftor 150 mg tablet orally q12h for 96 weeks during Part B (open-label extension period).
Ivacaftor/Ivacaftor – Part B Participants who received ivacaftor during Part A, received ivacaftor 150 mg tablet orally q12h for 96 weeks during Part B (open-label extension period).

Participant Flow for 2 periods

Period 1:   Part A (16-Week Double-Blind Treatment)
    Placebo – Part A     Ivacaftor – Part A     Placebo/Ivacaftor – Part B     Ivacaftor/Ivacaftor – Part B  
STARTED     28 [1]   112 [2]   0     0  
COMPLETED     26 [3]   104 [4]   0     0  
NOT COMPLETED     2     8     0     0  
Adverse Event                 2                 3                 0                 0  
Lost to Follow-up                 0                 1                 0                 0  
Noncompliance with Study Requirements                 0                 2                 0                 0  
Required Prohibited Medication                 0                 1                 0                 0  
Sponsor Decision                 0                 1                 0                 0  
[1] All subjects who received at least 1 dose of study drug (placebo)
[2] All subjects who received at least 1 dose of study drug (ivacaftor)
[3] Only 5 participants continued in Part B.
[4] Only 33 participants continued in Part B.

Period 2:   Part B (96-Week Open-Label Extension)
    Placebo – Part A     Ivacaftor – Part A     Placebo/Ivacaftor – Part B     Ivacaftor/Ivacaftor – Part B  
STARTED     0     0     5     33  
COMPLETED     0     0     0     0  
NOT COMPLETED     0     0     5     33  
Adverse Event                 0                 0                 0                 2  
Noncompliance with Study Requirements                 0                 0                 0                 1  
Required Prohibited Medication                 0                 0                 0                 1  
Study Termination by Sponsor                 0                 0                 4                 25  
Withdrawal by Subject                 0                 0                 1                 2  
Unspecified                 0                 0                 0                 2  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Placebo – Part A Placebo matched to ivacaftor tablet orally every 12 hours (q12h) for 16 weeks during Part A (double-blind treatment period).
Ivacaftor – Part A Ivacaftor 150 milligram (mg) tablet orally q12h for 16 weeks during Part A (double-blind treatment period).
Total Total of all reporting groups

Baseline Measures
    Placebo – Part A     Ivacaftor – Part A     Total  
Number of Participants  
[units: participants]
  28     112     140  
Age  
[units: years]
Mean (Standard Deviation)
  25.0  (8.35)     22.8  (10.26)     23.2  (9.91)  
Age, Customized  
[units: participants]
     
12 to 17 Years     6     44     50  
18 to 24 Years     10     32     42  
25 to 39 Years     12     26     38  
40 to 45 Years     0     5     5  
> 45 Years     0     5     5  
Gender  
[units: participants]
     
Female     12     54     66  
Male     16     58     74  
Race/Ethnicity, Customized  
[units: participants]
     
Hispanic or Latino     1     2     3  
Not Hispanic or Latino     27     110     137  
Race/Ethnicity, Customized  
[units: participants]
     
Black or African American     0     1     1  
White     28     111     139  
Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1), Continuous [1]
[units: percent predicted of FEV1]
Mean (Standard Deviation)
  74.8  (24.06)     79.7  (22.67)     78.7  (22.95)  
ppFEV1, Categorical [1]
[units: participants]
     
< 70%     15     38     53  
≥ 70% to ≤ 90%     5     35     40  
> 90%     8     39     47  
Weight  
[units: kilograms]
Mean (Standard Deviation)
  63.2  (14.96)     58.2  (13.49)     59.2  (13.89)  
Body Mass Index  
[units: kilogram per square meter]
Mean (Standard Deviation)
  22.2  (4.48)     21.2  (3.25)     21.4  (3.54)  
Sweat Chloride  
[units: millimoles per liter]
Mean (Standard Deviation)
  102.4  (7.91)     101.4  (10.28)     101.6  (9.83)  
[1] Percent predicted for age, gender, and height.



  Outcome Measures
  Hide All Outcome Measures

1.  Primary:   Part A : Absolute Change From Part A Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) Through Week 16   [ Time Frame: Part A baseline through Week 16 ]

Measure Type Primary
Measure Title Part A : Absolute Change From Part A Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) Through Week 16
Measure Description Spirometry (as measured by ppFEV1) is a standardized assessment to evaluate lung function that is the most widely used endpoint in cystic fibrosis studies. FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. ppFEV1 (predicted for age, gender, and height) was calculated using the Knudson method.
Time Frame Part A baseline through Week 16  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Part A Full Analysis Set (FAS) included all randomized participants who received at least 1 dose of study drug during Part A. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.

Reporting Groups
  Description
Placebo – Part A Placebo matched to ivacaftor tablet orally q12h for 16 weeks during Part A (double-blind treatment period).
Ivacaftor – Part A Ivacaftor 150 mg tablet orally q12h for 16 weeks during Part A (double-blind treatment period).

Measured Values
    Placebo – Part A     Ivacaftor – Part A  
Number of Participants Analyzed  
[units: participants]
  28     111  
Part A : Absolute Change From Part A Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) Through Week 16  
[units: percent predicted of FEV1]
Least Squares Mean (Standard Error)
  -0.2  (1.1)     1.5  (0.5)  


Statistical Analysis 1 for Part A : Absolute Change From Part A Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) Through Week 16
Groups [1] All groups
Method [2] Mixed Models Analysis
P Value [3] 0.1509
Mean Difference (Final Values) [4] 1.7
Standard Error of the mean (1.2)
95% Confidence Interval -0.6 to 4.1
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The primary analysis for the primary efficacy variable was based on a Mixed-Effects Model for Repeated Measures (MMRM). The model included absolute change from baseline in percent predicted forced expiratory volume in 1 second (FEV1) as the dependent variable, treatment (ivacaftor versus placebo) and visit as fixed effects, and participant as a random effect, with adjustment for age and continuous baseline value of percent predicted FEV1.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



2.  Secondary:   Part A : Absolute Change From Part A Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 16   [ Time Frame: Part A baseline through Week 16 ]

Measure Type Secondary
Measure Title Part A : Absolute Change From Part A Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 16
Measure Description The CFQ-R is a validated patient-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.
Time Frame Part A baseline through Week 16  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Part A FAS. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.

Reporting Groups
  Description
Placebo – Part A Placebo matched to ivacaftor tablet orally q12h for 16 weeks during Part A (double-blind treatment period).
Ivacaftor – Part A Ivacaftor 150 mg tablet orally q12h for 16 weeks during Part A (double-blind treatment period).

Measured Values
    Placebo – Part A     Ivacaftor – Part A  
Number of Participants Analyzed  
[units: participants]
  28     111  
Part A : Absolute Change From Part A Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 16  
[units: units on a scale]
Least Squares Mean (Standard Error)
  -1.4  (1.9)     -0.1  (1.0)  


Statistical Analysis 1 for Part A : Absolute Change From Part A Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 16
Groups [1] All groups
Method [2] Mixed Models Analysis
P Value [3] 0.5408
Mean Difference (Final Values) [4] 1.3
Standard Error of the mean (2.1)
95% Confidence Interval -2.9 to 5.6
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Analysis for the respiratory domain score endpoint was similar to that of the primary analysis of the primary efficacy endpoint. Estimates were from Mixed-Effects Model for Repeated Measures (MMRM) with the dependent variable being absolute change from baseline, fixed effects for categorical visit and treatment group, and adjustment for for age and baseline value for CFQ-R score, using unstructured covariance matrix
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



3.  Secondary:   Part A : Absolute Change From Part A Baseline in Sweat Chloride Concentration Through Week 16   [ Time Frame: Part A baseline through Week 16 ]

Measure Type Secondary
Measure Title Part A : Absolute Change From Part A Baseline in Sweat Chloride Concentration Through Week 16
Measure Description 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.
Time Frame Part A baseline through Week 16  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Part A FAS. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.

Reporting Groups
  Description
Placebo – Part A Placebo matched to ivacaftor tablet orally q12h for 16 weeks during Part A (double-blind treatment period).
Ivacaftor – Part A Ivacaftor 150 mg tablet orally q12h for 16 weeks during Part A (double-blind treatment period).

Measured Values
    Placebo – Part A     Ivacaftor – Part A  
Number of Participants Analyzed  
[units: participants]
  28     111  
Part A : Absolute Change From Part A Baseline in Sweat Chloride Concentration Through Week 16  
[units: millimole per liter (mmol/L)]
Least Squares Mean (Standard Error)
  0.1  (1.2)     -2.7  (0.6)  


Statistical Analysis 1 for Part A : Absolute Change From Part A Baseline in Sweat Chloride Concentration Through Week 16
Groups [1] All groups
Method [2] Mixed Models Analysis
P Value [3] 0.0384
Mean Difference (Final Values) [4] -2.9
Standard Error of the mean (1.4)
95% Confidence Interval -5.6 to -0.2
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Analysis for this variable was similar to that of the primary analysis of the primary efficacy endpoint. Estimates were from Mixed-Effects Model for Repeated Measures (MMRM) with dependent variable being absolute change from baseline, fixed effects for categorical visit and treatment group, and adjustment for continuous age and baseline value for age, sweat chloride, using unstructured covariance matrix.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



4.  Secondary:   Part A : Rate of Change From Baseline in Weight Through Week 16   [ Time Frame: Part A baseline through Week 16 ]

Measure Type Secondary
Measure Title Part A : Rate of Change From Baseline in Weight Through Week 16
Measure Description As malnutrition is common in participants 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.
Time Frame Part A baseline through Week 16  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Part A FAS. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.

Reporting Groups
  Description
Placebo – Part A Placebo matched to ivacaftor tablet orally q12h for 16 weeks during Part A (double-blind treatment period).
Ivacaftor – Part A Ivacaftor 150 mg tablet orally q12h for 16 weeks during Part A (double-blind treatment period).

Measured Values
    Placebo – Part A     Ivacaftor – Part A  
Number of Participants Analyzed  
[units: participants]
  28     112  
Part A : Rate of Change From Baseline in Weight Through Week 16  
[units: kilograms per 112 days]
Least Squares Mean (Standard Error)
  0.9  (0.4)     0.8  (0.2)  


Statistical Analysis 1 for Part A : Rate of Change From Baseline in Weight Through Week 16
Groups [1] All groups
Method [2] Mixed Models Analysis
P Value [3] 0.7265
Mean Difference (Final Values) [4] -0.2
Standard Error of the mean (0.5)
95% Confidence Interval -1.1 to 0.7
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The analysis used the linear mixed model with treatment as fixed effects, visit (days on study) and treatment by visit interaction as random effects, with adjustment for age group (< 18 years and ≥ 18 years) and percent predicted forced expiratory volume (FEV1) severity (< 70%, ≥ 70% to ≤ 90%, > 90%) at screening, with random intercept and random slope. Rate of change in the study period is the slope of weight versus time (days) multiplied by the number of days in the study period (112 days).
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



5.  Secondary:   Part B : Absolute Change From Part A and Part B Baseline in ppFEV1 Through Week 64   [ Time Frame: Change from Part A baseline: Part A Baseline, Week 64; Change from Part B baseline: Part B Baseline (Week 16), Week 64 ]

Measure Type Secondary
Measure Title Part B : Absolute Change From Part A and Part B Baseline in ppFEV1 Through Week 64
Measure Description ppFEV1 is defined in Outcome Measure 1.
Time Frame Change from Part A baseline: Part A Baseline, Week 64; Change from Part B baseline: Part B Baseline (Week 16), Week 64  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Part B FAS included all participants who received at least 1 dose of study drug during Part B. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.

Reporting Groups
  Description
Placebo/Ivacaftor – Part B Participants who received placebo during Part A, received ivacaftor 150 mg tablet orally q12h for 96 weeks during Part B (open-label extension period).
Ivacaftor/Ivacaftor – Part B Participants who received ivacaftor during Part A, received ivacaftor 150 mg tablet orally q12h for 96 weeks during Part B (open-label extension period).

Measured Values
    Placebo/Ivacaftor – Part B     Ivacaftor/Ivacaftor – Part B  
Number of Participants Analyzed  
[units: participants]
  4     27  
Part B : Absolute Change From Part A and Part B Baseline in ppFEV1 Through Week 64  
[units: percent predicted of FEV1]
Mean (Standard Deviation)
   
Change From Part A Baseline at Week 64     8.9398  (9.70300)     2.7233  (10.52046)  
Change From Part B Baseline at Week 64     3.5593  (7.95875)     -5.0565  (11.44783)  

No statistical analysis provided for Part B : Absolute Change From Part A and Part B Baseline in ppFEV1 Through Week 64



6.  Secondary:   Part B : Rate of Decline From Part A Baseline in ppFEV1 Through Week 64   [ Time Frame: Part A baseline through Week 64 ]

Measure Type Secondary
Measure Title Part B : Rate of Decline From Part A Baseline in ppFEV1 Through Week 64
Measure Description ppFEV1 is defined in Outcome Measure 1.
Time Frame Part A baseline through Week 64  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Part B FAS.

Reporting Groups
  Description
Placebo/Ivacaftor – Part B Participants who received placebo during Part A, received ivacaftor 150 mg tablet orally q12h for 96 weeks during Part B (open-label extension period).
Ivacaftor/Ivacaftor – Part B Participants who received ivacaftor during Part A, received ivacaftor 150 mg tablet orally q12h for 96 weeks during Part B (open-label extension period).

Measured Values
    Placebo/Ivacaftor – Part B     Ivacaftor/Ivacaftor – Part B  
Number of Participants Analyzed  
[units: participants]
  5     33  
Part B : Rate of Decline From Part A Baseline in ppFEV1 Through Week 64  
[units: percent predicted of FEV1 per 448 days]
Least Squares Mean (Standard Error)
  5.7445  (3.6810)     -1.0738  (1.5025)  

No statistical analysis provided for Part B : Rate of Decline From Part A Baseline in ppFEV1 Through Week 64



7.  Secondary:   Part B : Rate of Decline From Part B Baseline in ppFEV1 Through Week 64   [ Time Frame: Part B baseline through Week 64 ]

Measure Type Secondary
Measure Title Part B : Rate of Decline From Part B Baseline in ppFEV1 Through Week 64
Measure Description ppFEV1 is defined in Outcome Measure 1.
Time Frame Part B baseline through Week 64  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Part B FAS.

Reporting Groups
  Description
Placebo/Ivacaftor – Part B Participants who received placebo during Part A, received ivacaftor 150 mg tablet orally q12h for 96 weeks during Part B (open-label extension period).
Ivacaftor/Ivacaftor – Part B Participants who received ivacaftor during Part A, received ivacaftor 150 mg tablet orally q12h for 96 weeks during Part B (open-label extension period).

Measured Values
    Placebo/Ivacaftor – Part B     Ivacaftor/Ivacaftor – Part B  
Number of Participants Analyzed  
[units: participants]
  5     33  
Part B : Rate of Decline From Part B Baseline in ppFEV1 Through Week 64  
[units: percent predicted of FEV1 per 336 days]
Least Squares Mean (Standard Error)
  5.3409  (4.5790)     -5.2994  (1.8871)  

No statistical analysis provided for Part B : Rate of Decline From Part B Baseline in ppFEV1 Through Week 64



8.  Secondary:   Part B : Absolute Change From Part A and Part B Baseline in CFQ-R Respiratory Domain Score Through Week 64   [ Time Frame: Change from Part A baseline: Part A Baseline, Week 64; Change from Part B baseline: Part B Baseline (Week 16), Week 64 ]

Measure Type Secondary
Measure Title Part B : Absolute Change From Part A and Part B Baseline in CFQ-R Respiratory Domain Score Through Week 64
Measure Description The CFQ-R is a validated patient-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.
Time Frame Change from Part A baseline: Part A Baseline, Week 64; Change from Part B baseline: Part B Baseline (Week 16), Week 64  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Part B FAS. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.

Reporting Groups
  Description
Placebo/Ivacaftor – Part B Participants who received placebo during Part A, received ivacaftor 150 mg tablet orally q12h for 96 weeks during Part B (open-label extension period).
Ivacaftor/Ivacaftor – Part B Participants who received ivacaftor during Part A, received ivacaftor 150 mg tablet orally q12h for 96 weeks during Part B (open-label extension period).

Measured Values
    Placebo/Ivacaftor – Part B     Ivacaftor/Ivacaftor – Part B  
Number of Participants Analyzed  
[units: participants]
  4     26  
Part B : Absolute Change From Part A and Part B Baseline in CFQ-R Respiratory Domain Score Through Week 64  
[units: units on a scale]
Mean (Standard Deviation)
   
Change From Part A Baseline at Week 64     2.10  (11.443)     1.50  (15.778)  
Change From Part B Baseline at Week 64     2.08  (17.763)     2.62  (15.899)  

No statistical analysis provided for Part B : Absolute Change From Part A and Part B Baseline in CFQ-R Respiratory Domain Score Through Week 64



9.  Secondary:   Part B : Absolute Change From Part A and Part B Baseline in Sweat Chloride Concentration Through Week 64   [ Time Frame: Change from Part A baseline: Part A Baseline, Week 64; Change from Part B baseline: Part B Baseline (Week 16), Week 64 ]

Measure Type Secondary
Measure Title Part B : Absolute Change From Part A and Part B Baseline in Sweat Chloride Concentration Through Week 64
Measure Description 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.
Time Frame Change from Part A baseline: Part A Baseline, Week 64; Change from Part B baseline: Part B Baseline (Week 16), Week 64  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Part B FAS. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.

Reporting Groups
  Description
Placebo/Ivacaftor – Part B Participants who received placebo during Part A, received ivacaftor 150 mg tablet orally q12h for 96 weeks during Part B (open-label extension period).
Ivacaftor/Ivacaftor – Part B Participants who received ivacaftor during Part A, received ivacaftor 150 mg tablet orally q12h for 96 weeks during Part B (open-label extension period).

Measured Values
    Placebo/Ivacaftor – Part B     Ivacaftor/Ivacaftor – Part B  
Number of Participants Analyzed  
[units: participants]
  4     26  
Part B : Absolute Change From Part A and Part B Baseline in Sweat Chloride Concentration Through Week 64  
[units: mmol/L]
Mean (Standard Deviation)
   
Change From Part A Baseline at Week 64     -7.13  (15.612)     -3.65  (11.963)  
Change From Part B Baseline at Week 64     -3.88  (7.685)     -2.44  (11.037)  

No statistical analysis provided for Part B : Absolute Change From Part A and Part B Baseline in Sweat Chloride Concentration Through Week 64



10.  Secondary:   Part B : Absolute Change From Part A and Part B Baseline in Weight Through Week 64   [ Time Frame: Change from Part A baseline: Part A Baseline, Week 64; Change from Part B baseline: Part B Baseline (Week 16), Week 64 ]

Measure Type Secondary
Measure Title Part B : Absolute Change From Part A and Part B Baseline in Weight Through Week 64
Measure Description 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.
Time Frame Change from Part A baseline: Part A Baseline, Week 64; Change from Part B baseline: Part B Baseline (Week 16), Week 64  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Part B FAS. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.

Reporting Groups
  Description
Placebo/Ivacaftor – Part B Participants who received placebo during Part A, received ivacaftor 150 mg tablet orally q12h for 96 weeks during Part B (open-label extension period).
Ivacaftor/Ivacaftor – Part B Participants who received ivacaftor during Part A, received ivacaftor 150 mg tablet orally q12h for 96 weeks during Part B (open-label extension period).

Measured Values
    Placebo/Ivacaftor – Part B     Ivacaftor/Ivacaftor – Part B  
Number of Participants Analyzed  
[units: participants]
  4     27  
Part B : Absolute Change From Part A and Part B Baseline in Weight Through Week 64  
[units: kilograms (kg)]
Mean (Standard Deviation)
   
Change From Part A Baseline at Week 64     3.00  (3.550)     2.35  (5.600)  
Change From Part B Baseline at Week 64     1.28  (2.243)     1.45  (3.840)  

No statistical analysis provided for Part B : Absolute Change From Part A and Part B Baseline in Weight Through Week 64



11.  Secondary:   Part B : Number of Participants With Pulmonary Exacerbations   [ Time Frame: Part B baseline through Week 64 ]

Measure Type Secondary
Measure Title Part B : Number of Participants With Pulmonary Exacerbations
Measure Description Pulmonary exacerbation was defined as new, or changed, antibiotic therapy (intravenous, inhaled, or oral) for any 4 or more of the following signs/symptoms: change in sputum; new or increased hemoptysis; increased cough; increased dyspnea; malaise, fatigue, or lethargy; temperature above 38 degrees Celsius; anorexia or weight loss; sinus pain or tenderness; change in sinus discharge; change in physical examination of the chest; decrease in pulmonary function by 10 percent (%); and radiographic changes indicative of pulmonary infection.
Time Frame Part B baseline through Week 64  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Part B FAS.

Reporting Groups
  Description
Placebo/Ivacaftor – Part B Participants who received placebo during Part A, received ivacaftor 150 mg tablet orally q12h for 96 weeks during Part B (open-label extension period).
Ivacaftor/Ivacaftor – Part B Participants who received ivacaftor during Part A, received ivacaftor 150 mg tablet orally q12h for 96 weeks during Part B (open-label extension period).

Measured Values
    Placebo/Ivacaftor – Part B     Ivacaftor/Ivacaftor – Part B  
Number of Participants Analyzed  
[units: participants]
  5     33  
Part B : Number of Participants With Pulmonary Exacerbations  
[units: participants]
  4     16  

No statistical analysis provided for Part B : Number of Participants With Pulmonary Exacerbations



12.  Secondary:   Part B : Number of Pulmonary Exacerbation Events   [ Time Frame: Part B baseline through Week 64 ]

Measure Type Secondary
Measure Title Part B : Number of Pulmonary Exacerbation Events
Measure Description Pulmonary exacerbation was defined as new, or changed, antibiotic therapy (intravenous, inhaled, or oral) for any 4 or more of the following signs/symptoms: change in sputum; new or increased hemoptysis; increased cough; increased dyspnea; malaise, fatigue, or lethargy; temperature above 38 degrees Celsius; anorexia or weight loss; sinus pain or tenderness; change in sinus discharge; change in physical examination of the chest; decrease in pulmonary function by 10 percent (%); and radiographic changes indicative of pulmonary infection.
Time Frame Part B baseline through Week 64  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Part B FAS.

Reporting Groups
  Description
Placebo/Ivacaftor – Part B Participants who received placebo during Part A, received ivacaftor 150 mg tablet orally q12h for 96 weeks during Part B (open-label extension period).
Ivacaftor/Ivacaftor – Part B Participants who received ivacaftor during Part A, received ivacaftor 150 mg tablet orally q12h for 96 weeks during Part B (open-label extension period).

Measured Values
    Placebo/Ivacaftor – Part B     Ivacaftor/Ivacaftor – Part B  
Number of Participants Analyzed  
[units: participants]
  5     33  
Part B : Number of Pulmonary Exacerbation Events  
[units: events]
  6     26  

No statistical analysis provided for Part B : Number of Pulmonary Exacerbation Events



13.  Secondary:   Part B : Number of Pulmonary Exacerbation Events Per Participant Per Year   [ Time Frame: Part B baseline through Week 64 ]

Measure Type Secondary
Measure Title Part B : Number of Pulmonary Exacerbation Events Per Participant Per Year
Measure Description Pulmonary exacerbation was defined as new, or changed, antibiotic therapy (intravenous, inhaled, or oral) for any 4 or more of the following signs/symptoms: change in sputum; new or increased hemoptysis; increased cough; increased dyspnea; malaise, fatigue, or lethargy; temperature above 38 degrees Celsius; anorexia or weight loss; sinus pain or tenderness; change in sinus discharge; change in physical examination of the chest; decrease in pulmonary function by 10 percent (%); and radiographic changes indicative of pulmonary infection.
Time Frame Part B baseline through Week 64  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Part B FAS.

Reporting Groups
  Description
Placebo/Ivacaftor – Part B Participants who received placebo during Part A, received ivacaftor 150 mg tablet orally q12h for 96 weeks during Part B (open-label extension period).
Ivacaftor/Ivacaftor – Part B Participants who received ivacaftor during Part A, received ivacaftor 150 mg tablet orally q12h for 96 weeks during Part B (open-label extension period).

Measured Values
    Placebo/Ivacaftor – Part B     Ivacaftor/Ivacaftor – Part B  
Number of Participants Analyzed  
[units: participants]
  5     33  
Part B : Number of Pulmonary Exacerbation Events Per Participant Per Year  
[units: events per participant per year]
  1.10     0.82  

No statistical analysis provided for Part B : Number of Pulmonary Exacerbation Events Per Participant Per Year




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
In Part B, the treatment duration was 96 weeks; however, due to early study termination all analysis were performed up to Week 64, as planned.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Medical Monitor
Organization: Vertex
phone: 617-444-6777
e-mail: medicalinfo@vrtx.com


No publications provided by Vertex Pharmaceuticals Incorporated

Publications automatically indexed to this study:

Responsible Party: Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier: NCT00953706     History of Changes
Other Study ID Numbers: VX08-770-104, 2009-010261-23
Study First Received: August 4, 2009
Results First Received: February 27, 2012
Last Updated: July 29, 2015
Health Authority: United States: Food and Drug Administration