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Safety Study of Ivacaftor in Subjects With Cystic Fibrosis

This study has been completed.
Sponsor:
Collaborator:
Cystic Fibrosis Foundation
Information provided by (Responsible Party):
Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier:
NCT00457821
First received: April 5, 2007
Last updated: October 3, 2012
Last verified: October 2012
Results First Received: February 27, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety Study;   Intervention Model: Crossover Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Cystic Fibrosis
Interventions: Drug: Ivacaftor 25 mg/75 mg
Drug: Ivacaftor 75 mg/150 mg
Drug: Ivacaftor 150 mg or 250 mg
Drug: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Part 1 started on 10 May 2007 (signing of first informed consent). After obtaining consent, Part 1 screening evaluations were completed during Day -28 to Day -2. Part 2 started on 28 May 2008 (signing of first informed consent). Part 2 screening evaluations were also completed during Day -28 to Day -2 before the first dose of study drug.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
In Part 1, 21 subjects were randomized but 1 subject was excluded prior to dosing because the subject needed a protocol-prohibited medication. In Part 2, 20 subjects were randomized but 1 subject withdrew consent to the study prior to dosing.

Reporting Groups
  Description
Part 1: Placebo Part 1: placebo every 12 hours (q12h); 14 days/14 days.
Part 1: 25 mg/75 mg Part 1: Ivacaftor (25 mg/75 mg) every 12 hours (q12h); 14 days/14 days.
Part 1: 75 mg/25 mg Part 1: Ivacaftor (75 mg/25 mg) every 12 hours (q12h); 14 days/14 days.
Part 1: 75 mg/150 mg Part 1: Ivacaftor (75 mg/150 mg) every 12 hours (q12h); 14 days/14 days.
Part 1: 150 mg/75 mg Part 1: Ivacaftor (150 mg/75 mg) every 12 hours (q12h); 14 days/14 days.
Part 2: 150 mg Part 2: Ivacaftor (150 mg) q12h; 28 days
Part 2: 250 mg Part 2: Ivacaftor (250 mg) q12h; 28 days
Part 2: Placebo Part 2: placebo q12h; 28 days

Participant Flow for 2 periods

Period 1:   Part 1
    Part 1: Placebo     Part 1: 25 mg/75 mg     Part 1: 75 mg/25 mg     Part 1: 75 mg/150 mg     Part 1: 150 mg/75 mg     Part 2: 150 mg     Part 2: 250 mg     Part 2: Placebo  
STARTED     4 [1]   4 [1]   5 [1]   4 [1]   4 [1]   0 [2]   0 [2]   0 [2]
COMPLETED     4     4     4     4     4     0     0     0  
NOT COMPLETED     0     0     1     0     0     0     0     0  
[1] Number of subjects randomized
[2] Arm in Part 2 only

Period 2:   Part 2
    Part 1: Placebo     Part 1: 25 mg/75 mg     Part 1: 75 mg/25 mg     Part 1: 75 mg/150 mg     Part 1: 150 mg/75 mg     Part 2: 150 mg     Part 2: 250 mg     Part 2: Placebo  
STARTED     0 [1]   0 [1]   0 [1]   0 [1]   0 [1]   8 [2]   7 [2]   5 [3]
Completed Study Drug Treatment     0     0     0     0     0     8     7 [4]   4  
COMPLETED     0     0     0     0     0     8     7     4  
NOT COMPLETED     0     0     0     0     0     0     0     1  
Withdrawal by Subject                 0                 0                 0                 0                 0                 0                 0                 1  
[1] Arm in Part 1 only
[2] All subjects who received at least 1 dose of study drug (ivacaftor).
[3] All subjects who received at least 1 dose of study drug (placebo).
[4] 1 subject missed a 250-mg dose of ivacaftor on Day 28 of Part 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
Part 1: Placebo Part 1: placebo every 12 hours (q12h); 14 days/14 days.
Part 1: 25 mg/75 mg Part 1: Ivacaftor (25 mg/75 mg) every 12 hours (q12h); 14 days/14 days.
Part 1: 75 mg/25 mg Part 1: Ivacaftor (75 mg/25 mg) every 12 hours (q12h); 14 days/14 days.
Part 1: 75 mg/150 mg Part 1: Ivacaftor (75 mg/150 mg) every 12 hours (q12h); 14 days/14 days.
Part 1: 150 mg/75 mg Part 1: Ivacaftor (150 mg/75 mg) every 12 hours (q12h); 14 days/14 days.
Part 2: 150 mg Part 2: Ivacaftor (150 mg) q12h; 28 days
Part 2: 250 mg Part 2: Ivacaftor (250 mg) q12h; 28 days
Part 2: Placebo Part 2: placebo q12h; 28 days
Total Total of all reporting groups

Baseline Measures
    Part 1: Placebo     Part 1: 25 mg/75 mg     Part 1: 75 mg/25 mg     Part 1: 75 mg/150 mg     Part 1: 150 mg/75 mg     Part 2: 150 mg     Part 2: 250 mg     Part 2: Placebo     Total  
Number of Participants  
[units: participants]
  4     4     4     4     4     8     7     4     39  
Age  
[units: years]
Mean ± Standard Deviation
  34.5  ± 14.66     33.5  ± 12.50     38.5  ± 11.82     26.3  ± 7.85     23.5  ± 6.45     25.6  ± 7.98     26.0  ± 7.07     26.8  ± 10.69     28.7  ± 10.03  
Gender  
[units: participants]
                 
Female     2     3     0     3     3     5     3     1     20  
Male     2     1     4     1     1     3     4     3     19  
Race/Ethnicity, Customized  
[units: participants]
                 
Caucasian     4     4     4     4     4     8     7     4     39  
Weight  
[units: kilograms]
Mean ± Standard Deviation
  70.05  ± 16.507     66.05  ± 12.628     73.43  ± 14.366     57.48  ± 8.663     59.35  ± 18.401     61.19  ± 9.857     64.46  ± 13.027     63.50  ± 7.391     64.1  ± 12.42  
Body Mass Index  
[units: kilograms per square meter]
Mean ± Standard Deviation
  24.195  ± 3.2002     22.455  ± 2.3133     23.653  ± 3.6216     20.960  ± 2.2522     20.788  ± 4.1527     21.896  ± 0.9770     22.703  ± 1.3980     22.035  ± 0.6999     22.3  ± 2.37  
Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) [1]
[units: percentage of volume in liters]
Mean ± Standard Deviation
  64.902  ± 22.6821     71.073  ± 27.2307     54.885  ± 9.6772     68.284  ± 24.7014     49.270  ± 7.5615     70.443  ± 25.4442     72.674  ± 21.5223     79.351  ± 28.7018     67.3  ± 22.17  
Genotype  
[units: participants]
                 
G551D/1078 DEL T     1     0     0     0     0     0     0     0     1  
G551D/DELTA F508     3     4     4     2     3     7     5     4     32  
G551D/G551D     0     0     0     0     1     0     0     0     1  
G551D/N1303K     0     0     0     1     0     0     0     0     1  
G551D/R553X     0     0     0     1     0     0     0     0     1  
G551D/3849 AND 10KBC     0     0     0     0     0     0     1     0     1  
G551D/6214 + 1G > 7T     0     0     0     0     0     1     0     0     1  
G551D/G542X     0     0     0     0     0     0     1     0     1  
[1] Percent predicted for age, gender, and height.



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Number of Subjects With Adverse Events (Combined Part 1 and Part 2)   [ Time Frame: Baseline to Follow-up ]

2.  Primary:   Number of Adverse Events (Combined Part 1 and Part 2)   [ Time Frame: Baseline to Follow-up ]

3.  Secondary:   Change From Baseline in Nasal Potential Difference (Combined Part 1 and Part 2)   [ Time Frame: 14 days and 28 days ]

4.  Secondary:   Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second [FEV1] (Combined Part 1 and Part 2)   [ Time Frame: 14 days and 28 days ]

5.  Secondary:   Change From Baseline in the Cystic Fibrosis Questionnaire-Revised (CFQ-R) Score (Part 2 Only)(Respiratory Domain Score)   [ Time Frame: 14 days and 28 days ]

6.  Secondary:   Change From Baseline in Maximum Sweat Chloride Concentration (Combined Part 1 and Part 2)   [ Time Frame: 14 days and 28 days ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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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
No text entered.


  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


Publications of Results:
Publications automatically indexed to this study:

Responsible Party: Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier: NCT00457821     History of Changes
Other Study ID Numbers: VX06-770-101
Study First Received: April 5, 2007
Results First Received: February 27, 2012
Last Updated: October 3, 2012
Health Authority: United States: Food and Drug Administration