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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Cystic Fibrosis Foundation
Information provided by (Responsible Party):
Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier:
NCT00953706
First received: August 4, 2009
Last updated: October 25, 2012
Last verified: October 2012
History of Changes
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
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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 A started on 21 September 2009 (date of first informed consent). After obtaining consent and assent (where applicable), screening evaluations were completed during a period of 2 to 5 weeks (Day -35 to Day -15) 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 A, a total of 140 subjects were enrolled. All received at least 1 dose of the study drug. A 2-week run-in period was included to establish the baseline assessments on Day 1 after ensuring that subjects were properly adhering to their cystic fibrosis (CF) medication regimens.

Reporting Groups
  Description
Placebo Oral tablet every 12 hours (q12h) for 16 weeks
150 mg Ivacaftor q12h Oral tablet of 150 mg of ivacaftor q12h for 16 weeks

Participant Flow:   Overall Study
    Placebo     150 mg Ivacaftor q12h  
STARTED     28 [1]   112 [2]
COMPLETED     26 [3]   104 [3]
NOT COMPLETED     2     8  
Adverse Event                 2                 3  
Lost to Follow-up                 0                 1  
Noncompliance with Study Requirements                 0                 2  
Prohibited Medication                 0                 1  
Early Termination Per Sponsor Decision                 0                 1  
[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] Completed Part A Treatment Period (Through Week 16)



  Baseline Characteristics
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Reporting Groups
  Description
Placebo Oral tablet every 12 hours (q12h) for 16 weeks
150 mg Ivacaftor q12h Oral tablet of 150 mg of ivacaftor q12h for 16 weeks
Total Total of all reporting groups

Baseline Measures
    Placebo     150 mg Ivacaftor q12h     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 (FEV1), Continuous [1]
[units: percentage]
Mean ± Standard Deviation 		  74.8  ± 24.06     79.7  ± 22.67     78.7  ± 22.95  
Percent Predicted FEV1, 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
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1.  Primary:   Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 16   [ Time Frame: baseline through 16 weeks ]
  Show Outcome Measure 1

2.  Secondary:   Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Score Through Week 16 (Respiratory Domain Score, Pooled)   [ Time Frame: baseline through 16 weeks ]
  Show Outcome Measure 2

3.  Secondary:   Absolute Change From Baseline in Sweat Chloride Concentration Through Week 16   [ Time Frame: baseline through 16 weeks ]
  Show Outcome Measure 3

4.  Secondary:   Rate of Change From Baseline in Weight Through Week 16   [ Time Frame: baseline to 16 weeks ]
  Show Outcome Measure 4


  Serious Adverse Events
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  Other Adverse Events
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Time Frame Adverse events (serious and non-serious) were collected from signing of informed consent through the Week 16 visit if the subject continued to Part B of the study, or through the 4-week Follow-up if the subject did not participate in Part B.
Additional Description No text entered.

Frequency Threshold
Threshold above which other adverse events are reported   5%  

Reporting Groups
  Description
Placebo Oral tablet every 12 hours (q12h) for 16 weeks
150 mg Ivacaftor q12h Oral tablet of 150 mg of ivacaftor q12h for 16 weeks

Other Adverse Events
    Placebo     150 mg Ivacaftor q12h  
Total, other (not including serious) adverse events      
# participants affected / at risk     25/28     98/112  
Congenital, familial and genetic disorders      
Cystic fibrosis lung † 1 [3]    
# participants affected / at risk     7/28 (25.00%)     19/112 (16.96%)  
# events     8     24  
Gastrointestinal disorders      
Nausea † 1    
# participants affected / at risk     1/28 (3.57%)     10/112 (8.93%)  
# events     1     11  
Abdominal pain upper † 1    
# participants affected / at risk     1/28 (3.57%)     7/112 (6.25%)  
# events     4     8  
Diarrhoea † 1    
# participants affected / at risk     2/28 (7.14%)     6/112 (5.36%)  
# events     2     7  
General disorders      
Fatigue † 1    
# participants affected / at risk     3/28 (10.71%)     8/112 (7.14%)  
# events     3     8  
Pyrexia † 1    
# participants affected / at risk     2/28 (7.14%)     9/112 (8.04%)  
# events     2     10  
Chills † 1    
# participants affected / at risk     2/28 (7.14%)     0/112 (0.00%)  
# events     2     0  
Infections and infestations      
Upper respiratory tract infection † 1    
# participants affected / at risk     2/28 (7.14%)     11/112 (9.82%)  
# events     2     13  
Sinusitis † 1    
# participants affected / at risk     1/28 (3.57%)     8/112 (7.14%)  
# events     1     9  
Investigations      
C-reactive protein increased † 1    
# participants affected / at risk     1/28 (3.57%)     6/112 (5.36%)  
# events     1     6  
Pulmonary function test decreased † 1    
# participants affected / at risk     2/28 (7.14%)     3/112 (2.68%)  
# events     2     4  
Alanine aminotransferase increased † 1    
# participants affected / at risk     2/28 (7.14%)     1/112 (0.89%)  
# events     3     1  
Aspartate aminotransferase increased † 1    
# participants affected / at risk     2/28 (7.14%)     1/112 (0.89%)  
# events     3     1  
Musculoskeletal and connective tissue disorders      
Musculoskeletal chest pain † 1    
# participants affected / at risk     2/28 (7.14%)     3/112 (2.68%)  
# events     2     3  
Nervous system disorders      
Headache † 1    
# participants affected / at risk     2/28 (7.14%)     11/112 (9.82%)  
# events     3     17  
Dizziness † 1    
# participants affected / at risk     2/28 (7.14%)     2/112 (1.79%)  
# events     2     3  
Psychiatric disorders      
Anxiety † 1    
# participants affected / at risk     2/28 (7.14%)     1/112 (0.89%)  
# events     2     1  
Respiratory, thoracic and mediastinal disorders      
Cough † 1    
# participants affected / at risk     4/28 (14.29%)     34/112 (30.36%)  
# events     5     43  
Nasal congestion † 1    
# participants affected / at risk     2/28 (7.14%)     13/112 (11.61%)  
# events     2     14  
Oropharyngeal pain † 1    
# participants affected / at risk     3/28 (10.71%)     10/112 (8.93%)  
# events     3     12  
Productive cough † 1    
# participants affected / at risk     1/28 (3.57%)     9/112 (8.04%)  
# events     1     9  
Rhinorrhoea † 1    
# participants affected / at risk     2/28 (7.14%)     4/112 (3.57%)  
# events     2     5  
Skin and subcutaneous tissue disorders      
Rash † 1    
# participants affected / at risk     0/28 (0.00%)     9/112 (8.04%)  
# events     0     9  
Dermatitis contact † 1    
# participants affected / at risk     0/28 (0.00%)     6/112 (5.36%)  
# events     0     9  
† Events were collected by systematic assessment
1 Term from vocabulary, MedDRA (12.0)
[3] CF exacerbations were coded as "cystic fibrosis lung."



  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.


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
This study was primarily designed to collect safety information for subjects treated with ivacaftor and was not powered to detect a statistically significant treatment effect in any efficacy endpoints.  


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
Study First Received: August 4, 2009
Results First Received: February 27, 2012
Last Updated: October 25, 2012
Health Authority: United States: Food and Drug Administration