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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 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: August 27, 2015
Last verified: August 2015
History of Changes
Results First Received: February 27, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Participant, Care Provider, 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
  Hide Baseline Characteristics

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 
Overall Participants Analyzed 
[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) 
[1] Percent predicted for age, gender, and height.
ppFEV1, Categorical [1] 
[Units: Participants]
 		     
< 70%   15   38   53 
≥ 70% to ≤ 90%   5   35   40 
> 90%   8   39   47 
[1] Percent predicted for age, gender, and height.
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) 


  Outcome Measures
  Show 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 ]
  Show Outcome Measure 1

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 ]
  Show Outcome Measure 2

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 ]
  Show Outcome Measure 3

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

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 ]
  Show Outcome Measure 5

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

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

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 ]
  Show Outcome Measure 8

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 ]
  Show Outcome Measure 9

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 ]
  Show Outcome Measure 10

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

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

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


  Serious Adverse Events
  Hide Serious Adverse Events

Time Frame Adverse events (serious and non-serious) were collected from signing of informed consent through 2 years after last dose (in Part B) of study drug (median treatment duration: 112 days for Part A and 381 days for Part B)
Additional Description No text entered.

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 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).

Serious Adverse Events
    Placebo – Part A   Ivacaftor – Part A   Placebo/Ivacaftor – Part B   Ivacaftor/Ivacaftor – Part B
Total, Serious Adverse Events         
# participants affected / at risk   6/28 (21.43%)   15/112 (13.39%)   2/5 (40.00%)   14/33 (42.42%) 
Congenital, familial and genetic disorders         
Cystic fibrosis lung † 1 [3]         
# participants affected / at risk   5/28 (17.86%)   10/112 (8.93%)   2/5 (40.00%)   13/33 (39.39%) 
# events   6   12   4   20 
Gastrointestinal disorders         
Abdominal pain † 1         
# participants affected / at risk   0/28 (0.00%)   1/112 (0.89%)   0/5 (0.00%)   0/33 (0.00%) 
# events   0   2   0   0 
General disorders         
Fatigue † 1         
# participants affected / at risk   0/28 (0.00%)   1/112 (0.89%)   0/5 (0.00%)   0/33 (0.00%) 
# events   0   1   0   0 
Infections and infestations         
Bronchopneumonia † 1         
# participants affected / at risk   1/28 (3.57%)   0/112 (0.00%)   0/5 (0.00%)   0/33 (0.00%) 
# events   1   0   0   0 
Central line infection † 1         
# participants affected / at risk   0/28 (0.00%)   0/112 (0.00%)   0/5 (0.00%)   1/33 (3.03%) 
# events   0   0   0   1 
Lung infection † 1         
# participants affected / at risk   0/28 (0.00%)   0/112 (0.00%)   0/5 (0.00%)   1/33 (3.03%) 
# events   0   0   0   1 
Injury, poisoning and procedural complications         
Ankle fracture † 1         
# participants affected / at risk   0/28 (0.00%)   0/112 (0.00%)   0/5 (0.00%)   1/33 (3.03%) 
# events   0   0   0   1 
Pelvic fracture † 1         
# participants affected / at risk   0/28 (0.00%)   0/112 (0.00%)   0/5 (0.00%)   1/33 (3.03%) 
# events   0   0   0   1 
Traumatic brain injury † 1         
# participants affected / at risk   0/28 (0.00%)   0/112 (0.00%)   0/5 (0.00%)   1/33 (3.03%) 
# events   0   0   0   1 
Musculoskeletal and connective tissue disorders         
Myopathy † 1         
# participants affected / at risk   0/28 (0.00%)   1/112 (0.89%)   0/5 (0.00%)   0/33 (0.00%) 
# events   0   1   0   0 
Nervous system disorders         
Cognitive disorder † 1         
# participants affected / at risk   1/28 (3.57%)   0/112 (0.00%)   0/5 (0.00%)   0/33 (0.00%) 
# events   1   0   0   0 
Psychiatric disorders         
Anxiety † 1         
# participants affected / at risk   0/28 (0.00%)   0/112 (0.00%)   0/5 (0.00%)   1/33 (3.03%) 
# events   0   0   0   1 
Depression † 1         
# participants affected / at risk   0/28 (0.00%)   1/112 (0.89%)   0/5 (0.00%)   1/33 (3.03%) 
# events   0   1   0   1 
Suicidal ideation † 1         
# participants affected / at risk   0/28 (0.00%)   1/112 (0.89%)   0/5 (0.00%)   0/33 (0.00%) 
# events   0   1   0   0 
Respiratory, thoracic and mediastinal disorders         
Haemoptysis † 1         
# participants affected / at risk   0/28 (0.00%)   1/112 (0.89%)   0/5 (0.00%)   1/33 (3.03%) 
# events   0   1   0   3 
Hypoxia † 1         
# participants affected / at risk   0/28 (0.00%)   1/112 (0.89%)   0/5 (0.00%)   0/33 (0.00%) 
# events   0   1   0   0 
Nasal polyps † 1         
# participants affected / at risk   0/28 (0.00%)   1/112 (0.89%)   0/5 (0.00%)   0/33 (0.00%) 
# events   0   1   0   0 
Vascular disorders         
Venous thrombosis † 1         
# participants affected / at risk   1/28 (3.57%)   0/112 (0.00%)   0/5 (0.00%)   0/33 (0.00%) 
# events   1   0   0   0 
† Events were collected by systematic assessment
1 Term from vocabulary, MedDRA (12.0)
[3] CF exacerbations were coded as "cystic fibrosis lung."




  Other Adverse Events
  Show 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


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):


Responsible Party: Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier: NCT00953706     History of Changes
Other Study ID Numbers: VX08-770-104
2009-010261-23 ( EudraCT Number )
Study First Received: August 4, 2009
Results First Received: February 27, 2012
Last Updated: August 27, 2015