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Study of VX-661 Alone and in Combination With Ivacaftor in Subjects Homozygous or Heterozygous to the F508del-Cystic Fibrosis Transmembrane Conductance Regulator(CFTR) Mutation

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ClinicalTrials.gov Identifier: NCT01531673
Recruitment Status : Completed
First Posted : February 13, 2012
Results First Posted : April 13, 2018
Last Update Posted : April 13, 2018
Sponsor:
Information provided by (Responsible Party):
Vertex Pharmaceuticals Incorporated

Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Cystic Fibrosis
Interventions: Drug: VX-661
Drug: Ivacaftor
Drug: Placebo matched to VX-661
Drug: Placebo matched to ivacaftor

  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
A total of 194 participants were randomized of which 190 participants were treated.

Reporting Groups
  Description
Group 1-6d Combined: Placebo All participants in group 1, 2a, 2b, 3a, 3b, 4, 5a, 5b, 6a and 6d who received placebo matched to VX-661 tablet and/or placebo matched to ivacaftor tablet for up to 28 days.
Group 1: VX-661 10 mg qd All participants in group 1 who received VX-661 10 milligram (mg) tablet orally once daily (qd) for up to 28 days.
Group 2a: VX-661 30 mg qd All participants in group 2a who received VX-661 30 mg tablet orally qd and placebo matched to Ivacaftor tablet every 12 hours (q12h) for up to 28 days.
Group 2b: VX-661 10 mg qd/Ivacaftor 150 mg q12h All participants in group 2b who received VX-661 10 mg tablet qd and Ivacaftor 150 mg tablet q12h orally for up to 28 days.
Group 3a: VX-661 100 mg qd All participants in group 3a who received VX-661 100 mg tablet orally qd and placebo matched to Ivacaftor tablet q12h for up to 28 days.
Group 3b: VX-661 30 mg qd/Ivacaftor 150 mg q12h All participants in group 3b who received VX-661 30 mg tablet qd and Ivacaftor 150 mg tablet q12h orally for up to 28 days.
Group 4: VX-661 100 mg qd/Ivacaftor 150 mg q12h All participants in group 4 who received VX-661 100 mg tablet qd and Ivacaftor 150 mg tablet q12h orally for up to 28 days.
Group 5a: VX-661 150 mg qd All participants in group 5a who received VX-661 150 mg tablet orally qd for up to 28 days.
Group 5b: VX-661 150 mg qd/Ivacaftor 150 mg q12h All participants in group 5b who received VX-661 150 mg tablet qd and Ivacaftor 150 mg tablet q12h orally for up to 28 days.
Group 6a: VX-661 100 mg qd/Ivacaftor 50 mg q12h All participants in group 6a who received VX-661 100 mg tablet qd and Ivacaftor 50 mg tablet q12h orally for up to 28 days.
Group 6d: VX-661 50 mg q12h/Ivacaftor 150 mg q12h All participants in group 6d who received VX-661 50 mg tablet and Ivacaftor 150 mg tablet q12h orally for up to 28 days.
Group 7: Placebo All participants in group 7 who received placebo matched to VX-661 tablet orally qd in combination with physician-prescribed Kalydeco for up to 28 days.
Group 7: VX-661 100 mg qd All participants in group 7 who received VX-661 100 mg tablet orally qd in combination with physician-prescribed Kalydeco for up to 28 days.

Participant Flow:   Overall Study
    Group 1-6d Combined: Placebo   Group 1: VX-661 10 mg qd   Group 2a: VX-661 30 mg qd   Group 2b: VX-661 10 mg qd/Ivacaftor 150 mg q12h   Group 3a: VX-661 100 mg qd   Group 3b: VX-661 30 mg qd/Ivacaftor 150 mg q12h   Group 4: VX-661 100 mg qd/Ivacaftor 150 mg q12h   Group 5a: VX-661 150 mg qd   Group 5b: VX-661 150 mg qd/Ivacaftor 150 mg q12h   Group 6a: VX-661 100 mg qd/Ivacaftor 50 mg q12h   Group 6d: VX-661 50 mg q12h/Ivacaftor 150 mg q12h   Group 7: Placebo   Group 7: VX-661 100 mg qd
STARTED   33   8   8   18   8   19   17   9   17   19   16   4   14 
COMPLETED   33   7   8   17   7   18   17   9   17   18   16   4   14 
NOT COMPLETED   0   1   0   1   1   1   0   0   0   1   0   0   0 
Non-Compliance                0                0                0                0                0                1                0                0                0                0                0                0                0 
Adverse Event                0                1                0                0                0                0                0                0                0                0                0                0                0 
Lost to Follow-up                0                0                0                0                1                0                0                0                0                0                0                0                0 
Other                0                0                0                1                0                0                0                0                0                1                0                0                0 



  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
Group 1-6d Combined: Placebo All participants in group 1, 2a, 2b, 3a, 3b, 4, 5a, 5b, 6a and 6d who received placebo matched to VX-661 tablet and/or placebo matched to ivacaftor tablet for up to 28 days.
Group 1: VX-661 10 mg qd All participants in group 1 who received VX-661 10 mg tablet orally qd for up to 28 days.
Group 2a: VX-661 30 mg qd All participants in group 2a who received VX-661 30 mg tablet orally qd and placebo matched to Ivacaftor tablet q12h for up to 28 days.
Group 2b: VX-661 10 mg qd/Ivacaftor 150 mg q12h All participants in group 2b who received VX-661 10 mg tablet qd and Ivacaftor 150 mg tablet q12h orally for up to 28 days.
Group 3a: VX-661 100 mg qd All participants in group 3a who received VX-661 100 mg tablet orally qd and placebo matched to Ivacaftor tablet q12h for up to 28 days.
Group 3b: VX-661 30 mg qd/Ivacaftor 150 mg q12h All participants in group 3b who received VX-661 30 mg tablet qd and Ivacaftor 150 mg tablet q12h orally for up to 28 days.
Group 4: VX-661 100 mg qd/Ivacaftor 150 mg q12h All participants in group 4 who received VX-661 100 mg tablet qd and Ivacaftor 150 mg tablet q12h orally for up to 28 days.
Group 5a: VX-661 150 mg qd All participants in group 5a who received VX-661 150 mg tablet orally qd for up to 28 days.
Group 5b: VX-661 150 mg qd/Ivacaftor 150 mg q12h All participants in group 5b who received VX-661 150 mg tablet qd and Ivacaftor 150 mg tablet q12h orally for up to 28 days.
Group 6a: VX-661 100 mg qd/Ivacaftor 50 mg q12h All participants in group 6a who received VX-661 100 mg tablet qd and Ivacaftor 50 mg tablet q12h orally for up to 28 days.
Group 6d: VX-661 50 mg q12h/Ivacaftor 150 mg q12h All participants in group 6d who received VX-661 50 mg tablet and Ivacaftor 150 mg tablet q12h orally for up to 28 days.
Group 7: Placebo All participants in group 7 who received placebo matched to VX-661 tablet orally qd in combination with physician-prescribed Kalydeco for up to 28 days.
Group 7: VX-661 100 mg qd All participants in group 7 who received VX-661 100 mg tablet orally qd in combination with physician-prescribed Kalydeco for up to 28 days.
Total Total of all reporting groups

Baseline Measures
   Group 1-6d Combined: Placebo   Group 1: VX-661 10 mg qd   Group 2a: VX-661 30 mg qd   Group 2b: VX-661 10 mg qd/Ivacaftor 150 mg q12h   Group 3a: VX-661 100 mg qd   Group 3b: VX-661 30 mg qd/Ivacaftor 150 mg q12h   Group 4: VX-661 100 mg qd/Ivacaftor 150 mg q12h   Group 5a: VX-661 150 mg qd   Group 5b: VX-661 150 mg qd/Ivacaftor 150 mg q12h   Group 6a: VX-661 100 mg qd/Ivacaftor 50 mg q12h   Group 6d: VX-661 50 mg q12h/Ivacaftor 150 mg q12h   Group 7: Placebo   Group 7: VX-661 100 mg qd   Total 
Overall Participants Analyzed 
[Units: Participants]
 33   8   8   18   8   19   17   9   17   19   16   4   14   190 
Age 
[Units: Years]
Mean (Standard Deviation)
 30.7  (8.42)   35.3  (8.26)   30.8  (6.63)   28.3  (7.05)   29.1  (7.12)   29.2  (6.39)   31  (9.3)   28.2  (8.6)   28.2  (6.46)   27.9  (5.58)   32.8  (11.92)   34.5  (7.59)   26.6  (7.01)   29.8  (7.97) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
                           
Female      13  39.4%      4  50.0%      4  50.0%      6  33.3%      3  37.5%      6  31.6%      11  64.7%      3  33.3%      10  58.8%      7  36.8%      7  43.8%      3  75.0%      6  42.9%      83  43.7% 
Male      20  60.6%      4  50.0%      4  50.0%      12  66.7%      5  62.5%      13  68.4%      6  35.3%      6  66.7%      7  41.2%      12  63.2%      9  56.3%      1  25.0%      8  57.1%      107  56.3% 


  Outcome Measures

1.  Primary:   Safety as Determined by Adverse Events (AEs)   [ Time Frame: Start of study drug through the Follow-up Visit (Up to Day 56) ]

2.  Primary:   Change in Sweat Chloride From Baseline Through Study Day 28 for Group 1-5b   [ Time Frame: Baseline through Day 28 ]

3.  Primary:   Change in Sweat Chloride From Baseline Through Study Day 28 for Group 6   [ Time Frame: Baseline through Day 28 ]

4.  Primary:   Change in Sweat Chloride From Baseline Through Study Day 28 for Group 7   [ Time Frame: Baseline through Day 28 ]

5.  Secondary:   Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 1-5b   [ Time Frame: Baseline, Day 7, Day 14, Day 21, Day 28 ]

6.  Secondary:   Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 6   [ Time Frame: Baseline, Day 7, Day 14, Day 21, Day 28 ]

7.  Secondary:   Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 7   [ Time Frame: Baseline, Day 7, Day 14, Day 21, Day 28 ]

8.  Secondary:   Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b   [ Time Frame: Baseline, Day 7, Day 14, Day 21, Day 28 ]

9.  Secondary:   Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 6   [ Time Frame: Baseline, Day 7, Day 14, Day 21, Day 28 ]

10.  Secondary:   Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 7   [ Time Frame: Baseline, Day 7, Day 14, Day 21, Day 28 ]

11.  Secondary:   Change in FEV1 (Liter [L]) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b   [ Time Frame: Baseline, Day 7, Day 14, Day 21, Day 28 ]

12.  Secondary:   Change in FEV1 (L) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 6   [ Time Frame: Baseline, Day 7, Day 14, Day 21, Day 28 ]

13.  Secondary:   Change in FEV1 (L) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 7   [ Time Frame: Baseline, Day 7, Day 14, Day 21, Day 28 ]

14.  Secondary:   Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b   [ Time Frame: Baseline, Day 14, Day 28 ]

15.  Secondary:   Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 6   [ Time Frame: Baseline, Day 14, Day 28 ]

16.  Secondary:   Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 7   [ Time Frame: Baseline, Day 14, Day 28 ]

17.  Secondary:   Area Under the Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24h) of VX-661 After Administration of VX-661 Monotherapy   [ Time Frame: Day 28 ]

18.  Secondary:   AUC0-24h of VX-661 and AUC0-12h of Ivacaftor After Administration of VX-661 in Combination With Ivacaftor   [ Time Frame: Day 28 ]


  Serious Adverse Events


  Other Adverse Events


  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
Pharmacokinetic (PK) final data are not yet available. Once the data are available for PK endpoints, the posting will be updated to include the same.


  More Information

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 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 more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Medical Monitor
Organization: Vertex Pharmaceuticals Incorporated
phone: 617-341-6777
e-mail: medicalinfo@vrtx.com



Responsible Party: Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier: NCT01531673     History of Changes
Other Study ID Numbers: VX11-661-101
2011-003821-93 ( EudraCT Number )
First Submitted: February 1, 2012
First Posted: February 13, 2012
Results First Submitted: March 14, 2018
Results First Posted: April 13, 2018
Last Update Posted: April 13, 2018