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Study of VX-809 Alone and in Combination With VX-770 in Cystic Fibrosis (CF) Patients Homozygous or Heterozygous for the F508del-CFTR Mutation

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier:
NCT01225211
First received: October 15, 2010
Last updated: September 2, 2015
Last verified: September 2015
Results First Received: August 1, 2015  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Factorial Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator);   Primary Purpose: Treatment
Condition: Cystic Fibrosis
Interventions: Drug: Lumacaftor
Drug: Ivacaftor
Drug: Lumacaftor Placebo
Drug: Ivacaftor 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
Participants in each cohort are mutually exclusive. A total of 312 participants were randomized of which one participant did not receive any treatment and a total of 311 participants were treated.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Study included 4 cohorts which were studied in sequential manner. For results reporting, combined placebo arm was reported for Cohort 2 and 3 and results for these 2 cohorts are reported collectively.

Reporting Groups
  Description
Cohort 1: Placebo Participants homozygous (HO) for the F508del-CF transmembrane conductance regulator gene (CFTR) mutation received lumacaftor matched placebo once daily (qd) (Day 1 through Day 14), followed by lumacaftor matched placebo qd in combination with ivacaftor matched placebo every 12 hours (q12h) (Day 15 through Day 21).
Cohort 1: LUM 200 mg qd/LUM 200 mg qd+IVA 150 mg q12h Participants homozygous for the F508del-CFTR mutation received 200 milligram (mg) of lumacaftor (LUM) qd (Day 1 through Day 14), followed by 200 mg of lumacaftor qd in combination with 150 mg of ivacaftor (IVA) q12h (Day 15 through Day 21).
Cohort 1: LUM 200 mg qd/LUM 200 mg qd+IVA 250 mg q12h Participants homozygous for the F508del-CFTR mutation received 200 mg of lumacaftor alone qd (Day 1 through Day 14), followed by 200 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 15 through Day 21).
Cohort 2 and 3: Placebo (HO and HE) Participants homozygous or heterozygous for the F508del-CFTR mutation received lumacaftor matched placebo qd (Day 1 through Day 28), followed by lumacaftor matched placebo in combination with ivacaftor matched placebo q12h (Day 29 through Day 56).
Cohort 2: LUM 200 mg qd/LUM 200 mg qd+IVA 250 mg q12h (HO) Participants homozygous for the F508del-CFTR mutation received 200 mg of lumacaftor alone qd (Day 1 through Day 28), followed by 200 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56).
Cohort 2: LUM 400 mg qd/LUM 400 mg qd+IVA 250 mg q12h (HO) Participants homozygous for the F508del-CFTR mutation received 400 mg of lumacaftor alone qd (Day 1 through Day 28), followed by 400 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56).
Cohort 2: LUM 600 mg qd/LUM 600 mg qd+IVA 250 mg q12h (HO&HE) Participants homozygous or heterozygous for the F508del-CFTR mutation received 600 mg of lumacaftor alone qd (Day 1 through Day 28), followed by 600 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56).
Cohort 3: LUM 400 mg q12h/LUM 400 mg q12h+IVA 250 mg q12h (HO) Participants homozygous for the F508del-CFTR mutation received 400 mg of lumacaftor alone q12h (Day 1 through Day 28), followed by 400 mg of lumacaftor q12h in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56).
Cohort 4: Placebo Participants heterozygous for the F508del-CFTR mutation received lumacaftor in combination with ivacaftor matched placebo q12h (Day 1 through Day 56).
Cohort 4: LUM 400 mg q12h+IVA 250 mg q12h Participants heterozygous for the F508del-CFTR mutation received 400 mg of lumacaftor q12h in combination with 250 mg of ivacaftor q12h (Day 1 through Day 56).

Participant Flow:   Overall Study
    Cohort 1: Placebo   Cohort 1: LUM 200 mg qd/LUM 200 mg qd+IVA 150 mg q12h   Cohort 1: LUM 200 mg qd/LUM 200 mg qd+IVA 250 mg q12h   Cohort 2 and 3: Placebo (HO and HE)   Cohort 2: LUM 200 mg qd/LUM 200 mg qd+IVA 250 mg q12h (HO)   Cohort 2: LUM 400 mg qd/LUM 400 mg qd+IVA 250 mg q12h (HO)   Cohort 2: LUM 600 mg qd/LUM 600 mg qd+IVA 250 mg q12h (HO&HE)   Cohort 3: LUM 400 mg q12h/LUM 400 mg q12h+IVA 250 mg q12h (HO)   Cohort 4: Placebo   Cohort 4: LUM 400 mg q12h+IVA 250 mg q12h
STARTED   21   20   21   27   23   21   42   11   63   62 
COMPLETED   21   20   20   27   23   21   41   11   62   57 
NOT COMPLETED   0   0   1   0   0   0   1   0   1   5 
Adverse Event                0                0                1                0                0                0                0                0                0                1 
Withdrawal by Subject                0                0                0                0                0                0                1                0                1                3 
Unspecified                0                0                0                0                0                0                0                0                0                1 



  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.
Full Analysis Set (FAS) for Cohort 1, 2, and 3 included all randomized participants who received at least 1 dose of study drug and FAS for Cohort 4 included all randomized participants who received any amount of study drug.

Reporting Groups
  Description
Cohort 1: Placebo Participants homozygous for the F508del-CFTR mutation received lumacaftor matched placebo qd (Day 1 through Day 14), followed by lumacaftor matched placebo qd in combination with ivacaftor matched placebo q12h (Day 15 through Day 21).
Cohort 1: LUM 200 mg qd/LUM 200 mg qd+IVA 150 mg q12h Participants homozygous for the F508del-CFTR mutation received 200 mg of lumacaftor alone qd (Day 1 through Day 14), followed by 200 mg of lumacaftor qd in combination with 150 mg of ivacaftor q12h (Day 15 through Day 21).
Cohort 1: LUM 200 mg qd/LUM 200 mg qd+IVA 250 mg q12h Participants homozygous for the F508del-CFTR mutation received 200 mg of lumacaftor alone qd (Day 1 through Day 14), followed by 200 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 15 through Day 21).
Cohort 2 and 3: Placebo (HO and HE) Participants homozygous or heterozygous for the F508del-CFTR mutation received lumacaftor matched placebo qd (Day 1 through Day 28), followed by lumacaftor matched placebo in combination with ivacaftor matched placebo q12h (Day 29 through Day 56).
Cohort 2: LUM 200 mg qd/LUM 200 mg qd+IVA 250 mg q12h (HO) Participants homozygous for the F508del-CFTR mutation received 200 mg of lumacaftor alone qd (Day 1 through Day 28), followed by 200 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56).
Cohort 2: LUM 400 mg qd/LUM 400 mg qd+IVA 250 mg q12h (HO) Participants homozygous for the F508del-CFTR mutation received 400 mg of lumacaftor alone qd (Day 1 through Day 28), followed by 400 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56).
Cohort 2: LUM 600 mg qd/LUM 600 mg qd+IVA 250 mg q12h (HO&HE) Participants homozygous or heterozygous for the F508del-CFTR mutation received 600 mg of lumacaftor alone qd (Day 1 through Day 28), followed by 600 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56).
Cohort 3: LUM 400 mg q12h/LUM 400 mg q12h+IVA 250 mg q12h (HO) Participants homozygous for the F508del-CFTR mutation received 400 mg of lumacaftor alone q12h (Day 1 through Day 28), followed by 400 mg of lumacaftor q12h in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56).
Cohort 4: Placebo Participants heterozygous for the F508del-CFTR mutation received lumacaftor in combination with ivacaftor matched placebo q12h (Day 1 through Day 56).
Cohort 4: LUM 400 mg q12h+IVA 250 mg q12h Participants heterozygous for the F508del-CFTR mutation received 400 mg of lumacaftor q12h in combination with 250 mg of ivacaftor q12h (Day 1 through Day 56).
Total Total of all reporting groups

Baseline Measures
   Cohort 1: Placebo   Cohort 1: LUM 200 mg qd/LUM 200 mg qd+IVA 150 mg q12h   Cohort 1: LUM 200 mg qd/LUM 200 mg qd+IVA 250 mg q12h   Cohort 2 and 3: Placebo (HO and HE)   Cohort 2: LUM 200 mg qd/LUM 200 mg qd+IVA 250 mg q12h (HO)   Cohort 2: LUM 400 mg qd/LUM 400 mg qd+IVA 250 mg q12h (HO)   Cohort 2: LUM 600 mg qd/LUM 600 mg qd+IVA 250 mg q12h (HO&HE)   Cohort 3: LUM 400 mg q12h/LUM 400 mg q12h+IVA 250 mg q12h (HO)   Cohort 4: Placebo   Cohort 4: LUM 400 mg q12h+IVA 250 mg q12h   Total 
Overall Participants Analyzed 
[Units: Participants]
 21   20   21   27   23   21   42   11   63   62   311 
Age 
[Units: Participants]
                     
<=18 years   0   0   0   0   0   0   0   0   0   0   0 
Between 18 and 65 years   21   20   21   27   23   21   42   11   63   62   311 
>=65 years   0   0   0   0   0   0   0   0   0   0   0 
Gender 
[Units: Participants]
                     
Female   10   8   13   9   11   9   19   5   31   29   144 
Male   11   12   8   18   12   12   23   6   32   33   167 


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Cohort 1: Safety and Tolerability Based on Adverse Events (AEs)   [ Time Frame: Cohort 1: Day 1 up to 28 days after last dose (Last dose = Day 21) ]

2.  Primary:   Cohort 2 and 3: Safety and Tolerability Based on Adverse Events (AEs)   [ Time Frame: Cohort 2 and 3: Day 1 up to 28 days after last dose (Last dose = Day 56) ]

3.  Primary:   Cohort 4: Safety and Tolerability Assessed by Number of Participants With AEs and SAEs   [ Time Frame: Cohort 4: Day 1 up to 28 days after last dose (Last dose = Day 56) ]

4.  Primary:   Cohort 1: Absolute Change From Day 14 in Sweat Chloride at Day 21   [ Time Frame: Cohort 1: Day 14, Day 21 ]

5.  Primary:   Cohort 2 And 3: Absolute Change From Day 28 in Sweat Chloride at Day 56   [ Time Frame: Cohort 2 and 3: Day 28, Day 56 ]

6.  Primary:   Cohort 4: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 56   [ Time Frame: Cohort 4: Baseline, Day 56 ]

7.  Secondary:   Cohort 1: Absolute Change From Baseline in Sweat Chloride at Day 14   [ Time Frame: Cohort 1: Baseline, Day 14 ]

8.  Secondary:   Cohort 2 And 3: Absolute Change From Baseline in Sweat Chloride at Day 14   [ Time Frame: Cohort 2: Baseline, Day 14 ]

9.  Secondary:   Cohort 4: Absolute Change From Baseline in Sweat Chloride at Day 56   [ Time Frame: Cohort 4: Baseline, Day 56 ]

10.  Secondary:   Cohort 1: Absolute Change From Day 14 in FEV1 at Day 21   [ Time Frame: Cohort 1: Day 14, Day 21 ]

11.  Secondary:   Cohort 1: Absolute Change From Day 14 in ppFEV1 at Day 21   [ Time Frame: Cohort 1: Day 14, Day 21 ]

12.  Secondary:   Cohort 2 and 3: Absolute Change From Day 28 in ppFEV1 at Day 56   [ Time Frame: Cohort 2 and 3: Day 28, Day 56 ]

13.  Secondary:   Cohort 2 and 3: Relative Change From Day 28 in ppFEV1 at Day 56   [ Time Frame: Cohort 2 and 3: Day 28, Day 56 ]

14.  Secondary:   Cohort 2 and 3: Absolute Change From Baseline in ppFEV1 at Day 28 and 56   [ Time Frame: Cohort 2 and 3: Baseline, Day 28 and 56 ]

15.  Secondary:   Cohort 2 and 3: Relative Change From Baseline in FEV1 at Day 28 and 56   [ Time Frame: Cohort 2 and 3: Baseline, Day 28 and 56 ]

16.  Secondary:   Cohort 4: Relative Change From Baseline in Percent Predicted FEV1 at Day 56   [ Time Frame: Cohort 4: Baseline, Day 56 ]

17.  Secondary:   Cohort 2 and 3: Absolute Change From Day 28 in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Day 56   [ Time Frame: Cohort 2 and 3: Day 28, Day 56 ]

18.  Secondary:   Cohort 4: Absolute Change From Baseline in CFQ-R Respiratory Domain Score at Day 56   [ Time Frame: Cohort 4: Baseline, Day 56 ]

19.  Secondary:   Cohort 4: Absolute Change From Baseline in Body Mass Index (BMI) at Day 56   [ Time Frame: Cohort 4: Baseline, Day 56 ]

20.  Secondary:   Cohort 4: Absolute Change From Baseline in Weight at Day 56   [ Time Frame: Cohort 4: Baseline, Day 56 ]


  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
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  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 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


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

Responsible Party: Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier: NCT01225211     History of Changes
Other Study ID Numbers: VX09-809-102
2010-020413-90 ( EudraCT Number )
Study First Received: October 15, 2010
Results First Received: August 1, 2015
Last Updated: September 2, 2015
Health Authority: United States: Food and Drug Administration
Australia: Therapeutic Goods Administration
Belgium: Federal Agency for Medicinal Products and Health Products
Germany: Federal Institute for Drugs and Medical Devices
New Zealand: Medsafe
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Ireland: Ministry of Health
France: Afssaps - Agence française de sécurité sanitaire des produits de santé