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
  Purpose
The purpose of this study is to evaluate of the safety, efficacy, pharmacokinetics (PK) and pharmacodynamic (PD) effects of lumacaftor (VX-809) alone and when coadministered with ivacaftor (VX-770) in participants with cystic fibrosis, homozygous or heterozygous for the F508del-CFTR mutation.

Condition Intervention Phase
Cystic Fibrosis
Drug: Lumacaftor
Drug: Ivacaftor
Drug: Lumacaftor Placebo
Drug: Ivacaftor Placebo
Phase 2

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
Official Title: A Phase 2, Multicenter, Double-Blinded, Placebo-Controlled, Multiple-Dose Study to Evaluate Safety, Tolerability, Efficacy, Pharmacokinetics, and Pharmacodynamics of Lumacaftor Monotherapy, and Lumacaftor and Ivacaftor Combination Therapy in Subjects With Cystic Fibrosis, Homozygous or Heterozygous for the F508del-CFTR Mutation

Resource links provided by NLM:


Further study details as provided by Vertex Pharmaceuticals Incorporated:

Primary Outcome Measures:
  • 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) ] [ Designated as safety issue: Yes ]
    AE: any untoward medical occurrence in a participant during study; irrespective of relationship with treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after informed consent. AE includes serious AEs (SAEs) as well as Non-SAEs. SAE (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to study drug: death, life threatening adverse experience, in-patient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. Number of participants with AEs and SAEs are reported. AE that started at/after initial dosing of study drug, or increased in severity after initial dosing of study drug is considered treatment-emergent. Results are reported separately for monotherapy period (Period 1: Day 1 to Day 14) and combination therapy period (Period 2: Day 15 to Day 21).

  • 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) ] [ Designated as safety issue: Yes ]
    Detailed description is provided in Outcome Measure 1. Results are reported separately for monotherapy period (Period 1: Day 1 to Day 28) and combination therapy period (Period 2: Day 29 to Day 56).

  • 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) ] [ Designated as safety issue: Yes ]
    AEs and SAEs are defined in Outcome Measure 1.

  • Cohort 1: Absolute Change From Day 14 in Sweat Chloride at Day 21 [ Time Frame: Cohort 1: Day 14, Day 21 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
    FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. ppFEV1 (predicted for age, gender, and height) was calculated using the Hankinson method.


Secondary Outcome Measures:
  • Cohort 1: Absolute Change From Baseline in Sweat Chloride at Day 14 [ Time Frame: Cohort 1: Baseline, Day 14 ] [ Designated as safety issue: No ]
  • Cohort 2 And 3: Absolute Change From Baseline in Sweat Chloride at Day 14 [ Time Frame: Cohort 2: Baseline, Day 14 ] [ Designated as safety issue: No ]
  • Cohort 4: Absolute Change From Baseline in Sweat Chloride at Day 56 [ Time Frame: Cohort 4: Baseline, Day 56 ] [ Designated as safety issue: No ]
  • Cohort 1: Absolute Change From Day 14 in FEV1 at Day 21 [ Time Frame: Cohort 1: Day 14, Day 21 ] [ Designated as safety issue: No ]
    FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.

  • Cohort 1: Absolute Change From Day 14 in ppFEV1 at Day 21 [ Time Frame: Cohort 1: Day 14, Day 21 ] [ Designated as safety issue: No ]
    FEV1 and ppFEV1 are defined in Outcome Measure 6.

  • Cohort 2 and 3: Absolute Change From Day 28 in ppFEV1 at Day 56 [ Time Frame: Cohort 2 and 3: Day 28, Day 56 ] [ Designated as safety issue: No ]
    FEV1 and ppFEV1 are defined in Outcome Measure 6.

  • Cohort 2 and 3: Relative Change From Day 28 in ppFEV1 at Day 56 [ Time Frame: Cohort 2 and 3: Day 28, Day 56 ] [ Designated as safety issue: No ]
    FEV1 and ppFEV1 are defined in Outcome Measure 6.

  • 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 ] [ Designated as safety issue: No ]
    FEV1 and ppFEV1 are defined in Outcome Measure 6.

  • 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 ] [ Designated as safety issue: No ]
    FEV1 and ppFEV1 are defined in Outcome Measure 6.

  • Cohort 4: Relative Change From Baseline in Percent Predicted FEV1 at Day 56 [ Time Frame: Cohort 4: Baseline, Day 56 ] [ Designated as safety issue: No ]
    FEV1 and ppFEV1 are defined in Outcome Measure 6.

  • 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 ] [ Designated as safety issue: No ]
    The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for subjects with cystic fibrosis. Respiratory domain assessed respiratory symptoms (for example, coughing, congestion, wheezing), score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.

  • Cohort 4: Absolute Change From Baseline in CFQ-R Respiratory Domain Score at Day 56 [ Time Frame: Cohort 4: Baseline, Day 56 ] [ Designated as safety issue: No ]
    CFQ-R respiratory domain is defined in Outcome Measure 17.

  • Cohort 4: Absolute Change From Baseline in Body Mass Index (BMI) at Day 56 [ Time Frame: Cohort 4: Baseline, Day 56 ] [ Designated as safety issue: No ]
    BMI was defined as weight in kilogram (kg) divided by height*height in square meter (m^2).

  • Cohort 4: Absolute Change From Baseline in Weight at Day 56 [ Time Frame: Cohort 4: Baseline, Day 56 ] [ Designated as safety issue: No ]

Enrollment: 312
Study Start Date: October 2010
Study Completion Date: April 2014
Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: 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).
Drug: Lumacaftor Placebo
Matching placebo tablet.
Drug: Ivacaftor Placebo
Matching placebo tablet.
Experimental: 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).
Drug: Lumacaftor
Tablet
Other Name: VX-809, LUM
Drug: Ivacaftor
Tablet.
Other Name: VX-770, IVA
Experimental: 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).
Drug: Lumacaftor
Tablet
Other Name: VX-809, LUM
Drug: Ivacaftor
Tablet.
Other Name: VX-770, IVA
Placebo Comparator: 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).
Drug: Lumacaftor Placebo
Matching placebo tablet.
Drug: Ivacaftor Placebo
Matching placebo tablet.
Experimental: 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).
Drug: Lumacaftor
Tablet
Other Name: VX-809, LUM
Drug: Ivacaftor
Tablet.
Other Name: VX-770, IVA
Experimental: 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).
Drug: Lumacaftor
Tablet
Other Name: VX-809, LUM
Drug: Ivacaftor
Tablet.
Other Name: VX-770, IVA
Experimental: 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).
Drug: Lumacaftor
Tablet
Other Name: VX-809, LUM
Drug: Ivacaftor
Tablet.
Other Name: VX-770, IVA
Experimental: 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).
Drug: Lumacaftor
Tablet
Other Name: VX-809, LUM
Drug: Ivacaftor
Tablet.
Other Name: VX-770, IVA
Placebo Comparator: Cohort 4: Placebo
Participants heterozygous for the F508del-CFTR mutation received lumacaftor matched placebo in combination with ivacaftor matched placebo q12h (Day 1 through Day 56).
Drug: Lumacaftor Placebo
Matching placebo tablet.
Drug: Ivacaftor Placebo
Matching placebo tablet.
Experimental: 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).
Drug: Lumacaftor
Tablet
Other Name: VX-809, LUM
Drug: Ivacaftor
Tablet.
Other Name: VX-770, IVA

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female participants with confirmed diagnosis of CF
  • Must have the F508del-CFTR mutation on at least 1 allele.
  • FEV1 greater than equal (>=) 40% of predicted normal for age, gender, and height (Knudson standards)(Cohort 1, 2, and 3); FEV1 40-90% of predicted normal for age, gender, and height (Hankinson standards (Cohort 4)
  • Participant of child-bearing potential and who are sexually active must meet the contraception requirements

Exclusion Criteria:

  • History of any illness or condition that, in the opinion of the investigator might confound the results of the study or pose an additional risk in administering study drug to the participant (e.g., cirrhosis with portal hypertension).
  • An acute illness including acute upper or lower respiratory infection, pulmonary exacerbation or changes in therapy (including antibiotics) for pulmonary disease within 14 days (Cohort 1, 2, and 3) or 28 days (Cohort 4) before receiving the first dose of study drug.
  • History of solid organ or hematological transplantation.
  • History of alcohol abuse or drug addiction in the past year, including cannabis, cocaine, and opiates.
  • Ongoing participation in another therapeutic clinical study, or prior participation in an investigational drug study without appropriate washout
  • Pregnant or nursing females; females of childbearing potential who are unwilling or unable to use an acceptable method of non-hormonal contraception
  • Participants enrolled in Cohort 1 or Cohort 2 will not be eligible for Cohort 3
  • Ongoing or prior participation in an investigational drug study within 30 days of the Screening Visit
  • Heterozygous participants who participated in Cohort 2 and meet the eligibility criteria for Cohort 4 may participate in Cohort 4
  • Evidence of lens opacity or cataract as determined by the ophthalmologic examination (Cohort 4 only)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01225211

  Hide Study Locations
Locations
United States, Alabama
Birmingham, Alabama, United States
United States, Alaska
Anchorage, Alaska, United States
United States, California
La Jolla, California, United States
Long Beach, California, United States
Palo Alto, California, United States
Sacramento, California, United States
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Denver, Colorado, United States
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New Haven, Connecticut, United States
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Miami, Florida, United States
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Oklahoma City, Oklahoma, United States
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Australia
Adelaide, Australia
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Chermside, Australia
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Parkville Victoria, Australia
Westmead, Australia
Belgium
Leuven, Belgium
France
Pierre Benite Cedex, Rhone, France
Paris, France
Germany
Jena, Thueringen, Germany
Berlin, Germany
Bochum, Germany
Essen, Germany
Koeln, Germany
New Zealand
Auckland, New Zealand
Christchurch, New Zealand
United Kingdom
London, United Kingdom
Sponsors and Collaborators
Vertex Pharmaceuticals Incorporated
  More Information

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 
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

Additional relevant MeSH terms:
Cystic Fibrosis
Fibrosis
Digestive System Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Lung Diseases
Pancreatic Diseases
Pathologic Processes
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on May 22, 2016