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: August 19, 2014
Last verified: August 2014
  Purpose

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


Condition Intervention Phase
Cystic Fibrosis
Drug: VX-809
Drug: VX-770
Drug: VX-809 placebo
Drug: VX-770 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:
  • Change in sweat chloride when VX-770 is administered in combination with VX-809 [ Time Frame: From Day 14 to Day 21 (Cohort 1); Day 28 to Day 56 (Cohort 2 and Cohort 3) ] [ Designated as safety issue: No ]
  • Safety and tolerability assessments will be measured based on adverse events, plasma samples (hematology, clinical chemistry, coagulation), urinalysis, electrocardiograms, and vital signs [ Time Frame: Through Day 35 (Cohort 1); Day 70 (Cohort 2 and Cohort 3); Day 62 (Cohort 4) ] [ Designated as safety issue: Yes ]
  • Relative change in percent predicted FEV1 (Cohort 4) [ Time Frame: From baseline at Day 56 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in percent predicted Forced expiratory volume in 1 second (FEV1) [ Time Frame: Through Day 21 (Cohort 1); Day 56 (Cohort 2, Cohort 3 and Cohort 4) ] [ Designated as safety issue: No ]
  • Change in sweat chloride of increasing doses of VX-809 administered alone [ Time Frame: From Baseline to Day 14 (Cohort 1); From baseline to Day 28 (Cohort 2 and Cohort 3) ; From baseline to Day 56 (Cohort 4) ] [ Designated as safety issue: No ]
  • PK parameters, including exposure, concentration and half-life, of VX-809 and metabolite in plasma in the presence and absence of VX-770 [ Time Frame: Through Day 21 (Cohort 1); Day 56 (Cohort 2, Cohort 3 and Cohort 4) ] [ Designated as safety issue: No ]
    Blood samples drawn during the study will be analyzed to measure the PK parameters, such as concentration, exposure and half-life of VX-809 and its metabolite.

  • PK parameters, including exposure, concentration and half-life, of VX-770 and metabolites in plasma in the presence of VX-809 [ Time Frame: Through Day 21 (Cohort 1); Day 56 (Cohort 2, Cohort 3 and Cohort 4)) ] [ Designated as safety issue: No ]
    Blood samples drawn during the study will be analyzed to measure the PK parameters, such as concentration, exposure and half-life of VX-770 and its metabolites.

  • Cystic Fibrosis Questionnaire (CFQ-R) Score [ Time Frame: Through Day 56 (Cohort 2 ,Cohort 3 and Cohort 4) ] [ Designated as safety issue: No ]
  • Absolute change in body mass index (Cohort 4) [ Time Frame: From baseline at Day 56 ] [ Designated as safety issue: No ]
  • Absolute change in body weight (Cohort 4) [ Time Frame: From baseline at Day 56 ] [ Designated as safety issue: No ]

Enrollment: 316
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
Experimental: Treatment Arm (Cohort 1)
Subjects randomized to study drug will take VX-809 once daily (qd) for 14 days. Beginning on Day 15, subjects will take both VX-809 once qd and VX-770 taken every 12 hours (q12h) through Day 21.
Drug: VX-809 Drug: VX-770
Placebo Comparator: Placebo Arm (Cohort 1)
Subjects randomized to placebo will remain on placebo from Day 1 through Day 21. Subjects will be given tablets that match both VX-809 once daily (qd) and VX-770 taken every 12 hours (q12h)and will follow the same dosing regimen as subjects receiving study drug.
Drug: VX-809 placebo Drug: VX-770 placebo
Experimental: Treatment Arm (Cohort 2)
Subjects randomized to study drug will take VX-809 once daily (qd) for 28 days (Period 1). Beginning on Day 29, subjects will take both VX-809 once qd and VX-770 taken every 12 hours (q12h) through Day 56 (Period 2).
Drug: VX-809 Drug: VX-770
Experimental: Treatment Arm (Cohort 3)
Subjects randomized to study drug will take VX-809 taken every 12 hours (q12h) for 28 days (Period 1). Beginning on Day 29, subjects will take both VX-809 and VX-770 every q12h through Day 56 (Period 2).
Drug: VX-809 Drug: VX-770
Experimental: Treatment Arm (Cohort 4)
Subjects heterozygous will receive 400 mg of VX-809 tablet taken every 12 hours (q12h) in combination with 250 mg of VX-770 q12h through Day 56.
Drug: VX-809 Drug: VX-770
Placebo Comparator: Placebo Arm (Cohort 4)
Subjects heterozygous will receive Fixed-dose combination: VX-809/VX-770 Placebo tablet taken every 12 hours (q12h) through Day 56.
Drug: VX-809 placebo Drug: VX-770 placebo

  Eligibility

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

Inclusion Criteria:

  • Male or female subjects with confirmed diagnosis of CF
  • Must have the F508del-CFTR mutation on at least 1 allele.
  • FEV1 >= 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)
  • Subjects 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 subject (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
  • Subjects 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 subjects 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

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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
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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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Atlanta, Georgia, United States
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Iowa City, Iowa, United States
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Kansas City, Kansas, United States
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Lexington, Kentucky, United States
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Oklahoma City, Oklahoma, United States
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Charleston, South Carolina, United States
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Sioux Falls, South Dakota, United States
Australia
Adelaide, Australia
Brisbane, Australia
Chermside, Australia
Nedlands, Australia
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

No publications provided by Vertex Pharmaceuticals Incorporated

Additional 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
Last Updated: August 19, 2014
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
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on August 28, 2014