A Study of Lumacaftor in Combination With Ivacaftor in Cystic Fibrosis Subjects Aged 12 Years and Older Who Are Homozygous for the F508del-CFTR Mutation (TRANSPORT)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier:
NCT01807949
First received: March 4, 2013
Last updated: July 23, 2014
Last verified: July 2014
  Purpose

The purpose of this study is to evaluate the efficacy and safety of lumacaftor in combination with ivacaftor in persons 12 years and older with Cystic Fibrosis who are homozygous for the F508del mutation.


Condition Intervention Phase
Cystic Fibrosis, Homozygous for the F508del CFTR Mutation
Drug: Ivacaftor
Drug: Lumacaftor
Drug: Ivacaftor Placebo
Drug: Lumacaftor Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 3, Randomized, Double Blind, Placebo Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of Lumacaftor in Combination With Ivacaftor in Subjects Aged 12 Years and Older With Cystic Fibrosis, Homozygous for the F508del CFTR Mutation

Resource links provided by NLM:


Further study details as provided by Vertex Pharmaceuticals Incorporated:

Primary Outcome Measures:
  • Absolute change in percent predicted forced expiratory volume in 1 second (FEV1) [ Time Frame: From Baseline at Week 24 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Relative change in percent predicted FEV1 [ Time Frame: From Baseline at Week 24 ] [ Designated as safety issue: No ]
  • Absolute change in body mass index (BMI) [ Time Frame: From Baseline through Week 24 ] [ Designated as safety issue: No ]
  • Number of pulmonary exacerbations [ Time Frame: Through Week 24 ] [ Designated as safety issue: No ]
  • Absolute change in Cystic Fibrosis Questionnaire - Revised (CFQ R) respiratory domain score [ Time Frame: From Baseline at Week 24 ] [ Designated as safety issue: No ]
  • Absolute change in BMI z-score [ Time Frame: From Baseline at Week 24 ] [ Designated as safety issue: No ]
  • Absolute change in body weight [ Time Frame: From Baseline at Week 24 ] [ Designated as safety issue: No ]
  • Time-to-first pulmonary exacerbation [ Time Frame: Through Week 24 ] [ Designated as safety issue: No ]
  • Event of having at least 1 pulmonary exacerbation [ Time Frame: Through Week 24 ] [ Designated as safety issue: No ]
  • Absolute change in EuroQol 3 Level (EQ 5D 3L) score [ Time Frame: From Baseline at Week 24 ] [ Designated as safety issue: No ]
  • Absolute change in Treatment Satisfaction Questionnaire for Medication (TSQM) domains [ Time Frame: From Baseline at Week 24 ] [ Designated as safety issue: No ]
  • Safety and tolerability assessments based on adverse events (AEs), clinical laboratory values (hematology, serum chemistry, coagulation studies, and urinalysis), standard digital electrocardiograms (ECGs), vital signs, and pulse oximetry [ Time Frame: From Baseline and up to 28 Weeks ] [ Designated as safety issue: Yes ]
  • PK parameters of lumacaftor, M28 lumacaftor, ivacaftor, M1 ivacaftor, and M6 ivacaftor [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]

Enrollment: 563
Study Start Date: March 2013
Study Completion Date: April 2014
Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment Arm 1
Subjects randomized to study drug will take 600 mg of lumacaftor once daily (qd) and 250 mg of ivacaftor every 12 hours (q12h)
Drug: Ivacaftor
Other Name: VX-770
Drug: Lumacaftor
Other Name: VX-809
Experimental: Treatment Arm 2
Subjects randomized to study drug will take 400 mg of lumacaftor every 12 hours (q12h) and 250 mg of ivacaftor every 12 hours (q12h)
Drug: Ivacaftor
Other Name: VX-770
Drug: Lumacaftor
Other Name: VX-809
Experimental: Treatment Arm 3
Subjects randomized to placebo will remain on placebo through 24 weeks. Subjects will be given tablets that match both lumacaftor and ivacaftor and will follow the same dosing regimen as subjects receiving the study drug
Drug: Ivacaftor Placebo Drug: Lumacaftor Placebo

  Eligibility

Ages Eligible for Study:   12 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Males and females, aged 12 years or older on the date of informed consent or, where appropriate, date of assent
  • Confirmed diagnosis of CF
  • Homozygous for the F508del CFTR mutation
  • FEV1 ≥40% and ≤90% of predicted normal for age, sex, and height
  • Willing to remain on a stable CF medication regimen through Week 24 or, if applicable, the Safety Follow up Visit

Exclusion Criteria:

  • An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for pulmonary disease within 4 weeks before first dose of study drug
  • History of solid organ or hematological transplantation
  • History of alcohol or drug abuse in the past year
  • Ongoing or prior participation in an investigational drug study (including studies investigating lumacaftor and/or ivacaftor) within 30 days of screening.
  • Use of strong inhibitors, moderate inducers, or strong inducers of CYP3A , including consumption of certain herbal medications (e.g., St. John's Wort) and certain fruit and fruit juices within 14 days before Day 1 of dosing
  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: NCT01807949

  Show 82 Study Locations
Sponsors and Collaborators
Vertex Pharmaceuticals Incorporated
  More Information

No publications provided

Responsible Party: Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier: NCT01807949     History of Changes
Other Study ID Numbers: VX12-809-104
Study First Received: March 4, 2013
Last Updated: July 23, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
Spain: Ministry of Health and Consumption
Belgium: Federal Agency for Medicinal Products and Health Products
Denmark: Danish Medicines Agency
Austria: Austrian Medicines and Medical Devices Agency
Germany: Federal Institute for Drugs and Medical Devices
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Australia: Department of Health and Ageing Therapeutic Goods Administration

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

ClinicalTrials.gov processed this record on October 02, 2014