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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier:
NCT01531673
First received: February 1, 2012
Last updated: April 7, 2014
Last verified: April 2014
  Purpose

The purpose of this study is to evaluate the safety, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) effects of VX-661 alone and when coadministered with ivacaftor in subjects with CF who are homozygous or heterozygous for the F508del-CFTR mutation.


Condition Intervention Phase
Cystic Fibrosis
Drug: VX-661
Drug: ivacaftor
Drug: VX-661 placebo
Drug: ivacaftor placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2, Multicenter, Double-Blinded, Placebo Controlled Study to Evaluate Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of VX-661 Monotherapy and VX-661/Ivacaftor Cotherapy 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:
  • Safety and tolerability of active drug vs placebo [ Time Frame: Through Day 56 ] [ Designated as safety issue: Yes ]
    Measured by incidence of treatment-emergent adverse events

  • Safety and tolerability of active drug vs placebo [ Time Frame: Through Day 56 ] [ Designated as safety issue: Yes ]
    Measured by clinical laboratory values (serum chemistry, hematology, coagulation studies, and urinalysis)

  • Safety and tolerability of active drug vs placebo [ Time Frame: Through Day 56 ] [ Designated as safety issue: Yes ]
    Measured by 12-lead ECG outcomes

  • Safety and tolerability of active drug vs placebo [ Time Frame: Through Day 56 ] [ Designated as safety issue: Yes ]
    Measured by vital signs

  • Absolute change in sweat chloride [ Time Frame: From baseline across all visits through Day 28 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in sweat chloride [ Time Frame: From baseline to each visit up to Day 28 ] [ Designated as safety issue: No ]
  • Change in percent predicted forced expiratory volume in 1 second [ Time Frame: From baseline to each visit and from baseline through Day 28 ] [ Designated as safety issue: No ]
  • Change in forced expiratory volume in 1 second [ Time Frame: From baseline to each visit and from baseline through Day 28 ] [ Designated as safety issue: No ]
  • Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory domain score [ Time Frame: From baseline to each visit up to Day 28 ] [ Designated as safety issue: No ]
  • PK parameters [Cmax, Cmin, Cavg, area under the concentration versus time curve(AUC), tmax] of VX-661, ivacaftor, and their respective metabolites in plasma when VX-661 is administered alone and when the 2 drugs are administered together [ Time Frame: Through 56 days ] [ Designated as safety issue: No ]

Enrollment: 194
Study Start Date: February 2012
Study Completion Date: March 2014
Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1
F508d homozygous subjects to receive 10 mg VX-661 monotherapy once daily for 28 days.
Drug: VX-661
Tablet, taken once daily (qd)
Experimental: Group 2a
F508d homozygous subjects to receive 30 mg VX-661 monotherapy once daily for 28 days.
Drug: VX-661
Tablet, taken once daily (qd)
Experimental: Group 2b
F508d homozygous subjects to receive 10 mg VX-661 once daily and 150 mg ivacaftor twice daily for 28 days.
Drug: VX-661
Tablet, taken once daily (qd)
Drug: ivacaftor
Tablet, taken every 12 hours (q12h)
Experimental: Group 3a
F508d homozygous subjects to receive 100 mg VX-661 monotherapy once daily for 28 days.
Drug: VX-661
Tablet, taken once daily (qd)
Experimental: Group 3b
F508d homozygous subjects to receive 30 mg VX-661 once daily and ivacaftor 150mg twice daily for 28 days.
Drug: VX-661
Tablet, taken once daily (qd)
Drug: ivacaftor
Tablet, taken every 12 hours (q12h)
Experimental: Group 4
F508d homozygous subjects to receive 100 mg VX-661 once daily and ivacaftor 150mg twice daily for 28 days.
Drug: VX-661
Tablet, taken once daily (qd)
Drug: ivacaftor
Tablet, taken every 12 hours (q12h)
Experimental: Group 5a
F508d homozygous subjects to receive 150 mg VX-661 monotherapy once daily for 28 days.
Drug: VX-661
Tablet, taken once daily (qd)
Experimental: Group 5b
F508d homozygous subjects to receive 150 mg VX-661 once daily and ivacaftor 150 mg twice daily for 28 days.
Drug: VX-661
Tablet, taken once daily (qd)
Drug: ivacaftor
Tablet, taken every 12 hours (q12h)
Experimental: Group 6a
F508d homozygous subjects to receive 100 mg VX-661 once daily and ivacaftor 50 mg twice daily for 28 days.
Drug: VX-661
Tablet, taken once daily (qd)
Drug: ivacaftor
Tablet, taken every 12 hours (q12h)
Experimental: Group 6d
F508d homozygous subjects to receive 50 mg VX-661 twice daily and ivacaftor 150 mg twice daily for 28 days.
Drug: ivacaftor
Tablet, taken every 12 hours (q12h)
Drug: VX-661
Tablet, taken every 12 hours (q12h)
Experimental: Group 7
F508d/G551D subjects to receive 100 mg VX-661 once daily for 28 days
Drug: VX-661
Tablet, taken once daily (qd)
Placebo Comparator: Group 1 - Placebo
F508d homozygous subjects to receive VX-661-placebo monotherapy once daily for 28 days.
Drug: VX-661 placebo
Tablet, taken once daily (qd)
Placebo Comparator: Group 2a - Placebo
F508d homozygous subjects to receive VX-661-placebo monotherapy once daily for 28 days.
Drug: VX-661 placebo
Tablet, taken once daily (qd)
Placebo Comparator: Group 2b - Placebo
F508d homozygous subjects to receive VX-661-placebo once daily and ivacaftor-placebo twice daily for 28 days.
Drug: VX-661 placebo
Tablet, taken once daily (qd)
Drug: ivacaftor placebo
Tablet, taken every 12 hours (q12h)
Placebo Comparator: Group 3a - Placebo
F508d homozygous subjects to receive VX-661-placebo monotherapy once daily for 28 days.
Drug: VX-661 placebo
Tablet, taken once daily (qd)
Placebo Comparator: Group 3b - Placebo
F508d homozygous subjects to receive VX-661-placebo once daily and ivacaftor-placebo twice daily for 28 days.
Drug: VX-661 placebo
Tablet, taken once daily (qd)
Drug: ivacaftor placebo
Tablet, taken every 12 hours (q12h)
Placebo Comparator: Group 4 - Placebo
F508d homozygous subjects to receive VX-661-placebo once daily and ivacaftor-placebo twice daily for 28 days.
Drug: VX-661 placebo
Tablet, taken once daily (qd)
Drug: ivacaftor placebo
Tablet, taken every 12 hours (q12h)
Placebo Comparator: Group 5a - Placebo
F508d homozygous subjects to receive VX-661-placebo monotherapy once daily for 28 days.
Drug: VX-661 placebo
Tablet, taken once daily (qd)
Placebo Comparator: Group 5b - Placebo
F508d homozygous subjects to receive VX-661-placebo once daily and ivacaftor-placebo twice daily for 28 days.
Drug: VX-661 placebo
Tablet, taken once daily (qd)
Drug: ivacaftor placebo
Tablet, taken every 12 hours (q12h)
Placebo Comparator: Group 6a - Placebo
F508d homozygous subjects to receive VX-661-placebo once daily and ivacaftor-placebo twice daily for 28 days.
Drug: VX-661 placebo
Tablet, taken once daily (qd)
Drug: ivacaftor placebo
Tablet, taken every 12 hours (q12h)
Placebo Comparator: Group 6d - Placebo
F508d homozygous subjects to receive VX-661-placebo twice daily and ivacaftor-placebo twice daily for 28 days.
Drug: ivacaftor placebo
Tablet, taken every 12 hours (q12h)
Drug: VX-661 placebo
Tablet, taken every 12 hours (q12h)
Placebo Comparator: Group 7 - Placebo
F508d/G551D subjects to receive VX-661-placebo once daily for 28 days
Drug: VX-661 placebo
Tablet, taken once daily (qd)

Detailed Description:

This is a Phase 2, randomized, multicenter, double-blinded, placebo-controlled, study of VX 661 monotherapy, and VX 661/ivacaftor co-therapy in subjects with CF who are homozygous or heterozygous for the F508del CFTR mutation.

This study will be separated into seven groups: Group 1-7, respectively. Approximately 180 subjects will be randomized in a ratio of 4:1; active drug to matching placebo in each group.

  Eligibility

Ages Eligible for Study:   12 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female with confirmed diagnosis of CF
  • Must have the F508del-CFTR gene mutation in both alleles (Groups 1, 2, 3, 4, 5, 6). Group 7 subjects must have the F508del-CFTR mutation on 1 allele, and gating mutation G551D on the second allele and have been on their physician prescribed 150 mg KalydecoTM q12h (commercially available ivacaftor) for at least 28 days at the Screening Visit.
  • Forced expiratory volume in 1 second(FEV1) 40% to 90% (inclusive) of predicted normal for age, gender, and height (Knudson standards) at screening
  • Weight >40 kg and BMI >18.5
  • Subjects of child-bearing potential and who are sexually active must meet the contraception requirements.

Exclusion Criteria:

  • History of any illness 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.
  • An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for pulmonary disease within 4 weeks before Study Day 1.
  • History of solid organ or hematological transplantation
  • Participation in a clinical study involving administration of either an investigational or a marketed drug within 30 days or 5 terminal half-lives (whichever is longer) before screening
  • History of alcohol, medication, or illicit drug abuse within 1 year prior to screening
  • Pregnant, breast-feeding, or not willing to follow contraception requirements
  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: NCT01531673

  Show 36 Study Locations
Sponsors and Collaborators
Vertex Pharmaceuticals Incorporated
Investigators
Principal Investigator: Scott Donaldson, MD University of North Carolina
  More Information

No publications provided

Responsible Party: Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier: NCT01531673     History of Changes
Other Study ID Numbers: VX11-661-101, 2011-003821-93
Study First Received: February 1, 2012
Last Updated: April 7, 2014
Health Authority: United States: Food and Drug Administration

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 October 23, 2014