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

February 1, 2012
April 7, 2014
February 2012
March 2014   (final data collection date for primary outcome measure)
  • 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 ]
  • Safety and tolerability of active drug vs placebo [ Time Frame: Through Day 56 ] [ Designated as safety issue: No ]
    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: No ]
    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: No ]
    Measured by 12-lead ECG outcomes
  • Safety and tolerability of active drug vs placebo [ Time Frame: Through Day 56 ] [ Designated as safety issue: No ]
    Measured by vital signs
  • Absolute change in sweat chloride [ Time Frame: From baseline across all visits through Day 28 ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01531673 on ClinicalTrials.gov Archive Site
  • 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 ]
  • 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 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 ]
  • Maximum plasma concentration (Cmax) of VX-661, VX-770, and their respective metabolites in plasma when VX-661 is administered alone and when the 2 drugs are administered together. [ Time Frame: Through Day 56 ] [ Designated as safety issue: No ]
    PK blood samples will be drawn on Days 1, 7, 14, 21, 28, 35, 42, and at the follow-up visit.
  • Minimum plasma concentration (Cmin) of VX-661, VX-770, and their respective metabolites in plasma when VX-661 is administered alone and when the 2 drugs are administered together. [ Time Frame: Through Day 56 ] [ Designated as safety issue: No ]
    PK blood samples will be drawn on Days 1, 7, 14, 21, 28, 35, 42, and at the follow-up visit.
  • Average plasma concentration (Cavg) of VX-661, VX-770, and their respective metabolites in plasma when VX-661 is administered alone and when the 2 drugs are administered together. [ Time Frame: Through Day 56 ] [ Designated as safety issue: No ]
    PK blood samples will be drawn on Days 1, 7, 14, 21, 28, 35, 42, and at the follow-up visit.
  • Area under the plasma concentration versus time curve (AUC) of VX-661, VX-770, and their respective metabolites in plasma when VX-661 is administered alone and when the 2 drugs are administered together. [ Time Frame: Through Day 56 ] [ Designated as safety issue: No ]
    PK blood samples will be drawn on Days 1, 7, 14, 21, 28, 35, 42, and at the follow-up visit.
  • Time to attain maximum plasma concentration (tmax) of VX-661, VX-770, and their respective metabolites in plasma when VX-661 is administered alone and when the 2 drugs are administered together. [ Time Frame: Through Day 56 ] [ Designated as safety issue: No ]
    PK blood samples will be drawn on Days 1, 7, 14, 21, 28, 35, 42, and at the follow-up visit.
  • Apparent clearance after oral administration (CL/F) of VX-661, VX-770, and their respective metabolites in plasma when VX-661 is administered alone and when the 2 drugs are administered together. [ Time Frame: Through Day 56 ] [ Designated as safety issue: No ]
    PK blood samples will be drawn on Days 1, 7, 14, 21, 28, 35, 42, and at the follow-up visit.
  • Apparent volume of distribution (V/F) of VX-661, VX-770, and their respective metabolites in plasma when VX-661 is administered alone and when the 2 drugs are administered together. [ Time Frame: Through Day 56 ] [ Designated as safety issue: No ]
    PK blood samples will be drawn on Days 1, 7, 14, 21, 28, 35, 42, and at the follow-up visit.
  • Apparent terminal elimination half-life (t1/2z) of VX-661, VX-770, and their respective metabolites in plasma when VX-661 is administered alone and when the 2 drugs are administered together. [ Time Frame: Through Day 56 ] [ Designated as safety issue: No ]
    PK blood samples will be drawn on Days 1, 7, 14, 21, 28, 35, 42, and at the follow-up visit.
  • Accumulation and metabolic ratio of VX-661, VX-770, and their respective metabolites in plasma when VX-661 is administered alone and when the 2 drugs are administered together. [ Time Frame: Through Day 56 ] [ Designated as safety issue: No ]
    PK blood samples will be drawn on Days 1, 7, 14, 21, 28, 35, 42, and at the follow-up visit.
Not Provided
Not Provided
 
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
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

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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Cystic Fibrosis
  • Drug: VX-661
    Tablet, taken once daily (qd)
  • Drug: ivacaftor
    Tablet, taken every 12 hours (q12h)
  • Drug: VX-661 placebo
    Tablet, taken once daily (qd)
  • Drug: ivacaftor placebo
    Tablet, taken every 12 hours (q12h)
  • Drug: VX-661
    Tablet, taken every 12 hours (q12h)
  • Drug: VX-661 placebo
    Tablet, taken every 12 hours (q12h)
  • Experimental: Group 1
    F508d homozygous subjects to receive 10 mg VX-661 monotherapy once daily for 28 days.
    Intervention: Drug: VX-661
  • Experimental: Group 2a
    F508d homozygous subjects to receive 30 mg VX-661 monotherapy once daily for 28 days.
    Intervention: Drug: VX-661
  • Experimental: Group 2b
    F508d homozygous subjects to receive 10 mg VX-661 once daily and 150 mg ivacaftor twice daily for 28 days.
    Interventions:
    • Drug: VX-661
    • Drug: ivacaftor
  • Experimental: Group 3a
    F508d homozygous subjects to receive 100 mg VX-661 monotherapy once daily for 28 days.
    Intervention: Drug: VX-661
  • Experimental: Group 3b
    F508d homozygous subjects to receive 30 mg VX-661 once daily and ivacaftor 150mg twice daily for 28 days.
    Interventions:
    • Drug: VX-661
    • Drug: ivacaftor
  • Experimental: Group 4
    F508d homozygous subjects to receive 100 mg VX-661 once daily and ivacaftor 150mg twice daily for 28 days.
    Interventions:
    • Drug: VX-661
    • Drug: ivacaftor
  • Experimental: Group 5a
    F508d homozygous subjects to receive 150 mg VX-661 monotherapy once daily for 28 days.
    Intervention: Drug: VX-661
  • Experimental: Group 5b
    F508d homozygous subjects to receive 150 mg VX-661 once daily and ivacaftor 150 mg twice daily for 28 days.
    Interventions:
    • Drug: VX-661
    • Drug: ivacaftor
  • Experimental: Group 6a
    F508d homozygous subjects to receive 100 mg VX-661 once daily and ivacaftor 50 mg twice daily for 28 days.
    Interventions:
    • Drug: VX-661
    • Drug: ivacaftor
  • Experimental: Group 6d
    F508d homozygous subjects to receive 50 mg VX-661 twice daily and ivacaftor 150 mg twice daily for 28 days.
    Interventions:
    • Drug: ivacaftor
    • Drug: VX-661
  • Experimental: Group 7
    F508d/G551D subjects to receive 100 mg VX-661 once daily for 28 days
    Intervention: Drug: VX-661
  • Placebo Comparator: Group 1 - Placebo
    F508d homozygous subjects to receive VX-661-placebo monotherapy once daily for 28 days.
    Intervention: Drug: VX-661 placebo
  • Placebo Comparator: Group 2a - Placebo
    F508d homozygous subjects to receive VX-661-placebo monotherapy once daily for 28 days.
    Intervention: Drug: VX-661 placebo
  • Placebo Comparator: Group 2b - Placebo
    F508d homozygous subjects to receive VX-661-placebo once daily and ivacaftor-placebo twice daily for 28 days.
    Interventions:
    • Drug: VX-661 placebo
    • Drug: ivacaftor placebo
  • Placebo Comparator: Group 3a - Placebo
    F508d homozygous subjects to receive VX-661-placebo monotherapy once daily for 28 days.
    Intervention: Drug: VX-661 placebo
  • Placebo Comparator: Group 3b - Placebo
    F508d homozygous subjects to receive VX-661-placebo once daily and ivacaftor-placebo twice daily for 28 days.
    Interventions:
    • Drug: VX-661 placebo
    • Drug: ivacaftor placebo
  • Placebo Comparator: Group 4 - Placebo
    F508d homozygous subjects to receive VX-661-placebo once daily and ivacaftor-placebo twice daily for 28 days.
    Interventions:
    • Drug: VX-661 placebo
    • Drug: ivacaftor placebo
  • Placebo Comparator: Group 5a - Placebo
    F508d homozygous subjects to receive VX-661-placebo monotherapy once daily for 28 days.
    Intervention: Drug: VX-661 placebo
  • Placebo Comparator: Group 5b - Placebo
    F508d homozygous subjects to receive VX-661-placebo once daily and ivacaftor-placebo twice daily for 28 days.
    Interventions:
    • Drug: VX-661 placebo
    • Drug: ivacaftor placebo
  • Placebo Comparator: Group 6a - Placebo
    F508d homozygous subjects to receive VX-661-placebo once daily and ivacaftor-placebo twice daily for 28 days.
    Interventions:
    • Drug: VX-661 placebo
    • Drug: ivacaftor placebo
  • Placebo Comparator: Group 6d - Placebo
    F508d homozygous subjects to receive VX-661-placebo twice daily and ivacaftor-placebo twice daily for 28 days.
    Interventions:
    • Drug: ivacaftor placebo
    • Drug: VX-661 placebo
  • Placebo Comparator: Group 7 - Placebo
    F508d/G551D subjects to receive VX-661-placebo once daily for 28 days
    Intervention: Drug: VX-661 placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
194
March 2014
March 2014   (final data collection date for primary outcome measure)

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
Both
12 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   United Kingdom,   Canada,   Germany
 
NCT01531673
VX11-661-101, 2011-003821-93
Yes
Vertex Pharmaceuticals Incorporated
Vertex Pharmaceuticals Incorporated
Not Provided
Principal Investigator: Scott Donaldson, MD University of North Carolina
Vertex Pharmaceuticals Incorporated
April 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP