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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

October 15, 2010
September 2, 2015
October 2010
April 2014   (final data collection date for primary outcome measure)
  • 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.
  • Safety and Tolerability [ Time Frame: Through Day 35 ] [ Designated as safety issue: No ]
    Assessments will be measured based on adverse events, plasma samples (hematology, clinical chemistry, coagulation), urinalysis, electrocardiograms, and vital signs
  • Change in sweat chloride when VX-770 is administered in combination with VX-809 [ Time Frame: From Day 15 to Day 21 ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01225211 on ClinicalTrials.gov Archive Site
  • 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 ]
  • Change in percent predicted Forced expiratory volume in 1 second (FEV1) [ Time Frame: Through Day 28 ] [ Designated as safety issue: No ]
  • Change in sweat chloride from baseline to Day 14 at increasing doses of VX-809 administered alone [ Time Frame: From Baseline to Day 14 ] [ 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 28 ] [ 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 28 ] [ 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.
Not Provided
Not Provided
 
Study of VX-809 Alone and in Combination With VX-770 in Cystic Fibrosis (CF) Patients Homozygous or Heterozygous for the F508del-CFTR Mutation
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
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.
Not Provided
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Cystic Fibrosis
  • Drug: Lumacaftor
    Tablet
    Other Name: VX-809, LUM
  • Drug: Ivacaftor
    Tablet.
    Other Name: VX-770, IVA
  • Drug: Lumacaftor Placebo
    Matching placebo tablet.
  • Drug: Ivacaftor Placebo
    Matching placebo tablet.
  • 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).
    Interventions:
    • Drug: Lumacaftor Placebo
    • Drug: Ivacaftor Placebo
  • 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).
    Interventions:
    • Drug: Lumacaftor
    • Drug: Ivacaftor
  • 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).
    Interventions:
    • Drug: Lumacaftor
    • Drug: Ivacaftor
  • 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).
    Interventions:
    • Drug: Lumacaftor Placebo
    • Drug: Ivacaftor Placebo
  • 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).
    Interventions:
    • Drug: Lumacaftor
    • Drug: Ivacaftor
  • 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).
    Interventions:
    • Drug: Lumacaftor
    • Drug: Ivacaftor
  • 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).
    Interventions:
    • Drug: Lumacaftor
    • Drug: Ivacaftor
  • 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).
    Interventions:
    • Drug: Lumacaftor
    • Drug: Ivacaftor
  • 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).
    Interventions:
    • Drug: Lumacaftor Placebo
    • Drug: Ivacaftor Placebo
  • 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).
    Interventions:
    • Drug: Lumacaftor
    • Drug: Ivacaftor
Boyle MP, Bell SC, Konstan MW, McColley SA, Rowe SM, Rietschel E, Huang X, Waltz D, Patel NR, Rodman D; VX09-809-102 study group.. A CFTR corrector (lumacaftor) and a CFTR potentiator (ivacaftor) for treatment of patients with cystic fibrosis who have a phe508del CFTR mutation: a phase 2 randomised controlled trial. Lancet Respir Med. 2014 Jul;2(7):527-38. doi: 10.1016/S2213-2600(14)70132-8.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
312
April 2014
April 2014   (final data collection date for primary outcome measure)

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)
Both
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States,   Australia,   Belgium,   France,   Germany,   New Zealand,   United Kingdom
Ireland
 
NCT01225211
VX09-809-102, 2010-020413-90
Yes
Not Provided
Not Provided
Vertex Pharmaceuticals Incorporated
Vertex Pharmaceuticals Incorporated
Not Provided
Not Provided
Vertex Pharmaceuticals Incorporated
September 2015

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