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

October 15, 2010
August 19, 2014
October 2010
April 2014   (final data collection date for primary outcome measure)
  • 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 ]
  • 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 ]
  • 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
Complete list of historical versions of study NCT01225211 on ClinicalTrials.gov Archive Site
  • 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 ]
  • 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 VX-809 alone and when coadministered with VX-770 in subjects 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: VX-809
  • Drug: VX-770
  • Drug: VX-809 placebo
  • Drug: VX-770 placebo
  • 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.
    Interventions:
    • 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.
    Interventions:
    • 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).
    Interventions:
    • 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).
    Interventions:
    • 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.
    Interventions:
    • 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.
    Interventions:
    • Drug: VX-809 placebo
    • Drug: VX-770 placebo
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. Epub 2014 Jun 24.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
316
April 2014
April 2014   (final data collection date for primary outcome measure)

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)
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   United Kingdom,   Australia,   Belgium,   France,   Germany,   New Zealand
 
NCT01225211
VX09-809-102, 2010-020413-90
Yes
Vertex Pharmaceuticals Incorporated
Vertex Pharmaceuticals Incorporated
Not Provided
Not Provided
Vertex Pharmaceuticals Incorporated
August 2014

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