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Drug & research development » Clinical trials » NCT01225211

Study of VX-809 Alone and in Combination With VX-770 in Cystic Fibrosis (CF) Patients Homozygous or Heterozygous for the F508del-CFTR Mutation

Official title: 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

Clinical Trials gov number: NCT01225211

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Purpose: To evaluate the safety, efficacy, pharmacokinetics (PK) and pharmacodynamic (PD) effects of VX-809 alone and when coadministered with ivacaftor in CF patients, homozygous or heterozygous for the F508del-CFTR mutation.

Phase: 2

Type: Interventional, randomized, double-blind, factorial assignment

Study sponsor: Vertex Pharmaceuticals Incorporated

  • Male or female subjects with confirmed diagnosis of CF
  • Must have the F508del-CFTR mutation on ≥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

Intervention
Ivacaftor, Lumacaftor

Geographical Location
Australia, Belgium, France, Germany, United Kingdom, United States, New Zealand

Number of Participants
101-1000 (≥18 years)

Primary Endpoint

  • Change in sweat chloride when ivacaftor is administered in combination with lumacaftor from Day 14 to Day 21 (Cohort 1) and from Day 28 to Day 56 (Cohorts 2 and 3)
  • Safety and tolerability assessments based on adverse events, plasma samples (hematology, clinical chemistry, coagulation), urinalysis, electrocardiograms, and vital signs through to Day 21 (Cohort 1) and Day 56 (Cohorts 2, 3 and 4)
  • Relative change in percent predicted FEV1 (Cohort 4)

Secondary Endpoint

Through Day 21 (Cohort 1) and Day 56 (Cohorts 2, 3 and 4)

  • Change in percent predicted forced expiratory volume in 1 second (FEV1)
  • PK parameters in the presence and absence of ivacaftor
  • PK parameters of ivacaftor and metabolites in plasma in the presence of lumacaftor

From baseline (BL) to Day 14 (Cohort 1); from BL to Day 28 (Cohort 2 and Cohort 3); from BL to Day 56 (Cohort 4)

  • Change in sweat chloride of increasing doses of lumacaftor administered alone

From BL to Day 56

  • Cystic Fibrosis Questionnaire Score (Cohorts 2, 3 and 4)
  • Absolute change in body mass index (Cohort 4)
  • Absolute change in body weight (Cohort 4)

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  • Experimental treatment arm (Cohort 1)

Subjects randomized to study drug will take lumacaftor once daily (qd) for 14 days. Beginning on Day 15, subjects will take both lumacaftor once qd and ivacaftor taken every 12 hours (q12h) through Day 21.

  • Placebo comparator 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 lumacaftor once daily (qd) and ivacaftor taken every 12 hours (q12h) and will follow the same dosing regimen as subjects receiving study drug.

  • Experimental treatment arm (Cohort 2)

 Subjects randomized to study drug will take lumacaftor once daily (qd) for 28 days (Period 1). Beginning on Day 29, subjects will take both lumacaftor once qd and ivacaftor taken every 12 hours (q12h) through Day 56 (Period 2).

  • Experimental treatment arm (Cohort 3)

Subjects randomized to study drug will take lumacaftor taken every 12 hours (q12h) for 28 days (Period 1). Beginning on Day 29, subjects will take both lumacaftor and ivacaftor every q12h through Day 56 (Period 2).

  • Experimental treatment arm (Cohort 4)

Subjects heterozygous will receive 400 mg of lumacaftor tablet taken every 12 hours (q12h) in combination with 250 mg of ivacaftor q12h through Day 56.

  • Placebo comparator arm (Cohort 4)

Subjects heterozygous will receive Fixed-dose combination: lumacaftor/ivacaftor Placebo tablet taken every 12 hours (q12h) through Day 56.

Links:

http://www.ncbi.nlm.nih.gov/pubmed/24973281

References:

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. PubMed PMID: 24973281.

View Trial Results