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A Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of VX-661/Ivacaftor in Pediatric Subjects With Cystic Fibrosis

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ClinicalTrials.gov Identifier: NCT02953314
Recruitment Status : Completed
First Posted : November 2, 2016
Last Update Posted : October 5, 2018
Sponsor:
Information provided by (Responsible Party):
Vertex Pharmaceuticals Incorporated

Brief Summary:
This is a Phase 3, 2-part (Part A and Part B), open label, multicenter study evaluating the PK, safety, and tolerability of multiple doses of VX-661 in combination with ivacaftor in subjects 6 through 11 years of age with CF who are homozygous or heterozygous for the F508del-CFTR mutation.

Condition or disease Intervention/treatment Phase
Cystic Fibrosis Drug: VX-661 Drug: Ivacaftor Phase 3

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 70 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 3, Open Label Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of VX-661 in Combination With Ivacaftor in Subjects 6 Through 11 Years of Age With Cystic Fibrosis, Homozygous or Heterozygous for the F508del CFTR Mutation
Actual Study Start Date : October 2016
Actual Primary Completion Date : August 2018
Actual Study Completion Date : August 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cystic Fibrosis
Drug Information available for: Ivacaftor

Arm Intervention/treatment
Experimental: Part A: Cohort 1
VX-661 50 mg qd + IVA 75 mg q12h
Drug: VX-661
Drug: Ivacaftor
Experimental: Part A: Cohort 2
VX-661 50 mg qd + IVA 150 mg q12h
Drug: VX-661
Drug: Ivacaftor
Experimental: Part B: VX-661 + IVA
VX-661 + IVA 75 mg q 12h or IVA 150 mg q 12h
Drug: VX-661
Drug: Ivacaftor



Primary Outcome Measures :
  1. Part A: Maximum observed concentration (Cmax) of VX-661 and ivacaftor [ Time Frame: Day 1 and Day 14 ]
  2. Part A: Area under the concentration versus time curve during a dosing interval (AUCτ) of VX-661 and ivacaftor [ Time Frame: Day 1 and Day 14 ]
  3. Part B: Safety and tolerability of VX-661 in combination with ivacaftor as determined by adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: from baseline through 29 Weeks ]

Secondary Outcome Measures :
  1. Part A: Cmax of selected metabolites for VX-661 and Ivacaftor [ Time Frame: Day 1 and Day 14 ]
  2. Part A: AUCτ of selected metabolites for VX-661 and Ivacaftor [ Time Frame: Day 1 and Day 14 ]
  3. Part A: Safety and tolerability of VX-661 in combination with ivacaftor as determined by adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: from baseline through Day 31 ]
  4. Part B: Cmax of VX-661, M1-661, M2-661, ivacaftor, M1-ivacaftor, and M6-ivacaftor [ Time Frame: Day 1 through Week 16 ]
  5. Part B: AUCτ of VX-661, M1-661, M2-661, ivacaftor, M1-ivacaftor, and M6-ivacaftor [ Time Frame: Day 1 through Week 16 ]
  6. Part B: Absolute change in percent predicted forced expiratory volume in 1 second (ppFEV1) [ Time Frame: from baseline through Week 24 ]
  7. Part B: Relative change in ppFEV1 [ Time Frame: from baseline at Week 24 ]
  8. Part B: Absolute change in weight [ Time Frame: from baseline at Week 24 ]
  9. Part B: Absolute change in weight for age z-score [ Time Frame: from baseline at Week 24 ]
  10. Part B: Absolute change in height [ Time Frame: from baseline at Week 24 ]
  11. Part B: Absolute change in height for age z-score [ Time Frame: from baseline at Week 24 ]
  12. Part B: Absolute change in body mass index (BMI) [ Time Frame: from baseline at Week 24 ]
  13. Part B: Absolute change in BMI for age z-score [ Time Frame: from baseline at Week 24 ]
  14. Part B: Absolute change in sweat chloride [ Time Frame: from baseline through Week 4 ]
  15. Part B: Absolute change in sweat chloride [ Time Frame: from baseline through Week 24 ]
  16. Part B: Absolute change in Cystic Fibrosis Questionnaire Revised (CFQ-R) respiratory domain score [ Time Frame: from baseline through Week 24 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   6 Years to 11 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects who weigh ≥15 kg without shoes at the Screening Visit.
  • All genotypes as specified by the study protocol are eligible in Part A.
  • The following genotypes are eligible in Part B:

    • homozygous for the F508del CFTR mutation
    • heterozygous for the F508del CFTR mutation and with a second allele with a CFTR mutation predicted to have residual function.
    • heterozygous for the F508del CFTR mutation and with a second CFTR allele with a gating defect that is clinically demonstrated to be ivacaftor responsive
  • Subjects with a confirmed diagnosis of CF defined as a sweat chloride value ≥60 mmol/L or chronic sinopulmonary and/or gastrointestinal disease consistent with a diagnosis of CF. Subjects who are homozygous for the F508del-CFTR mutation must have a sweat chloride value ≥60 mmol/L.
  • Subjects with ppFEV1 of ≥40 percentage points at the Screening Visit
  • Subjects with stable CF disease as deemed by the investigator at the Screening Visit.
  • Subjects who are willing to remain on their stable CF medication regimen through Day 14 (Part A) or through Week 24 (Part B) or, if applicable, through the Safety Follow up Visit.
  • Subjects who are able to swallow tablets.
  • Female subjects of childbearing potential must have a negative serum pregnancy test at the Screening Visit and a negative urine pregnancy test at the Day 1 Visit before receiving the first dose of study drug.
  • Subjects of childbearing potential who are sexually active must meet the contraception requirements

Exclusion Criteria:

  • History of any comorbidity reviewed at the Screening Visit 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.
  • Any clinically significant laboratory abnormalities at the Screening Visit that would interfere with the study assessments or pose an undue risk for the subject.
  • An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy for pulmonary disease within 28 days before Day 1
  • Colonization with organisms associated with a more rapid decline in pulmonary status.
  • A standard 12 lead ECG demonstrating QTc >450 msec at the Screening Visit.
  • History of solid organ or hematological transplantation at the Screening Visit.
  • Ongoing or prior participation in an investigational drug study or use of commercially available CFTR modulator (except physician-prescribed Kalydeco for approved indications) within 30 days of screening.
  • Use of restricted medication or food within a specified duration before the Screening Visit or first dose of study drug and/or unwillingness to maintain the restrictions.
  • History or evidence of cataract, lens opacity, Y-suture, or lamellar rings determined to be clinically significant by the ophthalmologist during the ophthalmologic examination at the Screening Visit.
  • Pregnant and nursing females.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02953314


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Sponsors and Collaborators
Vertex Pharmaceuticals Incorporated

Responsible Party: Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier: NCT02953314     History of Changes
Other Study ID Numbers: VX15-661-113
First Posted: November 2, 2016    Key Record Dates
Last Update Posted: October 5, 2018
Last Verified: October 2018

Additional relevant MeSH terms:
Fibrosis
Cystic Fibrosis
Pathologic Processes
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Ivacaftor
Chloride Channel Agonists
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action