Cystic Fibrosis MedDRA version: 20.0 Level: PT Classification code 10011762 Term: Cystic fibrosis System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Sponsors
Vertex Pharmaceuticals Incorporated
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female with confirmed diagnosis of CF, defined as a sweat chloride value =60 mmol/L by quantitative pilocarpine iontophoresis OR 2 CF causing mutations. • A sweat chloride test must be performed if the sweat chloride value is not available in the subject’s medical records and the value is needed to establish eligibility. For subjects with sweat chloride values documented in their medical records and for whom it is not needed to establish eligibility, the sweat chloride test at screening is optional. 2. Have 1 of the following 9 CFTR mutations on at least 1 allele: G551D, G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P, or G1349D. Subjects who have an R117H-CFTR mutation will be eligible in regions where ivacaftor is approved for use in subjects with an R117H-CFTR mutation. Subjects eligible for Part A/B Cohort 8 may also have other ivacaftor-responsive mutations. • If a genotype test has been performed previously and is documented in the subject’s medical record, the subject's eligibility must be approved by the Vertex medical monitor. If a historic genotype result is not available at screening or if the historic genotype result is not approved by the Vertex medical monitor, the subject will be tested for CFTR genotype at screening and the results must be reviewed before the first dose of ivacaftor. Subjects who have been enrolled and whose screening genotype does not confirm study eligibility will not receive study drug. • Subjects who have an ivacaftor-responsive mutation on at least 1 allele will be eligible to enroll in Part A/B Cohort 8 in regions where ivacaftor is approved (consistent with the approved mutations in the region). o Subjects must be =1 to =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. 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. 2. An acute upper or lower respiratory infection, or pulmonary exacerbation, or changes in therapy (including antibiotics) for pulmonary disease within 4 weeks before Day 1 3. This exclusion criterion is waived for subjects enrolling in Part A/B Cohort 8. Colonization with organisms associated with a more rapid decline in pulmonary status (e.g., Burkholderia cenocepacia, Burkholderia dolosa, and Mycobacterium abscessus) at screening. The investigator could be guided by the following suggested criteria for a subject to be considered free of colonization: • The subject should have had 2 respiratory tract cultures negative for these organisms within the past 12 months, with no subsequent positive cultures. • These 2 respiratory tract cultures should have been separated by at least 3 months. • One of these 2 respiratory tract cultures should have been obtained within the past 6 months. 4. Abnormal liver function at screening or any prior history of clinically relevant elevated (>2 × upper limit of normal [ULN]) serum aspartate transaminase (AST), serum alanine transaminase (ALT), or bilirubin (excluding newborn hyperbilirubinemia) 5. History of solid organ or hematological transplantation 6. Any clinically significant "non-CF-related" illness within 2 weeks before Day 1. "Illness" is defined as an acute (serious or nonserious) condition (e.g., gastroenteritis) 7. Use of any moderate or strong inducers or inhibitors of cytochrome P450 (CYP) 3A within 2 weeks before Day 1 8. 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 or as determined by the local requirements) before screening 9. Hemoglobin <9.5 g/dL at screening 10. Chronic kidney disease of Stage 3 or above 11. An adequate slit-lamp examination could not be conducted at the screening OE 12. Presence of a lens opacity or cataract identified at the screening OE (excluding those considered congenital and nonprogressive, such as a suture cataract)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part A: Evaluate the safety of ivacaftor treatment in subjects with CF who are <24 months of age at treatment initiation & have a CF transmembrane conductance regulator gene gating mutation Evaluate the pharmacokinetics of ivacaftor & metabolites hydroxymethyl-ivacaftor (M1) & ivacaftor carboxylate (M6) in subjects with CF who are <24 months of age at treatment initiation and have a CFTR gating mutation Part B: Evaluate the safety of ivacaftor treatment in subjects with CF who are <24 months of age at treatment initiation and have a CFTR gating mutation Part A/B: Evaluate the safety of ivacaftor treatment in subjects with CF who are 1 to <4 months of age at treatment initiation and have an ivacaftor-responsive CFTR mutation (consistent with the approved mutations in the region) Evaluate the PK of ivacaftor and the ivacaftor metabolites M1 and M6 in subjects with CF who are 1 to <4 months of age at treatment initiation and have an ivacaftor-responsive CFTR mutation;Secondary Objective: Part A: Not applicable Part B : - To evaluate the PK of ivacaftor and metabolites M1 and M6 in subjects with CF who are <24 months of age at treatment initiation and have a CFTR gating mutation - To evaluate the pharmacodynamics (PD) of ivacaftor treatment in subjects with CF who are <24 months of age at treatment initiation and have a Part A/B Objectives - Cohort 8 • To evaluate the PD of ivacaftor treatment in subjects with CF who are 1 to <4 months of age at treatment initiation and have an ivacaftor-responsive CFTR mutation (consistent with the approved mutations in the region) ;Primary end point(s): Part A: - Safety, as determined by adverse events, clinical laboratory values (serum chemistry and hematology), standard 12-lead electrocardiograms (ECGs), vital signs, and ophthalmologic examinations (OEs) - PK parameter estimates of ivacaftor and metabolites M1 and M6 after 4 days of ivacaftor treatment Part B: - Safety, as determined by adverse events, cli | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Part A: - Not applicable Part B: - PK parameter estimates of ivacaftor and metabolites M1 and M6 - Absolute change from baseline in sweat chloride Part A/B Endpoints Cohort 8: - Absolute change from baseline in sweat chloride;Timepoint(s) of evaluation of this end point: 24 weeks | — |
Countries
Canada, Germany, Ireland, United Kingdom, United States
Contacts
Public ContactClinical Trials and Medical Info
Vertex Pharmaceuticals Incorporated
Outcome results
None listed