Clinical trial NCT01705145: Study of Ivacaftor in Cystic Fibrosis Subjects 2 Through 5 Years of Age With a CFTR Gating Mutation
Official title: A Phase 3, 2-Part, Open-Label Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of Ivacaftor in Subjects With Cystic Fibrosis Who Are 2 Through 5 Years of Age and Have a CFTR Gating Mutation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cystic Fibrosis
Keywords: Cystic Fibrosis
Lead sponsor: Vertex Pharmaceuticals Incorporated
Sponsor class: INDUSTRY
Collaborators: name: Cystic Fibrosis Foundation
First posted: 2012-10-12
Enrollment: 35
Sex: ALL
Minimum age (years): 2
Maximum age (years): 5
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety, pharmacokinetics (PK), and pharmacodynamics (PD), of ivacaftor in children with cystic fibrosis (CF) who are 2 through 5 years of age and have a CF Transmembrane Conductance Regulator (CFTR) gating mutation in at least 1 allele.

Part A is designed to evaluate the safety and PK of multiple-dose administration of ivacaftor in participants 2 through 5 years of age and to confirm the doses for Part B. Part B is designed to evaluate the safety, PK, PD, and efficacy of ivacaftor in participants 2 through 5 years of age.


Eligibility criteria: Inclusion Criteria:

* Male or female with confirmed diagnosis of CF
* Must have a CFTR gating mutation in at least 1 allele
* Aged 2 through 5 years at screening and Day 1
* Weight \>= 8 kg at screening and Day 1
* Hematology, serum chemistry, coagulation, and vital signs results at screening with no clinically significant abnormalities that would interfere with the study assessments, as judged by the investigator

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
* An acute upper or lower respiratory infection, or pulmonary exacerbation, or changes in therapy for pulmonary disease within 4 weeks before Day 1
* Abnormal liver function, at screening
* History of solid organ or hematological transplantation
* Use of any moderate or strong inducers or inhibitors of cytochrome P450 (CYP) 3A within 2 weeks before Day 1
* Participation in a clinical study involving administration of either an investigational or a marketed drug within 30 days or 5 terminal half-lives before screening

Primary outcomes:
measure: Part A: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Related AEs
timeFrame: Part A: Up to 93 Days
measure: Part B: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Related AEs
timeFrame: Part B: Up to 28 Weeks
measure: Part A: Plasma Concentration of Ivacaftor and Its Metabolites
timeFrame: Part A: up to 24 hours post-dose on Day 4
Secondary outcomes:
measure: Part B: Plasma Concentration of Ivacaftor and Its Metabolites
timeFrame: Part B: up to 24 hours post-dose on Day 168
measure: Part B: Absolute Change From Baseline in Sweat Chloride at Week 24
timeFrame: Part B: Baseline, Week 24
measure: Part B: Absolute Change From Baseline in Weight at Week 24
timeFrame: Part B: Baseline, Week 24
measure: Part B: Absolute Change From Baseline in Stature at Week 24
timeFrame: Part B: Baseline, Week 24
measure: Part B: Absolute Change From Baseline in Body Mass Index (BMI) at Week 24
timeFrame: Baseline, Week 24
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Aurora
country: United States
state: Colorado
city: Atlanta
country: United States
state: Georgia
city: Indianapolis
country: United States
state: Indiana
city: Lexington
country: United States
state: Kentucky
city: Boston
country: United States
state: Massachusetts
city: Detroit
country: United States
state: Michigan
city: Grand Rapids
country: United States
state: Michigan
city: Minneapolis
country: United States
state: Minnesota
city: Kansas City
country: United States
state: Missouri
city: Omaha
country: United States
state: Nebraska
city: Pittsburgh
country: United States
state: Pennsylvania
city: Salt Lake City
country: United States
state: Utah
city: Charlottesville
country: United States
state: Virginia
city: Richmond
country: United States
state: Virginia
city: Seattle
country: United States
state: Washington
city: Vancouver
country: Canada
city: Edinburgh
country: United Kingdom
city: Liverpool
country: United Kingdom
city: London
country: United Kingdom
Study officials:
affiliation: Seattle Children's Hospital
name: Margaret Rosenfeld, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Imperial College London
name: Jane Davies, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Davies JC, Cunningham S, Harris WT, Lapey A, Regelmann WE, Sawicki GS, Southern KW, Robertson S, Green Y, Cooke J, Rosenfeld M; KIWI Study Group. Safety, pharmacokinetics, and pharmacodynamics of ivacaftor in patients aged 2-5 years with cystic fibrosis and a CFTR gating mutation (KIWI): an open-label, single-arm study. Lancet Respir Med. 2016 Feb;4(2):107-15. doi: 10.1016/S2213-2600(15)00545-7. Epub 2016 Jan 21.