Study of Ivacaftor in Cystic Fibrosis Subjects 2 Through 5 Years of Age With a CFTR Gating Mutation

Phase 3

Completed

Conditions: Cystic Fibrosis

Interventions: Drug: Ivacaftor

Registration Number: NCT01705145

Lead Sponsor: Vertex Pharmaceuticals Incorporated

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 35

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Ivacaftor	Ivacaftor	Part A: Ivacaftor 50 milligram (mg) (for participants weighing less than \[\<\] 14 kilograms \[kg\]) or 75 mg (for participants weighing greater than or equal to \[\>=\] 14 kg) every 12 hours (q12h) from Day 1 through Day 3 and 1 morning dose on Day 4 during Part A of the study.. Part B: Ivacaftor 50 mg (for participants weighing \<14 kg) or 75 mg (for participants weighing \>=14 kg) q12h for 24 weeks during Part B of the study.

Primary Outcome Measures

Name	Time	Method
Part A: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Related AEs	Part A: Up to 93 Days	AE: any adverse change from participant's baseline (pre-treatment) condition, including any adverse experience, abnormal recording/clinical laboratory assessment which occurs during course of study, whether it is considered related to study drug or not. SAE: medical event or condition, which falls into any of following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, in-patient hospitalization/prolonged hospitalization, persistent/significant disability/incapacity, congenital anomaly/birth defect, important medical event. Related AEs includes all AEs for which the causality was either related to study drug or possibly related to study drug. Data was reported as per the dose received and for overall participants.
Part A: Plasma Concentration of Ivacaftor and Its Metabolites	Part A: up to 24 hours post-dose on Day 4	Plasma concentration was reported for ivacaftor and its metabolites (hydroxymethyl ivacaftor \[M1\] and ivacaftor carboxylate \[M6\]) up to 24 hours post-dose on Day 4 (Hour 0 \[pre-dose\] on Day 1 and Day 4; 2, 3, 6, 24 hours post-dose on Day 4). Data was planned to be reported for overall participants in the period.
Part B: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Related AEs	Part B: Up to 28 Weeks	AE: any adverse change from participant's baseline (pre-treatment) condition, including any adverse experience, abnormal recording/clinical laboratory assessment which occurs during course of study, whether it is considered related to study drug or not. AE includes both serious and non-serious AE. SAE: medical event or condition, which falls into any of following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, in-patient hospitalization/prolonged hospitalization, persistent/significant disability/incapacity, congenital anomaly/birth defect, important medical event. Related AEs includes all AEs for which the causality was either related to study drug or possibly related to study drug. Data was reported as per the dose received.

Secondary Outcome Measures

Name	Time	Method
Part B: Absolute Change From Baseline in Sweat Chloride at Week 24	Part B: Baseline, Week 24	Sweat samples were collected using an approved Macroduct (Wescor, Logan, Utah) collection device. A volume of greater than or equal to (\>=) 15 microliter was required for determination of sweat chloride. Data was reported as per the dose received and for overall participants.
Part B: Absolute Change From Baseline in Stature at Week 24	Part B: Baseline, Week 24	Stature was measured as height if children could stand unassisted and follow directions; otherwise, stature was measured as length. Data was reported as per the dose received and for overall participants.
Part B: Absolute Change From Baseline in Weight at Week 24	Part B: Baseline, Week 24	Data was reported as per the dose received and for overall participants.
Part B: Plasma Concentration of Ivacaftor and Its Metabolites	Part B: up to 24 hours post-dose on Day 168	Plasma concentration was reported for ivacaftor and its metabolites (M1 and M6) up to 24 hours post-dose on Day 168 (Hour 0 \[predose\] on Day 1, 14, 56, 112, and 168; 2, 3, 6 hours post-dose on Day 14; 1 hour post-dose on Day 56; 4, 6 hours post-dose on Day 112; 24 hours post-dose on Day 168). Data was planned to be reported for overall participants in the period.
Part B: Absolute Change From Baseline in Body Mass Index (BMI) at Week 24	Baseline, Week 24	BMI = (Weight \[in kg\]) divided by (Stature \[in meters\])\^2. Data was reported as per the dose received and for overall participants.