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

Vertex Pharmaceuticals Incorporated35 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Cystic Fibrosis

Interventions

Ivacaftor

Eligibility

Sex: ALLMin age: 2 YearsMax age: 5 Years

Medical Language ↔ Plain English

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

Locations (20)

Unnamed facility

Birmingham, Alabama, United States

Unnamed facility

Aurora, Colorado, United States

Unnamed facility

Atlanta, Georgia, United States

Unnamed facility

Indianapolis, Indiana, United States

Unnamed facility

Lexington, Kentucky, United States

Unnamed facility

Boston, Massachusetts, United States

Unnamed facility

Detroit, Michigan, United States

Unnamed facility

Grand Rapids, Michigan, United States

Unnamed facility

Minneapolis, Minnesota, United States

Unnamed facility

Kansas City, Missouri, United States

...and 10 more locations

Outcomes

Primary Outcomes

Part A: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Related AEs

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.

Time frame: Part A: Up to 93 Days

Part B: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Related AEs

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.

Time frame: Part B: Up to 28 Weeks

Part A: Plasma Concentration of Ivacaftor and Its Metabolites

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.

Time frame: Part A: up to 24 hours post-dose on Day 4

Secondary Outcomes

Part B: Plasma Concentration of Ivacaftor and Its Metabolites

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.

Time frame: Part B: up to 24 hours post-dose on Day 168

Part B: Absolute Change From Baseline in Sweat Chloride at 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.

Time frame: Part B: Baseline, Week 24

Part B: Absolute Change From Baseline in Weight at Week 24

Data was reported as per the dose received and for overall participants.

Time frame: Part B: Baseline, Week 24

Part B: Absolute Change From Baseline in Stature at 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.

Time frame: Part B: Baseline, Week 24

Part B: Absolute Change From Baseline in Body Mass Index (BMI) at Week 24

BMI = (Weight \[in kg\]) divided by (Stature \[in meters\])\^2. Data was reported as per the dose received and for overall participants.

Time frame: Baseline, Week 24