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

Cystic Fibrosis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01705145
• Other study ID #: VX11-770-108
• Secondary ID: KIWI
• Status: Completed
• Phase: Phase 3
• First received: October 8, 2012
• Last updated: April 23, 2015
• Start date: January 2013
• Est. completion date: March 2014

Study information

• Verified date: April 2015
• Source: Vertex Pharmaceuticals Incorporated
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyCanada: Health Canada
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35
• Est. completion date: March 2014
• Est. primary completion date: March 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 2 Years to 5 Years

Eligibility

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

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

Drug:
• Ivacaftor

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Vertex Pharmaceuticals Incorporated	Cystic Fibrosis Foundation Therapeutics

Countries where clinical trial is conducted

United States,  Canada,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Part A: Up to 93 Days	Yes
Primary	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.	Part B: Up to 28 Weeks	Yes
Primary	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.	Part A: up to 24 hours post-dose on Day 4	No
Secondary	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.	Part B: up to 24 hours post-dose on Day 168	No
Secondary	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.	Part B: Baseline, Week 24	No
Secondary	Part B: Absolute Change From Baseline in Weight at Week 24	Data was reported as per the dose received and for overall participants.	Part B: Baseline, Week 24	No
Secondary	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.	Part B: Baseline, Week 24	No
Secondary	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.	Baseline, Week 24	No