A Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Ivacaftor in Subjects With Cystic Fibrosis Who Are Less Than 24 Months of Age and Have an Ivacaftor-Responsive CFTR 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 Less Than 24 Months of Age and Have an Ivacaftor-Responsive CFTR Mutation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02725567
• Other study ID #: VX15-770-124
• Secondary ID: 2015-001997-16
• Status: Completed
• Phase: Phase 3
• Start date: June 2, 2016
• Est. completion date: June 28, 2022

Study information

• Verified date: August 2023
• Source: Vertex Pharmaceuticals Incorporated
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study was to evaluate the safety of ivacaftor treatment, and PK of ivacaftor and metabolites in participants with cystic fibrosis (CF) who are <24 months of age at treatment initiation and have an ivacaftor-responsive CF transmembrane conductance regulator (CFTR) gene mutation.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 57
• Est. completion date: June 28, 2022
• Est. primary completion date: June 28, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Month to 24 Months

Eligibility

Inclusion Criteria:

• Confirmed diagnosis of CF by sweat chloride value or CF mutation criteria.

• Have 1 of the following 10 CFTR mutations on at least 1 allele: G551D, G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P, G1349D or R117H (eligible in regions where ivacaftor is approved for use). Part A/B group may also have other ivacaftor-responsive mutations.

• Hematology, serum chemistry, 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

• Colonization with organisms associated with a more rapid decline in pulmonary status at screening (Only for Parts A and B)

• History of abnormal liver function or 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

• Hemoglobin (Hgb) <9.5 g/dL at screening

• Chronic kidney disease of Stage 3 or above

• Presence of a non-congenital or progressive lens opacity or cataract at Screening

Other protocol defined Inclusion/Exclusion Criteria may apply.

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

Drug:
• IVA
Granules in sachet for oral administration.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Vertex Pharmaceuticals Incorporated

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Ireland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part A: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious (TEAEs)		Day 1 through Day 70
Primary	Part A: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)		Pre-dose, 2-4 hours, 6-8 hours, 24-60 hours post-dose
Primary	Part B +A/B: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious (TEAEs)		Day 1 through Week 38
Primary	Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)		Day 4 (pre-dose, 2-4 hours, 6-8 hours post-dose); Day 15 (pre-dose); Week 4 (pre-dose); Week 8 (pre-dose, 2-4 hours, 6-8 hours post-dose); Week 12 (pre-dose); Week 18 (pre-dose) and Week 24 (pre-dose)
Secondary	Part B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)		Week 2 (pre-dose, 2-4 hours, 6-8 hours post-dose); Week 8 (pre-dose,1 hour, 4-hour post-dose); Week 24 (pre-dose, 2-4 hours post dose)
Secondary	Part B + A/B: Absolute Change From Baseline in Sweat Chloride	Sweat samples were collected using an approved collection device.	From Baseline at Week 24