Study of Lumacaftor in Combination With Ivacaftor in Subjects 6 Through 11 Years of Age With Cystic Fibrosis, Homozygous for the F508del-CFTR Mutation

Cystic Fibrosis Clinical Trial

Official title:

A Phase 3, Open-Label Study to Evaluate the Pharmacokinetics, Safety and Tolerability of Lumacaftor in Combination With Ivacaftor in Subjects 6 Through 11 Years of Age With Cystic Fibrosis, Homozygous for the F508del-CFTR Mutation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01897233
• Other study ID #: VX13-809-011
• Status: Completed
• Phase: Phase 3
• First received: July 8, 2013
• Last updated: December 1, 2015
• Start date: July 2013
• Est. completion date: October 2015

Study information

• Verified date: December 2015
• Source: Vertex Pharmaceuticals Incorporated
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This is a Phase 3, 2 part (Part A and Part B), open label, multicenter study to evaluate the pharmacokinetics, safety and tolerability of lumacaftor in combination with ivacaftor in subjects with cystic fibrosis aged 6 to 11 years who have the F508del-mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 58
• Est. completion date: October 2015
• Est. primary completion date: October 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 6 Years to 11 Years

Eligibility

Inclusion Criteria:

• Confirmed diagnosis of CF defined as:

• with 2 CF-causing mutations

• chronic sinopulmonary disease or gastrointestinal/nutritional abnormalities

• Subjects who weigh > 15 kg without shoes at Screening Visit

• Subjects who are homozygous for the F508del-CFTR mutation

• Subjects with percent predicted Forced Expiratory Volume in 1 second (FEV1) of 70% to 105% (inclusive) (Part A) or =40% (Part B) at the screening visit where the predicted values are adjusted for age, sex, and height using the Wang equation

• Subjects with stable CF disease and who are willing to remain on stable CF medication regimen

• Able to swallow tablets

Exclusion Criteria:

• History of any illness or condition that might confound the results of the study or pose an additional risk in administering study drug to the subject

• Acute respiratory infection, pulmonary exacerbation, or changes in therapy for pulmonary disease within 28 days before Day 1 of the study

• Abnormal liver function as defined in the protocol at Screening

• Abnormal renal function as defined in the protocol at Screening

• History of solid organ or hematological transplantation

• Ongoing participation in another therapeutic clinical study or prior participation in an investigational drug study within 30 days prior to Screening

• Evidence of lens opacity or cataract at the Screening

• Colonization with organisms associated with a more rapid decline in pulmonary status at Screening (Part A only)

• A standard 12-lead ECG demonstrating QtcF >450 msec at Screening

Study Design

Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

Drug:
• Lumacaftor

• Ivacaftor

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Vertex Pharmaceuticals Incorporated

Country where clinical trial is conducted

United States, 

References & Publications (1)

Wang X, Dockery DW, Wypij D, Fay ME, Ferris BG Jr. Pulmonary function between 6 and 18 years of age. Pediatr Pulmonol. 1993 Feb;15(2):75-88. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Lumacaftor and ivacaftor PK parameters, including Cmax and AUC (Part A)		up to 14 days	No
Primary	Safety and tolerability assessments based on AEs, clinical laboratory values (serum chemistry, hematology, coagulation studies, and urinalysis), standard 12 lead ECGs, vital signs, pulse oximetry, ophthalmologic examinations, and spirometry (Part B)		up to 24 weeks	Yes
Secondary	Lumacaftor and ivacaftor metabolite PK parameters including Cmax and AUC (Part A)		up to 14 days	No
Secondary	Safety and tolerability of lumacaftor in combination with ivacaftor as determined by clinical laboratory values, standard 12-lead electrocardiogram, vital signs, pulse oximetry, spirometry, and adverse events (Part A)		up to 24 days	Yes
Secondary	Average absolute change from baseline in sweat chloride (Part B)		at day 15 and at week 4	No
Secondary	Absolute change from baseline in body mass index (BMI) and BMI-for-age z- score (Part B)		at week 24	No
Secondary	Absolute change from baseline in weight and weight-for-age z-score (Part B)		at week 24	No
Secondary	Absolute change from baseline in height and height-for-age z-score (Part B)		at week 24	No
Secondary	Absolute change from baseline in Cystic Fibrosis Questionnaire Revised (CFQ R) respiratory domain score (Part B)		at week 24	No
Secondary	Absolute change from baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) domains (Part B)		at week 24	No
Secondary	Absolute change in sweat chloride (Part B)		from week 24 at week 26	No
Secondary	Pharmacokinetic parameters: estimated peak concentrations and trough concentrations (C3-6h and Ctrough) of lumacaftor, ivacaftor, and M1 ivacaftor (Part B)		Day 1, Day 15, Week 4, Week 16, Week 24	No