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

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT01897233
• Date of registration: 08/07/2013
• Prospective Registration: No
• Primary sponsor: Vertex Pharmaceuticals Incorporated
• Public title: Study of Lumacaftor in Combination With Ivacaftor in Subjects 6 Through 11 Years of Age With Cystic Fibrosis, Homozygous for the F508del-CFTR Mutation
• Scientific 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
• Date of first enrolment: July 2013
• Target sample size: 62
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01897233
• Study type: Interventional
• Study design: Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

Canada, United States

Key inclusion & exclusion criteria

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 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 Visit

- Abnormal renal function as defined in the protocol at Screening Visit

- History of solid organ or hematological transplantation

- Ongoing participation in an investigational drug study or prior participation in an
investigational drug study within 30 days prior of Screening Visit

- History or evidence of lens opacity or cataract at Screening Visit

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

- A standard 12-lead ECG demonstrating QTcF >450 msec at Screening Visit



Age minimum: 6 Years
Age maximum: 11 Years
Gender: All

Health Condition(s) or Problem(s) studied

Cystic Fibrosis

Intervention(s)

Drug: Ivacaftor

Drug: Lumacaftor

Primary Outcome(s)

Part A: Observed Plasma Concentration of Lumacaftor (LUM) and Ivacaftor (IVA) at Hour 4 Post-dose (C4h) on Day 1 [Time Frame: 4 hours post-morning dose on Day 1]

Part A: Area Under the Plasma Concentration-Time Curve From Time 0 to End of Dosing Interval (AUCtau) of Lumacaftor (LUM) and Ivacaftor (IVA) [Time Frame: Day 14 (pre-morning dose, 4, 6, 12, and 24 hours post-morning dose for LUM; pre-morning dose, 2, 4, 6, 12 hours post-morning dose for IVA)]

Part A: Observed Plasma Concentration of Lumacaftor (LUM) and Ivacaftor (IVA) at Hour 4 Post-dose (C4h) on Day 14 [Time Frame: 4 hours post-morning dose on Day 14]

Part B: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [Time Frame: Day 1 up to Week 26]

Secondary Outcome(s)

Part B: Absolute Change From Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Domains at Week 24 [Time Frame: Baseline, Week 24]

Part A: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [Time Frame: Day 1 up to Day 28]

Part B: Absolute Change From Baseline in Weight at Week 24 [Time Frame: Baseline, Week 24]

Part B: Absolute Change From Baseline in Height-for-age Z-score at Week 24 [Time Frame: Baseline, Week 24]

Part A: Observed Plasma Concentration of Lumacaftor Metabolite (M28-LUM) and Ivacaftor Metabolites (M1-IVA and M6-IVA) at Hour 4 Post-dose (C4h) on Day 1 and 14 [Time Frame: Day 1, Day 14]

Part B: Absolute Change From Baseline in BMI-for-age Z-score at Week 24 [Time Frame: Baseline, Week 24]

Part B: Average Absolute Change From Baseline in Sweat Chloride at Day 15 and at Week 4 [Time Frame: Baseline, Day 15 and Week 4]

Part B: Absolute Change From Baseline in Body Mass Index (BMI) at Week 24 [Time Frame: Baseline, Week 24]

Part B: Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Week 24 [Time Frame: Baseline, Week 24]

Part B: Pre-dose Concentration (Ctrough) and 3 to 6 Hours Post-dose Concentration (C3-6hr) of Lumacaftor, Lumacaftor Metabolite (M28-LUM), Ivacaftor and Ivacaftor Metabolites (M1-IVA and M6-IVA) [Time Frame: For Ctrough: pre-morning dose on Week 4, Week 6 and Week 24; For C3-6hr: 3 to 6 hours post-morning dose on Day 1, 15 and Week 4]

Part B: Absolute Change From Baseline in Height at Week 24 [Time Frame: Baseline, Week 24]

Part B: Absolute Change From Baseline in Weight-for-age Z-score at Week 24 [Time Frame: Baseline, Week 24]

Part B: Absolute Change in Sweat Chloride From Week 24 at Week 26 [Time Frame: Week 24, Week 26]

Secondary ID(s)

VX13-809-011

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 05/12/2016
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01897233