Phase 3
Completed N=10
Study of Lumacaftor in Combination With Ivacaftor in Subjects 6 Through 11 Years of Age With Cystic Fibrosis, Homozygous for the F508del-CFTR Mutation
Source: ClinicalTrials.gov NCT01897233 ↗Enrolled (actual)
10
Serious AEs
5.9%
Results posted
Dec 2016
Primary outcomePrimary: Part A: Observed Plasma Concentration of Lumacaftor (LUM) and Ivacaftor (IVA) at Hour 4 Post-dose (C4h) on Day 1 — 15200; 1920 nanogram per milliliter (ng/mL)
◆ Published Evidence
Highly cited
165citations · ~18 / year
Lumacaftor/Ivacaftor in Patients Aged 6-11 Years with Cystic Fibrosis and Homozygous for F508del-CFTR.
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.
Linked Publications (3)
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Lumacaftor/Ivacaftor in Patients Aged 6-11 Years with Cystic Fibrosis and Homozygous for F508del-CFTR.
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Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del).
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Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del).
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Part A: Observed Plasma Concentration of Lumacaftor (LUM) and Ivacaftor (IVA) at Hour 4 Post-dose (C4h) on Day 1 |
15200; 1920 | — |
| PRIMARY Part A: Observed Plasma Concentration of Lumacaftor (LUM) and Ivacaftor (IVA) at Hour 4 Post-dose (C4h) on Day 14 |
24500; 622 | — |
| PRIMARY Part A: Area Under the Plasma Concentration-Time Curve From Time 0 to End of Dosing Interval (AUCtau) of Lumacaftor (LUM) and Ivacaftor (IVA) |
387600; 6838 | — |
| PRIMARY Part B: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) |
55; 4 | — |
| SECONDARY 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 |
176; 3940; 1810; 2040; 2380; 4240 | — |
| SECONDARY Part A: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) |
4; 0; 3; 0 | — |
| SECONDARY Part B: Average Absolute Change From Baseline in Sweat Chloride at Day 15 and at Week 4 |
-19.7 | — |
| SECONDARY Part B: Absolute Change in Sweat Chloride From Week 24 at Week 26 |
21.3 | — |
| SECONDARY Part B: Absolute Change From Baseline in Body Mass Index (BMI) at Week 24 |
0.64 | — |
| SECONDARY Part B: Absolute Change From Baseline in BMI-for-age Z-score at Week 24 |
0.15 | — |
| SECONDARY Part B: Absolute Change From Baseline in Weight at Week 24 |
2.6 | — |
| SECONDARY Part B: Absolute Change From Baseline in Weight-for-age Z-score at Week 24 |
0.13 | — |
| SECONDARY Part B: Absolute Change From Baseline in Height at Week 24 |
2.9 | — |
| SECONDARY Part B: Absolute Change From Baseline in Height-for-age Z-score at Week 24 |
0.03 | — |
| SECONDARY Part B: Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Week 24 |
5.4 | — |
| SECONDARY Part B: Absolute Change From Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Domains at Week 24 |
9.2; -0.3; 11.1; 3.6 | — |
| SECONDARY 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) |
17100; 1980; 186; 4170; 2040; 21400 | — |
Eligibility 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
Data sourced from ClinicalTrials.gov (NCT01897233) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.