Phase 3
Completed N=12
Safety and Pharmacokinetic Study of Lumacaftor/Ivacaftor in Subjects Aged 2 Through 5 Years With Cystic Fibrosis, Homozygous for F508del
Source: ClinicalTrials.gov NCT02797132 ↗Enrolled (actual)
12
Serious AEs
5.6%
Results posted
Oct 2018
Primary outcomePrimary: Part A: Pre-dose Concentration (Ctrough) of LUM and IVA — 8710; 12300; 94.0; 216 nanogram per milliliter (ng/mL)
◆ Published Evidence
Highly cited
131citations · ~19 / year
Safety, pharmacokinetics, and pharmacodynamics of lumacaftor and ivacaftor combination therapy in children aged 2-5 years with cystic fibrosis homozygous for F508del-CFTR: an open-label phase 3 study.
Summary
This is a Phase 3, 2-part (Part A and Part B), open-label, multicenter study evaluating the pharmacokinetics (PK), safety, tolerability, and pharmacodynamics (PD) of multiple doses of lumacaftor/ivacaftor (LUM/IVA) in subjects 2 through 5 years of age (inclusive) with cystic fibrosis (CF), homozygous for F508del. Subjects who participate in Part A may participate in Part B, if they meet the eligibility criteria.
Linked Publications
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Safety, pharmacokinetics, and pharmacodynamics of lumacaftor and ivacaftor combination therapy in children aged 2-5 years with cystic fibrosis homozygous for F508del-CFTR: an open-label phase 3 study.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Part A: Pre-dose Concentration (Ctrough) of LUM and IVA |
8710; 12300; 94.0; 216 | — |
| PRIMARY Part B: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) |
19; 40; 2; 2 | — |
| SECONDARY Part A: Pre-dose Concentration (Ctrough) of LUM and IVA Metabolites |
1310; 1370; 475; 1240; 1510; 3270 | — |
| SECONDARY Part A: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) |
4; 6; 0; 0 | — |
| SECONDARY Part B: Absolute Change From Baseline in Sweat Chloride at Week 24 |
-33.5; -30.7 | — |
| SECONDARY Part B: Absolute Change From Baseline in Body Mass Index (BMI) at Week 24 |
0.22; 0.29 | — |
| SECONDARY Part B: Absolute Change From Baseline in Body Mass Index (BMI) For-Age Z-Score at Week 24 |
0.36; 0.26 | — |
| SECONDARY Part B: Absolute Change From Baseline in Weight at Week 24 |
1.4; 1.5 | — |
| SECONDARY Part B: Absolute Change From Baseline in Weight-for-age Z-Score at Week 24 |
0.44; 0.17 | — |
| SECONDARY Part B: Absolute Change From Baseline in Stature (Height) at Week 24 |
4.1; 3.4 | — |
| SECONDARY Part B: Absolute Change From Baseline in Stature-for-Age Z-Score |
0.19; 0.04 | — |
| SECONDARY Part B: Number of Pulmonary Exacerbations |
5; 20 | — |
| SECONDARY Part B: Number of Participants With at Least One Pulmonary Exacerbation Pulmonary Exacerbation Through Week 24 |
3; 15 | — |
| SECONDARY Part B: Number of Cystic Fibrosis (CF)-Related Hospitalizations |
1; 3 | — |
| SECONDARY Part B: Absolute Change From Baseline in Fecal Elastase-1 (FE-1) Levels at Week 24 |
38.4; 60.0 | — |
| SECONDARY Part B: Absolute Change From Baseline in Serum Levels of Immunoreactive Trypsinogen (IRT) Through Week 24 |
-262.1; -71.1 | — |
| SECONDARY Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24 |
18; 37; 0; 1; 19; 36 | — |
| SECONDARY Part B: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Week 24 |
0.5 | — |
| SECONDARY Part B: Absolute Change in Sweat Chloride From Week 24 at Week 26 |
34.4; 32.2 | — |
| SECONDARY Part B: Acceptability/Palatability of LUM/IVA Granules Measured Using Hedonic Scale |
9; 30; 4; 6; 3; 1 | — |
| SECONDARY Part B: Absolute Change From Baseline in Lung Clearance Index (LCI) 2.5 at Week 24 |
0.27; -0.76 | — |
| SECONDARY Part B: Absolute Change From Baseline in Lung Clearance Index (LCI) 5.0 at Week 24 |
0.24; -0.12 | — |
| SECONDARY Part B: Pre-dose Concentration (Ctrough) of LUM and IVA and Its Metabolites |
9060; 9390; 1420; 1510; 108; 110 | — |
Eligibility Criteria
Inclusion Criteria
- Subjects who weigh ≥8 kilogram (kg) without shoes and wearing light clothing at the Screening Visit
- Subjects with confirmed diagnosis of CF at the Screening Visit
- Subjects who are homozygous for the F508del-cystic fibrosis transmembrane conductance regulator (CFTR) mutation
Exclusion Criteria
- Any clinically significant laboratory abnormalities at the Screening Visit that would interfere with the study assessments or pose an undue risk for the subject
- An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for pulmonary disease within 28 days before Day 1
- A standard 12-lead ECG demonstrating QTc >450 millisecond (msec) at the Screening Visit.
- History of solid organ or hematological transplantation.
- Ongoing or prior participation in an investigational drug study (including studies investigating LUM and/or IVA) within 30 days of the Screening Visit.
- History of cataract/lens opacity or evidence of cataract/lens opacity determined to be clinically significant by a licensed ophthalmologist during the ophthalmologic examination at the Screening Visit
Data sourced from ClinicalTrials.gov (NCT02797132) 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.