Table 5 Summary of clinical studies investigating the efficacy of lumacaftor and ivacaftor in patients with Phe508del mutations
From: Targeted therapies to improve CFTR function in cystic fibrosis
Study name and reference | Boyle et al. 2014 [70] | TRAFFIC and TRANSPORT: Wainwright et al. 2015 [8] |
|---|---|---|
Type of study | Phase II RCT | Phase III RCT |
Number of participants and study design | Cohort 1: | Cohort 1: |
64 homozygotes | n = 368 | |
Lumacaftor 200Â mg/day for 14Â days | Lumacaftor 600Â mg/day plus ivacaftor 250Â mg every 12Â h | |
Followed by: | Cohort 2: | |
Ivacaftor 150 mg/250 mg every 12 h for 7 days | n = 369 | |
OR | Lumacaftor 400Â mg every 12Â h plus ivacaftor 250Â mg every 12Â h | |
Placebo for 21Â days | Cohort 3: | |
Cohorts 2 and 3: | n = 371 | |
96 homozygotes | Placabo plus placebo | |
28 compound heterozygotes | Â | |
Cohort 2: | ||
Lumacaftor 200Â mg, 400Â mg, 600Â mg/day for 56Â days | ||
Cohort 3: | ||
Lumacaftor 400Â mg every 12Â h for 56Â days | ||
Followed by: | ||
Ivacaftor 250Â mg every 12Â h after 28Â days | ||
OR | ||
Placebo for 56Â days | ||
Duration | Cohort 1: 21Â days | 24Â weeks |
Cohorts 2 and 3: 56Â days | ||
Inclusion criteria | ≥18 years | ≥12 years |
>1 Phe508del allele | Phe508del homozygous | |
FEV1 > 40 % | FEV1 40–90 % | |
Outcome measure | Treatment effect | Pooled analysis of treatment effect in TRAFFIC and TRANSORT |
Mean FEV1 (percentage predicted) | Cohort 2 with lumacaftor 600 mg/day: +5.6 (P = 0.013) | Cohort 1: +3.3 (P < 0.001) |
Cohort 3: no significant differences | Cohort 2: +2.8 (P < 0.001) | |
Sweat chloride levels (mmol/L) | Cohort 1 with 250 mg ivacaftor: −9.1 mmol/L (P < 0.001) Cohorts 2 and 3: no significant differences | – |
CFQ-R score (points) | – | Cohort 1: 3.1 (P = 0.007) |
Cohort 2: 2.2 (P = 0.05) | ||
BMI | – | Cohort 1: 0.28 (P < 0.001) |
Cohort 2: 0.24 (P < 0.001) | ||
Pulmonary exacerbations | – | Cohort 1: rate ratio 0.7 (P = 0.001) |
Cohort 2: rate ratio 0.61 (P < 0.001) |