Table 5.

Summary of clinical studies investigating the efficacy of lumacaftor and ivacaftor in patients with Phe508del mutations

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 200 mg/day for 14 days	Lumacaftor 600 mg/day plus ivacaftor 250 mg every 12 h
	Followed by:	Cohort 2:
	Ivacaftor 150 mg/250 mg every 12 h for 7 days	n = 369
	OR	Lumacaftor 400 mg every 12 h plus ivacaftor 250 mg every 12 h
	Placebo for 21 days	Cohort 3:
	Cohorts 2 and 3:	n = 371
	96 homozygotes	Placabo plus placebo
	28 compound heterozygotes
	Cohort 2:
	Lumacaftor 200 mg, 400 mg, 600 mg/day for 56 days
	Cohort 3:
	Lumacaftor 400 mg every 12 h for 56 days
	Followed by:
	Ivacaftor 250 mg every 12 h after 28 days
	OR
	Placebo for 56 days
Duration	Cohort 1: 21 days	24 weeks
	Cohorts 2 and 3: 56 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)

BMI body mass index (the weight in kilograms divided by the square of the height in meters), CFQ-R revised Cystic Fibrosis Questionnaire, FEV ₁ percentage predicted forced expiratory volume in 1 second for age, sex and height, RCT randomized controlled trial