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Table 4 Summary of clinical studies investigating the efficacy of ataluren in patients with nonsense cystic fibrosis mutations

From: Targeted therapies to improve CFTR function in cystic fibrosis

Study name and reference Kerem et al. 2008 [64] Sermet-Gaudelus et al. 2010 [46] Wilschanski et al. 2011 [65] Kerem et al. 2014 [66]
Type of study Phase II randomized crossover trial Phase II randomized crossover trial Extension of trial by Kerem et al. 2008 [45] Phase III RCT
Number of participants n = 23 n = 30 n = 19 n = 238
Duration Cycle 1: 16 mg/kg/day for 14 days; no treatment for 14 days 2 × 28 days 12 weeks 48 weeks
Cycle 2: 40 mg/kg/day for 14 days; no treatment for 14 days Cycle 1: 16 mg/kg/day for 14 days; no treatment for 14 days Cycle 2: 40 mg/kg/day for 14 days; no treatment for 14 days Group 1: 16 mg/kg/day Group 2 : 40 mg/kg/day  
Inclusion criteria ≥18 years 6–18 years ≥18 years ≥6 years
2 disease mutations, >1 nonsense 2 disease mutations, >1 nonsense 2 disease mutations, >1 nonsense Nonsense mutations
Sweat chloride >40 mmol/L Sweat chloride >40 mmol/L Sweat chloride >40 mmol/L Sweat chloride >40 mmol/L
Abnormal nasal potential difference Abnormal nasal potential difference Abnormal nasal potential difference Abnormal nasal potential difference
FEV1 > 40 % FEV1 > 40 % FEV1 > 40 % FEV1 40–90 %
O2 saturation ≥92 % room air O2 saturation ≥92 % room air O2 saturation ≥92 % room air O2 saturation ≥92 % room air
Weight ≥25 kg Weight ≥16 kg
Outcome measure Treatment effect Treatment effect Treatment effect Treatment effect
Mean FEV1 (percentage predicted) Small increase (P = 0.037) No significant difference No significant difference +3 % (P = 0.12)
Sweat chloride levels (mmol/L) No significant difference
Chloride transport Cycle 1: −7.1 (P < 0.0001) Cycle 1: −4.6 mV (P = 0.037) Group 1: −6.8 (P < 0.004)
Cycle 2: −3.7 (P = 0.032) Cycle 2: −3.9 mV (P = 0.046) Group 2: −3.4 (P = 0.025)
Nasal potential difference (mV) (Change in basal nasal potential difference)
Cycle 1: +3.3 (P = 0.04)
Cycle 2: +3.1 (P = 0.13)
Weight (kg) +0.6 kg (P < 0.0001) No significant difference
Pulmonary exacerbations Rate ratio 0.77 (P = 0.0992)
  1. FEV 1 percentage predicted forced expiratory volume in 1 second for age, sex and height, RCT randomized controlled trial