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: 40Â mg/kg/day for 14Â days; no treatment for 14Â days | Cycle 1: 16Â mg/kg/day for 14Â days; no treatment for 14Â days Cycle 2: 40Â mg/kg/day for 14Â days; no treatment for 14Â days | Group 1: 16Â mg/kg/day Group 2 : 40Â mg/kg/day | Â | |
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 >40Â mmol/L | Sweat chloride >40Â mmol/L | Sweat chloride >40Â mmol/L | Sweat chloride >40Â 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) |