Phase 2 studies in gefapixant for chronic cough
| Study | Subjects n | Design | Treatments | Summary of results |
| Protocol 006 (NCT01432730) | 24 | Randomised, double-blind, placebo-controlled, crossover study in patients with RCC; subjects were treated for 2 weeks and crossed-over after a 2-week washout | Placebo Gefapixant 600 mg twice daily | Cough frequency was reduced by a placebo-adjusted 75% with gefapixant 600 mg twice daily (p=0.0003). However, all patients who received gefapixant 600 mg twice daily had a taste-related adverse event and 25% of patients discontinued [16]. |
| Protocol 010 (NCT02349425) | 59 Cohort 1: n=29 Cohort 2: n=30 | Randomised, 2-cohort (high dose and low dose), double-blind, placebo-controlled, crossover, dose-escalation that recruited patients with RCC; subjects were assigned to receive ascending doses of gefapixant or placebo for 16 days (4 days for each dose) then crossed-over after washout | Cohort 1: 50, 100, 150 and 200 mg twice daily or placebo; Cohort 2: 7.5, 15, 30 and 50 mg twice daily or placebo | Reductions in cough frequency with gefapixant appeared to plateau at doses ≥30 mg; taste-related adverse events appeared to increase in a dose-related manner at doses ≥30 mg [17] |
| Protocol 012 (NCT02612610) | 253 | Randomised, double-blind, placebo-controlled, parallel group, study in RCC or UCC patients; subjects were treated for 12 weeks | Placebo Gefapixant 7.5 mg twice daily Gefapixant 20 mg twice daily Gefapixant 50 mg twice daily | Placebo-adjusted mean percent reduction in awake cough frequency was 22% for 7.5 and 20 mg (not statistically significant) and 37% for 50 mg (p=0.003); 81% of patients in the 50-mg dose group experienced taste-related adverse events, but only ∼10% reported taste-related adverse events on 7.5 mg [18]. |
RCC: refractory chronic cough; UCC: unexplained chronic cough.