Clinical phase II and phase III trial results assessing effects of P2X3 receptor antagonists versus placebo on cough severity (VAS) in patients with refractory chronic cough (RCC)
| Drug | Dose regimen (n); design, duration | Baseline cough severity (VAS) mm, mean±sd | End of treatment cough severity (VAS) mm, mean±sd | Estimated mean difference from baseline in cough severity (VAS) mm, (95% CI) | Mean change in cough severity versus placebo, (VAS) mm, (95% CI) | |||
| Placebo | Active | Placebo | Active | Placebo | Active | |||
| Gefapixant, (phase II) [42] | 600 mg twice daily (n=24); 2 weeks | 52.7±16.1 | 48.8±20.7 | 52.0±20.7 | 27.4±28.0 | NA | NA | −25.6 (−41.5, −9.6), p=0.003 |
| Gefapixant dose escalation (phase II) [43] | Part 1: 50–200 mg twice daily (n=29); crossover, 16 days Part 2: 7.5–50 mg twice daily (n=30); crossover, 16 days | Part 1: 52.2±19.2 Part 2: 57.2±23.7 | Part 1: 58.4±18.7 Part 2: 54.5±24.3 | Part 1: 55.6±24.1 Part 2: 48.0±27.0 | Part 1: 28.0±26.2 Part 2: 30.4±25.3 | NA | NA | Part 1: −20.0 (−33.6, −6.3) to −33.8 (−48.4, −19.1) Part 2: −15.6 (−27.6, −3.6) to −15.4 (−30.4, −0.5) |
| Gefapixant (phase IIb) [126] | 7.5–50 mg twice daily (n=253); 12 weeks | 57.4±23.1 | 56.7±20.7 to 58.3±25.1 | 39.3±28.1 | 27.9±22.4 to 35.0±23.6 | −16.7 (−22.7, −10.7) | −21.1 (−27.2, −15.1) to −27.9 (−34.1, −21.6) | –4.4 (–12.9, 4.0), p=0.3 to –11.2 (–19.7, –2.6), p=0.0108 |
| Eliapixant (phase IIa) [128] | 10–750 mg twice daily (n=40); crossover, 3 weeks | 70.6±17.3 | 71.4±16.3 (n=39) | 66.4±19.1 (n=39) | 10 mg: 67.2±21.8 (n=38) 50 mg: 61.0±21.4 (n=39) 200 mg: 58.5±23.2 (n=39) 750 mg: 53.0±23.3 (n=38) | 2.9 (−1.7, 7.5)#, ns | 10 mg: −4.2 (1.3, −9.7)#, ns 50 mg: −9.6 (−4.3, −15.1)#, p<0.05 200 mg: −12.2 (−6.8, −17.6)#, p<0.05 750 mg: −17.4 (−12.1, −22.9)#, p<0.05 | 10 mg: −1.4 (3.9, −6.4)#, ns 50 mg: −6.7 (−1.7, −11.7)#, p<0.05 200 mg: −9.3 (−4.1, −14.4)#, p<0.05 750 mg: −14.5 (−9.4, −19.6)#, p<0.05 |
| Filapixant (phase IIa) [129] | 20–250 mg twice daily (n=23); crossover, ascending-dose, 4 days per dose | NA | NA | NA | NA | NA | NA | 20 mg: NA, ns 80 mg: −8.1 (−1.9, −14.3), p=0.017 150 mg: −14.3 (−8.0, −20.7), p<0.001 250 mg: −20.8 (−14.7, −27.0), p<0.001 |
| Sivopixant (phase IIa) [132] | 150 mg every day (n=31); crossover, 2 weeks | NA | NA | NA | NA | −12.4 | −18.8 | −6.4, p=0.1334 |
Data are mean±sd unless otherwise stated. #: 90% credible limits. CI: confidence interval; NA: not available; ns: non-significant; VAS: visual analogue scale.