Post Hoc Subgroup Analysis
cough
In the subgroup of patients with ≥ 10 coughs/h at both screening Visits 1 and 2, placebo-adjusted changes in hourly cough counts in 24 h at Week 4 were 3.51%, − 4.78%, and − 22.85% with sivopixant 50, 150, and 300 mg, respectively (Fig. Percent change relative to placebo in hourly cough count in 24 h at Week 4: patients with a cough count of ≥ 10 at Visit 2 in the FAS. Treatment effects and their 95% CIs plotted are based on a mixed-effects model for the log-transformed ratio of the number of coughs/h in 24 h after 4 weeks of treatment, with treatment, week, and treatment by week as fixed effects; patient as random effect; and region and the log-transformed coughs/h in 24 h at baseline as covariates. Modeled estimates are presented as percent change relative to placebo from Visit 2. In the small subgroup of patients with a cough frequency ≥ 10 coughs/h at screening Visit 1 that decreased to < 10 coughs/h at screening Visit 2 (sivopixant: 50 mg: 13 patients; 150 mg: 13 patients; 300 mg: 10 patients and placebo: 11 patients), no sivopixant arm showed improvements in cough reduction vs placebo (e-Table 7, Online Resource).Similarly, consistently greater improvements were observed in VAS, LCQ total score, and PGIC with sivopixant vs placebo in patients with ≥ 10 coughs/h at screening Visits 1 and 2 than in patients with < 10 coughs/h at screening Visit 2 (e-Tables 8–11, Online Resource). In patients with ≥ 10 coughs/h at screening Visits 1 and 2, the percentage of patients who reported ≥ 1.3-point improvement in LCQ total score was 20.7% higher with sivopixant 300 mg than with placebo (OR 2.82; 95% CI 1.31, 6.07), and the percentage of patients who reported any improvements in PGIC was 18.7% higher with sivopixant 300 mg than with placebo (OR 3.59; 95% CI 1.51, 8.53) (e-Table 10, Online Resource). No improvements for any doses were observed for patients with < 10 coughs/h (e-Table 11, Online Resource).