Efficacy in SOOTHE, A Phase 2b Trial of BLU-5937 In Refractory Chronic Cough, Was Not Dependant of Taste Disturbance Adverse Events

Aims: Taste disturbances adverse events (TDAE) in studies of P2X3 antagonists for the treatment of refractory chronic cough (RCC) may be due to off-target inhibition of the related receptor P2X2/3. Novel antagonists with higher selectivity may have lower incidences of TDAEs. TDAEs may unblind participants to treatment, confounding measurement of efficacy. Here we characterize the TDAEs and impact on efficacy in SOOTHE, a phase 2b trial of the selective P2X3 antagonist BLU-5937 in the treatment of RCC. Methods: The primary endpoint in SOOTHE was the change from baseline in 24H cough frequency in RCC participants with a baseline awake cough frequency ≥25 coughs/h. Treatment-emergent AEs were collected throughout the randomized treatment period. Results: Treatment-emergent TDAEs were reported by 4.8, 6.5, 4.8 and 0% of participants in the 12.5, 50, 200 mg BID and placebo groups, respectively. Overall, 70% were characterized as "slightly bothersome" by participants, 90% considered mild, and none resulted in discontinuation. Changes in 24H cough frequency over placebo of -21.1, -34.4, and -34.2% were observed in the main population after 28 days of BLU 5937 treatment at 12.5, 50, and 200 mg BID, respectively. Participants who did not report TDAEs saw similar placebo-adjusted reductions in 24H cough frequency of -19.3, -31.9, and -33.2%, respectively. Conclusions: The limited incidence and mild nature of TDAEs reported during treatment with BLU-5937 in SOOTHE does not appear to have significantly confounded assessment of treatment effect.