The P2X3 antagonist BLU-5937 reduced cough frequency during waking hours among patients with refractory chronic cough, according to findings presented by lead author Jacky Smith, MBChB, FRCP, PhD, from Manchester University NHS Foundation Trust.
The RELIEF trial is a proof-of-concept, phase IIa, two-period crossover dose-escalation study designed to evaluate the efficacy and safety of BLU-5937 in patients with refractory chronic cough.
A total of 69 patients were randomized to a 16-day treatment period of placebo or BLU-5937 at doses of 25, 50, 100, and 200 mg twice-daily. Dose escalation occurred every four days. After a 10- to 14-day washout period, participants were crossed over to the other regimen. Cough frequency was measured over a 24-hour period using a cough recorder device at the end of each dose level.
In the primary endpoint analysis, defined as placebo-adjusted change from baseline in awake cough frequency, improvements appeared to be dependent on the subject’s baseline cough frequency. For example, in patients with an awake cough frequency ≥20/hour (who represented 80% of the intent-to-treat population), patients experienced reductions of –23.8%, –19.1%, and –27.3% at 25, 50, and 200 mg dose levels, respectively, over placebo.
Also, in patients with an awake cough frequency ≥32.4/hour at baseline, cough recordings over a 24-hour period demonstrated improvements over placebo in awake cough frequency of –29.0%, –28.8%, –27.1%, and –32.1% at 25, 50, 100, and 200 mg dose levels, respectively.
The authors also found that placebo-adjusted reductions from baseline in nighttime cough frequency favored BLU-5937 at all doses.
“RELIEF demonstrated reductions in 24-hour cough frequency with BLU-5937 treatment in patients with [high] awake cough frequencies,” the researchers concluded. “Moreover, benefits were also seen during nighttime in the same populations.”