P2X3 Receptor Antagonist Investigated for Chronic Cough

The treatment was evaluated in a trial of 253 patients with refractory chronic cough for over 1 year
The treatment was evaluated in a trial of 253 patients with refractory chronic cough for over 1 year

Merck announced that a Phase 2 trial of their investigational cough treatment ‘MK-7264', showed reductions in Awake Cough Frequency (coughs/hour) by 37% from baseline when compared to placebo (P=0.003).

MK-7264 – an orally-administered, non-narcotic, P2X3 receptor antagonist – was evaluated in a trial of 253 patients with refractory chronic cough; defined by ATS/BTS guidelines as having a chronic cough for ≥1 year. Participants were randomized to receive either placebo (n=63), 7.5mg (n=63), 20mg (n=63), or 50mg (n=63) MK-7264 doses twice daily.

Results, measured by a recording device, found that those in the 50mg MK-7264 group had a statistically significant reduction in cough frequency of 37% when compared with placebo (P<0.05). The 7.5mg and 20mg doses were both associated with a 22% reduction in cough frequency, not deemed to be statistically significant.

Patient reported Cough Severity as measured by the Visual Analog Scale (0–100mm) demonstrated reductions of 15.2mm for the placebo group and 19.2mm for 7.5mg, 23.4mm for 20mg and 31.1mm for 50mg doses of MK-7264.

“These results, from the largest study to date in chronic cough, provide evidence to continue evaluating MK-7264,” said Dr. Andrew M. Tershakovec, executive director, clinical research, Merck Research Laboratories. 

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The most frequent adverse event was dysgeusia, which was reported in 47.6% of patients taking the 50mg dose; six patients in the 50mg treatment group and one in the placebo group discontinued because of  taste-related adverse effects.

It is believed that excessive activation of P2X3 receptors is associated with hyper-sensitization of sensory neurons. Neuronal hyper-sensitization in the airways and lungs, triggered by injury or infection, can cause an exaggerated, persistent and frequent urge to cough. 

“We look forward to further discussions with regulatory agencies this year to discuss next steps,” said Dr. Tershakovec.

For more information visit Merck.com.