WASHINGTON — Refractory chronic cough can be relieved with a P2X3 inhibitor, evidence from a phase 2b clinical trial shows.

This is "potentially life-changing," said investigator Jacky Smith, MB, ChB, PhD, from the University of Manchester in the United Kingdom.

Patients with refractory chronic cough have tried a lot of different treatments and usually end up frustrated, she explained here at the American Thoracic Society 2017 International Conference.

"These people are coughing hundreds, sometimes thousands, of times a day," she told Medscape Medical News, which can result in "awful complications," like urinary continuance and vomiting.

"This drug blocks the neuronal activation, and blocks the cough," Dr Smith explained. Studies have shown that current drugs, such as dextromethorphan, only reduce cough by about 12%. "We're showing 30% or more. It's an empty market; we really need some new drugs that work."

In their study, Dr Smith and her colleagues compared MK-7264 with placebo in patients with refractory chronic cough from 46 sites in the United Kingdom and the United States. Of the 253 study participants, 64 were randomly assigned to a 7.5 mg dose of MK-7264 for 12 weeks, 63 were assigned to a 20 mg dose, 63 were assigned to a 50 mg dose, and 63 were assigned to placebo.

Average age in the study cohort was 60 years, and 76% of the patients were women.

The investigators assessed cough frequency with a VitaloJAK digital recording device, from Vitalograph, and cough severity with a visual analog scale.

The higher the dose of MK-7264, the better the results.

Table. Change in Cough Compared With Placebo at 12 Weeks

MK-7264 Dose Change in Frequency, % Change in Severity, mm
50 mg –37.0 –31.1
20 mg –22.2 –23.4
7.5 mg –22.0 –19.2


The number of patients who reported dysgeusia — a taste disorder in which a foul, salty, rancid, or metallic taste persists in the mouth — increased as the dose increased. In fact, six patients in the 50 mg group discontinued the drug because of this.

Although some patients were unable to tolerate the dysgeusia, in the real world, patients could mitigate this adverse effect by changing their dose. "In the trial, it had to be a fixed dose, but in the real world, patients would dose down," Dr Smith explained.

Patients in the placebo group also reported a reduction in cough. "We didn't expect that," she said.

In a previous phase 2 trial, MK-7262 (then called AF-219) was shown to be effective, but all 34 participants reported taste disturbances with the 600 mg twice-daily dose (Lancet. 2015;385:1198-1205).

In their larger trial, Dr Smith and her colleagues showed that the drug is still effective at lower doses.

"Chronic cough is a major contributor to medical visits," said Sonye Danoff, MD, PhD, from Johns Hopkins Medicine in Baltimore.

"The data generated here provide an optimistic view that we may be able to address this problem for some fraction of the patients," she said. Cough is obviously not a life-threatening symptom, but can have a substantial impact on quality of life, she added.

This is a preliminary trial, not a definitive study, she cautioned. "The safety and, to some degree, tolerability may play a role in treatment."

However, it is unusual for pulmonary medicine specialists to discuss patients adjusting their own doses of a drug, Dr Danoff explained. "That's a fairly unique paradigm for pulmonary medicine; perhaps in pain this kind of study is seen, but it's unusual in pulmonary," she pointed out.

"I think these preliminary studies are very interesting and provocative," said Dr Danoff.

Dr Smith is named on the patent for VitaloJAK, the cough frequency recording device used in this study. Dr Danoff is a consultant for Boehringer-Ingelheim clinical trials, Global Blood Therapeutics, and a Genentech/Roche clinical trial.

American Thoracic Society (ATS) 2017 International Conference: Abstract 7608. Presented May 22, 2017.

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