Birring SS, et al. - This study entailed an assessment of the efficacy and safety of inhaled PA101 in patients with idiopathic pulmonary fibrosis (IPF) and chronic cough and explored the antitussive mechanism of PA101 by examining patients with chronic idiopathic cough (CIC). In IPF, a possible disease-specific mechanism of cough was suggested. For patients with IPF, inhaled PA101 could serve as a treatment option for chronic cough.

Methods

• This pilot, proof-of-concept study included a randomised, double-blind, placebo-controlled trial and a parallel study of similar design in patients with IPF and chronic cough and patients with CIC, respectively.
• Site staff randomly assigned (1:1, using a computer-generated randomisation schedule) patients with IPF and chronic cough, recruited from seven centres in the UK and the Netherlands, to receive PA101 (40 mg) or matching placebo three times a day via oral inhalation for 2 weeks, followed by a 2 week washout, and then crossed over to the other arm.
• Until the study completion in all participants, study participants, investigators, study staff, and the sponsor were masked to group assignment.
• The primary efficacy endpoint was change from baseline in objective daytime cough frequency (from 24 h acoustic recording, Leicester Cough Monitor).
• All participants who received at least one dose of study drug and had at least one post-baseline efficacy measurement were included in the primary efficacy analysis and all those who took at least one dose of study drug were included in the safety analysis.
• In the second cohort, participants with CIC were randomly assigned in a study across four centres with similar design and endpoints.

Results

• A total of 24 participants with IPF were randomly assigned to treatment groups between Feb 13, 2015, and Feb 2, 2016.
• During the same period, 28 participants with CIC were enrolled and, 27 were treated.
• Findings revealed that treatment with PA101 versus placebo afforded reduction of daytime cough frequency by 31·1% at day 14 in patients with IPF; daytime cough frequency decreased from a mean 55 (SD 55) coughs per h at baseline to 39 (29) coughs per h at day 14 following treatment with PA101, versus 51 (37) coughs per h at baseline to 52 (40) cough per h following placebo treatment (ratio of least-squares [LS] means 0·67, 95% CI 0·48–0·94, p=0·0241).
• In the CIC cohort, PA101 did not afford treatment benefit; mean reduction of daytime cough frequency at day 14 for PA101 adjusted for placebo was 6·2% (ratio of LS means 1·27, 0·78–2·06, p=0·31).
• PA101 showed good tolerability in both cohorts.
• PA101 and placebo treatments were similar in terms of incidence of adverse events, it was noted that most adverse events were mild in severity, and no severe adverse events or serious adverse events were reported.