Phase 2 Efficacy and Safety Study of Orvepitant for Chronic Cough in Patients with IPF
Research type
Research Study
Full title
A DOUBLE-BLIND, RANDOMISED, PLACEBO CONTROLLED, TWO PERIOD CROSS-OVER STUDY TO EVALUATE THE EFFICACY AND SAFETY OF ORVEPITANT IN CHRONIC COUGH IN PATIENTS WITH IDIOPATHIC PULMONARY FIBROSIS
IRAS ID
1004546
Contact name
Susan Seymore
Contact email
Sponsor organisation
NeRRe Therapeutics Ltd
Eudract number
2021-006278-22
ISRCTN Number
ISRCTN12372820
Clinicaltrials.gov Identifier
Research summary
This clinical trial will be conducted in the USA, Europe and the UK, at approximately 30 sites, 10 of which are planned to be in the UK. This trial examines the efficacy and safety of the study medication, orvepitant (2 dose levels), compared to placebo, as a treatment for chronic cough in patients with idiopathic pulmonary fibrosis (IPF), a rare, progressive condition in which the lungs become scarred and breathing becomes increasingly difficult.
Approximately 88 participants may be enrolled, but this may be increased to 108 depending on the variance in emerging data.
The study will start with a screening period of up to 28 days to determine participants' eligibility after which eligible subjects will be randomised to one of two dose groups (Cohorts). All participants will receive both orvepitant and placebo in two different 4 week treatment periods in a cross-over design. Participants in Cohort 1 will receive 30 mg orvepitant and placebo (in a random order), and those in Cohort 2 will receive 10 mg orvepitant and placebo, again in a random order. All study medication will be a once daily tablet taken for 4 weeks. There will be a wash-out period of 3 weeks between the two treatment periods during which no study medication is taken. Neither the participants, nor the study doctor and their team will know what dose group the participant was allocated to, or the order in which treatment was taken (double-blind).
Participants will complete a daily electronic diary throughout the study to record the severity of their cough and other symptoms, and will complete several questionnaires relating to their cough and general well-being at the clinic visits. They will also wear a cough frequency monitor for three 24 hour periods during the study. Routine safety assessments will be undertaken including ECGs, blood and urine sampling and lung function tests.
There are 8 visits in total. Six of these are clinic visits and two are video or phone calls.Lay Summary of Results
This study was designed to see whether the study medication (called orvepitant) was safe and would reduce the severity of coughing in patients who have chronic cough due to IPF. The study had a cross-over design which means that every participant took both orvepitant and placebo. Each treatment was taken for 4 weeks. Two different doses of orvepitant (10 mg and 30 mg) were tested.
A total of 80 patients took part in the study. Three subjects withdrew before the end, the rest (77) completed the study either completely or largely as planned.
The effect of orvepitant was assessed using rating scales which the participants completed in a daily diary, and questionnaires that were completed at clinic visits. Patients reported lower (better) coughing severity scores on the rating scale when receiving orvepitant 30 mg than when receiving placebo. The difference was around 1.2 points on an 11-point scale when analysed using one method and around 0.6 when analysed with a second method. Participants also reported that the frequency of their coughing reduced and the feeling of the urge to cough was less with orvepitant 30 mg. The questionnaires showed an improvement in health-related quality of life with orvepitant. Most of the improvements were statistically significant, meaning that they were unlikely to have occurred by chance. There was no difference between orvepitant 10 mg and placebo on any of these measures, showing that this low dose is not effective.
Orvepitant was well tolerated and no safety concerns were identified in this study. More participants reported adverse events when taking orvepitant than when taking placebo, but there was no difference in the number who had adverse events considered related to treatment. One participant withdrew because of dizziness which may have been due to orvepitant. Seven participants had serious adverse events. None of these were considered related to treatment with orvepitant and they occurred with similar frequency during orvepitant and placebo treatment periods. There were no treatment related findings in any of the safety tests done during the study (ECGs, blood tests, lung function tests and vital signs).
The study findings suggest that orvepitant is safe and well tolerated by patients with IPF and that it may reduce the severity of the chronic cough that many patients with this disease experience."REC name
London - Surrey Borders Research Ethics Committee
REC reference
22/LO/0208
Date of REC Opinion
22 Apr 2022
REC opinion
Further Information Favourable Opinion