Efficacy and Safety Study of Orvepitant for Chronic Cough in Patients With Idiopathic Pulmonary Fibrosis

Study Overview
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Brief Summary
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ORV-PF-01 is a two way, placebo controlled, cross-over study, to evaluate the effect of two doses of orvepitant on cough in patients with IPF.

Detailed Description
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The study will be a multi-center, double-blind, randomised, placebo-controlled 2-period cross-over study in subjects with chronic cough due to idiopathic pulmonary fibrosis (IPF). Subjects will participate in one of two cohorts (Cohort 1 and Cohort 2). Cohort 1 will evaluate a 30 mg orvepitant dose and Cohort 2 the 10 mg dose. Within each cohort, subjects will be randomised to receive either orvepitant or placebo in the first treatment period (Treatment Period A) followed by the alternate treatment in Treatment Period B. There will be a wash-out period of 3 weeks between the two treatment periods. Subjects will be randomised 1:1 to each of the two treatment orders and 1:1 to each cohort. Subjects will enter a screening period of between 14 and 28 days to determine eligibility. Eligible subjects will be randomised at the Baseline visit and will participate in two identical 28 day treatment periods with the wash-out period between them. There will be a total of 8 visits including the Screening, Baseline and final Follow-up visits.

Official Title
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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

Conditions
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Cough, Idiopathic Pulmonary Fibrosis

Intervention / Treatment
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* Drug: Orvepitant Maleate
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Diagnosis of IPF established according to the 2018 or 2022 joint ATS/ERS/JRS/ALAT Clinical Practice Guideline FEV1/FVC ratio ≥0.65 at the screening visit Haemoglobin-corrected diffusion capacity of carbon monoxide (Hb-corrected DLCO) ≥25% within 12 months of the screening visit Arterial oxygen saturation on room air or oxygen ≥90% at Screening Life expectancy of at least 12 months Cough that is attributed to IPF, which has not responded to anti-tussive treatment, and which has been present for at least 8 weeks prior to Screening Mean daily IPF Coughing Severity Scale score ≥5 (after rounding) during the second week of the baseline assessment period Key Exclusion Criteria: Recent respiratory tract infection (<8 weeks prior to Screening) Recent acute exacerbation of IPF (<8 weeks prior to Screening) Current smokers or ex-smokers with <6 months' abstinence prior to Screening Emphysema ≥50% on high-resolution computed tomography, or the extent of emphysema is greater than the extent of fibrosis according to the reported results of the most recent scan Mean early morning cough scale score ≥5 and rest of the day cough scale score <5 (after rounding) during the second week of the baseline assessment period (assessed at Visit 2) Cough that is predominantly productive in nature and attributable to lung pathology such as chronic bronchitis or bronchiectasis

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Orvepitant 30mg<br>Orvepitant 30mg tablet once daily for 4 weeks | Drug: Orvepitant Maleate<br>* Orvepitant tablets 30mg or 10mg<br>|
| Experimental: Orvepitant 10mg<br>Orvepitant 10mg tablet once daily for 4 weeks | Drug: Orvepitant Maleate<br>* Orvepitant tablets 30mg or 10mg<br>|
| Placebo Comparator: Placebo<br>Placebo tablet once daily for 4 weeks | Drug: Placebo<br>* Placebo tablets to match orvepitant 30mg and 10mg tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change from Baseline in weekly average of the daily Idiopathic Pulmonary Fibrosis Coughing Severity Scale | A numerical rating scale from 0 (no coughing) to 10 (coughing as bad as you can imagine) | Week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change from Baseline in weekly average of the early morning IPF Coughing Severity Scale | A numerical rating scale from 0 (no coughing) to 10 (coughing as bad as you can imagine) | Week 4 | 
| Mean change from Baseline in weekly average of the rest of the day IPF Coughing Severity Scale | A numerical rating scale from 0 (no coughing) to 10 (coughing as bad as you can imagine) | Week 4 | 
| Mean change from Baseline in weekly average of the daily urge to cough scale | A numerical rating scale from 0 (no urge to cough) to 10 (urge to cough as bad as you can imagine) | Week 4 | 
| Mean change from Baseline in weekly average of the daily cough frequency scale | A numerical rating scale from 0 (no coughing) to 10 (coughing as often as you can imagine) | Week 4 | 
| Mean change from Baseline in weekly average of the daily dyspnoea scale | A numerical rating scale from 0 (no shortness of breath) to 10 (shortness of breath as bad as you can imagine) | Week 4 | 
| Mean change from Baseline in 24-hour cough frequency | Cough frequency assessed using an ambulatory cough monitoring device | Week 4 | 
| Mean change from Baseline in awake cough frequency | Cough frequency assessed using an ambulatory cough monitoring device | Week 4 | 
| Mean change from Baseline in night-time cough frequency | Cough frequency assessed using an ambulatory cough monitoring device | Week 4 | 
| Mean change from Baseline in the number of coughing bouts | Cough frequency assessed using an ambulatory cough monitoring device | Week 4 |