E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic cough in patients with idiopathic pulmonary fibrosis |
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E.1.1.1 | Medical condition in easily understood language |
Chronic cough in patients with lung fibrosis of unknown cause |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10066656 |
E.1.2 | Term | Chronic cough |
E.1.2 | System Organ Class | 100000004855 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
• To evaluate the effect of orvepitant once daily on cough severity, as perceived by patients, with IPF
• To evaluate the safety of orvepitant once daily in patients with IPF |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the effect of orvepitant once daily on other measures of cough burden and on health-related quality of life in patients with IPF
• To evaluate the effect of orvepitant on other comorbidities in patients with IPF |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male and female subjects ≥40 years of age 2. Able to understand and comply with the requirements of the study and give informed consent 3. Diagnosis of IPF established according to the 2018 joint ATS/ERS/JRS/ALAT Clinical Practice Guideline 4. FEV1/FVC ratio ≥0.65 at the screening visit 5. Haemoglobin-corrected diffusion capacity of carbon monoxide (Hb-corrected DLCO) ≥25% within 12 months of the screening visit 6. Arterial oxygen saturation on room air or oxygen ≥90% at Screening 7. Life expectancy of at least 12 months 8. 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 9. Mean daily IPF Coughing Severity Scale score ≥5.0 during the second week of the baseline assessment period (assessed at Visit 2) 10. If taking pirfenidone or nintedanib, the dose must have been stable dose for at least 3 months prior to Screening |
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E.4 | Principal exclusion criteria |
1. Recent respiratory tract infection (<8 weeks prior to Screening) 2. Recent acute exacerbation of IPF (<8 weeks prior to Screening) 3. Current smokers or ex-smokers with <6 months’ abstinence prior to Screening 4. 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 5. Mean early morning cough scale score ≥5.0 and rest of the day cough scale score <5 during the second week of the baseline assessment period (assessed at Visit 2) 6. Cough that is predominantly productive in nature and attributable to lung pathology such as chronic bronchitis or bronchiectasis 7. Known clinically significant pulmonary hypertension 8. Inability to comply with the use of prohibited and allowed medications as described below: a. Strong or moderate inhibitors of CYP3A4 are not allowed from Screening until 1 week after the last dose of study medication b. Strong or moderate inducers of CYP3A4 are not allowed from Screening until 1 week after the last dose of study medication c. Strong or moderate P-glycoprotein inhibitors are not allowed from Screening until 1 week after the last dose of study medication d. Angiotensin converting enzyme (ACE) inhibitors are not allowed within 3 months of Screening and throughout Part 1 e. Other treatments for cough management (including opioids, dextromethorphan, gabapentin, pregabalin, baclofen, antihistamines, thalidomide or tricyclic antidepressants (e.g. amitriptyline)) are not allowed from 4 weeks before the Baseline visit until Visit 8. Medications in these classes may be continued provided they have been prescribed solely for the management of another comorbidity and the dose has been stable for at least 4 weeks before the screening visit. f. The use of other NK1 antagonists (eg aprepitant, fosaprepitant, rolapitant) is not permitted for any reason from 4 weeks before the Baseline visit until completion of Visit 8 g. Immune-suppressant drugs and systemic corticosteroids taken for co-morbidities are permitted provided the dose has been stable for at least 2 weeks before the screening visit and they are expected to be used at this dose throughout Part 1. Any other use is prohibited h. Supplemental oxygen is permitted provided it has been used for at least 2 weeks before the screening visit and is expected to be used throughout
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the mean change from Baseline (the last 7 days prior to randomisation) to Week 4 (the last 7 days of treatment) in weekly average of the daily IPF Coughing Severity Scale score. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Week 4 (the last 7 days of treatment) |
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E.5.2 | Secondary end point(s) |
IPF Coughing Severity Scale • Mean change from Baseline to Week 2 in weekly average of the daily IPF Coughing Severity Scale Early morning cough scale • Mean change from Baseline to Weeks 2 and 4 in weekly average of the daily early morning cough scale Rest of the day cough scale • Mean change from Baseline to Weeks 2 and 4 in weekly average of the daily rest of the day cough scale Urge to cough scale • Mean change from Baseline to Weeks 2 and 4 in weekly average of the daily urge to cough scale Cough frequency scale • Mean change from Baseline to Weeks 2 and 4 in weekly average of the daily cough frequency scale Dyspnoea scale • Mean change from Baseline to Weeks 2 and 4 in weekly average of the daily dyspnoea scale Patient global ratings of status for all coughing, early morning coughing and rest of the day coughing • Proportion of subjects in each category at Weeks 2 and 4 Patient global ratings of change for all coughing, early morning coughing and rest of the day coughing • Proportion of subjects in each category at Weeks 2 and 4 Cough frequency measured using the Leicester Cough Monitor ambulatory cough monitor • Mean change from Baseline to Week 4 in 24-hour cough frequency • Mean change from Baseline to Week 4 in awake cough frequency • Mean change from Baseline to Week 4 in night-time cough frequency • Mean change from Baseline to Week 4 in the number of coughing bouts Leicester Cough Questionnaire (LCQ) • Mean change from Baseline to Week 4 in LCQ total and domain (Physical, Social, Psychological) scores King’s Brief Interstitial Lung Disease health status questionnaire (K-BILD) • Mean change from Baseline to Week 4 in K-BILD total and domain (Psychological, Breathlessness and Chest Symptoms) scores • Proportion of patients with a clinically relevant improvement in total K-BILD score PROMIS SF SD 8b sleep assessment questionnaire • Mean change from Baseline to Week 4 in the PROMIS SF SD 8b score Hospital Anxiety and Depression Scale (HADS) questionnaire • Mean change from Baseline to Week 4 in the HADS score Hull Airway Reflux Questionnaire (HARQ) • Mean change from Baseline to Week 4 in HARQ score |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
United States |
Netherlands |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 9 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 16 |