E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic cough in Idiopathic Pulmonary Fibrosis |
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E.1.1.1 | Medical condition in easily understood language |
Patients who cough on average 15 times per hour during their waking day due to their co-existing lung disease for which the cause is unknown |
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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 | 16.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10066656 |
E.1.2 | Term | Chronic cough |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10011224 |
E.1.2 | Term | Cough |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To see how effective a single dose of VRP700 is in reducing how often a patient coughs over 24 hours, and the patients assessment on how severe their cough and their urge to cough is in a patients with IPF. |
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E.2.2 | Secondary objectives of the trial |
To assess patients’ treatment preferences To assess the impact of VRP700 on the Global Rating of Change scale To assess the safety of VRP700, and how well it is tolerated To evaluate the effectiveness of VRP700 on the sensation of dyspnoea
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Male or female patients, women (or female partners of male patients) to be of non childbearing potential, or of child bearing potential who either abstain from sexual intercourse, have a sterile partner or practice two medically approved methods of contraception Aged ≥18 years Self-reported history of troublesome daily cough for more than 8 weeks Self-reported stable clinical condition and cough frequency for more than 4 weeks prior to screening Diagnosis of idiopathic pulmonary fibrosis following review by a Multi-Disciplinary Team (MDT). The diagnosis of IPF requires the following: a.Exclusion of other known causes of ILD (e.g. domestic or occupational environmental exposures, connective tissue disease, or drug toxicity) and b.Either the presence of the usual interstitial pneumonia (UIP) pattern on high-resolution computed tomography (HRCT) in patients not subjected to surgical lung biopsy c.Or specific combinations of HRCT and surgical lung biopsy pattern in patients subjected to surgical lung biopsy Have given written informed consent Ability to comply with the requirements of the study
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E.4 | Principal exclusion criteria |
Current smokers, including ‘social smokers’ and those who have given up less than 6 months ago Concurrent use of medications likely to suppress / affect cough including; immunosuppressives (eg azathioprine), codeine and related products, morphine, pregabalin, gabapentin, amitriptylline angiotensin converting enzyme inhibitors (type 1), baclofen or high dose systemic steroids i.e. prednisolone >20mg daily or equivalent. Those patients on lower doses of steroids for >1 month and still complaining of cough, and those patients taking Nacetyl cysteine, and those taking amitriptyline for reasons other than cough may be included. Concurrent use of pirfenidone, unless receiving a stable dose for at least 4 weeks prior to Screening Resting blood oxygen saturation of <90 % Patients with clinically apparent heart failure or a clinically significant abnormal ECG at Screening Self-reported history of chest or upper airway infection within the past 4 weeks Any condition that may affect cough response, such as stroke, Parkinson’s disease or diabetics with autonomic neuropathy. Clinically stable diabetics (i.e. on stable medication for >1 month and not experiencing symptoms of hypoglycaemia) without known autonomic neuropathy may be enrolled A history of asthma or obstructive airway disease, or those with an FEV1/FVC ratio at screening of <70% A history of epilepsy or myasthenia gravis Evidence of significant of hepatic or renal dysfunction Any clinically significant abnormal laboratory safety test (biochemistry, haematology and dipstick urinalysis) at screening Pregnancy or breast feeding Participation in another trial or use of an investigational drug within the preceding 4 weeks A history of active alcohol abuse or drug addiction
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E.5 End points |
E.5.1 | Primary end point(s) |
To see how effective a single dose of VRP700 is in reducing how often a patient coughs over 24 hours, and the patients assessment on how severe their cough and their urge to cough is in patients with IPF. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Number of coughs during the 4 hour period following the end of nebulisation. |
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E.5.2 | Secondary end point(s) |
To assess patients' treatment preferences To assess the impact of VRP700 on the Global Rating of Change Scale To assess the safety of VRP700 and how well it is tolerated To evaluate the effectiveness of VRP700 on the sensation of dyspnoea |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Total number of coughs over 24 hours following the end of nebulisation, compared to baseline, active vs placebo Change in number of coughs each hour for 24 hours, compared to baseline Cough severity score VAS measured at baseline, pre-dose, 1hr, 2hr, 4hr, end of day and 24 hour post dose Urge to cough severity score VAS measured at baseline, pre-dose, 1hr, 2hr, 4hr, end of day Global rating of change scale at 4hr post-dose Subject's treatment preference at the end of study assessment |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
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 | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
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 | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
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 | 0 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |