E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Refractory and/or unexplained chronic cough (RUCC) |
|
E.1.1.1 | Medical condition in easily understood language |
Long-standing cough with or without clear causes |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Symptoms and general pathology [C23] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10080782 |
E.1.2 | Term | Refractory chronic cough |
E.1.2 | System Organ Class | 100000004855 |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10080781 |
E.1.2 | Term | Unexplained chronic cough |
E.1.2 | System Organ Class | 100000004855 |
|
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 |
Assess the efficacy of P2X3 receptor antagonist BAY1817080 as
compared with placebo in terms of change in 24-hour cough count from
baseline to week 12 |
|
E.2.2 | Secondary objectives of the trial |
Further assess the efficacy, safety and tolerability profile of
BAY1817080 in patients with RCC |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Adults ≥ 18 years of age at the time of signing the informed consent.
2. A cough that has lasted for at least 12 months (unresponsive to treatment options) with a diagnosis of refractory chronic cough and/or idiopathic (unexplained) chronic cough.
3. Persistent cough for at least the last 8 weeks before screening.
4. Cough severity as measured by VAS ≥40 scale units at screening.
5. Women of childbearing potential must agree to use acceptable effective or highly effective birth control methods during the study and
for at least 30 days after the last dose.
6. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. |
|
E.4 | Principal exclusion criteria |
1. Smoking history within the last 12 months before screening (all forms of smoking, including e-cigarettes, cannabis and others), and any former
smoker with more than 20 pack-years.
2. Ongoing or previous exposure to inhalational toxic fumes (e.g., ammonia, chlorine, nitrogen dioxide, phosgene and sulfur dioxide)
within the last 12 months before screening.
3. Chest radiograph or CT within the last 24 months before screening and subsequent to the onset of chronic cough with presence of any obvious lung disease that could be responsible or contributing for the cough (e.g., bronchiectasis, cavitary lesions, interstitial pulmonary fibrosis, pneumothorax, pleural disease, unstable rib fracture, tuberculosis).
4. Forced expiratory volume in 1 second (FEV1)/ Forced vital capacity (FVC) ratio < 60% or a history of frequent exacerbations of chronic obstructive pulmonary disease (COPD).
5. Respiratory tract infection within 4 weeks before screening.
6. History of chronic bronchitis.
7. Active state of massive hemoptysis or pulmonary hemorrhage, including those events managed by bronchial artery embolization or any history of bronchial artery embolization or massive hemoptysis within 3 months prior to screening.
8. Moderate-to-severe hepatic impairment defined as Child-Pugh Class B or C.
9. ALT >2xULN, or AST >2xULN, or total bilirubin greater than ULN, or alkaline phosphatase (AP) >2x ULN, or INR greater than ULN (unless related to anticoagulation treatment).
10. Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 calculated by Modification of Diet in Renal Disease (MDRD) formula.
11. Systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 100 mmHg at screening visit.
12. Esophageal achalasia.
13. Positive SARS-CoV-2 virus RNA and/or serology IgG tests at screening visit. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in 24-hour cough count (measured by cough
recording digital wearable monitoring device) after 12 weeks of
intervention |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
From baseline up to 12 weeks |
|
E.5.2 | Secondary end point(s) |
1. Frequency and associated severity of treatment-emergent adverse events (TEAEs)
2. Percentage of participants with a ≥30% reduction from baseline in
24-hour cough count after 12 weeks of intervention (measured by cough
recording digital wearable monitoring device)
3. Change from baseline in 24-hour cough count after 2, 4, and 8 weeks
of intervention (measured by cough recording digital wearable
monitoring device)
4. Change from baseline in awake cough frequency per hour after 2, 4, 8
and 12 weeks of intervention (measured by cough recording digital
wearable monitoring device)
5. Change from baseline in cough related quality of life (measured by
Leicester Cough Questionnaire [LCQ]) after 12 weeks of intervention
6. Change from baseline in cough severity after 12 weeks of intervention
(measured by Cough Severity Visual Analogue Scale [VAS])
7. Percentage of participants with a ≥30 scale units reduction from
baseline after 12 weeks of intervention (measured by cough Severity
VAS)
8. Percentage of participants with a ≥1.3-point increase from baseline
after 12 weeks of intervention (measured with LCQ Total Score) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. From the start of study intervention until 14 days after the last study medication intake
2. From baseline up to 12 weeks
3. From baseline up to 2 weeks, 4 weeks, and 8 weeks
4. From baseline up to 2 weeks, 4 weeks, 8 weeks, and 12 weeks
5 - 8. From baseline up to 12 weeks |
|
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 | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
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 | Yes |
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 | 4 |
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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 58 |
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 |
Argentina |
Australia |
Belgium |
Canada |
Czechia |
France |
Germany |
Hungary |
Italy |
Japan |
Netherlands |
Poland |
Russian Federation |
Slovakia |
Spain |
Taiwan |
Turkey |
United Kingdom |
United States |
|
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
|
The end of the study is defined as the date of the last visit (SFU) of the last participant in the trial globally. |
|
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 | 0 |
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 | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |