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 |
|
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 with persistently
bothersome refractory (unresponsive to treatment options) or idiopathic
(unexplained) chronic cough that has lasted for at least 8 weeks before
screening.
3. 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.
4. Capable of giving signed informed consent. |
|
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. Respiratory tract infection within 4 weeks before screening.
4. History of chronic bronchitis.
5. Uncontrolled hypertension despite optimal treatment with
antihypertensive(s), indicated by a sitting systolic blood pressure ≥ 180
mmHg and/or diastolic blood pressure ≥ 110 mmHg. |
|
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 of adverse events (AEs), serious and/or drug related AEs
and dose-dependency of taste-related AEs
2. Severity of adverse events
3. The incidence of AEs during safety follow-up
4. 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)
5. Change from baseline in 24-hour cough count after 2, 4, and 8 weeks
of intervention (measured by cough recording digital wearable
monitoring device)
6. 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)
7. Change from baseline in cough related quality of life (measured by
Leicester Cough Questionnaire [LCQ]) after 12 weeks of intervention
8. Change from baseline in cough severity after 12 weeks of intervention
(measured by Cough Severity Visual Analogue Scale [VAS])
9. Percentage of participants with a ≥30 scale units reduction from
baseline after 12 weeks of intervention (measured by cough Severity
VAS)
10. 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 - 2: From the start of study intervention until the safety follow-up visit
(up to 16 weeks)
3: During safety follow-up (approximately 4 weeks)
4: From baseline up to 12 weeks
5: From baseline up to 2 weeks, 4 weeks, and 8 weeks
6: From baseline up to 2 weeks, 4 weeks, 8 weeks, and 12 weeks
7 - 10: 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 | 2 |
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 |
Czech Republic |
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
|
Last Patient Last Visit (last Safety follow-up Visit) |
|
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 | |
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 |