Refractory and/or Unexplained Chronic Cough Clinical Trial
— PAGANINIOfficial title:
Randomized, Double-blind, Parallel Group, Phase 2b Dose-finding, Efficacy and Safety Study of 12-week Twice Daily Oral Administration of BAY 1817080 Compared to Placebo in the Treatment of Refractory and/or Unexplained Chronic Cough (RUCC)
| Verified date | July 2022 |
| Source | Bayer |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
Researchers in this study want to find the optimal therapeutic dose of drug BAY1817080 for patients with long-standing cough with or without clear causes (refractory and/or unexplained chronic cough, RUCC). Study drug BAY1817080 is a new drug under development for the treatment of long-standing cough. It blocks proteins that are expressed by the airway sensory nerves which are oversensitive in patients with long-standing cough. This prevents the urge to cough. Researchers also want to learn the safety of the study drug and how well it works in reducing the cough frequency, severity and urge-to-cough. Participants in this study will receive either the study drug or placebo (a placebo looks like the test drug but does not have any medicine in it) tablets twice daily for 12 weeks. Observation for each participant will last about 18 weeks in total. Participants will be asked to wear a digital device to record the cough and to complete questionnaires every day to document the symptoms. Blood samples will be collected from the participants to monitor the safety and measure the blood level of the study drug.
| Status | Completed |
| Enrollment | 310 |
| Est. completion date | July 23, 2021 |
| Est. primary completion date | June 22, 2021 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | Inclusion Criteria: - Adults = 18 years of age at the time of signing the informed consent. - 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. - Persistent cough for at least the last 8 weeks before screening. - 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. - Capable of giving signed informed consent. Exclusion Criteria: - 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. - 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. - Respiratory tract infection within 4 weeks before screening. - History of chronic bronchitis. - Systolic blood pressure = 160 mmHg and/or diastolic blood pressure = 100 mmHg at screening visit. - Positive SARS-CoV-2 virus RNA and/or serology IgG tests at screening visit. |
| Country | Name | City | State |
|---|---|---|---|
| Argentina | Centro Médico Dra. De Salvo - Clinical Research Center | Buenos Aires | Ciudad Auton. De Buenos Aires |
| Argentina | Centro de Investigaciones Clínicas | Caba | Ciudad Auton. De Buenos Aires |
| Argentina | Fundación CIDEA | Caba | Ciudad Auton. De Buenos Aires |
| Argentina | Investigación en Alergias y Enfermedades Respiratorias-INAER | Caba | Ciudad Auton. De Buenos Aires |
| Argentina | Instituto Ave Pulmo | Mar del Plata | Buenos Aires |
| Argentina | Centro Respiratorio Quilmes | Quilmes | Buenos Aires |
| Argentina | Investigaciones en Patologías Respiratorias | San Miguel de Tucumán | Tucuman |
| Australia | Royal Adelaide Hospital | Adelaide | South Australia |
| Australia | Macquarie University Hospital | Macquarie University | New South Wales |
| Australia | Maroubra Medical Centre | Maroubra | New South Wales |
| Australia | Western Respiratory Trial Specialists | Spearwood | Western Australia |
| Australia | Holdsworth House Medical Practice | Sydney | New South Wales |
| Belgium | Dr. MARTINOT Jean-Benoît | Erpent | |
| Belgium | UZ Gent | Gent | |
| Belgium | UZ Leuven Gasthuisberg | Leuven | |
| Belgium | CHU de Liège | Liege | |
| Belgium | VZW Emmaus | Mechelen | |
| Canada | Burlington Lung Clinic (BLC) Clinical Research | Burlington | Ontario |
| Canada | Clinique de pneumologie et du sommeil de Lanaudière (CPSL) | St-Charles-Borromée | Quebec |
| Czechia | MUDr Otakar Hokynar - Plicni ambulance | Kralupy nad Vltavou | |
| Czechia | Ordinace pro TBC a respiracni nemoci, s.r.o. | Olomouc | |
| Czechia | Dawon s.r.o. | Praha 4 | |
| Czechia | Plicní stredisko Teplice, s.r.o. | Teplice | |
| Czechia | MUDr. Milan Sklenar | Varnsdorf | |
| France | Cochin - Paris | Paris | |
| France | CHU de Toulouse - Hôpital Larrey | TOULOUSE Cedex 9 | |
| Germany | Praxis f. Lungen- und Bronchialheilkunde, | Berlin | |
| Germany | Medizinische Hochschule Hannover (MHH) | Hannover | Niedersachsen |
| Germany | Pneumologicum im Südstadt Forum | Hannover | Niedersachsen |
| Germany | Klinikum Konstanz | Konstanz | Baden-Württemberg |
| Germany | Priv.-Doz. Dr. med. Christian Gessner | Leipzig | Sachsen |
| Germany | Zentrum f. ambulante pneumologische Forschung Marburg GbR | Marburg | Hessen |
| Germany | Ballenberger, Freytag, Wenisch | Neu-Isenburg | Hessen |
| Hungary | D.Kenessey A Hospital | Balassagyarmat | |
| Hungary | EKBC, Uj Szent Janos Korhaz es Szakrendelo | Budapest | |
| Hungary | Erzsebet Gondozohaz | Godollo | |
| Hungary | Da Vinci Maganklinika | Pecs | |
| Hungary | Farmakontroll Bt. | Szazhalombatta | |
| Italy | A.O.U. Careggi | Firenze | Toscana |
| Italy | ASST Lodi | Lodi | Lombardia |
| Italy | A.O.U.I. Verona | Verona | Veneto |
| Italy | IRCCS Ospedale Sacro Cuore Don Calabria | Verona | Veneto |
| Japan | Fukushima Medical University Hospital | Fukushima | |
| Japan | Hamamatsu Rosai Hospital | Hamamatsu | Shizuoka |
| Japan | Japan community health care organization Kanazawa Hospital | Kanazawa | Ishikawa |
| Japan | University of Occupational and Environmental Health | Kitakyushu | Fukuoka |
| Japan | Komatsu Municipal Hospital | Komatsu | Ishikawa |
| Japan | Matsusaka Municipal Hospital | Matsusaka | Mie |
| Japan | Nagoya City University Hospital | Nagoya | Aichi |
| Japan | Idaimae Minami Yojo | Sapporo | Hokkaido |
| Japan | Tokyo Shinagawa Hospital | Shinagawa-ku | Tokyo |
| Japan | Saiseikai Yokohamashi Nanbu Hospital | Yokohama | Kanagawa |
| Japan | Yokohama City Minato Red Cross Hospital | Yokohama | Kanagawa |
| Japan | University of Fukui Hospital | Yoshida | Fukui |
| Netherlands | Catharina Ziekenhuis | Eindhoven | Noord-Brabant |
| Netherlands | Isala | Zwolle | |
| Poland | Centrum Medycyny Oddechowej Mroz Spolka Jawna | Bialystok | |
| Poland | KLIMED Marek Klimkiewicz | Bychawa | |
| Poland | Centrum Alergologii Sp. z o.o. | Lublin | |
| Poland | Ostrowieckie Centrum Medyczne Sp. Cyw. A.O-C. K.C. | Ostrowiec Swietokrzyski | |
| Poland | Centrum Medyczne Lucyna Andrzej Dymek | Strzelce Opolskie | |
| Russian Federation | Region Clinical Emergency Hospital n.a. M.A.Podgorbunskogo | Kemerovo | |
| Russian Federation | City Clinical Hospital n.a. D.D. Pletnev | Moscow | |
| Russian Federation | LLC "Medical Center "SibNovoMed"" | Novosibirsk | |
| Russian Federation | City Clinical Hospital #4 Samara | Samara | |
| Russian Federation | City Consultative and Diagnostic Center #1 | St. Petersburg | |
| Russian Federation | LLC Astarta | St. Petersburg | |
| Russian Federation | Voronezh Regional Clinical Hospital #1 | Voronezh | |
| Slovakia | ALIAN s.r.o. | Bardejov | |
| Slovakia | INSPIRO, s.r.o. | Humenne | |
| Slovakia | AlergoImunocentrum, s.r.o. | Kezmarok | |
| Slovakia | Plucna ambulancia s.r.o. | Poprad | |
| Slovakia | Ambulancia klin. imunologie a alergologie, ANA JJ, s.r.o. | Topolcany | |
| Spain | Hospital Universitari Germans Trias i Pujol | Badalona | Barcelona |
| Spain | Hospital Clínic i Provincial de Barcelona | Barcelona | |
| Spain | Hospital Clínico Universitario de Santiago de Compostela | Santiago de Compostela | A Coruña |
| Taiwan | Chang Gung Memorial Hospital Keelung | Keelung | |
| Taiwan | Far Eastern Memorial Hospital | New Taipei City | |
| Taiwan | Taichung Veterans General Hospital | Taichung | |
| Taiwan | National Taiwan University Hospital | Taipei | |
| Taiwan | Taipei Medical University Hospital | Taipei | |
| Turkey | Akdeniz Universitesi Tip Fakultesi Hastanesi | Antalya | |
| Turkey | Istanbul Universitesi Cerrahpasa-Cerrahpasa Tip Fakultesi | Istanbul | |
| Turkey | Ege Universitesi Tip Fakultesi | Izmir | |
| Turkey | Sureyyapasa Gogus Hasalikleri. ve Gogus Cerrahisi EAH | Maltepe | |
| Turkey | Mersin Universitesi Tip Fakultesi | Mersin | |
| United Kingdom | West Walk Surgery | Bristol | |
| United Kingdom | Castle Hill Hospital | Cottingham | |
| United Kingdom | King's College Hospital - NHS Foundation Trust | London | |
| United Kingdom | University Hospital of South Manchester | Manchester | |
| United Kingdom | North Tyneside General Hospital | North Shields | Tyne And Wear |
| United States | Bellingham Asthma, Allergy & Immunology Clinic | Bellingham | Washington |
| United States | Pharmaceutical Research & Consulting, Inc. | Dallas | Texas |
| United States | Minnesota Lung Center | Edina | Minnesota |
| United States | Florida Pediatrics | Largo | Florida |
| United States | California Allergy & Asthma Medical Group & Research Center | Los Angeles | California |
| United States | Montana Medical Research, Inc | Missoula | Montana |
| United States | Vanderbilt University Medical School | Nashville | Tennessee |
| United States | Chesapeake Clinical Research, Inc. | White Marsh | Maryland |
| Lead Sponsor | Collaborator |
|---|---|
| Bayer |
United States, Argentina, Australia, Belgium, Canada, Czechia, France, Germany, Hungary, Italy, Japan, Netherlands, Poland, Russian Federation, Slovakia, Spain, Taiwan, Turkey, United Kingdom,
Fletcher MC. Selectivity of the P2X3 receptor antagonist Eliapixant, and its potential use in the treatment of endometriosis. Purinergic Signal. 2022 Mar;18(1):1-3. doi: 10.1007/s11302-021-09831-5. Epub 2022 Jan 3. — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Change From Baseline in 24-hour Cough Count After 12 Weeks of Intervention | The raw 24-hour cough count measured by cough recording digital wearable monitoring device was standardized to an average hourly count. For the ratio between the geometric means of 24-hour cough count, the geometric mean of 24-hour cough count after 12 weeks of intervention was divided by the geometric mean of 24-hour cough count at baseline.
btw = between geo = geometric |
From baseline up to 12 weeks | |
| Secondary | Percentage of Participants With a =30% Reduction From Baseline in 24-hour Cough Count After 12 Weeks of Intervention | The raw 24-hour cough count measured by cough recording digital wearable monitoring device was standardized to an average hourly count. The change from baseline in 24-hour cough count was calculated by the geometric mean of 24-hour cough count after 12 weeks of intervention minus the geometric mean at baseline divided by the geometric mean at baseline. The percentage of participants with a reduction of =30% is shown | From baseline up to 12 weeks | |
| Secondary | Change From Baseline in 24-hour Cough Count After 2, 4, and 8 Weeks of Intervention | The raw 24-hour cough count measured by cough recording digital wearable monitoring device was standardized to an average hourly count. For the ratio between the geometric means of 24-hour cough count, the geometric mean of 24-hour cough count after 2, 4, and 8 weeks of intervention was divided by the geometric mean of 24-hour cough count at baseline.
btw = between geo = geometric |
From baseline up to 2 weeks, 4 weeks and 8 weeks | |
| Secondary | 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
btw = between geo = geometric |
From baseline up to 2 weeks, 4 weeks, 8 weeks and 12 weeks | |
| Secondary | Change From Baseline in Cough Related Quality of Life After 12 Weeks of Intervention | Measured by Leicester Cough Questionnaire (LCQ) total score. The LCQ was a 19-item instrument that asked about the impact of chronic cough on various aspects of participants' lives using a recall period of two weeks. The 8 items: 1, 2, 3, 9, 10, 11, 14, 15 built the physical domain. 7 items: 4, 5, 6, 12, 13, 16, 17 built the psychological domain. Further 4 items: 7, 8, 18 and 19 built the social domain. Study participants responded to the items using a 7-point Likert scale from 1 (all of the time) to 7 (none of the time) and entered their assessments on a tablet device. Completion of the LCQ took approximately five minutes. The LCQ total score was calculated as a mean score for each of the three domains ranging from 1 to 7, with the LCQ total score ranging from 3 to 21. | From baseline up to 12 weeks | |
| Secondary | Change From Baseline in Cough Severity After 12 Weeks of Intervention | Measured by Cough Severity Visual Analogue Scale (VAS). The Cough Severity VAS was a single item instrument, asking the study participant to assess the severity of his/her cough using a 0-100 VAS.
This was a vertically oriented line ordered from 0-100, with 0 = "No Cough" and 100 = "Extremely Severe Cough". |
From baseline up to 12 weeks | |
| Secondary | Percentage of Participants With a =30 Scale Units Reduction From Baseline After 12 Weeks of Intervention | Measured by cough Severity VAS | From baseline up to 12 weeks | |
| Secondary | Percentage of Participants With a =1.3-point Increase From Baseline After 12 Weeks of Intervention | Measured by LCQ total score. The LCQ was a 19-item instrument that asked about the impact of chronic cough on various aspects of participants' lives using a recall period of two weeks. The 8 items: 1, 2, 3, 9, 10, 11, 14, 15 built the physical domain. 7 items: 4, 5, 6, 12, 13, 16, 17 built the psychological domain. Further 4 items: 7, 8, 18 and 19 built the social domain. Study participants responded to the items using a 7-point Likert scale from 1 (all of the time) to 7 (none of the time) and entered their assessments on a tablet device. Completion of the LCQ took approximately five minutes. The LCQ total score was calculated as a mean score for each of the three domains ranging from 1 to 7, with the LCQ total score ranging from 3 to 21. The percentage of participants with a >= 1.3-point increase in LCQ total score is shown. | From baseline up to 12 weeks | |
| Secondary | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Associated Severity | Adverse event (AE) was defined as any untoward medical occurrence in a study participant, whether or not considered related to the study intervention, occurring from the time of signing the informed consent until the follow-up visit.
TEAE was defined as any event occurring or worsening after the start of study intervention administration until 14 days after the last intake of study intervention. |
From the start of study intervention administration until 14 days after the last study medication intake, with an average of 80.0 + 14 days |