Clinical Study to Evaluate the Efficacy and Safety of Three Different Doses of BAY1817080 Compared to Placebo in Patients With Chronic Cough (PAGANINI)

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)

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.

Study Overview

• Status: Completed
• Conditions: Refractory and/or Unexplained Chronic Cough
• Intervention / Treatment: Drug: BAY1817080; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 310
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires
    • Mar del Plata, Buenos Aires, Argentina
      • Instituto Ave Pulmo
    • Quilmes, Buenos Aires, Argentina
      • Centro Respiratorio Quilmes
  • Ciudad Auton. De Buenos Aires
    • Buenos Aires, Ciudad Auton. De Buenos Aires, Argentina, C1426ABP
      • Centro Médico Dra. De Salvo - Clinical Research Center
    • Caba, Ciudad Auton. De Buenos Aires, Argentina, C1018DES
      • Centro de Investigaciones Clinicas
    • Caba, Ciudad Auton. De Buenos Aires, Argentina, C1121ABE
      • Fundacion CIDEA
    • Caba, Ciudad Auton. De Buenos Aires, Argentina, C1425
      • Investigación en Alergias y Enfermedades Respiratorias-INAER
  • Tucuman
    • San Miguel de Tucumán, Tucuman, Argentina
      • Investigaciones en Patologias Respiratorias
• Australia
  • New South Wales
    • Macquarie University, New South Wales, Australia, 2109
      • Macquarie University Hospital
    • Maroubra, New South Wales, Australia, 2035
      • Maroubra MEdical Centre
    • Sydney, New South Wales, Australia, 2010
      • Holdsworth House Medical Practice
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
  • Western Australia
    • Spearwood, Western Australia, Australia, 6163
      • Western Respiratory Trial Specialists
• Belgium
  • Erpent, Belgium, 5101
    • Dr. MARTINOT Jean-Benoît
  • Gent, Belgium, 9000
    • UZ Gent
  • Leuven, Belgium, 3000
    • UZ Leuven Gasthuisberg
  • Liege, Belgium, 4000
    • CHU de Liège
  • Mechelen, Belgium, 2800
    • VZW Emmaus
• Canada
  • Ontario
    • Burlington, Ontario, Canada, L7N 3V2
      • Burlington Lung Clinic (BLC) Clinical Research
  • Quebec
    • St-Charles-Borromée, Quebec, Canada, J6E 2B4
      • Clinique de pneumologie et du sommeil de Lanaudière (CPSL)
• Czechia
  • Kralupy nad Vltavou, Czechia, 278 01
    • MUDr Otakar Hokynar - Plicni ambulance
  • Olomouc, Czechia, 772 00
    • Ordinace pro TBC a respiracni nemoci, s.r.o.
  • Praha 4, Czechia, 14800
    • Dawon s.r.o.
  • Teplice, Czechia, 415 01
    • Plicní stredisko Teplice, s.r.o.
  • Varnsdorf, Czechia, 407 47
    • MUDr. Milan Sklenar
• France
  • Paris, France, 75674
    • Cochin - Paris
  • TOULOUSE Cedex 9, France, 31059
    • CHU de Toulouse - Hopital Larrey
• Germany
  • Berlin, Germany, 10717
    • Praxis f. Lungen- und Bronchialheilkunde,
  • Baden-Württemberg
    • Konstanz, Baden-Württemberg, Germany, 78464
      • Klinikum Konstanz
  • Hessen
    • Marburg, Hessen, Germany, 35037
      • Zentrum f. ambulante pneumologische Forschung Marburg GbR
    • Neu-Isenburg, Hessen, Germany, 63263
      • Ballenberger, Freytag, Wenisch
  • Niedersachsen
    • Hannover, Niedersachsen, Germany, 30625
      • Medizinische Hochschule Hannover (MHH)
    • Hannover, Niedersachsen, Germany, 30173
      • Pneumologicum im Südstadt Forum
  • Sachsen
    • Leipzig, Sachsen, Germany, 04357
      • Priv.-Doz. Dr. med. Christian Gessner
• Hungary
  • Balassagyarmat, Hungary, 2660
    • D.Kenessey A Hospital
  • Budapest, Hungary, 1122
    • EKBC, Uj Szent Janos Korhaz es Szakrendelo
  • Godollo, Hungary, 2100
    • Erzsebet Gondozohaz
  • Pecs, Hungary, 7635
    • Da Vinci Maganklinika
  • Szazhalombatta, Hungary, 2440
    • Farmakontroll Bt.
• Italy
  • Lombardia
    • Lodi, Lombardia, Italy, 26845
      • ASST Lodi
  • Toscana
    • Firenze, Toscana, Italy, 50134
      • A.O.U. Careggi
  • Veneto
    • Verona, Veneto, Italy, 37024
      • IRCCS Ospedale Sacro Cuore Don Calabria
    • Verona, Veneto, Italy, 37126
      • A.O.U.I. Verona
• Japan
  • Fukushima, Japan, 960-1295
    • Fukushima Medical University Hospital
  • Aichi
    • Nagoya, Aichi, Japan, 467-8602
      • Nagoya City University Hospital
  • Fukui
    • Yoshida, Fukui, Japan, 910-1193
      • University of Fukui Hospital
  • Fukuoka
    • Kitakyushu, Fukuoka, Japan, 807-8556
      • University of Occupational and Environmental Health
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 064-0804
      • Idaimae Minami Yojo
  • Ishikawa
    • Kanazawa, Ishikawa, Japan, 920-8610
      • Japan community health care organization Kanazawa Hospital
    • Komatsu, Ishikawa, Japan, 923-8560
      • Komatsu Municipal Hospital
  • Kanagawa
    • Yokohama, Kanagawa, Japan, 231-8682
      • Yokohama City Minato Red Cross Hospital
    • Yokohama, Kanagawa, Japan, 234-8503
      • Saiseikai Yokohamashi Nanbu Hospital
  • Mie
    • Matsusaka, Mie, Japan, 515-8544
      • Matsusaka Municipal Hospital
  • Shizuoka
    • Hamamatsu, Shizuoka, Japan, 430-8525
      • Hamamatsu Rosai Hospital
  • Tokyo
    • Shinagawa-ku, Tokyo, Japan, 140-8522
      • Tokyo Shinagawa Hospital
• Netherlands
  • Zwolle, Netherlands, 8025 AB
    • Isala
  • Noord-Brabant
    • Eindhoven, Noord-Brabant, Netherlands, 5623 EJ
      • Catharina Ziekenhuis
• Poland
  • Bialystok, Poland, 15-044
    • Centrum Medycyny Oddechowej Mroz Spolka Jawna
  • Bychawa, Poland, 23-100
    • KLIMED Marek Klimkiewicz
  • Lublin, Poland, 20-552
    • Centrum Alergologii Sp. z o.o.
  • Ostrowiec Swietokrzyski, Poland, 27-400
    • Ostrowieckie Centrum Medyczne Sp. Cyw. A.O-C. K.C.
  • Strzelce Opolskie, Poland, 47-100
    • Centrum Medyczne Lucyna Andrzej Dymek
• Russian Federation
  • Kemerovo, Russian Federation, 650000
    • Region Clinical Emergency Hospital n.a. M.A.Podgorbunskogo
  • Moscow, Russian Federation, 105077
    • City Clinical Hospital n.a. D.D. Pletnev
  • Novosibirsk, Russian Federation, 630005
    • LLC "Medical Center "SibNovoMed""
  • Samara, Russian Federation, 453056
    • City Clinical Hospital #4 Samara
  • St. Petersburg, Russian Federation, 194354
    • City Consultative and Diagnostic Center #1
  • St. Petersburg, Russian Federation, 199226
    • LLC Astarta
  • Voronezh, Russian Federation, 394066
    • Voronezh Regional Clinical Hospital #1
• Slovakia
  • Bardejov, Slovakia, 085 01
    • ALIAN s.r.o.
  • Humenne, Slovakia, 066 01
    • Inspiro, s.r.o.
  • Kezmarok, Slovakia, 060 01
    • AlergoImunocentrum, s.r.o.
  • Poprad, Slovakia, 058 01
    • Plucna ambulancia s.r.o.
  • Topolcany, Slovakia, 955 01
    • Ambulancia klin. imunologie a alergologie, ANA JJ, s.r.o.
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic i Provincial de Barcelona
  • A Coruña
    • Santiago de Compostela, A Coruña, Spain, 15706
      • Hospital Clínico Universitario de Santiago de Compostela
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Hospital Universitari Germans Trias i Pujol
• Taiwan
  • Keelung, Taiwan, 20401
    • Chang Gung Memorial Hospital Keelung
  • New Taipei City, Taiwan, 220
    • Far Eastern Memorial Hospital
  • Taichung, Taiwan, 40705
    • Taichung Veterans General Hospital
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital
  • Taipei, Taiwan, 110
    • Taipei Medical University Hospital
• Turkey
  • Antalya, Turkey, 07058
    • Akdeniz Universitesi Tip Fakultesi Hastanesi
  • Istanbul, Turkey, 34098
    • Istanbul Universitesi Cerrahpasa-Cerrahpasa Tip Fakultesi
  • Izmir, Turkey, 35100
    • Ege Universitesi Tip Fakultesi
  • Maltepe, Turkey, 34844
    • Sureyyapasa Gogus Hasalikleri. ve Gogus Cerrahisi EAH
  • Mersin, Turkey, 33343
    • Mersin Üniversitesi Tip Fakültesi
• United Kingdom
  • Bristol, United Kingdom, BS37 4AX
    • West Walk Surgery
  • Cottingham, United Kingdom, HU16 5JQ
    • Castle Hill Hospital
  • London, United Kingdom, SE5 9RS
    • King's College Hospital - NHS Foundation Trust
  • Manchester, United Kingdom, M23 9LT
    • University Hospital of South Manchester
  • Tyne And Wear
    • North Shields, Tyne And Wear, United Kingdom, NE29 8NH
      • North Tyneside General Hospital
• United States
  • California
    • Los Angeles, California, United States, 90025
      • California Allergy & Asthma Medical Group & Research Center
  • Florida
    • Largo, Florida, United States, 33778
      • Florida Pediatrics
  • Maryland
    • White Marsh, Maryland, United States, 21162
      • Chesapeake Clinical Research, Inc.
  • Minnesota
    • Edina, Minnesota, United States, 55435
      • Minnesota Lung Center
  • Montana
    • Missoula, Montana, United States, 59808
      • Montana Medical Research, Inc
  • Tennessee
    • Nashville, Tennessee, United States, 37212-1610
      • Vanderbilt University Medical School
  • Texas
    • Dallas, Texas, United States, 75231
      • Pharmaceutical Research & Consulting, Inc.
  • Washington
    • Bellingham, Washington, United States, 98225
      • Bellingham Asthma, Allergy & Immunology Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BAY1817080 dose A BID; Each participant will be randomized to receive one of three oral doses of BAY 1817080 or placebo, administered twice daily over the course of 12 weeks.	Drug: BAY1817080; Study drug BAY1817080 will be administered orally as tablet.
Experimental: BAY1817080 dose B BID; Each participant will be randomized to receive one of three oral doses of BAY 1817080 or placebo, administered twice daily over the course of 12 weeks.	Drug: BAY1817080; Study drug BAY1817080 will be administered orally as tablet.
Experimental: BAY1817080 dose C BID; Each participant will be randomized to receive one of three oral doses of BAY 1817080 or placebo, administered twice daily over the course of 12 weeks.	Drug: BAY1817080; Study drug BAY1817080 will be administered orally as tablet.
Placebo Comparator: Placebo; Each participant will be randomized to receive one of three oral doses of BAY 1817080 or placebo, administered twice daily over the course of 12 weeks.	Drug: Placebo; Matching Placebo for BAY1817080 will be administered orally as tablet.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

General Publications

• 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. No abstract available.

Helpful Links

• Click here to find information about studies related to Bayer Healthcare products conducted in Europe
• Click here to find results for studies related to Bayer products

Study record dates

Study Major Dates

• Study Start (Actual): October 2, 2020
• Primary Completion (Actual): June 22, 2021
• Study Completion (Actual): July 23, 2021

Study Registration Dates

• First Submitted: September 18, 2020
• First Submitted That Met QC Criteria: September 18, 2020
• First Posted (Actual): September 24, 2020

Study Record Updates

• Last Update Posted (Actual): August 18, 2022
• Last Update Submitted That Met QC Criteria: July 24, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: P2X3 receptor antagonist; Chronic cough; RUCC
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Cough
• Other Study ID Numbers: 20393; 2019-004169-42 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

IPD Plan Description

Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access.

As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014.

Interested researchers can use www.clinicalstudydatarequest.com to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the Study sponsors section of the portal.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No