Evaluation of S-600918 in Adults With Refractory Chronic Cough

Chronic Cough Clinical Trial

Official title:

A Phase 2b, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, Dose-selection Study of S-600918 in Patients With Refractory Chronic Cough

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04110054
• Other study ID #: 1812VA323
• Status: Completed
• Phase: Phase 2
• Start date: February 13, 2020
• Est. completion date: December 28, 2020

Study information

• Verified date: March 2024
• Source: Shionogi Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective of this study is to determine the optimal dose of S-600918 in patients with refractory chronic cough by evaluating the change from baseline in 24-hour cough frequency (coughs per hour) with S-600918 compared with placebo.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 406
• Est. completion date: December 28, 2020
• Est. primary completion date: December 8, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Key Inclusion Criteria:

• Having refractory chronic cough (including unexplained chronic cough) for at least 1 year.

• If female and of childbearing potential, agreement to use one of the allowed contraceptive methods.

• Capable of giving signed informed consent.

Key Exclusion Criteria:

• Currently smokes or uses potentially irritating inhalational agents (eg, e-cigarettes, smokeless cigarettes, vaping); stopped smoking or using potentially irritating inhalational agents within the last year; or has a smoking history of 20 pack-years or more.

• Has chronic obstructive pulmonary disease or uncontrolled asthma.

• Has a clinically unstable medical condition.

• History of or ongoing significant psychiatric disorder.

• History of respiratory tract infection or significant change in lung function or a pulmonary condition in the last 4 weeks.

• History of malignancy in the last 5 years.

• History of severe drug allergy.

• History of alcohol or drug abuse in the last year or currently uses any form of marijuana or illicit drugs.

• Has a clinically significant finding on a chest x-ray or chest computed tomography (CT) scan in the last year.

• Has systolic blood pressure > 160 mm Hg or diastolic blood pressure > 90 mm Hg.

• Received S-600918 previously.

• Received an investigational drug in the last 3 months.

• Received an angiotensin converting enzyme (ACE) inhibitor in the last 3 months or requires such treatment.

• Has a positive serologic test for human immunodeficiency virus (HIV) antigen or antibody, hepatitis B virus surface antigen, or hepatitis C virus ribonucleic acid (RNA).

• If female, pregnant or trying to become pregnant or breastfeeding.

Related Conditions & MeSH terms

• Chronic Cough
• Cough

Intervention

Drug:
• S-600918
Tablets for oral administration
• Placebo to S-600918
Tablets for oral administration

Locations

Country	Name	City	State
Czechia	MUDr. I. Cierná-Peterová s.r.o.	Brandýs nad Labem-Stará Boleslav
Czechia	Fakultní Nemocnice Olomouc	Olomouc	Czech Republic
Czechia	Plicní Ambulance Rokycany s.r.o.	Rokycany
Czechia	MUDr. Jaroslav Mareš -	Strakonice
Czechia	Plicní stredisko Teplice s.r.o.	Teplice
Czechia	Pneumologie Varnsdorf s.r.o.	Varnsdorf
Japan	Mazda Hospital of Mazda Motor Corporation	Aki-gun	Hiroshima
Japan	Fukuwa Clinic	Chuo-ku	Tokyo
Japan	Nihonbashi Medical & Allergy Clinic	Chuo-ku	Tokyo
Japan	Fujisawa City Hospital	Fujisawa	Kanagawa
Japan	Fukui Prefectural Hospital	Fukui-shi	Fukui
Japan	Kyushu Central Hospital of the Mutual Aid Association of Public School Teachers	Fukuoka City	Fukuoka
Japan	Nishi Fukuoka Hospital	Fukuoka-shi	Fukuoka
Japan	Fukushima Medical University Hospital	Fukushima-shi	Fukushima
Japan	Japan Mutual Aid Association of Public School Teachers Chugoku Central Hospital	Fukuyama	Hiroshima
Japan	Japan Organization of Occupational Health and Safety Hamamatsu Rosai Hospital	Hamamatsu-shi	Shizuoka
Japan	Nakatani Hospital	Himeji	Hyogo
Japan	Hitachi, Ltd. Hitachinaka General Hospital	Hitachinaka-shi	Ibaraki
Japan	Iizuka Hospital	Iizuka	Fukuoka
Japan	Ishikawa Prefectural Central Hospital	Kanazawa-shi	Ishikawa
Japan	Kobe University Hospital	Kobe City	Hyogo
Japan	Takahashi Medical Clinic	Kokubunji-shi	Tokyo
Japan	Kyoto University Hospital	Kyoto-shi	Kyoto
Japan	Tohno Chuo Clinic	Mizunami-shi	Gifu
Japan	Nagoya City University Hospital	Nagoya	Aichi
Japan	National Hospital Organization Ibarakihigashi National Hospital	Naka-gun	Ibaraki
Japan	Lee's Clinic	Osaka-shi	Osaka
Japan	Senzoku Kokyuuki Allergy Clinic	Ota-ku	Tokyo
Japan	National Hospital Organization Sagamihara National Hospital	Sagamihara-shi	Kanagawa
Japan	National Hospital Organization Kinki-Chuo Chest Medical Center	Sakai-shi	Osaka
Japan	Sakaide City Hospital	Sakaide-shi	Kagawa
Japan	Idaimae Minamiyojo Int Clinic	Sapporo	Hokkaido
Japan	Makita Hospital	Sapporo-city	Hokkaido
Japan	Tohoku Rosai Hospital	Sendai-City	Miyagi
Japan	Yoga Allergy Clinic	Setagaya	Tokyo
Japan	KONO Medical Clinic	Setagaya-ku	Tokyo
Japan	Koukokukai Ebisu Clinic	Shibuya-shi	Tokyo
Japan	Shimonoseki City Hospital	Shimonoseki-shi	Yamaguchi
Japan	Tokyo Shinagawa Hospital Medical Corporation Association Tokyokyojuno-kai	Shinagawa-ku	Tokyo
Japan	Shizuoka General Hospital	Shizuoka-shi	Shizuoka
Japan	Kamei Internal Medicine and Respiratory Clinic	Takamatsu	Kagawa
Japan	Kouwakai Kouwa Clinic	Toshima-ku	Tokyo
Japan	Kaiseikai Kita Shin Yokohama Internal Medicine Clinic	Yokohama-shi	Kanagawa
Japan	Yokohama City Minato Red Cross Hospital	Yokohama-shi	Kanagawa
Poland	Centrum Medycyny Oddechowej Mroz sp. j.	Bialystok
Poland	Prywatny Gabinet lnternistyczno-Alergologiczny	Bialystok
Poland	Centrum Medyczne Pratia Bydgoszcz	Bydgoszcz
Poland	Centrum Medyczne Pratia Gdynia	Gdynia
Poland	Centrum Medyczne Silmedic Sp. z o. o.	Katowice
Poland	Gyncentrum Sp. Z o. o.	Katowice
Poland	Diamond Clinic	Krakow
Poland	Poradnia Alergologiczna SPZOZ USK nr 1 UM w Lodzi	Lodz
Poland	Ostrowieckie CM S.C. A. Olech-Cudzik, K. Cudzik	Ostrowiec Swietokrzyski
Poland	Centrum Alergologii Teresa Hofman Sp. Z o.o.	Poznan
Poland	RCMed Oddz. Sochaczew	Sochaczew
Poland	Centrum Medyczne Lucyna Andrzej Dymek	Strzelce Opolskie
Poland	Alergo-Med Specjalistyczna Przychodnia Lekarska	Tarnow
Ukraine	Chernihiv City Hospital #2, Therapy Department	Chernihiv
Ukraine	City Clinical Hospital #13	Kharkiv
Ukraine	Communal Non-Commercial Enterprize of Kharkiv Regional Council Regional Clinical Hospital, Pulmonary-Allergological Department with Immunological and Therapeutic Beds	Kharkiv
Ukraine	Medical and Sanitary Unit of Private Joint Stock Company Kharkiv Tractor Plant, Therapeutic Department, Kharkiv Medical Academy of Postgraduate Education, Chair of General Practice-family Medicine	Kharkiv
Ukraine	Communal Non-profit Enterprise "Kherson City Clinical Hospital named after Ye. Ye. Karabelesh" of the Kherson City Council, Pulmonary Therapeutic Department	Kherson
Ukraine	Clinic of SI National Research Centre of Radiation Medicine of NAMS of Ukraine, Unit of Pulmonology of Department of Therapy of Radiation Consequences of Clinical Radiology Institute	Kyiv
Ukraine	Kyiv Railway Clinical Hospital No2 of Branch Health Center of the JSC Ukrainian Rail, Department of Pulmonology	Kyiv
Ukraine	Medical Center of Edelweiss Medics LLC , Treatment and Prevention Department	Kyiv
Ukraine	Medical Center of LLC Medbud-Clinic, Treatment and Prevention Department	Kyiv
Ukraine	Medical Center of LLC Medical Clinic Blagomed	Kyiv
Ukraine	Municipal Non-commercial Enterprise "Consultative-Diagnostics Center" of Desnyanskyi District of Kyiv, Therapy Department	Kyiv
Ukraine	National Institute of Phthisiology and Pulmonology, Department of Pulmonology	Kyiv
Ukraine	SI "National Institute of Phthisiology and Pulmonology n.a. F.G.Yanovskyi under NAMS of Ukraine," Department of Diagnostic, Therapy and Clinical Pharmacology of Lung Diseases	Kyiv
Ukraine	Municipal Enterprise Volyn Regional Clinical Hospital of Volyn Regional Council, Pulmonology Department	Lutsk
Ukraine	The 1st City Clinical Hospital of Poltava City Council	Poltava
Ukraine	CNE Vinnytsia Regional Clinical Hospital named after N.I. Pirogov VRC, Regional Treatment and Diagnostic Pulmonology Center, Chair of Internal Medicine #1, Vinnytsia National Medical University n.a.M.I.Pyrogov	Vinnytsia
Ukraine	Small Business Private Enterprise Medical Centre "Pulse", Therapeutic Department	Vinnytsya
United Kingdom	Belfast City Hospital	Belfast
United Kingdom	Medinova Yorkshire Quality Research Site	Bradford	West Yorkshire
United Kingdom	Medinova Research Northamptonshire Quality Research Site	Corby	Northamptonshire
United Kingdom	Respiratory Clinical Trials	Cottingham	East Yorkshire
United Kingdom	Kings College Hospital	London
United Kingdom	Wythenshawe Hospital	Manchester	Greater Manchester
United Kingdom	Northumbria Healthcare NHS Foundation Trust, North Tyneside General Hospital	North Shields	Northumberland
United Kingdom	BMI Bishops Wood Hospital	Northwood	Middlesex
United Kingdom	MeDiNova North London Quality Research Site	Northwood	Middlesex
United Kingdom	MeDiNova South London Quality Research Site	Sidcup	Kent
United Kingdom	West Walk Surgery	Yate
United States	Shionogi Research Site	Bangor	Maine
United States	St. Joseph's Hospital	Bangor	Maine
United States	Montefiore Medical Center	Bronx	New York
United States	American Health Research Inc	Charlotte	North Carolina
United States	Rush University Medical Center	Chicago	Illinois
United States	New Horizons Clinical Research	Cincinnati	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	University of Missouri Hospital - Clinical Research Center	Columbia	Missouri
United States	University of Missouri Hospital and Clinics, ENT & Allergy Center of Missouri	Columbia	Missouri
United States	University of Missouri Hospital and Clinics, Hearing and Balance Center	Columbia	Missouri
United States	Pharmaceutical Research & Consulting, Inc	Dallas	Texas
United States	Intermountain Clinical Research	Draper	Utah
United States	Clinical Research Associates of Central PA, LLC	DuBois	Pennsylvania
United States	Minnesota Lung Center	Edina	Minnesota
United States	Abraham Research PLLC	Fort Mitchell	Kentucky
United States	Clinical Research of Gastonia	Gastonia	North Carolina
United States	Allergy, Asthma & Sinus Center, S.C.	Greenfield	Wisconsin
United States	ADAC Research, PA	Greenville	South Carolina
United States	MCA Research	Houston	Texas
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	University of Kansas Medical Center-Hospital	Kansas City	Kansas
United States	Sher Allergy Specialist/Center for Cough	Largo	Florida
United States	Medical Research Of Central Florida, LLC	Leesburg	Florida
United States	Research Solutions of Arizona	Litchfield Park	Arizona
United States	Southern California Institute For Respiratory Diseases, Inc.	Los Angeles	California
United States	Metroplex Pulmonary and Sleep Center	McKinney	Texas
United States	Allergy & Asthma Associates of Southern California dba Southern California Research	Mission Viejo	California
United States	Montana Medical Research, Inc.	Missoula	Montana
United States	Sneeze, Wheeze, & Itch Associates, LLC	Normal	Illinois
United States	California Medical Research Associates, Inc.	Northridge	California
United States	Atlantic Research Center, LLC	Ocean City	New Jersey
United States	Creighton University Clinical Research Office	Omaha	Nebraska
United States	Center for Clinical Trials, LLC	Paramount	California
United States	Pulmonary Associates, PA	Phoenix	Arizona
United States	Northwest Research Center	Portland	Oregon
United States	Mayo Clinic Pulmonary Clinical Research Unit	Rochester	Minnesota
United States	Mayo Clinic, Division of Pulmonary and Critical Care Medicine	Rochester	Minnesota
United States	Clinical Research of Rock Hill	Rock Hill	South Carolina
United States	Associated Specialists in Medicine, PC	Saint Louis	Missouri
United States	Clayton Sleep Institute, LLC	Saint Louis	Missouri
United States	The Clinical Research Center, LLC	Saint Louis	Missouri
United States	Diagnostics Research Group	San Antonio	Texas
United States	Institute of HealthCare Assessment, Inc.	San Diego	California
United States	Lenus Research & Medical Group, LLC	Sweetwater	Florida
United States	Alliance for Multispecialty Research	Tempe	Arizona
United States	Allergy and Asthma Care of Waco	Waco	Texas
United States	Allergy Asthma Research Institute	Waco	Texas
United States	AAPRI Clinical Research Institute	Warwick	Rhode Island
United States	Tidewater Physicians Multispecialty Group Clinical Research	Williamsburg	Virginia
United States	Southeastern Research Center	Winston-Salem	North Carolina
United States	Minnesota Lung Center	Woodbury	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Shionogi

Countries where clinical trial is conducted

United States,  Czechia,  Japan,  Poland,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent Change in Number of Coughs Per Hour in 24 Hours Following 4 Weeks of Study Treatment	Change in cough was calculated based upon the number of coughs per hour in 24 hours at Week 4 and baseline. Results are presented as percent change from baseline. Reported percent change is based on a mixed model for the log-transformed ratio of the number of coughs per hour in 24 hours at each visit with treatment, week, and treatment-by-week as fixed effect, participant as random effect, and region (Japan, Europe, or the United States) and the log-transformed coughs per hour in 24 hours at baseline as covariates. The number of coughs per hour while awake was measured using a cough monitor.	Baseline to Week 4
Secondary	Number of Participants With 30%, 50%, and 70% Reduction in Number of Coughs Per Hour Over 24 Hours After 4 Weeks of Study Treatment	The number of coughs per hour for 24 hours was measured using a cough monitor.	Baseline to Week 4
Secondary	Percent Change in Number of Coughs Per Hour While Awake Following 4 Weeks of Study Treatment	Change in cough was calculated based upon the number of coughs per hour in 24 hours at Week 4 and baseline. Results are presented as percent change from baseline. Reported percent change is based on a mixed model for the log-transformed ratio of the number of coughs per hour while awake at each visit with treatment, week, and treatment-by-week as fixed effect, participants as random effect, and region and the log-transformed coughs per hour while awake at baseline as covariates. The number of coughs per hour while awake was measured using a cough monitor.	Baseline to Week 4
Secondary	Number of Participants With 30%, 50% and 70% Reduction in Number of Coughs Per Hour While Awake After 4 Weeks of Study Treatment	The number of coughs per hour while awake was measured using a cough monitor.	Baseline to Week 4
Secondary	Percent Change in Number of Coughs Per Hour While Asleep Following 4 Weeks of Study Treatment	Change in cough was calculated based upon the number of coughs per hour in 24 hours at Week 4 and baseline. Results are presented as percent change from baseline. Reported percent change is based on a mixed model for the log-transformed ratio of the number of coughs per hour while asleep at each visit with treatment, week, and treatment-by-week as fixed effect, participants as random effect, and region and the log-transformed coughs per hour while asleep at baseline as covariates. The number of coughs per hour while awake was measured using a cough monitor.	Baseline to Week 4
Secondary	Change From Baseline in Weekly Cough Severity Following 4 Weeks of Study Treatment	Cough severity was assessed by the participant by a visual analog scale with numbers from 0 to 100. Results are presented as change from baseline. Reported change is based on a mixed model for the change in weekly cough severity score after 4 weeks of treatment with treatment, week, and treatment-by-week as fixed effect, participant as random effect, and region (Japan, Europe, or the United States) and the severity score at baseline as covariates. Higher scores indicated higher cough severity.	Baseline to Week 4
Secondary	Change From Baseline in Leicester Cough Questionnaire (LCQ) Total Score	The LCQ is a patient-reported quality of life (QOL) measure of chronic cough. The questionnaire consists of 19 items to which the participant responds on a 7-point Likert response scale (from 1 to 7). Each item assesses symptoms during cough and the effect of cough on 3 main domains: physical, psychological and social. Domain scores range from 1-7, and the total score ranges from 3 - 21. Higher score indicates a better quality of life. Results are presented as change from baseline. Reported change is based on a mixed model for the change in LCQ Total Score after 4 weeks of treatment with treatment, week, and treatment-by-week as fixed effect, participant as random effect, and region (Japan, Europe, or the United States) and the LCQ Score of corresponding domain at baseline as covariates.	Baseline to Week 4
Secondary	Number of Responders Defined as Participants With an Increase in LCQ of = 1.3 Points	The LCQ is a patient-reported quality of life (QOL) measure of chronic cough. The questionnaire consists of 19 items to which the participant responds on a 7-point Likert response scale (from 1 to 7). Each item assesses symptoms during cough and the effect of cough on 3 main domains: physical, psychological and social. Domain scores range from 1-7, and the total score ranges from 3 - 2. A higher score indicates a better quality of life.	Baseline to Week 4
Secondary	Change From Baseline in International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF)	The ICIQ-SF is a questionnaire used to evaluate the frequency, severity, and impact of urinary incontinence on the quality of life. The questionnaire includes 3 items with responses measured on Likert scales, and 1 item that is measured via a qualitative response. The 3 nominal responses are summed to give the ICIQ score (this total ICIQ-SF score can range from 0 to 21), where a higher score indicates more severe symptoms. The 1 item remaining that is measured via qualitative response is not given a score; rather, the participant selects 1 description out of 8 possible descriptions of this item.	Baseline to Week 4
Secondary	Change From Baseline in Short Form (36) Health Survey (SF-36)	The SF-36 is a 36-item questionnaire to assesses a participant's health status using 8 health concepts: limitations in physical activities because of health problems; limitations in social activities because of physical or emotional problems; limitations in usual role activities because of physical health problems; bodily pain; general mental health (psychological distress and well-being); limitations in usual role activities because of emotional problems; vitality (energy and fatigue); and general health perceptions. The mental component reports the average of all the emotionally relevant items and the physical component reports the average of all the physically relevant items. Each component is directly transformed into a 0 to 100 scale on the assumption that each question carries equal weight. A score of 0 is equal to maximum disability, and a score of 100 indicates no disability. Median change can range from -100 to 100. A positive median change indicates an improved outcome.	Baseline to Week 4
Secondary	Number of Responders as Assessed by Patient Global Impression of Change (PGIC)	The PGIC is a patient-reported measure of overall health status and consists of 1 item adapted from the Clinical Global Impressions scale. The participant selects 1 description out of 7 possible descriptions of this item. The descriptions are numbered from 1 through 7, where lower numbers indicate better quality of life. Participants were considered responders if they reported "Very much improved", "Much improved", or "Minimally improved" from baseline on the PGIC assessment.	Week 4