A Study of Gefapixant (MK-7264) in Adult Participants With Chronic Cough (MK-7264-027)

Chronic Cough Clinical Trial

Official title:

A Phase 3, Randomized, Double-Blind, Placebo-Controlled, 12-Month Study to Evaluate the Efficacy and Safety of MK-7264 in Adult Participants With Chronic Cough (PN027)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03449134
• Other study ID #: 7264-027
• Secondary ID: MK-7264-0272017-
• Status: Completed
• Phase: Phase 3
• Start date: March 14, 2018
• Est. completion date: August 17, 2020

Study information

• Verified date: June 2021
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The main objectives of this study will be to evaluate the efficacy of gefapixant in reducing cough frequency as measured over a 24-hour period at Week 12, and to evaluate the safety and tolerability of gefapixant. The primary hypothesis is that at least one gefapixant dose is superior to placebo in reducing coughs per hour (over 24 hours) at Week 12.

Description:

The study will include a screening period to determine participant inclusion, and the Baseline visit will include 24 hours of objective measurement of cough. The study will consist of two treatment periods, a main 12-week treatment period and a 40-week extension period (52 weeks total treatment), followed by a 14-day telephone follow-up period. Participants at selected sites and countries who complete the main and extension study periods may consent to participate in an observational, 3-month, Off-treatment Durability Study Period, which extends the Estimated Study Completion Date. The Off-treatment Durability Study Period will explore the impact of withdrawing gefapixant in refractory or unexplained chronic cough participants who have been treated for 1 year.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 732
• Est. completion date: August 17, 2020
• Est. primary completion date: June 5, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Chest radiograph or computed tomography scan of the thorax (within 5 years of Screening/Visit 1 and after the onset of chronic cough) not demonstrating any abnormality considered to be significantly contributing to the chronic cough or any other clinically significant lung disease in the opinion of the principal investigator or the sub-investigator
• Has had chronic cough for at least 1 year with a diagnosis of refractory chronic cough or unexplained chronic cough
• Female participants are eligible if not pregnant, not breastfeeding, and either not of childbearing potential, or agree to follow contraceptive guidance
• Provides written informed consent and is willing and able to comply with the study protocol (including use of the digital cough recording device and completion of study questionnaires)

Exclusion Criteria:

• Is a current smoker or has given up smoking within 12 months of Screening
• Has forced expiratory volume in 1 second (FEV1)/ forced vital capacity (FVC) ratio <60%
• Has a history of respiratory tract infection or recent clinically significant change in pulmonary status
• Has a history of chronic bronchitis
• Is currently taking an angiotensin converting enzyme inhibitor (ACEI), or has used an ACEI within 3 months of Screening
• Has an estimated glomerular filtration rate (eGFR) <30mL/min/1.73 m^2 at Screening OR eGFR =30 mL/min/1.73 m^2 and <50 mL/min/1.73 m^2 at Screening with unstable renal function
• Has a history of malignancy <=5 years
• Is a user of recreational or illicit drugs or has had a recent history of drug or alcohol abuse or dependence
• Has a history of anaphylaxis or cutaneous adverse drug reaction (with or without systemic symptoms) to sulfonamide antibiotics or other sulfonamide-containing drugs
• Has systolic blood pressure >160 mm Hg or diastolic blood pressure >90 mm Hg at Screening
• Has a known allergy/sensitivity or contraindication to gefapixant
• Has donated or lost >=1 unit of blood within 8 weeks prior to the first dose of gefapixant
• Has previously received gefapixant or is currently participating in or has participated in an interventional clinical study
• Had significantly abnormal laboratory tests at Screening

Related Conditions & MeSH terms

• Chronic Cough
• Cough

Intervention

Drug:
• Placebo
Participants receive dose-matched placebo tablets orally BID during the 12-week main study period and during the 40-week extension period.
• Gefapixant
Gefapixant 15 mg or 45 mg tablet administered orally BID during the 12-week main study period and during the 40-week extension period, according to randomization.

Locations

Country	Name	City	State
Argentina	Centro Medico Dra De Salvo ( Site 0310)	Buenos Aires
Argentina	InAER Investigaciones en Alergia y Enfermedades Respiratorias ( Site 0324)	Caba	Buenos Aires
Argentina	CEMEDIC - Centro de Especialidades Medicas ( Site 0304)	Ciudad Autonoma de Buenos Aires
Argentina	Fundacion CIDEA ( Site 0323)	Ciudad de Buenos Aires	Buenos Aires
Argentina	Hospital Privado Universitario de Cordoba ( Site 0313)	Cordoba
Argentina	Instituto Ave Pulmo ( Site 0322)	Mar del Plata	Buenos Aires
Argentina	Fundacion Scherbovsky ( Site 0300)	Mendoza
Argentina	Centro Medico Privado de Reumatologia ( Site 0309)	San Miguel de Tucuman	Tucuman
Argentina	Investigaciones en Patologias Respiratorias ( Site 0325)	San Miguel de Tucuman	Tucuman
Canada	167877 Canada Inc. Dr. Jaime Del Carpio ( Site 0506)	Montreal	Quebec
Canada	Recherche GCP Research ( Site 0500)	Montreal	Quebec
Canada	Dynamik Research ( Site 0505)	Pointe-Claire	Quebec
Canada	Diex Recherche Quebec Inc ( Site 0515)	Quebec
Canada	Q & T Research Sherbrooke Inc. ( Site 0512)	Sherbrooke	Quebec
Canada	Canadian Phase Onward Inc. ( Site 0509)	Toronto	Ontario
Canada	CIC Mauricie Inc. ( Site 0503)	Trois-Rivieres	Quebec
Czechia	MUDr. I. Cierna Peterova s.r.o. ( Site 0707)	Brandys nad Labem
Czechia	Plicni ambulance ( Site 0701)	Rokycany
Czechia	Plicni stredisko Teplice s. r. o ( Site 0700)	Teplice
Czechia	Pneumologie Varnsdorf S.R.O. ( Site 0706)	Varnsdorf
Denmark	CCBR AS Aalborg, Center for Clinical & Basic Research ( Site 0802)	Aalborg
Denmark	Herlev Hospital ( Site 0803)	Herlev
Denmark	CCBR AS Vejle, Center for Clinical & Basic Research ( Site 0801)	Vejle
France	Hopital Cavale Blanche ( Site 0909)	Brest
France	Hopital Nord du Marseille ( Site 0910)	Marseille
France	Hopital Arnaud de Villeneuve ( Site 0905)	Montpellier
France	CHU Hotel Dieu Nantes ( Site 0906)	Nantes
France	CHU de Toulouse - Hopital Larrey ( Site 0900)	Toulouse
Hungary	Dr Kenessey Albert Korhaz-Rendelointezet ( Site 1200)	Balassagyarmat
Hungary	Erzsebet Gondozohaz ( Site 1207)	Godollo
Hungary	Petz Aladar Megyei Oktato Korhaz ( Site 1206)	Gyor
Hungary	Synexus Magyarorszag Kft. ( Site 1210)	Gyula
Hungary	CRU Hungary KFT ( Site 1205)	Miskolc
Israel	Hillel Yaffe Medical Center ( Site 1303)	Hadera
Israel	Carmel Medical Center ( Site 1305)	Haifa
Israel	Meir Medical Center ( Site 1301)	Kfar Saba
Israel	Rabin Medical Center ( Site 1302)	Petah-Tikva
Israel	Chaim Sheba Medical Center. ( Site 1304)	Ramat Gan
Japan	Fujisawa City Hospital ( Site 1505)	Fujisawa	Kanagawa
Japan	National Hospital Organization Fukuoka Hospital ( Site 1552)	Fukuoka
Japan	Osaka Habikino Medical Center ( Site 1546)	Habikino	Osaka
Japan	Tokyo Medical University Hachioji Medical Center ( Site 1569)	Hachioji	Tokyo
Japan	Kawaguchi Respiratory Clinic ( Site 1504)	Higashiosaka	Osaka
Japan	Terada Clinic Respiratory Medicine & General Practice ( Site 1565)	Himeji	Hyogo
Japan	Hiroshima Allergy & Respiratory Clinic ( Site 1529)	Hiroshima
Japan	Itami City Hospital ( Site 1580)	Itami	Hyogo
Japan	Kinki Central Hospital ( Site 1576)	Itami	Hyogo
Japan	Ishikawa Prefectural Central Hospital ( Site 1554)	Kanazawa	Ishikawa
Japan	Kanazawa University Hospital ( Site 1536)	Kanazawa	Ishikawa
Japan	National Hospital Organization Tokyo National Hospital ( Site 1557)	Kiyose	Tokyo
Japan	Komatsu Municipal Hospital ( Site 1508)	Komatsu	Ishikawa
Japan	Kyoto University Hospital ( Site 1547)	Kyoto
Japan	Matsusaka City Hospital ( Site 1525)	Matsusaka	Mie
Japan	Nagaoka Red Cross Hospital ( Site 1507)	Nagaoka	Niigata
Japan	Nagoya City University Hospital ( Site 1528)	Nagoya	Aichi
Japan	National Hospital Organization Nagoya Medical Center ( Site 1539)	Nagoya	Aichi
Japan	National Hospital Organization Ibarakihigashi National Hospital ( Site 1526)	Naka-gun	Ibaraki
Japan	JA Niigatakoseiren Niigata Medical Center ( Site 1522)	Niigata
Japan	National Hospital Organization Kinki-chuo Chest Medical Center ( Site 1519)	Sakai	Osaka
Japan	Idaimae Minamiyojo Int Clinic ( Site 1521)	Sapporo	Hokkaido
Japan	Shimonoseki City Hospital ( Site 1573)	Shimonoseki	Yamaguchi
Japan	Shizuoka Prefectural Hospital Organization Shizuoka General Hospital ( Site 1524)	Shizuoka
Japan	National Hospital Organization Disaster Medical Center ( Site 1558)	Tachikawa	Tokyo
Japan	Kamei Internal Medicine and Respiratory Clinic ( Site 1509)	Takamatsu	Kagawa
Japan	Center Hospital of the National Center for Global Health and Medicine ( Site 1574)	Tokyo
Japan	Juntendo University Hospital ( Site 1578)	Tokyo
Japan	Showa University Hospital ( Site 1531)	Tokyo
Japan	Tokyo Metropolitan Geriatric Hospital ( Site 1577)	Tokyo
Japan	Tokyo Shinagawa Hospital ( Site 1560)	Tokyo
Japan	National Hospital Organization Ehime Medical Center ( Site 1556)	Toon	Ehime
Japan	National Hospital Organization Minami-Okayama Medical Center ( Site 1553)	Tsukubo-gun	Okayama
Japan	Urasoe General Hospital ( Site 1572)	Urasoe	Okinawa
Japan	Kanagawa Cardiovascular and Respiratory Center ( Site 1503)	Yokohama	Kanagawa
Japan	Medical Corporation Shintokai Yokohama Minoru Clinic ( Site 1568)	Yokohama	Kanagawa
Japan	Saiseikai Yokohamashi Nanbu Hospital ( Site 1533)	Yokohama	Kanagawa
Japan	Yokohama City Minato Red Cross Hospital ( Site 1506)	Yokohama	Kanagawa
Korea, Republic of	Hallym University Sacred Heart Hospital ( Site 2208)	Anyang si	Gyeonggi Do
Korea, Republic of	Incheon St. Mary s Hospital ( Site 2200)	Incheon
Korea, Republic of	Asan Medical Center ( Site 2203)	Seoul
Korea, Republic of	Konkuk University Medical Center ( Site 2205)	Seoul
Korea, Republic of	Korea University Guro Hospital ( Site 2213)	Seoul
Korea, Republic of	Samsung Medical Center ( Site 2212)	Seoul
Korea, Republic of	Seoul National University Hospital ( Site 2210)	Seoul
Korea, Republic of	Severance Hospital ( Site 2204)	Seoul
Korea, Republic of	The Catholic University of Korea Eunpyeong St Mary s Hospital ( Site 2209)	Seoul
Korea, Republic of	The Catholic University of Korea St. Mary s Hospital ( Site 2215)	Seoul
Korea, Republic of	Ajou University Hospital ( Site 2211)	Suwon	Gyeonggi-do
Korea, Republic of	Wonju Severance Christian Hospital ( Site 2214)	Wonju-si	Gangwon-do
Peru	Hospital Nacional Adolfo Guevara Velasco ( Site 1808)	Cusco
Peru	Asociacion Civil por la Salud ( Site 1805)	Lima
Peru	Hospital Chancay y Servicios Basicos de Salud ( Site 1810)	Lima
Peru	Clinica Ricardo Palma ( Site 1802)	San Isidro	Lima
Poland	Centrum Medycyny Oddechowej Mroz Spolka Jawna ( Site 1918)	Bialystok
Poland	Prywatny Gabinet Internistyczno ( Site 1928)	Bialystok
Poland	Centrum Medyczne Pratia Bydgoszcz ( Site 1418)	Bydgoszcz
Poland	Centrum Medyczne Pratia Czestochowa ( Site 1926)	Czestochowa
Poland	Centrum Medyczne Pratia Gdynia ( Site 1910)	Gdynia
Poland	Specjalistyczny osrodek .All-Med. Grazyna Pulka ( Site 1919)	Krakow
Poland	Prywatny Gabinet Specjalistyczny ( Site 1927)	Lodz
Poland	USK nr 1 ( Site 1921)	Lodz
Poland	NZOZCentrum Medyczne Kermed ( Site 1905)	Znin
Spain	Hospital Clinic ( Site 2302)	Barcelona
Spain	Hospital General Universitario Gregorio Maranon ( Site 2309)	Madrid
Spain	Hospital Parc Tauli ( Site 2308)	Sabadell
Spain	Hospital Clinico Universitario de Santiago ( Site 2303)	Santiago de Compostela
Taiwan	Changhua Christian Hospital ( Site 2403)	Changhua
Taiwan	Chang Gung Medical Foundation - Keelung Branch ( Site 2404)	Keelung
Taiwan	Far Eastern Memorial Hospital ( Site 2402)	New Taipei City
Taiwan	Taichung Veterans General Hospital ( Site 2401)	Taichung
Taiwan	National Taiwan University Hospital ( Site 2400)	Taipei
Turkey	Hacettepe Universitesi Tip Fakultesi Hastanesi ( Site 2613)	Ankara
Turkey	I.U. Cerrahpasa Tip Fakultesi Gogus Hastaliklari Anabilim Dali ( Site 2600)	Fatih
Turkey	Yedikule Gogus Hast. ve Gogus Cer. Egitim ve Arastirma Hastanesi ( Site 2601)	Istanbul
Turkey	Kocaeli Universitesi Tip Fakultesi ( Site 2611)	Kocaeli
Turkey	Recep Tayyip Erdogan Universitesi Tip Fakultesi Egitim ve Aras. Has ( Site 2620)	Rize
Turkey	Ondokuz Mayis Universitesi Tip Fakultesi Hastanesi ( Site 2606)	Samsun
Ukraine	F.G.Yanovskyy Institute of Phthisiology and Pulmonology ( Site 2830)	Kyiv
Ukraine	City Polyclinic N20 ( Site 2822)	Odesa
Ukraine	Private Small-Scale Enterprise Medical Centre "Pulse" ( Site 2815)	Vinnytsya
United Kingdom	Belfast City Hospital ( Site 2705)	Belfast
United Kingdom	Broomfield Hospital ( Site 2722)	Chelmsford
United Kingdom	Medinova Lakeside Dedicated Research Centre ( Site 2710)	Corby	Northamptonshire
United Kingdom	Glenfield Hospital ( Site 2701)	Leicester
United Kingdom	Royal Brompton Hospital ( Site 2703)	London
United Kingdom	Wythenshawe Hospital ( Site 2700)	Manchester
United Kingdom	Churchill Hospital ( Site 2706)	Oxford
United Kingdom	Royal Preston Hospital ( Site 2709)	Preston	Lancashire
United Kingdom	Rothwell Medical Centre ( Site 2712)	Rothwell
United Kingdom	MeDiNova Yorkshire Dedicated Research Centre ( Site 2708)	Shipley
United States	Sirius Clinical Research, LLC ( Site 0102)	Austin	Texas
United States	American Health Research ( Site 0082)	Charlotte	North Carolina
United States	Charlottesville Medical Research Center, LLC ( Site 0006)	Charlottesville	Virginia
United States	Bernstein Clinical Research Center, LLC ( Site 0005)	Cincinnati	Ohio
United States	Pharmaceutical Research & Consulting, Inc. ( Site 0029)	Dallas	Texas
United States	Mainland Medical Research Institute ( Site 0003)	Dickinson	Texas
United States	Intermountain Clinical Research ( Site 0033)	Draper	Utah
United States	Asthma Nasal Disease & Allergy Research Center of New England ( Site 0075)	East Providence	Rhode Island
United States	Clinical Research of Gastonia ( Site 0043)	Gastonia	North Carolina
United States	The Center for Pharmaceutical Research PC ( Site 0016)	Kansas City	Missouri
United States	Biosolutions Clinical Research Center ( Site 0070)	La Mesa	California
United States	Sher Allergy Specialists/Center For Cough ( Site 0078)	Largo	Florida
United States	Research Solutions of Arizona PC ( Site 0036)	Litchfield Park	Arizona
United States	Well Pharma Medical Research, Corp. ( Site 0093)	Miami	Florida
United States	Clinical Research Institute LLC ( Site 0004)	Minneapolis	Minnesota
United States	Midwest Allergy Sinus Asthma, SC ( Site 0081)	Normal	Illinois
United States	Center for Clinical Trials, LLC ( Site 0059)	Paramount	California
United States	National Clinical Research-Richmond, Inc. ( Site 0073)	Richmond	Virginia
United States	Pulmonary Associates of Richmond Inc. ( Site 0101)	Richmond	Virginia
United States	Diagnostics Research Group ( Site 0035)	San Antonio	Texas
United States	Medical Research of AZ ( Site 0060)	Scottsdale	Arizona
United States	BreatheAmerica Inc ( Site 0048)	Shreveport	Louisiana
United States	Cotton-O'Neil Clinical Research Center ( Site 0052)	Topeka	Kansas
United States	Vital Prospects Clinical Research Institute, PC ( Site 0037)	Tulsa	Oklahoma
United States	Allergy & Asthma Center ( Site 0001)	Waco	Texas
United States	Lung and Sleep Specialists ( Site 0091)	Williamsburg	Virginia
United States	Florida Pulmonary Research Institute, LLC ( Site 0019)	Winter Park	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

Countries where clinical trial is conducted

United States,  Argentina,  Canada,  Czechia,  Denmark,  France,  Hungary,  Israel,  Japan,  Korea, Republic of,  Peru,  Poland,  Spain,  Taiwan,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Model-Based Geometric Mean Ratio (GMR) of 24-hour Objective Coughs Per Hour (Week 12/Baseline)	24-hour objective coughs per hour was defined as the total number of cough events during the monitoring period (24-hour interval) divided by 24 hours (denominator could be different if the recording period was actually <24 hours but =20 hours). Assessment was based on 24-hour sound recordings using a digital recording device which recorded sounds from the lungs and trachea through a chest contact sensor, as well as ambient sounds through a lapel microphone. A longitudinal analysis of covariance (ANCOVA) model was applied to log-transformed cough counts to determine geometric mean (GM) 24-hour objective coughs per hour at baseline and Week 12 on the original scale. The GMR corresponding to the Week 12 GM 24-hour objective coughs per hour divided by the Baseline GM 24-hour objective coughs per hour was reported for all treatment study arms.	Baseline, Week 12
Primary	Number of Participants Experiencing At Least One Adverse Event (AE) During Treatment and Follow-up	An AE was defined as any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants with at least one AE during either the 52-week treatment period or 2-week telephone follow-up was reported for all treatment study arms.	Up to approximately 54 weeks
Primary	Number of Participants Who Discontinued Treatment Due to AEs	An AE was defined as any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who discontinued study intervention during the 52-week treatment period due to an AE for which the action taken was listed as 'drug withdrawn' was reported for all treatment study arms.	Up to approximately 52 weeks
Secondary	Model-Based Geometric Mean Ratio (GMR) of Awake Objective Coughs Per Hour (Week 12/Baseline)	Awake objective coughs per hour was defined as the total number of cough events during the monitoring period (24-hour interval) while the participant is awake divided by the total duration (in hours) for the monitoring period that the participant was awake. Assessment was based on 24-hour sound recordings using a digital recording device which recorded sounds from the lungs and trachea through a chest contact sensor, as well as ambient sounds through a lapel microphone. A longitudinal ANCOVA model was applied to log-transformed cough counts to determine GM awake objective coughs per hour at baseline and Week 12 on the original scale. The GMR corresponding to the Week 12 GM awake objective coughs per hour divided by the Baseline GM awake objective coughs per hour was reported for all treatment study arms.	Baseline, Week 12
Secondary	Percentage of Participants (Model-Based) With a = -30% Change From Baseline in 24-hour Objective Coughs Per Hour at Week 12	24-hour coughs per hour was defined as the total number of cough events during the monitoring period (24-hour interval) divided by 24 hours (denominator could be different if the recording period was actually <24 hours but =20 hours). Assessment based on 24-hour sound recordings using a digital recording device. Percent change in 24-hour coughs per hour = (change from baseline in 24-hour coughs per hour / baseline 24-hour coughs per hour) ×100%. Negative values indicate a decrease in cough rate, while positive values indicate an increase in cough rate. A participant was considered a responder if the percent change from baseline in 24-hour coughs per hour was = -30% (or a =30% reduction from baseline); a participant was considered a non-responder otherwise. The percentage of participants (logistic regression model-based) with a = -30% change from baseline in 24-hour coughs per hour at Week 12 (=30% reduction from baseline) was reported for all treatment study arms.	Baseline, Week 12
Secondary	Percentage of Participants (Model-Based) With a = -1.3-point Change From Baseline in Mean Weekly Cough Severity Diary (CSD) Total Score at Week 12	The CSD evaluates frequency of cough, intensity of cough and disruption and has a total of 7 items, each with scores ranging from 0 (best) to 10 (worst). The total daily CSD score was the sum of these seven item scores (Min=0, Max=70). Mean weekly total score was defined as the average of the mean total daily scores collected during the week prior to each visit. Baseline was defined as the average CSD scores collected during the week prior to Day 1 (Day -6 to Day 0). Participants were considered responders if the change from baseline in mean weekly CSD total score was = -1.3 points (or a =1.3 point reduction from baseline); and considered a non-responder otherwise. Negative values indicate a decrease in cough severity, while positive values indicate an increase in cough severity. The percentage of participants (logistic regression model-based) with a = -1.3 point change from baseline in CSD at Week 12 (or =1.3 point reduction from baseline) was reported for all treatment study arms.	Baseline, Week 12
Secondary	Percentage of Participants (Model-Based) With a = -2.7-point Change From Baseline in Mean Weekly CSD Total Score at Week 12	The CSD evaluates frequency of cough, intensity of cough and disruption and has a total of 7 items, each with scores ranging from 0 (best) to 10 (worst). The total daily CSD score was the sum of these seven item scores (Min=0, Max=70). Mean weekly total score was defined as the average of the mean total daily scores collected during the week prior to each visit. Baseline was defined as the average CSD scores collected during the week prior to Day 1 (Day -6 to Day 0). Participants were considered responders if the change from baseline in mean weekly CSD total score was = -2.7 points (or a =2.7 point reduction from baseline); and considered a non-responder otherwise. Negative values indicate a decrease in cough severity, while positive values indicate an increase in cough severity. The percentage of participants (logistic regression model-based) with a = -2.7 point change from baseline in CSD at Week 12 (or =2.7 point reduction from baseline) was reported for all treatment study arms.	Baseline, Week 12
Secondary	Percentage of Participants (Model-Based) With a = -30 Millimeter (mm) Change From Baseline in Cough Severity Visual Analog Scale (VAS) Score at Week 12	Cough severity was scored using the Cough Severity VAS, a single-item question asking the participant to rate the severity of their cough "today" using a 100 mm VAS (100-point scale) ranging from 0 ("No Cough") to 100 ("Extremely Severe Cough"). Mean weekly VAS score was derived as the average of VAS scores collected during the week prior to each visit. Baseline was defined as the average VAS scores collected during the week prior to Day 1 (Day -6 to Day 0). A participant was considered a responder if the change from baseline in mean weekly Cough Severity VAS score was =-30 mm (or a =30 mm reduction from baseline); participants considered non-responders otherwise. Negative values indicate a decrease in cough severity, while positive values indicate an increase in cough severity. The percentage of participants (logistic regression model-based) with = -30 mm change from baseline in Cough Severity VAS at Week 12 (=30 mm reduction from baseline) was reported for all treatment study arms.	Baseline, Week 12
Secondary	Percentage of Participants (Model-Based) With a =1.3-point Change From Baseline in Leicester Cough Questionnaire (LCQ) Total Score at Week 12	The LCQ assesses the impact of chronic cough on health-related quality of life. It consists of 19 items which are divided over 3 domains: Physical (items 1, 2, 3, 9, 10, 11, 14 and 15), Psychological (4, 5, 6, 12, 13, 16, and 17), and Social (7, 8, 18, 19). A 7-point Likert scale is used to rate each item. For each domain, the domain score (range 1-7) is the sum of individual item score within the domain divided by the number of items in the domain. LCQ total score is the sum of the three domain scores and ranges from 3-21; with a higher score corresponding to a better health status. A participant was considered a responder if the change from baseline in LCQ total score was =1.3-points (increase from baseline); a participant was considered a non-responder otherwise. The percentage of participants (logistic regression model-based) with a =1.3-point change from baseline in LCQ total score at Week 12 was reported for all treatment study arms.	Baseline, Week 12