Clinical trial NCT03449134: A Study of Gefapixant (MK-7264) in Adult Participants With Chronic Cough (MK-7264-027)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Cough
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2018-02-28
Enrollment: 732
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants with refractory or unexplained chronic cough will be randomized to 1 of 3 treatment groups during the Treatment Period: Placebo, gefapixant 15 mg twice daily (BID), or gefapixant 45 mg BID. Participants will remain on their assigned treatment throughout the study. A safety follow-up phone call will be conducted at a minimum of 14 days after last dose of study treatment.
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Model-Based Geometric Mean Ratio (GMR) of 24-hour Objective Coughs Per Hour (Week 12/Baseline)
timeFrame: Baseline, Week 12
measure: Number of Participants Experiencing At Least One Adverse Event (AE) During Treatment and Follow-up
timeFrame: Up to approximately 54 weeks
measure: Number of Participants Who Discontinued Treatment Due to AEs
timeFrame: Up to approximately 52 weeks
Secondary outcomes:
measure: Model-Based Geometric Mean Ratio (GMR) of Awake Objective Coughs Per Hour (Week 12/Baseline)
timeFrame: Baseline, Week 12
measure: Percentage of Participants (Model-Based) With a ≤ -30% Change From Baseline in 24-hour Objective Coughs Per Hour at Week 12
timeFrame: Baseline, Week 12
measure: 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
timeFrame: Baseline, Week 12
measure: Percentage of Participants (Model-Based) With a ≤ -2.7-point Change From Baseline in Mean Weekly CSD Total Score at Week 12
timeFrame: Baseline, Week 12
measure: Percentage of Participants (Model-Based) With a ≤ -30 Millimeter (mm) Change From Baseline in Cough Severity Visual Analog Scale (VAS) Score at Week 12
timeFrame: Baseline, Week 12
measure: Percentage of Participants (Model-Based) With a ≥1.3-point Change From Baseline in Leicester Cough Questionnaire (LCQ) Total Score at Week 12
timeFrame: Baseline, Week 12
Other outcomes:
Locations:
city: Litchfield Park
country: United States
facility: Research Solutions of Arizona PC ( Site 0036)
state: Arizona
city: Scottsdale
country: United States
facility: Medical Research of AZ ( Site 0060)
state: Arizona
city: La Mesa
country: United States
facility: Biosolutions Clinical Research Center ( Site 0070)
state: California
city: Paramount
country: United States
facility: Center for Clinical Trials, LLC ( Site 0059)
state: California
city: Largo
country: United States
facility: Sher Allergy Specialists/Center For Cough ( Site 0078)
state: Florida
city: Miami
country: United States
facility: Well Pharma Medical Research, Corp. ( Site 0093)
state: Florida
city: Winter Park
country: United States
facility: Florida Pulmonary Research Institute, LLC ( Site 0019)
state: Florida
city: Normal
country: United States
facility: Midwest Allergy Sinus Asthma, SC ( Site 0081)
state: Illinois
city: Topeka
country: United States
facility: Cotton-O'Neil Clinical Research Center ( Site 0052)
state: Kansas
city: Shreveport
country: United States
facility: BreatheAmerica Inc ( Site 0048)
state: Louisiana
city: Minneapolis
country: United States
facility: Clinical Research Institute LLC ( Site 0004)
state: Minnesota
city: Kansas City
country: United States
facility: The Center for Pharmaceutical Research PC ( Site 0016)
state: Missouri
city: Charlotte
country: United States
facility: American Health Research ( Site 0082)
state: North Carolina
city: Gastonia
country: United States
facility: Clinical Research of Gastonia ( Site 0043)
state: North Carolina
city: Cincinnati
country: United States
facility: Bernstein Clinical Research Center, LLC ( Site 0005)
state: Ohio
city: Tulsa
country: United States
facility: Vital Prospects Clinical Research Institute, PC ( Site 0037)
state: Oklahoma
city: East Providence
country: United States
facility: Asthma Nasal Disease & Allergy Research Center of New England ( Site 0075)
state: Rhode Island
city: Austin
country: United States
facility: Sirius Clinical Research, LLC ( Site 0102)
state: Texas
city: Dallas
country: United States
facility: Pharmaceutical Research & Consulting, Inc. ( Site 0029)
state: Texas
city: Dickinson
country: United States
facility: Mainland Medical Research Institute ( Site 0003)
state: Texas
city: San Antonio
country: United States
facility: Diagnostics Research Group ( Site 0035)
state: Texas
city: Waco
country: United States
facility: Allergy & Asthma Center ( Site 0001)
state: Texas
city: Draper
country: United States
facility: Intermountain Clinical Research ( Site 0033)
state: Utah
city: Charlottesville
country: United States
facility: Charlottesville Medical Research Center, LLC ( Site 0006)
state: Virginia
city: Richmond
country: United States
facility: Pulmonary Associates of Richmond Inc. ( Site 0101)
state: Virginia
city: Richmond
country: United States
facility: National Clinical Research-Richmond, Inc. ( Site 0073)
state: Virginia
city: Williamsburg
country: United States
facility: Lung and Sleep Specialists ( Site 0091)
state: Virginia
city: Caba
country: Argentina
facility: InAER Investigaciones en Alergia y Enfermedades Respiratorias ( Site 0324)
state: Buenos Aires
city: Ciudad de Buenos Aires
country: Argentina
facility: Fundacion CIDEA ( Site 0323)
state: Buenos Aires
city: Mar del Plata
country: Argentina
facility: Instituto Ave Pulmo ( Site 0322)
state: Buenos Aires
city: San Miguel de Tucuman
country: Argentina
facility: Centro Medico Privado de Reumatologia ( Site 0309)
state: Tucuman
city: San Miguel de Tucuman
country: Argentina
facility: Investigaciones en Patologias Respiratorias ( Site 0325)
state: Tucuman
city: Buenos Aires
country: Argentina
facility: Centro Medico Dra De Salvo ( Site 0310)
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: CEMEDIC - Centro de Especialidades Medicas ( Site 0304)
city: Cordoba
country: Argentina
facility: Hospital Privado Universitario de Cordoba ( Site 0313)
city: Mendoza
country: Argentina
facility: Fundacion Scherbovsky ( Site 0300)
city: Toronto
country: Canada
facility: Canadian Phase Onward Inc. ( Site 0509)
state: Ontario
city: Montreal
country: Canada
facility: Recherche GCP Research ( Site 0500)
state: Quebec
city: Montreal
country: Canada
facility: 167877 Canada Inc. Dr. Jaime Del Carpio ( Site 0506)
state: Quebec
city: Pointe-Claire
country: Canada
facility: Dynamik Research ( Site 0505)
state: Quebec
city: Sherbrooke
country: Canada
facility: Q & T Research Sherbrooke Inc. ( Site 0512)
state: Quebec
city: Trois-Rivieres
country: Canada
facility: CIC Mauricie Inc. ( Site 0503)
state: Quebec
city: Quebec
country: Canada
facility: Diex Recherche Quebec Inc ( Site 0515)
city: Brandys nad Labem
country: Czechia
facility: MUDr. I. Cierna Peterova s.r.o. ( Site 0707)
city: Rokycany
country: Czechia
facility: Plicni ambulance ( Site 0701)
city: Teplice
country: Czechia
facility: Plicni stredisko Teplice s. r. o ( Site 0700)
city: Varnsdorf
country: Czechia
facility: Pneumologie Varnsdorf S.R.O. ( Site 0706)
city: Aalborg
country: Denmark
facility: CCBR AS Aalborg, Center for Clinical & Basic Research ( Site 0802)
city: Herlev
country: Denmark
facility: Herlev Hospital ( Site 0803)
city: Vejle
country: Denmark
facility: CCBR AS Vejle, Center for Clinical & Basic Research ( Site 0801)
city: Brest
country: France
facility: Hopital Cavale Blanche ( Site 0909)
city: Marseille
country: France
facility: Hopital Nord du Marseille ( Site 0910)
city: Montpellier
country: France
facility: Hopital Arnaud de Villeneuve ( Site 0905)
city: Nantes
country: France
facility: CHU Hotel Dieu Nantes ( Site 0906)
city: Toulouse
country: France
facility: CHU de Toulouse - Hopital Larrey ( Site 0900)
city: Balassagyarmat
country: Hungary
facility: Dr Kenessey Albert Korhaz-Rendelointezet ( Site 1200)
city: Godollo
country: Hungary
facility: Erzsebet Gondozohaz ( Site 1207)
city: Gyor
country: Hungary
facility: Petz Aladar Megyei Oktato Korhaz ( Site 1206)
city: Gyula
country: Hungary
facility: Synexus Magyarorszag Kft. ( Site 1210)
city: Miskolc
country: Hungary
facility: CRU Hungary KFT ( Site 1205)
city: Hadera
country: Israel
facility: Hillel Yaffe Medical Center ( Site 1303)
city: Haifa
country: Israel
facility: Carmel Medical Center ( Site 1305)
city: Kfar Saba
country: Israel
facility: Meir Medical Center ( Site 1301)
city: Petah-Tikva
country: Israel
facility: Rabin Medical Center ( Site 1302)
city: Ramat Gan
country: Israel
facility: Chaim Sheba Medical Center. ( Site 1304)
city: Nagoya
country: Japan
facility: National Hospital Organization Nagoya Medical Center ( Site 1539)
state: Aichi
city: Nagoya
country: Japan
facility: Nagoya City University Hospital ( Site 1528)
state: Aichi
city: Toon
country: Japan
facility: National Hospital Organization Ehime Medical Center ( Site 1556)
state: Ehime
city: Sapporo
country: Japan
facility: Idaimae Minamiyojo Int Clinic ( Site 1521)
state: Hokkaido
city: Himeji
country: Japan
facility: Terada Clinic Respiratory Medicine & General Practice ( Site 1565)
state: Hyogo
city: Itami
country: Japan
facility: Kinki Central Hospital ( Site 1576)
state: Hyogo
city: Itami
country: Japan
facility: Itami City Hospital ( Site 1580)
state: Hyogo
city: Naka-gun
country: Japan
facility: National Hospital Organization Ibarakihigashi National Hospital ( Site 1526)
state: Ibaraki
city: Kanazawa
country: Japan
facility: Ishikawa Prefectural Central Hospital ( Site 1554)
state: Ishikawa
city: Kanazawa
country: Japan
facility: Kanazawa University Hospital ( Site 1536)
state: Ishikawa
city: Komatsu
country: Japan
facility: Komatsu Municipal Hospital ( Site 1508)
state: Ishikawa
city: Takamatsu
country: Japan
facility: Kamei Internal Medicine and Respiratory Clinic ( Site 1509)
state: Kagawa
city: Fujisawa
country: Japan
facility: Fujisawa City Hospital ( Site 1505)
state: Kanagawa
city: Yokohama
country: Japan
facility: Yokohama City Minato Red Cross Hospital ( Site 1506)
state: Kanagawa
city: Yokohama
country: Japan
facility: Medical Corporation Shintokai Yokohama Minoru Clinic ( Site 1568)
state: Kanagawa
city: Yokohama
country: Japan
facility: Saiseikai Yokohamashi Nanbu Hospital ( Site 1533)
state: Kanagawa
city: Yokohama
country: Japan
facility: Kanagawa Cardiovascular and Respiratory Center ( Site 1503)
state: Kanagawa
city: Matsusaka
country: Japan
facility: Matsusaka City Hospital ( Site 1525)
state: Mie
city: Nagaoka
country: Japan
facility: Nagaoka Red Cross Hospital ( Site 1507)
state: Niigata
city: Tsukubo-gun
country: Japan
facility: National Hospital Organization Minami-Okayama Medical Center ( Site 1553)
state: Okayama
city: Urasoe
country: Japan
facility: Urasoe General Hospital ( Site 1572)
state: Okinawa
city: Habikino
country: Japan
facility: Osaka Habikino Medical Center ( Site 1546)
state: Osaka
city: Higashiosaka
country: Japan
facility: Kawaguchi Respiratory Clinic ( Site 1504)
state: Osaka
city: Sakai
country: Japan
facility: National Hospital Organization Kinki-chuo Chest Medical Center ( Site 1519)
state: Osaka
city: Hachioji
country: Japan
facility: Tokyo Medical University Hachioji Medical Center ( Site 1569)
state: Tokyo
city: Kiyose
country: Japan
facility: National Hospital Organization Tokyo National Hospital ( Site 1557)
state: Tokyo
city: Tachikawa
country: Japan
facility: National Hospital Organization Disaster Medical Center ( Site 1558)
state: Tokyo
city: Shimonoseki
country: Japan
facility: Shimonoseki City Hospital ( Site 1573)
state: Yamaguchi
city: Fukuoka
country: Japan
facility: National Hospital Organization Fukuoka Hospital ( Site 1552)
city: Hiroshima
country: Japan
facility: Hiroshima Allergy & Respiratory Clinic ( Site 1529)
city: Kyoto
country: Japan
facility: Kyoto University Hospital ( Site 1547)
city: Niigata
country: Japan
facility: JA Niigatakoseiren Niigata Medical Center ( Site 1522)
city: Shizuoka
country: Japan
facility: Shizuoka Prefectural Hospital Organization Shizuoka General Hospital ( Site 1524)
city: Tokyo
country: Japan
facility: Juntendo University Hospital ( Site 1578)
city: Tokyo
country: Japan
facility: Tokyo Shinagawa Hospital ( Site 1560)
city: Tokyo
country: Japan
facility: Showa University Hospital ( Site 1531)
city: Tokyo
country: Japan
facility: Center Hospital of the National Center for Global Health and Medicine ( Site 1574)
city: Tokyo
country: Japan
facility: Tokyo Metropolitan Geriatric Hospital ( Site 1577)
city: Wonju-si
country: Korea, Republic of
facility: Wonju Severance Christian Hospital ( Site 2214)
state: Gangwon-do
city: Anyang si
country: Korea, Republic of
facility: Hallym University Sacred Heart Hospital ( Site 2208)
state: Gyeonggi Do
city: Suwon
country: Korea, Republic of
facility: Ajou University Hospital ( Site 2211)
state: Gyeonggi-do
city: Incheon
country: Korea, Republic of
facility: Incheon St. Mary s Hospital ( Site 2200)
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital ( Site 2210)
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea Eunpyeong St Mary s Hospital ( Site 2209)
city: Seoul
country: Korea, Republic of
facility: Severance Hospital ( Site 2204)
city: Seoul
country: Korea, Republic of
facility: Konkuk University Medical Center ( Site 2205)
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center ( Site 2203)
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center ( Site 2212)
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea St. Mary s Hospital ( Site 2215)
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital ( Site 2213)
city: San Isidro
country: Peru
facility: Clinica Ricardo Palma ( Site 1802)
state: Lima
city: Cusco
country: Peru
facility: Hospital Nacional Adolfo Guevara Velasco ( Site 1808)
city: Lima
country: Peru
facility: Asociacion Civil por la Salud ( Site 1805)
city: Lima
country: Peru
facility: Hospital Chancay y Servicios Basicos de Salud ( Site 1810)
city: Bialystok
country: Poland
facility: Prywatny Gabinet Internistyczno ( Site 1928)
city: Białystok
country: Poland
facility: Centrum Medycyny Oddechowej Mroz Spolka Jawna ( Site 1918)
city: Bydgoszcz
country: Poland
facility: Centrum Medyczne Pratia Bydgoszcz ( Site 1418)
city: Czestochowa
country: Poland
facility: Centrum Medyczne Pratia Czestochowa ( Site 1926)
city: Gdynia
country: Poland
facility: Centrum Medyczne Pratia Gdynia ( Site 1910)
city: Krakow
country: Poland
facility: Specjalistyczny osrodek .All-Med. Grazyna Pulka ( Site 1919)
city: Lodz
country: Poland
facility: USK nr 1 ( Site 1921)
city: Lodz
country: Poland
facility: Prywatny Gabinet Specjalistyczny ( Site 1927)
city: Znin
country: Poland
facility: NZOZCentrum Medyczne Kermed ( Site 1905)
city: Barcelona
country: Spain
facility: Hospital Clinic ( Site 2302)
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon ( Site 2309)
city: Sabadell
country: Spain
facility: Hospital Parc Tauli ( Site 2308)
city: Santiago de Compostela
country: Spain
facility: Hospital Clinico Universitario de Santiago ( Site 2303)
city: Changhua
country: Taiwan
facility: Changhua Christian Hospital ( Site 2403)
city: Keelung
country: Taiwan
facility: Chang Gung Medical Foundation - Keelung Branch ( Site 2404)
city: New Taipei City
country: Taiwan
facility: Far Eastern Memorial Hospital ( Site 2402)
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital ( Site 2401)
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital ( Site 2400)
city: Ankara
country: Turkey
facility: Hacettepe Universitesi Tip Fakultesi Hastanesi ( Site 2613)
city: Fatih
country: Turkey
facility: I.U. Cerrahpasa Tip Fakultesi Gogus Hastaliklari Anabilim Dali ( Site 2600)
city: Istanbul
country: Turkey
facility: Yedikule Gogus Hast. ve Gogus Cer. Egitim ve Arastirma Hastanesi ( Site 2601)
city: Kocaeli
country: Turkey
facility: Kocaeli Universitesi Tip Fakultesi ( Site 2611)
city: Rize
country: Turkey
facility: Recep Tayyip Erdogan Universitesi Tip Fakultesi Egitim ve Aras. Has ( Site 2620)
city: Samsun
country: Turkey
facility: Ondokuz Mayis Universitesi Tip Fakultesi Hastanesi ( Site 2606)
city: Kyiv
country: Ukraine
facility: F.G.Yanovskyy Institute of Phthisiology and Pulmonology ( Site 2830)
city: Odesa
country: Ukraine
facility: City Polyclinic N20 ( Site 2822)
city: Vinnytsya
country: Ukraine
facility: Private Small-Scale Enterprise Medical Centre "Pulse" ( Site 2815)
city: Preston
country: United Kingdom
facility: Royal Preston Hospital ( Site 2709)
state: Lancashire
city: Corby
country: United Kingdom
facility: Medinova Lakeside Dedicated Research Centre ( Site 2710)
state: Northamptonshire
city: Belfast
country: United Kingdom
facility: Belfast City Hospital ( Site 2705)
city: Chelmsford
country: United Kingdom
facility: Broomfield Hospital ( Site 2722)
city: Leicester
country: United Kingdom
facility: Glenfield Hospital ( Site 2701)
city: London
country: United Kingdom
facility: Royal Brompton Hospital ( Site 2703)
city: Manchester
country: United Kingdom
facility: Wythenshawe Hospital ( Site 2700)
city: Oxford
country: United Kingdom
facility: Churchill Hospital ( Site 2706)
city: Rothwell
country: United Kingdom
facility: Rothwell Medical Centre ( Site 2712)
city: Shipley
country: United Kingdom
facility: MeDiNova Yorkshire Dedicated Research Centre ( Site 2708)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Dicpinigaitis PV, Birring SS, Blaiss M, McGarvey LP, Morice AH, Pavord ID, Satia I, Smith JA, La Rosa C, Li Q, Nguyen AM, Schelfhout J, Tzontcheva A, Muccino D. Demographic, clinical, and patient-reported outcome data from 2 global, phase 3 trials of chronic cough. Ann Allergy Asthma Immunol. 2023 Jan;130(1):60-66. doi: 10.1016/j.anai.2022.05.003. Epub 2022 May 13.
citation: McGarvey LP, Birring SS, Morice AH, Dicpinigaitis PV, Pavord ID, Schelfhout J, Nguyen AM, Li Q, Tzontcheva A, Iskold B, Green SA, Rosa C, Muccino DR, Smith JA; COUGH-1 and COUGH-2 Investigators. Efficacy and safety of gefapixant, a P2X3 receptor antagonist, in refractory chronic cough and unexplained chronic cough (COUGH-1 and COUGH-2): results from two double-blind, randomised, parallel-group, placebo-controlled, phase 3 trials. Lancet. 2022 Mar 5;399(10328):909-923. doi: 10.1016/S0140-6736(21)02348-5.