A Study of Gefapixant (MK-7264) in Japanese Adult Partici... | NCT03696108

ID	Type	Description	Link
MK-7264-038	Other Identifier	Merck Protocol Number
184154	Registry Identifier	JAPIC-CTI

Label	Type	Description	Intervention Names
Gefapixant 15 mg BID	Experimental	Participants will receive gefapixant 15 mg tablet and placebo tablet to match gefapixant 45 mg twice daily (BID) during the study period (52 weeks).	Drug: Gefapixant Drug: Placebo
Gefapixant 45 mg BID	Experimental	Participants will receive gefapixant 45 mg tablet and placebo tablet to match gefapixant 15 mg BID during the study period (52 weeks).	Drug: Gefapixant Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Gefapixant	Drug	Gefapixant 15 mg or 45 mg tablet administered orally BID	Gefapixant 15 mg BID Gefapixant 45 mg BID

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Participants Who Experienced at Least One Adverse Event (AE)	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.	Up to 54 Weeks
Number of Participants Who Discontinued Study Drug Due to an AE	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.	Up to 52 Weeks

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline in the Leicester Cough Questionnaire (LCQ) Total Score at Week 12	The LCQ is a 19-item cough-specific health-related quality of life (HRQoL) questionnaire which contains three domains (physical, psychological and social), calculated as a mean score for each domain ranging from 1 to 7 and total score ranging from 3 to 21. Each item on the LCQ is assessed using a 7-point Likert scale ranging from 1 to 7. Higher scores indicate better HRQoL. The least squares mean of the change from baseline is based on a longitudinal analysis of covariance (ANCOVA) model.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Chest radiograph or computed tomography scan of the thorax 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.
Chronic cough for ≥ 4 months and a diagnosis of refractory or unexplained chronic cough.
Persistent cough, despite treatment in accordance with the latest guideline of cough from the Japanese Respiratory Society, cough is a burden to the participant, and needs further treatment.
If female, is not pregnant, not breast-feeding, and either is not a woman of childbearing potential or agrees to follow the contraceptive guidance.

Exclusion Criteria:

Current smoker, or has given up smoking within 12 months of Screening.
History of upper or lower respiratory tract infection or recent clinically significant change in pulmonary status.
Has a history of chronic bronchitis.
Current use of an angiotensin converting enzyme inhibitor (ACEI) or has taken an ACEI within 3 months of Screening.
Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m^2 OR ≥30 mL/min/1.73 m^2 and <50 mL/min/1.73 m^2 at Visit 1 with unstable renal function (defined as a ≥50% increase of serum creatinine compared to a value obtained at least 6 months prior to Visit 1).
History of malignancy ≤ 5 years.
User of recreational or illicit drugs or has had a recent history (within the last year) of drug or alcohol abuse or dependence.
Systolic blood pressure >160 mm Hg or a diastolic blood pressure >90 mm Hg at Screening.
History of cutaneous adverse drug reaction to sulfonamide antibiotics or other sulfonamide-containing drugs.
Known allergy/sensitivity or contraindication to gefapixant.
Donated or lost ≥1 unit of blood within 8 weeks prior to the first dose of gefapixant.
Previously received gefapixant or is currently participating in or has participated in an interventional clinical study.

Name	Affiliation	Role
Medical Director	Merck Sharp & Dohme LLC	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Chubu Rosai Hospital ( Site 3839)		Nagoya	Aichi-ken	455-8530	Japan
National Hospital Organization Nagoya Medical Center ( Site 3898)

PubMed Identifier	Type	Citation	Retractions
35752582	Derived	Niimi A, Sagara H, Kikuchi M, Arano I, Sato A, Shirakawa M, La Rosa C, Muccino D. A phase 3, randomized, double-blind, clinical study to evaluate the long-term safety and efficacy of gefapixant in Japanese adult participants with refractory or unexplained chronic cough. Allergol Int. 2022 Oct;71(4):498-504. doi: 10.1016/j.alit.2022.05.006. Epub 2022 Jun 23.

ID	Title	Description
FG000	Gefapixant 15 mg BID	Participants received a gefapixant 15 mg tablet and a placebo tablet to match gefapixant 45 mg twice daily (BID) for 52 weeks
FG001	Gefapixant 45 mg BID

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Sep 26, 2018

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Participants Who Experienced at Least One Adverse Event (AE)

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.

All randomized participants who received at least one dose of study treatment.

Posted

Count of Participants

Participants

Up to 54 Weeks

ID	Title	Description
OG000	Gefapixant 15 mg BID	Participants received a gefapixant 15 mg tablet and a placebo tablet to match gefapixant 45 mg BID for 52 weeks
OG001	Gefapixant 45 mg	Participants received a gefapixant 45 mg tablet and a placebo tablet to match gefapixant 15 mg BID for 52 weeks

Units	Counts
Participants	OG00084 OG00185

Title

Denominators

Categories

Title	Measurements
	OG00079 OG00182

Primary

Number of Participants Who Discontinued Study Drug Due to an AE

All randomized participants who received at least one dose of study treatment.

Posted

Count of Participants

Participants

Up to 52 Weeks

ID	Title	Description
OG000	Gefapixant 15 mg BID	Participants received a gefapixant 15 mg tablet and a placebo tablet to match gefapixant 45 mg BID for 52 weeks
OG001	Gefapixant 45 mg	Participants received a gefapixant 45 mg tablet and a placebo tablet to match gefapixant 15 mg BID for 52 weeks

Units	Counts
Participants

Secondary

Change From Baseline in the Leicester Cough Questionnaire (LCQ) Total Score at Week 12

The LCQ is a 19-item cough-specific health-related quality of life (HRQoL) questionnaire which contains three domains (physical, psychological and social), calculated as a mean score for each domain ranging from 1 to 7 and total score ranging from 3 to 21. Each item on the LCQ is assessed using a 7-point Likert scale ranging from 1 to 7. Higher scores indicate better HRQoL. The least squares mean of the change from baseline is based on a longitudinal analysis of covariance (ANCOVA) model.

All randomized participants who have taken at least one dose of study treatment and provided at least one baseline and one post-baseline endpoint observations during the treatment period.

Posted

Least Squares Mean

95% Confidence Interval

Scores on a Scale

Baseline, Week 12

ID	Title	Description
OG000	Gefapixant 15 mg BID	Participants received a gefapixant 15 mg tablet and a placebo tablet to match gefapixant 45 mg BID for 52 weeks
OG001	Gefapixant 45 mg	Participants received a gefapixant 45 mg tablet and a placebo tablet to match gefapixant 15 mg BID for 52 weeks

Units	Counts

Secondary

Change From Baseline in LCQ Total Score

The LCQ is a 19-item cough-specific HRQoL questionnaire which contains three domains (physical, psychological and social), calculated as a mean score for each domain ranging from 1 to 7 and total score ranging from 3 to 21. Each item on the LCQ is assessed using a 7-point Likert scale ranging from 1 to 7. Higher scores indicate better HRQoL. The least squares mean of the change from baseline is based on a longitudinal analysis of covariance (ANCOVA) model at weeks 4, 8, 12, 24, 38 and 52 of treatment.

All randomized participants who have taken at least one dose of study treatment and provided at least one baseline and one post-baseline endpoint observations during the treatment period.

Posted

Least Squares Mean

95% Confidence Interval

Scores on a Scale

Baseline, up to 52 Weeks

ID	Title	Description
OG000	Gefapixant 15 mg BID	Participants received a gefapixant 15 mg tablet and a placebo tablet to match gefapixant 45 mg BID for 52 weeks
OG001	Gefapixant 45 mg	Participants received a gefapixant 45 mg tablet and a placebo tablet to match gefapixant 15 mg BID for 52 weeks

Units	Counts

Secondary

Percentage of Participants With a ≥1.3 Point Change From Baseline in the LCQ Total Score

The LCQ is a 19-item cough-specific HRQoL questionnaire which contains three domains (physical, psychological and social), calculated as a mean score for each domain ranging from 1 to 7 and total score ranging from 3 to 21. Each item on the LCQ is assessed using a 7-point Likert scale ranging from 1 to 7. Higher scores indicate better HRQoL. A clinically meaningful improvement from baseline in HRQoL was defined as ≥1.3-point increase in the LCQ total score at weeks 4, 8, 12, 24, 38 and 52 of treatment.

All randomized participants who have taken at least one dose of study treatment and provided at least one baseline and one post-baseline endpoint observations during the treatment period.

Posted

Number

Percentage of Participants

Baseline, Up to 52 Weeks

ID	Title	Description
OG000	Gefapixant 15 mg BID	Participants received a gefapixant 15 mg tablet and a placebo tablet to match gefapixant 45 mg BID for 52 weeks
OG001	Gefapixant 45 mg	Participants received a gefapixant 45 mg tablet and a placebo tablet to match gefapixant 15 mg BID for 52 weeks

Units	Counts

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Large intestine polyp	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected84 at risk EG0011 events1 affected85 at risk
Hepatic function abnormal	Hepatobiliary disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected84 at risk EG0011 events1 affected85 at risk
Bronchitis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected84 at risk EG0010 events0 affected85 at risk
Pneumonia	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected84 at risk EG0013 events3 affected85 at risk
Pneumonia bacterial	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected84 at risk EG0010 events0 affected85 at risk
Radius fracture	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected84 at risk EG0011 events1 affected85 at risk
Hypophagia	Metabolism and nutrition disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected84 at risk EG0011 events1 affected85 at risk
Bladder transitional cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected84 at risk EG0011 events1 affected85 at risk
Ovarian germ cell teratoma benign	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected84 at risk EG0011 events1 affected85 at risk
Embolic cerebral infarction	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected84 at risk EG0011 events1 affected85 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0002 events2 affected84 at risk EG0010 events0 affected85 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Constipation	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0006 events6 affected84 at risk EG0012 events2 affected85 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0007 events7 affected84 at risk EG0012 events2 affected85 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0006 events6 affected84 at risk EG0011 events1 affected85 at risk
Paraesthesia oral	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected84 at risk EG0015 events5 affected85 at risk
Pyrexia	General disorders	MedDRA 23.0	Systematic Assessment	EG0005 events5 affected84 at risk EG0017 events6 affected85 at risk
Bronchitis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG00011 events10 affected84 at risk EG0013 events3 affected85 at risk
Gastroenteritis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0003 events2 affected84 at risk EG0016 events6 affected85 at risk
Nasopharyngitis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG00060 events25 affected84 at risk EG00161 events33 affected85 at risk
Pharyngitis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG00010 events8 affected84 at risk EG0016 events4 affected85 at risk
Accidental overdose	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0005 events5 affected84 at risk EG0013 events3 affected85 at risk
Ageusia	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected84 at risk EG0015 events5 affected85 at risk
Dysgeusia	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG00017 events14 affected84 at risk EG00140 events40 affected85 at risk
Headache	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG00011 events9 affected84 at risk EG0013 events3 affected85 at risk
Hypogeusia	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0009 events9 affected84 at risk EG00114 events14 affected85 at risk
Taste disorder	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0006 events6 affected84 at risk EG00110 events10 affected85 at risk
Insomnia	Psychiatric disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected84 at risk EG0015 events5 affected85 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG00015 events10 affected84 at risk EG0019 events6 affected85 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG00034 events19 affected84 at risk EG00122 events11 affected85 at risk

ID	Term
D003371	Cough
D012120	Respiration Disorders
D012140	Respiratory Tract Diseases
D012818	Signs and Symptoms, Respiratory
D012816	Signs and Symptoms
D013568	Pathological Conditions, Signs and Symptoms

ID	Title	Description
BG000	Gefapixant 15 mg BID	Participants received a gefapixant 15 mg tablet and a placebo tablet to match gefapixant 45 mg twice daily (BID) for 52 weeks
BG001	Gefapixant 45 mg BID	Participants received a gefapixant 45 mg tablet and a placebo tablet to match gefapixant 15 mg BID for 52 weeks
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Gefapixant 15 mg	Participants received a gefapixant 15 mg tablet and a placebo tablet to match gefapixant 45 mg twice daily (BID) for 52 weeks	0	84	2	84	73	84
EG001	Gefapixant 45 mg	Participants received a gefapixant 45 mg tablet and a placebo tablet to match gefapixant 15 mg BID for 52 weeks	0	85	10	85	76	85