Study of Gefapixant (MK-7264) in Acute Cough for Participants With Induced Viral Upper Respiratory Tract Infection (URTI) (MK-7264-013)

• Sponsor: Merck Sharp & Dohme LLC (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT03569033
• Collaborator: (none)
• Enrollment: 46
• Location: 1
• Arms: 2
• Actual Duration (Months): 4.5
• Patients Per Site Per Month: 10.1

Study Details

Study Description

Brief Summary

The purpose of the study is to evaluate the efficacy, safety, and tolerability of gefapixant (MK-7264) in adult participants with induced viral upper respiratory tract infections (URTI).

Condition or Disease	Intervention/Treatment	Phase
Acute Cough	Drug: Gefapixant; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 46 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 2a, Randomized, Placebo-Controlled Clinical Trial to Evaluate the Efficacy, Safety and Tolerability of MK-7264 on Acute Cough in Participants With Induced Viral Upper Respiratory Tract Infection
• Actual Study Start Date: Jul 4, 2018
• Actual Primary Completion Date: Oct 31, 2018
• Actual Study Completion Date: Nov 19, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Gefapixant 45 mg BID Participants will receive a gefapixant 45 mg tablet twice daily (BID) for 7 days.	Drug: Gefapixant; Gefapixant 45 mg will be administered orally.; Other Names: MK-7264
Placebo Comparator: Placebo BID Participants will receive a matching placebo tablet BID for 7 days.	Drug: Placebo; Placebo tablet matching gefapixant will be administered orally.

Outcome Measures

Primary Outcome Measures

1. Awake Coughs Per Hour on Day 3 [Day 3]

   Awake cough frequency (coughs per hour) was assessed by an objective digital cough-counting device (VitaloJAK™ cough monitor) on Day 3.

Secondary Outcome Measures

1. Change From Baseline in the Cough Severity Visual Analog Scale (VAS) Score on Day 3 [Baseline and Day 3]

   The Cough Severity VAS was scored from 0 to 100 using a 100 mm visual analogue scale. Participants were asked to mark on a 100 mm scale between 0 (no cough) and 100 (the worst cough severity). Cough VAS was evaluated at Baseline and on Day 3.

2. Change From Baseline in the Mean Total Daily Cough Severity Diary (CSD) Score on Day 3 [Baseline and Day 3]

   The Mean Total Daily CSD Score is calculated using the daily CSD instrument, a 7-item, disease-specific, patient-reported outcome measure with a recall period of "today" (the current day). The measure evaluates frequency of cough (3 items); intensity of cough (2 items); and disruption due to cough (2 items). Each of these 7 items is rated on an 11-point scale, ranging from 0 (best) to 10 (worst), with higher scores indicating greater severity. The total daily CSD score is the sum of these 7 item scores (Min=0, Max=70). The Mean Total Daily CSD Score (the sum of these 7 item scores divided by 7) was calculated at Baseline and on Day 3.

3. Change From Baseline in the Leicester Cough Questionnaire (LCQ)-Acute Score on Day 3 [Baseline and Day 3]

   The LCQ-Acute is a 19-item health-related quality-of-life (HRQoL) questionnaire specific for acute cough which contains three domains (i.e., physical, psychological, and social). It is 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-acute assesses symptoms or the impact of symptoms on HRQoL in the last 24 hours using a 7-point Likert scale ranging from 1 to 7. Higher scores indicate better HRQoL. Participants' perception of their cough severity was assessed, based on the LCQ-Acute score, at Baseline and on Day 3.

4. Percentage of Participants Who Experienced One or More Adverse Events (AEs) [Up to 21 days]

   An AE is any untoward medical occurrence in a study participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.

5. Percentage of Participants Who Discontinued Treatment Due to an Adverse Event (AE) [Up to Day 7]

   An AE is any untoward medical occurrence in a study participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• In good general health

• Susceptible to human rhinovirus type 16 (HRV-16)

• Male or non-pregnant and non-breast feeding female

• If female of reproductive potential, agrees to use 1 form of acceptable birth control

Exclusion Criteria:

• Donated blood within 56 days or donated plasma within 7 days prior to dosing

• History of significant multiple and/or severe allergies

• Recent history of respiratory tract infection

• History of cancer

• Body mass index <18 kg/m^{2 or ≥40 kg/m}2

• History of major surgery or loss of 1 unit of blood

• History of allergic reaction to sulfonamides

• Received medications within 14 days prior to randomization

• Significantly abnormal laboratory tests at Screening

• Current smoker, smoked within 5 years of Screening, or significant past smoking history

• History of alcohol or drug abuse

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hvivo Service Limited. Queen Mary BioEnterprises ( Site 0003)	London		United Kingdom	E1 2AX

Sponsors and Collaborators

• Merck Sharp & Dohme LLC

Investigators

• Study Director: Medical Director, Merck Sharp & Dohme LLC

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Oct 13, 2017

More Information

Publications

None provided.

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT03569033
• Other Study ID Numbers: 7264-013; MK-7264-013; 2017-000472-28
• First Posted: Jun 26, 2018
• Last Update Posted: Dec 10, 2019
• Last Verified: Nov 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Additional relevant MeSH terms: Respiratory Tract Infections; Cough

Study Results

Participant Flow

Arm/Group Title	Gefapixant 45 mg BID	Placebo BID
Arm/Group Description	Participants received a gefapixant 45 mg tablet twice daily (BID) for 7 days.	Participants received a matching placebo tablet BID for 7 days.
Period Title: Overall Study
STARTED	23	23
COMPLETED	23	23
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Gefapixant 45 mg BID	Placebo BID	Total
Arm/Group Description	Participants received a gefapixant 45 mg tablet twice daily (BID) for 7 days.	Participants received a matching placebo tablet BID for 7 days.	Total of all reporting groups
Overall Participants	23	23	46
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	24.9 (7.4)	24.3 (5.6)	24.6 (6.5)
Sex: Female, Male (Count of Participants)
Female	4 17.4%	4 17.4%	8 17.4%
Male	19 82.6%	19 82.6%	38 82.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	1 4.3%	1 2.2%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 4.3%	1 4.3%	2 4.3%
White	21 91.3%	21 91.3%	42 91.3%
More than one race	1 4.3%	0 0%	1 2.2%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Awake Coughs Per Hour on Day 3
Description	Awake cough frequency (coughs per hour) was assessed by an objective digital cough-counting device (VitaloJAK™ cough monitor) on Day 3.
Time Frame	Day 3

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of trial intervention and had confirmation of viral shedding at 72 hours post inoculation with human rhinovirus type 16 (HRV-16)

Arm/Group Title	Gefapixant 45 mg BID	Placebo BID
Arm/Group Description	Participants received a gefapixant 45 mg tablet twice daily (BID) for 7 days.	Participants received a matching placebo tablet BID for 7 days.
Measure Participants	23	19
Least Squares Mean (95% Confidence Interval) [Coughs per hour]	2.38	2.70

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gefapixant 45 mg BID, Placebo BID
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.748
	Comments
	Method	Longitudinal Data Analysis
	Comments
Method of Estimation	Estimation Parameter	Difference in Least Squares Means
	Estimated Value	-0.32
	Confidence Interval	(2-Sided) 95%; -2.29 to 1.66
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline in the Cough Severity Visual Analog Scale (VAS) Score on Day 3
Description	The Cough Severity VAS was scored from 0 to 100 using a 100 mm visual analogue scale. Participants were asked to mark on a 100 mm scale between 0 (no cough) and 100 (the worst cough severity). Cough VAS was evaluated at Baseline and on Day 3.
Time Frame	Baseline and Day 3

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of trial intervention and had confirmation of viral shedding at 72 hours post inoculation with HRV-16

Arm/Group Title	Gefapixant 45 mg BID	Placebo BID
Arm/Group Description	Participants received a gefapixant 45 mg tablet twice daily (BID) for 7 days.	Participants received a matching placebo tablet BID for 7 days.
Measure Participants	23	19
Least Squares Mean (95% Confidence Interval) [Scores on a scale]	6.07	5.08

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gefapixant 45 mg BID, Placebo BID
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.754
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in Least Squares Means
	Estimated Value	0.99
	Confidence Interval	(2-Sided) 95%; -5.33 to 7.30
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline in the Mean Total Daily Cough Severity Diary (CSD) Score on Day 3
Description	The Mean Total Daily CSD Score is calculated using the daily CSD instrument, a 7-item, disease-specific, patient-reported outcome measure with a recall period of "today" (the current day). The measure evaluates frequency of cough (3 items); intensity of cough (2 items); and disruption due to cough (2 items). Each of these 7 items is rated on an 11-point scale, ranging from 0 (best) to 10 (worst), with higher scores indicating greater severity. The total daily CSD score is the sum of these 7 item scores (Min=0, Max=70). The Mean Total Daily CSD Score (the sum of these 7 item scores divided by 7) was calculated at Baseline and on Day 3.
Time Frame	Baseline and Day 3

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of trial intervention and had confirmation of viral shedding at 72 hours post inoculation with HRV-16

Arm/Group Title	Gefapixant 45 mg BID	Placebo BID
Arm/Group Description	Participants received a gefapixant 45 mg tablet twice daily (BID) for 7 days.	Participants received a matching placebo tablet BID for 7 days.
Measure Participants	23	19
Least Squares Mean (95% Confidence Interval) [Scores on a scale]	2.71	1.91

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gefapixant 45 mg BID, Placebo BID
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.627
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in Least Squares Means
	Estimated Value	0.80
	Confidence Interval	(2-Sided) 95%; -2.50 to 4.10
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Change From Baseline in the Leicester Cough Questionnaire (LCQ)-Acute Score on Day 3
Description	The LCQ-Acute is a 19-item health-related quality-of-life (HRQoL) questionnaire specific for acute cough which contains three domains (i.e., physical, psychological, and social). It is 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-acute assesses symptoms or the impact of symptoms on HRQoL in the last 24 hours using a 7-point Likert scale ranging from 1 to 7. Higher scores indicate better HRQoL. Participants' perception of their cough severity was assessed, based on the LCQ-Acute score, at Baseline and on Day 3.
Time Frame	Baseline and Day 3

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of trial intervention and had confirmation of viral shedding at 72 hours post inoculation with HRV-16

Arm/Group Title	Gefapixant 45 mg BID	Placebo BID
Arm/Group Description	Participants received a gefapixant 45 mg tablet twice daily (BID) for 7 days.	Participants received a matching placebo tablet BID for 7 days.
Measure Participants	23	19
Least Squares Mean (95% Confidence Interval) [Scores on a scale]	-0.26	-0.35

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gefapixant 45 mg BID, Placebo BID
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.631
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in Least Squares Means
	Estimated Value	0.09
	Confidence Interval	(2-Sided) 95%; -0.28 to 0.45
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Percentage of Participants Who Experienced One or More Adverse Events (AEs)
Description	An AE is any untoward medical occurrence in a study participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.
Time Frame	Up to 21 days

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study treatment

Arm/Group Title	Gefapixant 45 mg BID	Placebo BID
Arm/Group Description	Participants received a gefapixant 45 mg tablet twice daily (BID) for 7 days.	Participants received a matching placebo tablet BID for 7 days.
Measure Participants	23	23
Number [Percentage of participants]	100 434.8%	95.7 416.1%

6. Secondary Outcome

Title	Percentage of Participants Who Discontinued Treatment Due to an Adverse Event (AE)
Description	An AE is any untoward medical occurrence in a study participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.
Time Frame	Up to Day 7

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study treatment

Arm/Group Title	Gefapixant 45 mg BID	Placebo BID
Arm/Group Description	Participants received a gefapixant 45 mg tablet twice daily (BID) for 7 days.	Participants received a matching placebo tablet BID for 7 days.
Measure Participants	23	23
Number [Percentage of participants]	0.0 0%	0.0 0%

Adverse Events

Time Frame	Up to 21 days
Adverse Event Reporting Description	All randomized participants who received at least 1 dose of study treatment
Arm/Group Title	MK-7264 45 mg BID		Placebo
Arm/Group Description	Participants received a gefapixant 45 mg tablet BID for 7 days.		Participants received a matching placebo tablet BID for 7 days.
All Cause Mortality
	MK-7264 45 mg BID		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/23 (0%)		0/23 (0%)
Serious Adverse Events
	MK-7264 45 mg BID		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/23 (0%)		0/23 (0%)
Other (Not Including Serious) Adverse Events
	MK-7264 45 mg BID		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	23/23 (100%)		22/23 (95.7%)
Gastrointestinal disorders
Diarrhoea	0/23 (0%)	0	2/23 (8.7%)	2
Nausea	3/23 (13%)	4	0/23 (0%)	0
Salivary hypersecretion	2/23 (8.7%)	2	0/23 (0%)	0
General disorders
Medical device site erythema	16/23 (69.6%)	16	17/23 (73.9%)	17
Infections and infestations
Upper respiratory tract infection	20/23 (87%)	20	21/23 (91.3%)	22
Injury, poisoning and procedural complications
Post procedural haemorrhage	0/23 (0%)	0	2/23 (8.7%)	2
Metabolism and nutrition disorders
Decreased appetite	2/23 (8.7%)	2	1/23 (4.3%)	1
Nervous system disorders
Dysgeusia	2/23 (8.7%)	10	0/23 (0%)	0
Hypogeusia	3/23 (13%)	5	0/23 (0%)	0
Respiratory, thoracic and mediastinal disorders
Dyspnoea	2/23 (8.7%)	3	0/23 (0%)	0

Limitations/Caveats

This study was terminated because the data did not support study endpoints for acute cough, based on an interim efficacy analysis; not due to safety concerns.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The sponsor will generally support publication of multicenter studies only in their entirety and not as individual site data. In this case, a coordinating investigator will be designated by mutual agreement. If publication activity is not directed by the sponsor, the investigator agrees to submit all manuscripts or abstracts to the sponsor before submission. This allows the sponsor to protect proprietary information and to provide comments.