Acute Cough
Conditions
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).
Interventions
DRUGGefapixant
Gefapixant 45 mg will be administered orally.
DRUGPlacebo
Placebo tablet matching gefapixant will be administered orally.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Gefapixant 45 mg BID Participants received a gefapixant 45 mg tablet twice daily (BID) for 7 days. | 23 |
| Placebo BID Participants received a matching placebo tablet BID for 7 days. | 23 |
| Total | 46 |
Baseline characteristics
| Characteristic | Placebo BID | Total | Gefapixant 45 mg BID |
|---|---|---|---|
| Age, Continuous | 24.3 Years STANDARD_DEVIATION 5.6 | 24.6 Years STANDARD_DEVIATION 6.5 | 24.9 Years STANDARD_DEVIATION 7.4 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 21 Participants | 42 Participants | 21 Participants |
| Sex: Female, Male Female | 4 Participants | 8 Participants | 4 Participants |
| Sex: Female, Male Male | 19 Participants | 38 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 23 | 0 / 23 |
| other Total, other adverse events | 23 / 23 | 22 / 23 |
| serious Total, serious adverse events | 0 / 23 | 0 / 23 |
Outcome results
Primary
Awake Coughs Per Hour on Day 3
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
Population: 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 | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Gefapixant 45 mg BID | Awake Coughs Per Hour on Day 3 | 2.38 Coughs per hour |
| Placebo BID | Awake Coughs Per Hour on Day 3 | 2.70 Coughs per hour |
p-value: 0.74895% CI: [-2.29, 1.66]Longitudinal Data Analysis
Secondary
Change From Baseline in the Cough Severity Visual Analog Scale (VAS) Score on 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.
Time frame: Baseline and Day 3
Population: 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 | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Gefapixant 45 mg BID | Change From Baseline in the Cough Severity Visual Analog Scale (VAS) Score on Day 3 | 6.07 Scores on a scale |
| Placebo BID | Change From Baseline in the Cough Severity Visual Analog Scale (VAS) Score on Day 3 | 5.08 Scores on a scale |
p-value: 0.75495% CI: [-5.33, 7.3]ANCOVA
Secondary
Change From Baseline in the Leicester Cough Questionnaire (LCQ)-Acute Score on 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.
Time frame: Baseline and Day 3
Population: 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 | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Gefapixant 45 mg BID | Change From Baseline in the Leicester Cough Questionnaire (LCQ)-Acute Score on Day 3 | -0.26 Scores on a scale |
| Placebo BID | Change From Baseline in the Leicester Cough Questionnaire (LCQ)-Acute Score on Day 3 | -0.35 Scores on a scale |
p-value: 0.63195% CI: [-0.28, 0.45]ANCOVA
Secondary
Change From Baseline in the Mean Total Daily Cough Severity Diary (CSD) Score on 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.
Time frame: Baseline and Day 3
Population: 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 | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Gefapixant 45 mg BID | Change From Baseline in the Mean Total Daily Cough Severity Diary (CSD) Score on Day 3 | 2.71 Scores on a scale |
| Placebo BID | Change From Baseline in the Mean Total Daily Cough Severity Diary (CSD) Score on Day 3 | 1.91 Scores on a scale |
p-value: 0.62795% CI: [-2.5, 4.1]ANCOVA
Secondary
Percentage of Participants Who Discontinued Treatment Due to an Adverse Event (AE)
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
Population: All randomized participants who received at least 1 dose of study treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Gefapixant 45 mg BID | Percentage of Participants Who Discontinued Treatment Due to an Adverse Event (AE) | 0.0 Percentage of participants |
| Placebo BID | Percentage of Participants Who Discontinued Treatment Due to an Adverse Event (AE) | 0.0 Percentage of participants |
Secondary
Percentage of Participants Who Experienced One or More Adverse Events (AEs)
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
Population: All randomized participants who received at least 1 dose of study treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Gefapixant 45 mg BID | Percentage of Participants Who Experienced One or More Adverse Events (AEs) | 100 Percentage of participants |
| Placebo BID | Percentage of Participants Who Experienced One or More Adverse Events (AEs) | 95.7 Percentage of participants |