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Gefapixant

Phase 3

Chronic Cough | Small molecule | Other |Merck & Company, Inc.|Last Updated: Nov 5, 2024

Success Probability
Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
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Market & Valuation
rNPV $3.2B
Market Size $9.4B
Revenue Basis $1.6B
Competitors 6
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Trial Design
RandomizedDouble-BlindPLACEBO_CONTROLLEDDMCBiomarker
Total Trials7
Total Enrollment3,066
FDA Designations
No designations recorded
Clinical Trials (7)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT04193202Efficacy and Safety of Gefapixant (MK-7264) in Adult Participants With Recent Onset Chronic Cough (MK-7264-043)PHASE3 COMPLETED 419May 21, 2020Nov 3, 2021May 16, 202391 United States, Canada +10
NCT04193176Efficacy and Safety of Gefapixant (MK-7264) in Women With Chronic Cough and Stress Urinary Incontinence (MK-7264-042)PHASE3 COMPLETED 376May 10, 2020Sep 2, 2022Nov 5, 202490 United States, Argentina +10
NCT03696108A Study of Gefapixant (MK-7264) in Japanese Adult Participants With Refractory or Unexplained Chronic Cough (MK-7264-038)PHASE3 COMPLETED 175Oct 31, 2018Oct 7, 2020Nov 1, 202161 Japan
NCT03449147A Study of Gefapixant (MK-7264) in Adult Participants With Chronic Cough (MK-7264-030)PHASE3 COMPLETED 1,317Mar 15, 2018Oct 30, 2020Sep 2, 2021171 United States, Australia +18
NCT03449134A Study of Gefapixant (MK-7264) in Adult Participants With Chronic Cough (MK-7264-027)PHASE3 COMPLETED 732Mar 14, 2018Aug 17, 2020Jun 16, 2021156 United States, Argentina +15
NCT03482713Study of Gefapixant (MK-7264) in Adult Japanese Participants With Unexplained or Refractory Chronic Cough (MK-7264-033)PHASE2 COMPLETED 23Mar 16, 2018Jun 7, 2018Oct 17, 201916 Japan
NCT01432730A Study to Assess the Efficacy of Gefapixant (MK-7264/AF-219), in Participants With Chronic Cough (MK-7264-006)PHASE2 COMPLETED 24Sep 22, 2011Feb 21, 2013Nov 24, 2020 -
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Study Endpoints
Primary Endpoints
Change From Baseline in the Leicester Cough Questionnaire (LCQ) Total Score at Week 12
Baseline, Week 12

Participants will be asked to complete the LCQ to assess the impact of their cough severity on health related quality of life (HRQoL) over the past 2 weeks. The LCQ is a 19-item, cough-specific HRQoL questionnaire. Each item on the LCQ assesses symptoms using a 7-point scale ranging from 1 to 7. The LCQ contains three domains on physical, psychological, and social functioning, and each domain score is calculated as the mean score of the items (range: 1 to 7) within the domain. The LCQ total score is the sum of the 3 domains, with a range from 3 (lowest total score) to 21 (highest total score). Higher scores indicate better HRQoL. The change from baseline in LCQ total score is calculated.

Percent Change From Baseline in Average Daily Cough-induced Stress Urinary Incontinence (SUI) Episodes at Week 12
Baseline and week 12

Cough-induced SUI episodes were assessed using an event-driven electronic Incontinence Diary where the participant recorded the main cause of each urinary incontinence episode as coughing, another stress reason, or other cause. Episodes of incontinence were recorded for the week before baseline and treatment visit. Average daily cough induced SUI episodes were calculated as (sum of daily cough-induced SUI episodes in a week)/number of days recorded. The percent change from baseline in the average daily cough-induced SUI episodes to Week 12 are presented.

Number of Participants Who Experienced at Least One Adverse Event (AE)
Up to 54 Weeks

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.

Number of Participants Who Discontinued Study Drug Due to an AE
Up to 52 Weeks

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.

Model-Based Geometric Mean Ratio (GMR) of 24-Hour Coughs Per Hour at Week 24/Baseline
Baseline, Week 24

24-hour coughs per hour was defined as the average hourly cough frequency based on 24-hour sound recordings using a digital recording device (cough monitor). A longitudinal analysis of covariance (ANCOVA) model was applied to log-transformed cough data to determine geometric mean (GM) 24-hour coughs per hour at baseline and week 24. The GMR (Week 24 GM 24-hour coughs per hour divided by Baseline GM 24-hour coughs per hour) is reported.

Number of Participants Who Experienced At Least One Adverse Event (AE) During Treatment and Follow-up
Up to 54 Weeks

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.

Number of Participants Who Discontinued a Study Drug Due to an AE
Up to 52 weeks

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.

Model-Based Geometric Mean Ratio (GMR) of 24-hour Objective Coughs Per Hour (Week 12/Baseline)
Baseline, Week 12

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.

Number of Participants Experiencing At Least One Adverse Event (AE) During Treatment and Follow-up
Up to approximately 54 weeks

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.

Number of Participants Who Discontinued Treatment Due to AEs
Up to approximately 52 weeks

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.

Number of Participants Who Experienced an Adverse Event
Up to 6 weeks

An adverse event is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment.

Number of Participants Who Discontinued Study Treatment Due to an Adverse Event
Up to 4 weeks

An adverse event is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment.

Change From Baseline in Daytime Objective Cough Frequency
Baseline (Day 0) and Day 14 of each study period

Daytime Objective Cough Frequency (per hour) is the total number of cough events during the monitoring period (in general, 24-hr interval) the participant is awake divided by the total duration (in hours) for the monitoring period the participants is awake. 24-hour sound recordings were collected using a digital recording device. Change from baseline in awake cough frequency = (post-treatment awake cough frequency - baseline awake cough frequency). A negative result indicates a decrease in cough frequency, while a positive result indicates an increase in cough frequency.

Secondary Endpoints
Change From Baseline in the Cough Severity Visual Analog Scale (VAS) Score at Week 12
Baseline, Week 12
Percentage of Participants With One or More Adverse Events (AEs)
Up to approximately 14 weeks
Percentage of Participants Who Discontinue Study Drug Due to an AE
Up to approximately 12 weeks
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Study Design & Arms
AllocationRANDOMIZED
MaskingQUADRUPLE
ModelPARALLEL
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
GefapixantEXPERIMENTALParticipants will receive gefapixant at a dose of 45 mg administered as an oral tablet twice daily for 12 weeks.
PlaceboPLACEBO_COMPARATORParticipants will receive placebo matching gefapixant, administered as an oral tablet twice daily for 12 weeks.
Gefapixant 15 mg BIDEXPERIMENTALParticipants will receive gefapixant 15 mg tablet and placebo tablet to match gefapixant 45 mg twice daily (BID) during the study period (52 weeks).
Gefapixant 45 mg BIDEXPERIMENTALParticipants will receive gefapixant 45 mg tablet and placebo tablet to match gefapixant 15 mg BID during the study period (52 weeks).
Gefapixant 45 mgEXPERIMENTALParticipants will receive a gefapixant 45 mg film-coated tablet BID for 28 days.
Gefapixant 600 mg>PlaceboEXPERIMENTALGefapixant, 600 mg, twice daily (BID), taken orally for 2 weeks followed by a 2-week washout period and then placebo to gefapixant, BID, taken orally for 2 weeks.
Placebo>Gefapixant 600 mgEXPERIMENTALPlacebo to gefapixant BID, taken orally for 2 weeks followed by a 2-week washout period and then gefapixant, 600 mg, BID, taken orally for 2 weeks.
Interventions
NameTypeDescription
GefapixantDRUGAdministered twice daily as an oral tablet of 45 mg
PlaceboDRUGAdministered twice daily as a placebo oral tablet matching gefapixant
Gefapixant 15 mg BIDDRUGGefapixant 15 mg tablet administered orally BID
Gefapixant 45 mg BIDDRUGGefapixant 45 mg tablet administered orally BID
Gefapixant 45 mgDRUGGefapixant 45 mg (film-coated tablet) to be administered orally BID
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Eligibility Criteria
Age Range18 Years — N/A
SexALL
Healthy VolunteersNo
Study Sites91

Inclusion Criteria: * Chest radiograph or CT thorax (within 1 year 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 pr...

Countries:United StatesCanadaColombiaGermanyGuatemalaPeruPolandRussiaSouth KoreaSpainUkraineUnited KingdomArgentinaIsraelJapanAustraliaChinaCzechiaDenmarkHungaryItalyMalaysiaNew ZealandSouth AfricaTurkey (Türkiye)FranceTaiwan
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