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Phase 2 N=50 Randomized Quadruple-blind Treatment

Effect of Gefapixant (AF-219/MK-7264) on Cough Reflex Sensitivity (MK-7264-015)

Refractory Chronic Cough

Enrolled (actual)
50
Serious AEs
0.0%
Results posted
Feb 2021
Primary outcome: Primary: Cough Reflex Sensitivity to Capsaicin Measured by Maximal Cough Response (Emax) — 4.14; 4.14; 7.57; 3.66 Emax (Explosive coughs/15 sec) — p=< 0.0001

Study Design & Population

Study type
Interventional
Phase
Phase 2
Interventions
Gefapixant (Drug); Placebo (Drug)
Age
Adult, Older Adult · 18+ yrs
Sex
All
Sponsor
Afferent Pharmaceuticals, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
Primary completion
Apr 2016

Outcome Measures

OutcomeResultp-value
PRIMARY
Cough Reflex Sensitivity to Capsaicin Measured by Maximal Cough Response (Emax)
4.14; 4.14; 7.57; 3.66; 3.37; 6.17 < 0.0001 sig
PRIMARY
Cough Reflex Sensitivity to Capsaicin Measured by the Tussive Concentration Required to Achieve 50% of Emax (ED50)
33; 33; 9.56; 33; 33; 9.56 < 0.0001 sig
SECONDARY
Cough Reflex Sensitivity to Adenosine Triphosphate (ATP) Measured by Maximal Cough Response (Emax)
2.35; 2.35; 5.4; 2.35; 2.35; 5.4
SECONDARY
Cough Reflex Sensitivity to ATP Measured by the Tussive Concentration Required to Achieve 50% of Emax (ED50)
54.9; 54.9; 8.63; 119.13; 155.92; 24.51
SECONDARY
Concentrations of Capsaicin Inducing 2 or More Coughs (C2)
31.25; 31.25; 3.90; 7.81; 15.62; 23.44
SECONDARY
Concentrations of Capsaicin Inducing 5 or More Coughs (C5)
31.25; 62.50; 3.90; 11.72; 250.00; 125.00
SECONDARY
Concentrations of ATP Inducing 2 or More Coughs (C2)
192.00; 64.00; 8.00; 1.00; 16.00; 24.00
SECONDARY
Concentrations of ATP Inducing 5 or More Coughs (C5)
192.00; 128.00; 8.00; 16.50; 64.00; 32.00
SECONDARY
Urge-to-Cough in Response to Capsaicin Challenge (Chronic Cough Participants Only)
28.9; 38.6; 36.6; 20.5; 28.2; 46.7
SECONDARY
Urge-to-Cough in Response to ATP Challenge (Chronic Cough Participants Only)
19.8; 34.4; 21.5; 25.3; 21.6; 39.8
SECONDARY
Cough Severity in Response to Capsaicin Challenge (Chronic Cough Participants Only)
28.2; 35.7; 30.9; 20.5; 25.8; 44.3
SECONDARY
Cough Severity in Response to ATP Challenge (Chronic Cough Participants Only)
21.5; 32.7; 21.2; 23.5; 18.9; 36.8
SECONDARY
Daytime Cough Frequency in Participants With Chronic Cough Who Underwent Capsaicin Challenge
13.7; 19.1; 15.5; 20.3
SECONDARY
Daytime Cough Frequency in Participants With Chronic Cough Who Underwent ATP Challenge
10.3; 22.3; 15.6; 26.4
SECONDARY
Percentage of Participants Who Experienced at Least One Adverse Event
100.0; 35.7; 100.0; 58.3; 75.0; 33.3
SECONDARY
Percentage of Participants Who Discontinued Study Treatment Due to an Adverse Event
0.0; 0.0; 0.0; 0.0; 0.0; 0.0

Summary

The primary objective of this double-blind crossover study is to assess the effect of single doses of 50 mg and 300 mg gefapixant (AF-219/MK-7264) on cough reflex sensitivity to capsaicin in both healthy participants and participants with chronic cough. This study will also assess the effect of single doses of gefapixant on cough reflex sensitivity to adenosine triphosphate (ATP) in healthy participants and participants with chronic cough.

Eligibility Criteria

Inclusion Criteria

  • Have provided written informed voluntary consent;
  • Be able to speak, read, and understand English;
  • Be males or females, of any race, between 18 and 80 years of age, inclusive;
  • Have a body mass index (BMI) ≥18 and 20 pack-year smoking history(chronic cough subjects), or >10 pack-year smoking history (healthy subjects);
  • History of upper respiratory tract infection or recent significant change in pulmonary status within 4 weeks prior to Screening or prior to randomization;
  • History of concurrent malignancy or recurrence of malignancy within 2 years prior to Screening (with the exception of < 3 excised basal cell carcinomas);
  • History of a diagnosis of drug or alcohol dependency or abuse within the last 3 years;
  • In the opinion of the Principal Investigator, an uncontrolled or unstable clinically significant neurological, psychiatric, respiratory, cardiovascular, peripheral vascular, gastrointestinal, hepatic, pancreatic, endocrinological, hematological, or immunological disorder or an active infection;
  • Clinically significant abnormal electrocardiogram (ECG) at Screening
  • Significantly abnormal laboratory tests at Screening
  • Breastfeeding;
  • In the judgement of the Principal Investigator, other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with trial participation or investigational product administration or may interfere with the interpretation of trial results and would make the subject inappropriate for entry into this trial.
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT02397460). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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