Refractory Chronic CoughPhase 2NCT02612610

A 12-Week Study in Participants With Refractory Chronic Cough (MK-7264-012)

A Phase 2 study testing Gefapixant in people with Refractory Chronic Cough, run by Afferent Pharmaceuticals, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA).

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 80 years
Conditions the study is for: Refractory Chronic Cough
What is being tested?: Gefapixant
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 253 participants
Where: No sites listed yet
Study dates: 15 Dec 2015to 4 Nov 2016
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 80 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Women and Men between 18 and 80 years of age inclusive
Have refractory chronic cough
Women of child-bearing potential must use 2 forms of acceptable birth control - Have provided written informed consent.
Are willing and able to comply with all aspects of the protocol

Who cannot join

Current smoker
Forced Expiratory Volume in 1 second (FEV1)/Forced Vital Capacity (FVC) ratio <60%
History of upper or lower respiratory tract infection or recent significant change in pulmonary status within 4 weeks of the Baseline Visit
History of opioid use within 1 week of the Baseline Visit
Body mass index (BMI) <18 kg/m^2 or ≥ 40 kg/m^2
History of concurrent malignancy or recurrence of malignancy within 2 years prior to Screening (not including subjects with <3 excised basal cell carcinomas)

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Screening systolic blood pressure (SBP) >160 mm Hg or a diastolic blood pressure (DBP) >90 mm Hg
Clinically significant abnormal electrocardiogram (ECG) at Screening
Significantly abnormal laboratory tests at Screening
Pregnant or Breastfeeding
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, in the judgment of the Investigator or Sponsor, would make the participant inappropriate for entry into this trial

About this study

Official title: A 12-Week Study to Assess the Efficacy and Safety of AF 219 in Subjects With Refractory Chronic Cough

This study is designed to evaluate the efficacy of three dose regimens of gefapixant ([MK-7264] 7.5 mg, 20 mg, and 50 mg) relative to placebo in reducing awake objective cough frequency. The primary hypothesis for this trial is that at least one dose regimen of gefapixant is superior to placebo with respect to the mean change from baseline in awake cough frequency (on the log scale).

Conditions: Refractory Chronic Cough
Being tested: Gefapixant, Placebo (for gefapixant)
Medical subject headings: Chronic Cough

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

GefapixantDrug
Also called AF-219, MK-7264
Gefapixant administered as one 7.5 mg, 20 mg, or 50 mg tablet twice daily, depending upon randomization.
Placebo (for gefapixant)Drug
Also called Dose-matched placebo tablet to gefapixant administered twice daily.

Study groups in NCT02612610
Study group	Role	What they receive
Placebo	Placebo comparator	Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks. Receives: Drug: Placebo (for gefapixant)
Gefapixant 7.5 mg	Experimental	Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks. Receives: Drug: Gefapixant
Gefapixant 20 mg	Experimental	Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks. Receives: Drug: Gefapixant
Gefapixant 50 mg	Experimental	Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks. Receives: Drug: Gefapixant

What is being measured

The primary outcome is the main question the study is designed to answer.

Change From Baseline in Awake Objective Cough Frequency After 12 Weeks of Treatment (Day 84)
Awake Objective Cough Frequency (per hour) was defined as the total number of cough events during the monitoring period (in general, 24-hr interval) while the participant was awake divided by the total duration (in hours) for the monitoring period that the participant was awake. 24 hour sound recordings were made at Baseline (Study Day -1) and at Week 12 (Day 84) using a digital recording device. An independent cough monitoring center documented the time of each cough event over the 24 hour period, as well as the time when the participant went to sleep and the time the participant woke. Least-squares (LS) mean change from baseline (in log scale) with associated standard error (SE) reported for each treatment group. Change from Baseline in Awake Objective Cough Frequency = (Post-Treatment Awake Cough Frequency minus Baseline Awake Cough Frequency).
Measured: Baseline Visit (Day -1), Day 84

Secondary outcomes (58)

Change From Baseline in 24-Hour Objective Cough Frequency After 4 Weeks of Treatment (Day 28)
24-hr Objective Cough Frequency was defined as the total number of cough events during the monitoring period divided by the total duration in hours for the monitoring period (generally 24 hours). 24 hour sound recordings were made at Baseline (Study Day -1) and at Week 4 (Day 28) using a digital recording device. An independent cough monitoring center documented the time of each cough event over the 24 hour period, as well as the time when the participant went to sleep and the time the participant woke. LS mean change from baseline (in log scale) with associated SE reported for each treatment group. Change from Baseline in 24-Hour Objective Cough Frequency = (Post-Treatment 24-Hour Cough Frequency minus Baseline 24-Hour Cough Frequency).
Measured: Baseline (Study Day -1), Day 28
Change From Baseline in 24-Hour Objective Cough Frequency After 8 Weeks of Treatment (Day 56)
24-hr Objective Cough Frequency was defined as the total number of cough events during the monitoring period divided by the total duration in hours for the monitoring period (generally 24 hours). 24 hour sound recordings were made at Baseline (Study Day -1) and at Week 8 (Day 56) using a digital recording device. An independent cough monitoring center documented the time of each cough event over the 24 hour period, as well as the time when the participant went to sleep and the time the participant woke. LS mean change from baseline (in log scale) with associated SE reported for each treatment group. Change from Baseline in 24-Hour Objective Cough Frequency = (Post-Treatment 24-Hour Cough Frequency minus Baseline 24-Hour Cough Frequency).
Measured: Baseline (Study Day -1), Day 56
Change From Baseline in 24-Hour Objective Cough Frequency After 12 Weeks of Treatment (Day 84)
24-hr Objective Cough Frequency was defined as the total number of cough events during the monitoring period divided by the total duration in hours for the monitoring period (generally 24 hours). 24 hour sound recordings were made at Baseline (Study Day -1) and at Week 12 (Day 84) using a digital recording device. An independent cough monitoring center documented the time of each cough event over the 24 hour period, as well as the time when the participant went to sleep and the time the participant woke. LS mean change from baseline (in log scale) with associated SE reported for each treatment group. Change from Baseline in 24-Hour Objective Cough Frequency = (Post-Treatment 24-Hour Cough Frequency minus Baseline 24-Hour Cough Frequency).
Measured: Baseline (Study Day -1), Day 84
Change From Baseline in Awake Objective Cough Frequency After 4 Weeks of Treatment (Day 28)
Awake Objective Cough Frequency (per hour) was defined as the total number of cough events during the monitoring period (in general, 24-hr interval) while the participant was awake divided by the total duration (in hours) for the monitoring period that the participant was awake. 24 hour sound recordings were made at Baseline (Study Day -1) and at Week 4 (Day 28) using a digital recording device. An independent cough monitoring center documented the time of each cough event over the 24 hour period, as well as the time when the participant went to sleep and the time the participant woke. LS mean change from baseline (in log scale) with associated SE reported for each treatment group. Change from Baseline in Awake Objective Cough Frequency = (Post-Treatment Awake Cough Frequency minus Baseline Awake Cough Frequency).
Measured: Baseline (Study Day -1), Day 28,
Change From Baseline in Awake Objective Cough Frequency After 8 Weeks of Treatment (Day 56)
Awake Objective Cough Frequency (per hour) was defined as the total number of cough events during the monitoring period (in general, 24-hr interval) while the participant was awake divided by the total duration (in hours) for the monitoring period that the participant was awake. 24 hour sound recordings were made at Baseline (Study Day -1) and at Week 8 (Day 56) using a digital recording device. An independent cough monitoring center documented the time of each cough event over the 24 hour period, as well as the time when the participant went to sleep and the time the participant woke. LS mean change from baseline (in log scale) with associated SE reported for each treatment group. Change from Baseline in Awake Objective Cough Frequency = (Post-Treatment Awake Cough Frequency minus Baseline Awake Cough Frequency).
Measured: Baseline (Study Day -1), Day 56
Change From Baseline in Awake Objective Cough Frequency at the Follow-up Visit (Day 98)
Awake Objective Cough Frequency (per hour) was defined as the total number of cough events during the monitoring period (in general, 24-hr interval) while the participant was awake divided by the total duration (in hours) for the monitoring period that the participant was awake. 24 hour sound recordings were made at Baseline (Study Day -1) and at the Follow-up visit (Day 98) using a digital recording device. An independent cough monitoring center documented the time of each cough event over the 24 hour period, as well as the time when the participant went to sleep and the time the participant woke. Change from Baseline in Awake Objective Cough Frequency = (Post-Treatment Awake Cough Frequency minus Baseline Awake Cough Frequency).
Measured: Baseline (Study Day -1), Day 98
Change From Baseline in Cough Severity Visual Analogue Scale (VAS) After 4 Weeks of Treatment (Day 28)
Cough 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 (Study Day -1) and at Week 4 (Day 28). Baseline cough VAS was defined as the cough VAS at Baseline (Study Day -1). LS mean change from baseline with associated SE reported for each treatment group.
Measured: Baseline (Study Day -1), Day 28
Change From Baseline in Cough Severity VAS After 8 Weeks of Treatment (Day 56)
Cough 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 (Study Day -1) and at Week 8 (Day 56). Baseline cough VAS was defined as the cough VAS at Baseline (Study Day -1). LS mean change from baseline with associated SE reported for each treatment group.
Measured: Baseline (Study Day -1), Day 56
Change From Baseline in Cough Severity VAS After 12 Weeks of Treatment (Day 84)
Cough 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 (Study Day -1) and at Week 12 (Day 84). Baseline cough VAS was defined as the cough VAS at Baseline (Study Day -1). LS mean change from baseline with associated SE reported for each treatment group.
Measured: Baseline (Study Day -1), Day 84
Change From Baseline in Cough Severity VAS At Day 85/Early Termination
Cough 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 (Study Day -1) and at Day 85/Early Termination. Baseline cough VAS was defined as the cough VAS at Baseline (Study Day -1). LS mean change from baseline with associated SE reported for each treatment group.
Measured: Baseline (Study Day -1), Day 85
Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in Awake Objective Cough Frequency After 4 Weeks of Treatment (Day 28)
Awake Objective Cough Frequency (per hour) was defined as the total number of cough events during the monitoring period (in general, 24-hr interval) while the participant was awake divided by the total duration (in hours) for the monitoring period that the participant was awake. 24 hour sound recordings were made at Baseline (Study Day -1) and at Week 4 (Day 28) using a digital recording device. An independent cough monitoring center documented the time of each cough event over the 24 hour period, as well as the time when the participant went to sleep and the time the participant woke. The percentage of participants that met responder criteria for ≥70%, ≥50%, and ≥30% change (reduction) from baseline levels in Awake Objective Cough Frequency were reported for each treatment group at Day 28.
Measured: Baseline (Study Day -1), Day 28
Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in Awake Objective Cough Frequency After 8 Weeks of Treatment (Day 56)
Awake Objective Cough Frequency (per hour) was defined as the total number of cough events during the monitoring period (in general, 24-hr interval) while the participant was awake divided by the total duration (in hours) for the monitoring period that the participant was awake. 24 hour sound recordings were made at Baseline (Study Day -1) and at Week 8 (Day 56) using a digital recording device. An independent cough monitoring center documented the time of each cough event over the 24 hour period, as well as the time when the participant went to sleep and the time the participant woke. The percentage of participants that met responder criteria for ≥70%, ≥50%, and ≥30% change (reduction) from baseline levels in Awake Objective Cough Frequency were reported for each treatment group at Day 56.
Measured: Baseline (Study Day -1), Day 56
Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in Awake Objective Cough Frequency After 12 Weeks of Treatment (Day 84)
Awake Objective Cough Frequency (per hour) was defined as the total number of cough events during the monitoring period (in general, 24-hr interval) while the participant was awake divided by the total duration (in hours) for the monitoring period that the participant was awake. 24 hour sound recordings were made at Baseline (Study Day -1) and at Week 12 (Day 84) using a digital recording device. An independent cough monitoring center documented the time of each cough event over the 24 hour period, as well as the time when the participant went to sleep and the time the participant woke. The percentage of participants that met responder criteria for ≥70%, ≥50%, and ≥30% change (reduction) from baseline levels in Awake Objective Cough Frequency were reported for each treatment group at Day 84.
Measured: Baseline (Study Day -1), Day 84
Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in Awake Objective Cough Frequency at the Follow-up Visit (Day 98)
Awake Objective Cough Frequency (per hour) was defined as the total number of cough events during the monitoring period (in general, 24-hr interval) while the participant was awake divided by the total duration (in hours) for the monitoring period that the participant was awake. 24 hour sound recordings were made at Baseline (Study Day -1) and at the Follow-up visit (Day 98) using a digital recording device. An independent cough monitoring center documented the time of each cough event over the 24 hour period, as well as the time when the participant went to sleep and the time the participant woke. The percentage of participants that met responder criteria for ≥70%, ≥50%, and ≥30% change (reduction) from baseline levels in Awake Objective Cough Frequency were reported for each treatment group at Day 98.
Measured: Baseline (Study Day -1), Day 98
Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in 24-Hour Objective Cough Frequency After 4 Weeks of Treatment (Day 28)
24-hr Objective Cough Frequency was defined as the total number of cough events during the monitoring period divided by the total duration in hours for the monitoring period (generally 24 hours). 24 hour sound recordings were made at Baseline (Study Day -1) and at Week 4 (Day 28) using a digital recording device. An independent cough monitoring center documented the time of each cough event over the 24 hour period, as well as the time when the participant went to sleep and the time the participant woke. The percentage of participants that met responder criteria for ≥70%, ≥50%, and ≥30% change (reduction) from baseline levels in 24-hr Objective Cough Frequency were reported for each treatment group at Day 28.
Measured: Baseline (Study Day -1), Day 28
Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in 24-Hour Objective Cough Frequency After 8 Weeks of Treatment (Day 56)
24-hr Objective Cough Frequency was defined as the total number of cough events during the monitoring period divided by the total duration in hours for the monitoring period (generally 24 hours). 24 hour sound recordings were made at Baseline (Study Day -1) and at Week 8 (Day 56) using a digital recording device. An independent cough monitoring center documented the time of each cough event over the 24 hour period, as well as the time when the participant went to sleep and the time the participant woke. The percentage of participants that met responder criteria for ≥70%, ≥50%, and ≥30% change (reduction) from baseline levels in 24-hr Objective Cough Frequency were reported for each treatment group at Day 56.
Measured: Baseline (Study Day -1), Day 56
Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in 24-Hour Objective Cough Frequency After 12 Weeks of Treatment (Day 84)
24-hr Objective Cough Frequency was defined as the total number of cough events during the monitoring period divided by the total duration in hours for the monitoring period (generally 24 hours). 24 hour sound recordings were made at Baseline (Study Day -1) and at Week 12 (Day 84) using a digital recording device. An independent cough monitoring center documented the time of each cough event over the 24 hour period, as well as the time when the participant went to sleep and the time the participant woke. The percentage of participants that met responder criteria for ≥70%, ≥50%, and ≥30% change (reduction) from baseline levels in 24-hr Objective Cough Frequency were reported for each treatment group at Day 84.
Measured: Baseline (Study Day -1), Day 84
Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in 24-Hour Objective Cough Frequency at the Follow-up Visit (Day 98)
24-hr Objective Cough Frequency was defined as the total number of cough events during the monitoring period divided by the total duration in hours for the monitoring period (generally 24 hours). 24 hour sound recordings were made at Baseline (Study Day -1) and at Week 14 (Day 98) using a digital recording device. An independent cough monitoring center documented the time of each cough event over the 24 hour period, as well as the time when the participant went to sleep and the time the participant woke. The percentage of participants that met responder criteria for ≥70%, ≥50%, and ≥30% change (reduction) from baseline levels in 24-hr Objective Cough Frequency were reported for each treatment group at Day 98.
Measured: Baseline (Study Day -1), Day 98
Change From Baseline in Sleep Objective Cough Frequency After 4 Weeks of Treatment (Day 28)
Sleep Objective Cough Frequency was defined as the total number of cough events during the monitoring period while the participant was asleep divided by the total duration in hours for the monitoring period that the participant was asleep. 24 hour sound recordings were made at Baseline (Study Day -1) and at Week 4 (Day 28) using a digital recording device. An independent cough monitoring center documented the time of each cough event over the 24 hour period, as well as the time when the participant went to sleep and the time the participant woke. LS mean change from baseline (in log scale) with associated SE reported for each treatment group. Change from Baseline in Sleep Objective Cough Frequency = (Post-Treatment Objective Sleep Cough Frequency minus Baseline Sleep Cough Frequency).
Measured: Baseline (Study Day -1), Day 28
Change From Baseline in Sleep Objective Cough Frequency After 8 Weeks of Treatment (Day 56)
Sleep Objective Cough Frequency was defined as the total number of cough events during the monitoring period while the participant was asleep divided by the total duration in hours for the monitoring period that the participant was asleep. 24 hour sound recordings were made at Baseline (Study Day -1) and at Week 8 (Day 56) using a digital recording device. An independent cough monitoring center documented the time of each cough event over the 24 hour period, as well as the time when the participant went to sleep and the time the participant woke. LS mean change from baseline (in log scale) with associated SE reported for each treatment group. Change from Baseline in Sleep Objective Cough Frequency = (Post-Treatment Objective Sleep Cough Frequency minus Baseline Sleep Cough Frequency).
Measured: Baseline (Study Day -1), Day 56
Change From Baseline in Sleep Objective Cough Frequency After 12 Weeks of Treatment (Day 84)
Sleep Objective Cough Frequency was defined as the total number of cough events during the monitoring period while the participant was asleep divided by the total duration in hours for the monitoring period that the participant was asleep. 24 hour sound recordings were made at Baseline (Study Day -1) and at Week 12 (Day 84) using a digital recording device. An independent cough monitoring center documented the time of each cough event over the 24 hour period, as well as the time when the participant went to sleep and the time the participant woke. LS mean change from baseline (in log scale) with associated SE reported for each treatment group. Change from Baseline in Sleep Objective Cough Frequency = (Post-Treatment Objective Sleep Cough Frequency minus Baseline Sleep Cough Frequency).
Measured: Baseline (Study Day -1), Day 84
Change From Baseline in Weekly Mean Daily Cough Severity Diary (CSD) Total Score at Week 1
The daily CSD instrument has a total of 7 items, each with scores ranging from 0 (best) to 10 (worst). The total daily CSD is the sum of these 7 item scores (Min=0, Max=70). Mean total daily score (the sum of 7 item scores divided by 7) was derived for each day. Weekly mean total daily score was defined as the average of the mean total daily scores for each week. LS mean change from baseline of the weekly mean total daily CSD score was reported for each treatment group with associated SE. Baseline was defined as the average CSD scores collected during the week prior to Day 1 (Study Day -7 to Day -1).
Measured: Baseline, Week 1
Change From Baseline in Weekly Mean Daily CSD Total Score at Week 2
The daily CSD instrument has a total of 7 items, each with scores ranging from 0 (best) to 10 (worst). The total daily CSD is the sum of these 7 item scores (Min=0, Max=70). Mean total daily score (the sum of 7 item scores divided by 7) was derived for each day. Weekly mean total daily score was defined as the average of the mean total daily scores for each week. LS mean change from baseline of the weekly mean total daily CSD score was reported for each treatment group with associated SE. Baseline was defined as the average CSD scores collected during the week prior to Day 1 (Study Day -7 to Day -1).
Measured: Baseline, Week 2
Change From Baseline in Weekly Mean Daily CSD Total Score at Week 3
The daily CSD instrument has a total of 7 items, each with scores ranging from 0 (best) to 10 (worst). The total daily CSD is the sum of these 7 item scores (Min=0, Max=70). Mean total daily score (the sum of 7 item scores divided by 7) was derived for each day. Weekly mean total daily score was defined as the average of the mean total daily scores for each week. LS mean change from baseline of the weekly mean total daily CSD score was reported for each treatment group with associated SE. Baseline was defined as the average CSD scores collected during the week prior to Day 1 (Study Day -7 to Day -1).
Measured: Baseline, Week 3
Change From Baseline in Weekly Mean Daily CSD Total Score at Week 4
The daily CSD instrument has a total of 7 items, each with scores ranging from 0 (best) to 10 (worst). The total daily CSD is the sum of these 7 item scores (Min=0, Max=70). Mean total daily score (the sum of 7 item scores divided by 7) was derived for each day. Weekly mean total daily score was defined as the average of the mean total daily scores for each week. LS mean change from baseline of the weekly mean total daily CSD score was reported for each treatment group with associated SE. Baseline was defined as the average CSD scores collected during the week prior to Day 1 (Study Day -7 to Day -1).
Measured: Baseline, Week 4
Change From Baseline in Weekly Mean Daily CSD Total Score at Week 5
The daily CSD instrument has a total of 7 items, each with scores ranging from 0 (best) to 10 (worst). The total daily CSD is the sum of these 7 item scores (Min=0, Max=70). Mean total daily score (the sum of 7 item scores divided by 7) was derived for each day. Weekly mean total daily score was defined as the average of the mean total daily scores for each week. LS mean change from baseline of the weekly mean total daily CSD score was reported for each treatment group with associated SE. Baseline was defined as the average CSD scores collected during the week prior to Day 1 (Study Day -7 to Day -1).
Measured: Baseline, Week 5
Change From Baseline in Weekly Mean Daily CSD Total Score at Week 6
The daily CSD instrument has a total of 7 items, each with scores ranging from 0 (best) to 10 (worst). The total daily CSD is the sum of these 7 item scores (Min=0, Max=70). Mean total daily score (the sum of 7 item scores divided by 7) was derived for each day. Weekly mean total daily score was defined as the average of the mean total daily scores for each week. LS mean change from baseline of the weekly mean total daily CSD score was reported for each treatment group with associated SE. Baseline was defined as the average CSD scores collected during the week prior to Day 1 (Study Day -7 to Day -1).
Measured: Baseline, Week 6
Change From Baseline in Weekly Mean Daily CSD Total Score at Week 7
The daily CSD instrument has a total of 7 items, each with scores ranging from 0 (best) to 10 (worst). The total daily CSD is the sum of these 7 item scores (Min=0, Max=70). Mean total daily score (the sum of 7 item scores divided by 7) was derived for each day. Weekly mean total daily score was defined as the average of the mean total daily scores for each week. LS mean change from baseline of the weekly mean total daily CSD score was reported for each treatment group with associated SE. Baseline was defined as the average CSD scores collected during the week prior to Day 1 (Study Day -7 to Day -1).
Measured: Baseline, Week 7
Change From Baseline in Weekly Mean Daily CSD Total Score at Week 8
The daily CSD instrument has a total of 7 items, each with scores ranging from 0 (best) to 10 (worst). The total daily CSD is the sum of these 7 item scores (Min=0, Max=70). Mean total daily score (the sum of 7 item scores divided by 7) was derived for each day. Weekly mean total daily score was defined as the average of the mean total daily scores for each week. LS mean change from baseline of the weekly mean total daily CSD score was reported for each treatment group with associated SE. Baseline was defined as the average CSD scores collected during the week prior to Day 1 (Study Day -7 to Day -1).
Measured: Baseline, Week 8
Change From Baseline in Weekly Mean Daily CSD Total Score at Week 9
The daily CSD instrument has a total of 7 items, each with scores ranging from 0 (best) to 10 (worst). The total daily CSD is the sum of these 7 item scores (Min=0, Max=70). Mean total daily score (the sum of 7 item scores divided by 7) was derived for each day. Weekly mean total daily score was defined as the average of the mean total daily scores for each week. LS mean change from baseline of the weekly mean total daily CSD score was reported for each treatment group with associated SE. Baseline was defined as the average CSD scores collected during the week prior to Day 1 (Study Day -7 to Day -1).
Measured: Baseline, Week 9
Change From Baseline in Weekly Mean Daily CSD Total Score at Week 10
The daily CSD instrument has a total of 7 items, each with scores ranging from 0 (best) to 10 (worst). The total daily CSD is the sum of these 7 item scores (Min=0, Max=70). Mean total daily score (the sum of 7 item scores divided by 7) was derived for each day. Weekly mean total daily score was defined as the average of the mean total daily scores for each week. LS mean change from baseline of the weekly mean total daily CSD score was reported for each treatment group with associated SE. Baseline was defined as the average CSD scores collected during the week prior to Day 1 (Study Day -7 to Day -1).
Measured: Baseline, Week 10
Change From Baseline in Weekly Mean Daily CSD Total Score at Week 11
The daily CSD instrument has a total of 7 items, each with scores ranging from 0 (best) to 10 (worst). The total daily CSD is the sum of these 7 item scores (Min=0, Max=70). Mean total daily score (the sum of 7 item scores divided by 7) was derived for each day. Weekly mean total daily score was defined as the average of the mean total daily scores for each week. LS mean change from baseline of the weekly mean total daily CSD score was reported for each treatment group with associated SE. Baseline was defined as the average CSD scores collected during the week prior to Day 1 (Study Day -7 to Day -1).
Measured: Baseline, Week 11
Change From Baseline in Weekly Mean Daily CSD Total Score at Week 12
The daily CSD instrument has a total of 7 items, each with scores ranging from 0 (best) to 10 (worst). The total daily CSD is the sum of these 7 item scores (Min=0, Max=70). Mean total daily score (the sum of 7 item scores divided by 7) was derived for each day. Weekly mean total daily score was defined as the average of the mean total daily scores for each week. LS mean change from baseline of the weekly mean total daily CSD score was reported for each treatment group with associated SE. Baseline was defined as the average CSD scores collected during the week prior to Day 1 (Study Day -7 to Day -1).
Measured: Baseline, Week 12
Change From Baseline in Weekly Mean Daily Cough Score (DCS) at Week 1
The DCS has a score ranging from 0 (best) to 10 (worst). Weekly mean daily score was defined as the average of the daily scores for each week. Baseline was defined as the average DCS score collected during the week prior to Day 1 (Day -7 to Day -1). Participants rated the severity of their cough using the DCS each day. LS mean change from baseline of the weekly mean Daily Cough Score with associated SE was reported for each treatment group.
Measured: Baseline, Week 1
Change From Baseline in Weekly Mean DCS at Week 2
The DCS has a score ranging from 0 (best) to 10 (worst). Weekly mean daily score was defined as the average of the daily scores for each week. Baseline was defined as the average DCS score collected during the week prior to Day 1 (Day -7 to Day -1). Participants rated the severity of their cough using the DCS each day. LS mean change from baseline of the weekly mean Daily Cough Score with associated SE was reported for each treatment group.
Measured: Baseline, Week 2
Change From Baseline in Weekly Mean DCS at Week 3
The DCS has a score ranging from 0 (best) to 10 (worst). Weekly mean daily score was defined as the average of the daily scores for each week. Baseline was defined as the average DCS score collected during the week prior to Day 1 (Day -7 to Day -1). Participants rated the severity of their cough using the DCS each day. LS mean change from baseline of the weekly mean Daily Cough Score with associated SE was reported for each treatment group.
Measured: Baseline, Week 3
Change From Baseline in Weekly Mean DCS at Week 4
The DCS has a score ranging from 0 (best) to 10 (worst). Weekly mean daily score was defined as the average of the daily scores for each week. Baseline was defined as the average DCS score collected during the week prior to Day 1 (Day -7 to Day -1). Participants rated the severity of their cough using the DCS each day. LS mean change from baseline of the weekly mean Daily Cough Score with associated SE was reported for each treatment group.
Measured: Baseline, Week 4
Change From Baseline in Weekly Mean DCS at Week 5
The DCS has a score ranging from 0 (best) to 10 (worst). Weekly mean daily score was defined as the average of the daily scores for each week. Baseline was defined as the average DCS score collected during the week prior to Day 1 (Day -7 to Day -1). Participants rated the severity of their cough using the DCS each day. LS mean change from baseline of the weekly mean Daily Cough Score with associated SE was reported for each treatment group.
Measured: Baseline, Week 5
Change From Baseline in Weekly Mean DCS at Week 6
The DCS has a score ranging from 0 (best) to 10 (worst). Weekly mean daily score was defined as the average of the daily scores for each week. Baseline was defined as the average DCS score collected during the week prior to Day 1 (Day -7 to Day -1). Participants rated the severity of their cough using the DCS each day. LS mean change from baseline of the weekly mean Daily Cough Score with associated SE was reported for each treatment group.
Measured: Baseline, Week 6
Change From Baseline in Weekly Mean DCS at Week 7
The DCS has a score ranging from 0 (best) to 10 (worst). Weekly mean daily score was defined as the average of the daily scores for each week. Baseline was defined as the average DCS score collected during the week prior to Day 1 (Day -7 to Day -1). Participants rated the severity of their cough using the DCS each day. LS mean change from baseline of the weekly mean Daily Cough Score with associated SE was reported for each treatment group.
Measured: Baseline, Week 7
Change From Baseline in Weekly Mean DCS at Week 8
The DCS has a score ranging from 0 (best) to 10 (worst). Weekly mean daily score was defined as the average of the daily scores for each week. Baseline was defined as the average DCS score collected during the week prior to Day 1 (Day -7 to Day -1). Participants rated the severity of their cough using the DCS each day. LS mean change from baseline of the weekly mean Daily Cough Score with associated SE was reported for each treatment group.
Measured: Baseline, Week 8
Change From Baseline in Weekly Mean DCS at Week 9
The DCS has a score ranging from 0 (best) to 10 (worst). Weekly mean daily score was defined as the average of the daily scores for each week. Baseline was defined as the average DCS score collected during the week prior to Day 1 (Day -7 to Day -1). Participants rated the severity of their cough using the DCS each day. LS mean change from baseline of the weekly mean Daily Cough Score with associated SE was reported for each treatment group.
Measured: Baseline, Week 9
Change From Baseline in Weekly Mean DCS at Week 10
The DCS has a score ranging from 0 (best) to 10 (worst). Weekly mean daily score was defined as the average of the daily scores for each week. Baseline was defined as the average DCS score collected during the week prior to Day 1 (Day -7 to Day -1). Participants rated the severity of their cough using the DCS each day. LS mean change from baseline of the weekly mean Daily Cough Score with associated SE was reported for each treatment group.
Measured: Baseline, Week 10
Change From Baseline in Weekly Mean DCS at Week 11
The DCS has a score ranging from 0 (best) to 10 (worst). Weekly mean daily score was defined as the average of the daily scores for each week. Baseline was defined as the average DCS score collected during the week prior to Day 1 (Day -7 to Day -1). Participants rated the severity of their cough using the DCS each day. LS mean change from baseline of the weekly mean Daily Cough Score with associated SE was reported for each treatment group.
Measured: Baseline, Week 11
Change From Baseline in Weekly Mean DCS at Week 12
The DCS has a score ranging from 0 (best) to 10 (worst). Weekly mean daily score was defined as the average of the daily scores for each week. Baseline was defined as the average DCS score collected during the week prior to Day 1 (Day -7 to Day -1). Participants rated the severity of their cough using the DCS each day. LS mean change from baseline of the weekly mean Daily Cough Score with associated SE was reported for each treatment group.
Measured: Baseline, Week 12
Change From Baseline in Leicester Cough Questionnaire (LCQ) Total Score After 4 Weeks of Treatment (Day 28)
The LCQ instrument is designed to assess the impact of cough on various aspects of a participant's life over the preceding 2 weeks. It consists of 19 items which are divided over 3 domains: Physical (items 1, 2, 3, 9, 10, 11, 14 and 15), Psychological (4, 5, 6, 12, 13, 16, and 17), and Social (7, 8, 18, 19). A 7-point Likert scale is used to rate each item. For each domain, the domain score (range 1-7) is the sum of the individual item scores within the domain divided by the number of items in the domain. The total score is the sum of the three domain scores and ranges from 3-21; a higher score corresponds to a better health status. Baseline LCQ was defined as the LCQ collected at Baseline (Study Day -1). LS mean change from baseline in total LCQ score was reported for each treatment group with associated SE.
Measured: Baseline, Day 28
Change From Baseline in Leicester Cough Questionnaire (LCQ) Total Score After 8 Weeks of Treatment (Day 56)
The LCQ instrument is designed to assess the impact of cough on various aspects of a participant's life over the preceding 2 weeks. It consists of 19 items which are divided over 3 domains: Physical (items 1, 2, 3, 9, 10, 11, 14 and 15), Psychological (4, 5, 6, 12, 13, 16, and 17), and Social (7, 8, 18, 19). A 7-point Likert scale is used to rate each item. For each domain, the domain score (range 1-7) is the sum of the individual item scores within the domain divided by the number of items in the domain. The total score is the sum of the three domain scores and ranges from 3-21; a higher score corresponds to a better health status. Baseline LCQ was defined as the LCQ collected at Baseline (Study Day -1). LS mean change from baseline in total LCQ score was reported for each treatment group with associated SE.
Measured: Baseline, Day 56
Change From Baseline in Leicester Cough Questionnaire (LCQ) Total Score At Day 85/Early Termination
The LCQ instrument is designed to assess the impact of cough on various aspects of a participant's life over the preceding 2 weeks. It consists of 19 items which are divided over 3 domains: Physical (items 1, 2, 3, 9, 10, 11, 14 and 15), Psychological (4, 5, 6, 12, 13, 16, and 17), and Social (7, 8, 18, 19). A 7-point Likert scale is used to rate each item. For each domain, the domain score (range 1-7) is the sum of the individual item scores within the domain divided by the number of items in the domain. The total score is the sum of the three domain scores and ranges from 3-21; a higher score corresponds to a better health status. Baseline LCQ was defined as the LCQ collected at Baseline (Study Day -1). LS mean change from baseline in total LCQ score was reported for each treatment group with associated SE.
Measured: Baseline, Day 85/Early Termination
Percentage of Participants Reporting "Very Much Improved" or "Much Improved" According to the Patient's Global Impression of Change (PGIC) After 4 Weeks of Treatment (Day 28)
The self-reported measure Patient's Global Impression of Change (PGIC) reflects a participant's belief about the efficacy of treatment. PGIC is a 7-point scale depicting a patient's rating of overall improvement. Participants rate their change as "very much improved," "much improved," "minimally improved," "no change," "minimally worse," "much worse," or "very much worse." The counts and percentages of ordered responses to the participant's global perception of change were computed for each treatment group on Day 28 and the percentage of participants with improvements (either "very much improved" or "much improved" on the PGIC scale) was reported for each treatment group.
Measured: Day 28
Percentage of Participants Reporting "Very Much Improved" or "Much Improved" According to the PGIC After 8 Weeks of Treatment (Day 56)
The self-reported measure Patient's Global Impression of Change (PGIC) reflects a participant's belief about the efficacy of treatment. PGIC is a 7-point scale depicting a patient's rating of overall improvement. Participants rate their change as "very much improved," "much improved," "minimally improved," "no change," "minimally worse," "much worse," or "very much worse." The counts and percentages of ordered responses to the participant's global perception of change were computed for each treatment group on Day 28 and the percentage of participants with improvements (either "very much improved" or "much improved" on the PGIC scale) was reported for each treatment group.
Measured: Day 56
Percentage of Participants Reporting "Very Much Improved" or "Much Improved" According to the PGIC at Day 85/Early Termination
The self-reported measure Patient's Global Impression of Change (PGIC) reflects a participant's belief about the efficacy of treatment. PGIC is a 7-point scale depicting a patient's rating of overall improvement. Participants rate their change as "very much improved," "much improved," "minimally improved," "no change," "minimally worse," "much worse," or "very much worse." The counts and percentages of ordered responses to the participant's global perception of change were computed for each treatment group on Day 28 and the percentage of participants with improvements (either "very much improved" or "much improved" on the PGIC scale) was reported for each treatment group.
Measured: Day 85/Early Termination
Percentage of Participants Rated as "Very Much Improved" or "Much Improved" by Clinicians According to the Clinician's Global Impression of Change (CGIC) at Day 85/Early Termination
The Clinician's Global Impression of Change (CGIC) reflects a clinician's belief about the efficacy of treatment. CGIC is a 7-point scale depicting a clinician's rating of a participant's overall improvement. Clinicians rated the participant's change at Week 12 (Day 85) as "very much improved," "much improved," "minimally improved," "no change," "minimally worse," "much worse," or "very much worse." The counts and percentages of ordered responses to the clinician's global perception of change were computed for each treatment group, and the percentage of participants rated by clinicians as having improvement (either "very much improved" or "much improved" on the CGIC scale) was reported for each treatment group.
Measured: Day 85/Early Termination
Acceptability Questionnaire: Percentage of Participants That Were Likely to Take Study Medication For At Least One Year
At the end of the treatment period (Day 85), participants were asked "How likely would you be to take this medication?" This question was asked in reference to the time frame of "At least one year". The counts and percentages of ordered categorical responses to this question were computed for each treatment group.
Measured: Day 85/Early Termination
Acceptability Questionnaire: Percentage of Participants That Were Likely to Take Study Medication For At Least Six Months
At the end of the treatment period (Day 85), participants were asked "How likely would you be to take this medication?" This question was asked in reference to the time frame of "At least six months". The counts and percentages of ordered categorical responses to this question were computed for each treatment group.
Measured: Day 85/Early Termination
Acceptability Questionnaire: Percentage of Participants That Were Likely to Take Study Medication For At Least Four Weeks
At the end of the treatment period (Day 85), participants were asked "How likely would you be to take this medication?" This question was asked in reference to the time frame of "At least four weeks". The counts and percentages of ordered categorical responses to this question were computed for each treatment group.
Measured: Day 85/Early Termination
Acceptability Questionnaire: Percentage of Participants That Were Likely to Take Study Medication Twice Daily
At the end of the treatment period (Day 85), participants were asked "How likely would you be to take this medication?" This question was asked in reference to the time frame of "Twice daily". The counts and percentages of ordered categorical responses to this question were computed for each treatment group.
Measured: Day 85/Early Termination
Taste Questionnaire: Percentage of Participants That Experienced Taste Effect After Taking Medication by Frequency After 12 Weeks of Treatment (Day 84)
The tolerance to taste-related adverse events (AEs) was evaluated at the end of the study (Day 84) and a structured taste questionnaire was administered to participants experiencing a taste-related AE. Participants were asked to indicate the frequency that they experienced the taste effect by answering the question "How frequently do you experience the taste effect after taking each dose of medication?" The counts and percentages of categorical frequency responses to the individual items were computed for each treatment group.
Measured: Day 84
Taste Questionnaire: Percentage of Participants That Found Taste Effect of Study Medication Bothersome After 12 Weeks of Treatment (Day 84)
The tolerance to taste-related adverse events (AEs) was evaluated at the end of the study (Day 84) and a structured taste questionnaire was administered to participants experiencing a taste-related AE to determine what degree the participant found the taste effect bothersome by answering the question "How bothersome is the taste effect of the medication? The counts and percentages of categorical responses to the individual items were computed for each treatment group.
Measured: Day 84

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

15 Dec 20154 Nov 2016

First posted24 Nov 2015 (estimated)
Study start15 Dec 2015
Primary completion31 Oct 2016
Study completion4 Nov 2016

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (5)Papers the sponsor has linked to this study.
Other trials for Refractory Chronic CoughStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 253 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02612610
Sponsor's protocol ID: 7264-012
Other IDs: AF219-012, 2015-005064-42, 2015
Status last verified: Jun 2020
First submitted: 20 Nov 2015
Last updated: 30 Jun 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Publications

Schelfhout J, Nguyen AM, Birring SS, Bacci ED, Vernon M, Muccino DR, La Rosa C, Smith JA. Validation and Meaningful Change Thresholds for an Objective Cough Frequency Measurement in Chronic Cough. Lung. 2022 Dec;200(6):717-724. doi: 10.1007/s00408-022-00587-2. Epub 2022 Nov 8.
PubMed 36348054
Nguyen AM, Schelfhout J, Muccino D, Bacci ED, La Rosa C, Vernon M, Birring SS. Leicester Cough Questionnaire validation and clinically important thresholds for change in refractory or unexplained chronic cough. Ther Adv Respir Dis. 2022 Jan-Dec;16:17534666221099737. doi: 10.1177/17534666221099737.
PubMed 35614875
Martin Nguyen A, Bacci ED, Vernon M, Birring SS, Rosa C, Muccino D, Schelfhout J. Validation of a visual analog scale for assessing cough severity in patients with chronic cough. Ther Adv Respir Dis. 2021 Jan-Dec;15:17534666211049743. doi: 10.1177/17534666211049743.
PubMed 34697975
Morice AH, Birring SS, Smith JA, McGarvey LP, Schelfhout J, Martin Nguyen A, Xu ZJ, Wu WC, Muccino DR, Sher MR. Characterization of Patients With Refractory or Unexplained Chronic Cough Participating in a Phase 2 Clinical Trial of the P2X3-Receptor Antagonist Gefapixant. Lung. 2021 Apr;199(2):121-129. doi: 10.1007/s00408-021-00437-7. Epub 2021 Apr 7.
PubMed 33825965
Smith JA, Kitt MM, Morice AH, Birring SS, McGarvey LP, Sher MR, Li YP, Wu WC, Xu ZJ, Muccino DR, Ford AP; Protocol 012 Investigators. Gefapixant, a P2X3 receptor antagonist, for the treatment of refractory or unexplained chronic cough: a randomised, double-blind, controlled, parallel-group, phase 2b trial. Lancet Respir Med. 2020 Aug;8(8):775-785. doi: 10.1016/S2213-2600(19)30471-0. Epub 2020 Feb 25.
PubMed 32109425

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

RecruitingPhase 2
The Effect of Nalbuphine Extended-Release (NAL ER) on Cough in Participants With Refractory Chronic Cough (RCC)
Refractory Chronic Cough
Not yet recruitingPhase 4
A 2x2 Factorial, Randomized, Open-label Trial to Evaluate Neuromodulators and Cough Control Therapy in Patients With Refractory or Unexplained Chronic Cough
Cough, Refractory Chronic Cough
RecruitingPhase 2
A Study to Investigate the Efficacy and Safety of SC0032, a Magnesium Salt Oral Spray, in Adults With Refractory or Unexplained Chronic Cough
Refractory Chronic Cough and Unexplained Chronic Cough
RecruitingPhase 2
Mechanisms of Change in Behavioral Cough Suppression Therapy for Refractory Chronic Cough
Chronic Cough (CC), Refractory Chronic Cough
Active, not recruitingPhase 3
A 24-Week Study of the Efficacy and Safety of BLU-5937 in Adults With Refractory Chronic Cough
Cough, Refractory Chronic Cough

All Refractory Chronic Cough trials

Study at a glance

From the registry record, last updated by the sponsor on 30 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A 12-Week Study to Assess the Efficacy and Safety of AF 219 in Subjects With Refractory Chronic Cough
ClinicalTrials.gov ID: NCT02612610
Acronym / sponsor ID: 7264-012
Conditions: Refractory Chronic Cough
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 253 participants (actual)
Lead sponsor: Afferent Pharmaceuticals, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)Industry (pharma, biotech, devices)
Study start: 15 Dec 2015 (actual)
Primary completion: 31 Oct 2016 (actual)
Study completion: 4 Nov 2016 (actual)
First posted: 24 Nov 2015 (estimated)
Results: Posted 14 Feb 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 4

Arm	Type	Receives
Placebo	Placebo comparator	Drug: Placebo (for gefapixant)Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.
Gefapixant 7.5 mg	Experimental	Drug: GefapixantParticipants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.
Gefapixant 20 mg	Experimental	Drug: GefapixantParticipants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.
Gefapixant 50 mg	Experimental	Drug: GefapixantParticipants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.

Who may qualify

Ages: 18 to 80 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

Women and Men between 18 and 80 years of age inclusive
Have refractory chronic cough
Women of child-bearing potential must use 2 forms of acceptable birth control - Have provided written informed consent.
Are willing and able to comply with all aspects of the protocol

Key exclusion criteria (11 listed)

Current smoker
Forced Expiratory Volume in 1 second (FEV1)/Forced Vital Capacity (FVC) ratio <60%
History of upper or lower respiratory tract infection or recent significant change in pulmonary status within 4 weeks of the Baseline Visit
History of opioid use within 1 week of the Baseline Visit
Body mass index (BMI) <18 kg/m^2 or ≥ 40 kg/m^2

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
GefapixantAlso: AF-219, MK-7264Gefapixant administered as one 7.5 mg, 20 mg, or 50 mg tablet twice daily, depending upon randomization.	Drug	Gefapixant 20 mg, Gefapixant 50 mg, Gefapixant 7.5 mg
Placebo (for gefapixant)Also: Dose-matched placebo tablet to gefapixant administered twice daily.	Drug	Placebo

Primary outcome

Change From Baseline in Awake Objective Cough Frequency After 12 Weeks of Treatment (Day 84)
Time frame: Baseline Visit (Day -1), Day 84
Awake Objective Cough Frequency (per hour) was defined as the total number of cough events during the monitoring period (in general, 24-hr interval) while the participant was awake divided by the total duration (in hours) for the monitoring period that the participant was awake. 24 hour sound recordings were made at Baseline (Study Day -1) and at Week 12 (Day 84) using a digital recording device. An independent cough monitoring center documented the time of each cough event over the 24 hour period, as well as the time when the participant went to sleep and the time the participant woke. Least-squares (LS) mean change from baseline (in log scale) with associated standard error (SE) reported for each treatment group. Change from Baseline in Awake Objective Cough Frequency = (Post-Treatment Awake Cough Frequency minus Baseline Awake Cough Frequency).

58 secondary outcomes

Change From Baseline in 24-Hour Objective Cough Frequency After 4 Weeks of Treatment (Day 28)
Time frame: Baseline (Study Day -1), Day 28
Change From Baseline in 24-Hour Objective Cough Frequency After 8 Weeks of Treatment (Day 56)
Time frame: Baseline (Study Day -1), Day 56
Change From Baseline in 24-Hour Objective Cough Frequency After 12 Weeks of Treatment (Day 84)
Time frame: Baseline (Study Day -1), Day 84
Change From Baseline in Awake Objective Cough Frequency After 4 Weeks of Treatment (Day 28)
Time frame: Baseline (Study Day -1), Day 28,
Change From Baseline in Awake Objective Cough Frequency After 8 Weeks of Treatment (Day 56)
Time frame: Baseline (Study Day -1), Day 56
Change From Baseline in Awake Objective Cough Frequency at the Follow-up Visit (Day 98)
Time frame: Baseline (Study Day -1), Day 98
Change From Baseline in Cough Severity Visual Analogue Scale (VAS) After 4 Weeks of Treatment (Day 28)
Time frame: Baseline (Study Day -1), Day 28
Change From Baseline in Cough Severity VAS After 8 Weeks of Treatment (Day 56)
Time frame: Baseline (Study Day -1), Day 56
Change From Baseline in Cough Severity VAS After 12 Weeks of Treatment (Day 84)
Time frame: Baseline (Study Day -1), Day 84
Change From Baseline in Cough Severity VAS At Day 85/Early Termination
Time frame: Baseline (Study Day -1), Day 85
Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in Awake Objective Cough Frequency After 4 Weeks of Treatment (Day 28)
Time frame: Baseline (Study Day -1), Day 28
Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in Awake Objective Cough Frequency After 8 Weeks of Treatment (Day 56)
Time frame: Baseline (Study Day -1), Day 56
Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in Awake Objective Cough Frequency After 12 Weeks of Treatment (Day 84)
Time frame: Baseline (Study Day -1), Day 84
Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in Awake Objective Cough Frequency at the Follow-up Visit (Day 98)
Time frame: Baseline (Study Day -1), Day 98
Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in 24-Hour Objective Cough Frequency After 4 Weeks of Treatment (Day 28)
Time frame: Baseline (Study Day -1), Day 28
Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in 24-Hour Objective Cough Frequency After 8 Weeks of Treatment (Day 56)
Time frame: Baseline (Study Day -1), Day 56
Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in 24-Hour Objective Cough Frequency After 12 Weeks of Treatment (Day 84)
Time frame: Baseline (Study Day -1), Day 84
Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in 24-Hour Objective Cough Frequency at the Follow-up Visit (Day 98)
Time frame: Baseline (Study Day -1), Day 98
Change From Baseline in Sleep Objective Cough Frequency After 4 Weeks of Treatment (Day 28)
Time frame: Baseline (Study Day -1), Day 28
Change From Baseline in Sleep Objective Cough Frequency After 8 Weeks of Treatment (Day 56)
Time frame: Baseline (Study Day -1), Day 56
Change From Baseline in Sleep Objective Cough Frequency After 12 Weeks of Treatment (Day 84)
Time frame: Baseline (Study Day -1), Day 84
Change From Baseline in Weekly Mean Daily Cough Severity Diary (CSD) Total Score at Week 1
Time frame: Baseline, Week 1
Change From Baseline in Weekly Mean Daily CSD Total Score at Week 2
Time frame: Baseline, Week 2
Change From Baseline in Weekly Mean Daily CSD Total Score at Week 3
Time frame: Baseline, Week 3
Change From Baseline in Weekly Mean Daily CSD Total Score at Week 4
Time frame: Baseline, Week 4
Change From Baseline in Weekly Mean Daily CSD Total Score at Week 5
Time frame: Baseline, Week 5
Change From Baseline in Weekly Mean Daily CSD Total Score at Week 6
Time frame: Baseline, Week 6
Change From Baseline in Weekly Mean Daily CSD Total Score at Week 7
Time frame: Baseline, Week 7
Change From Baseline in Weekly Mean Daily CSD Total Score at Week 8
Time frame: Baseline, Week 8
Change From Baseline in Weekly Mean Daily CSD Total Score at Week 9
Time frame: Baseline, Week 9
Change From Baseline in Weekly Mean Daily CSD Total Score at Week 10
Time frame: Baseline, Week 10
Change From Baseline in Weekly Mean Daily CSD Total Score at Week 11
Time frame: Baseline, Week 11
Change From Baseline in Weekly Mean Daily CSD Total Score at Week 12
Time frame: Baseline, Week 12
Change From Baseline in Weekly Mean Daily Cough Score (DCS) at Week 1
Time frame: Baseline, Week 1
Change From Baseline in Weekly Mean DCS at Week 2
Time frame: Baseline, Week 2
Change From Baseline in Weekly Mean DCS at Week 3
Time frame: Baseline, Week 3
Change From Baseline in Weekly Mean DCS at Week 4
Time frame: Baseline, Week 4
Change From Baseline in Weekly Mean DCS at Week 5
Time frame: Baseline, Week 5
Change From Baseline in Weekly Mean DCS at Week 6
Time frame: Baseline, Week 6
Change From Baseline in Weekly Mean DCS at Week 7
Time frame: Baseline, Week 7

Results and safety

Results posted to the registry on 14 Feb 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo	63	58
Gefapixant 7.5 mg	64	56
Gefapixant 20 mg	63	58
Gefapixant 50 mg	63	50

Primary outcome: Change From Baseline in Awake Objective Cough Frequency After 12 Weeks of Treatment (Day 84)

Time frame: Baseline Visit (Day -1), Day 84. Least squares mean (Standard Error). Unit: log coughs/hour

Measure	Placebo n = 61	Gefapixant 7.5 mg n = 59	Gefapixant 20 mg n = 59	Gefapixant 50 mg n = 57
Value	-0.40 (0.11)	-0.64 (0.11)	-0.65 (0.11)	-0.86 (0.11)

Placebo vs Gefapixant 7.5 mg: LS Mean Difference: -0.25 (95% CI -0.54 to 0.05), p = 0.0971, Mixed Effect Repeated Measures model
Placebo vs Gefapixant 20 mg: LS Mean Difference: -0.25 (95% CI -0.54 to 0.04), p = 0.0928, Mixed Effect Repeated Measures model
Placebo vs Gefapixant 50 mg: LS Mean Difference: -0.46 (95% CI -0.76 to -0.16), p = 0.0027, Mixed Effect Repeated Measures model

Population analysed: All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline primary endpoint observation during the treatment period.

58 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to ~14 weeks (Day 99). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo	0 of 63 (0%)	21 of 63 (33.3%)	Not reported
Gefapixant 7.5 mg	0 of 63 (0%)	26 of 63 (41.3%)	Not reported
Gefapixant 20 mg	0 of 63 (0%)	45 of 63 (71.4%)	Not reported
Gefapixant 50 mg	1 of 63 (1.6%)	52 of 63 (82.5%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 30 Jun 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 36348054Schelfhout J, Nguyen AM, Birring SS, Bacci ED, Vernon M, Muccino DR, La Rosa C, Smith JA. Validation and Meaningful Change Thresholds for an Objective Cough Frequency Measurement in Chronic Cough. Lung. 2022 Dec;200(6):717-724. doi: 10.1007/s00408-022-00587-2. Epub 2022 Nov 8.
Derived from this study: PubMed 35614875Nguyen AM, Schelfhout J, Muccino D, Bacci ED, La Rosa C, Vernon M, Birring SS. Leicester Cough Questionnaire validation and clinically important thresholds for change in refractory or unexplained chronic cough. Ther Adv Respir Dis. 2022 Jan-Dec;16:17534666221099737. doi: 10.1177/17534666221099737.
Derived from this study: PubMed 34697975Martin Nguyen A, Bacci ED, Vernon M, Birring SS, Rosa C, Muccino D, Schelfhout J. Validation of a visual analog scale for assessing cough severity in patients with chronic cough. Ther Adv Respir Dis. 2021 Jan-Dec;15:17534666211049743. doi: 10.1177/17534666211049743.
Derived from this study: PubMed 33825965Morice AH, Birring SS, Smith JA, McGarvey LP, Schelfhout J, Martin Nguyen A, Xu ZJ, Wu WC, Muccino DR, Sher MR. Characterization of Patients With Refractory or Unexplained Chronic Cough Participating in a Phase 2 Clinical Trial of the P2X3-Receptor Antagonist Gefapixant. Lung. 2021 Apr;199(2):121-129. doi: 10.1007/s00408-021-00437-7. Epub 2021 Apr 7.
Derived from this study: PubMed 32109425Smith JA, Kitt MM, Morice AH, Birring SS, McGarvey LP, Sher MR, Li YP, Wu WC, Xu ZJ, Muccino DR, Ford AP; Protocol 012 Investigators. Gefapixant, a P2X3 receptor antagonist, for the treatment of refractory or unexplained chronic cough: a randomised, double-blind, controlled, parallel-group, phase 2b trial. Lancet Respir Med. 2020 Aug;8(8):775-785. doi: 10.1016/S2213-2600(19)30471-0. Epub 2020 Feb 25.
Individual participant dataSharing planned: Yes. http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Related trials for Refractory Chronic Cough

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The Effect of Nalbuphine Extended-Release (NAL ER) on Cough in Participants With Refractory Chronic Cough (RCC)
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Afferent Pharmaceuticals Clinical Research study director

Afferent Pharmaceuticals, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Gefapixant in people with Refractory Chronic Cough, run by Afferent Pharmaceuticals, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA).

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Feb 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in Awake Objective Cough Frequency After 12 Weeks of Treatment (Day 84) (time frame: Baseline Visit (Day -1), Day 84). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02612610, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jun 2020.