Idiopathic Pulmonary FibrosisPhase 2NCT02502097
A Study of Gefapixant (AF-219/MK-7264) in Participants With Idiopathic Pulmonary Fibrosis (IPF) With Persistent Cough (MK-7264-016)
A Phase 2 study testing Gefapixant in people with Idiopathic Pulmonary Fibrosis and Cough, run by Afferent Pharmaceuticals, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA).
Trial summary
A randomized, double-blind, placebo-controlled, crossover, dose escalation study of gefapixant (AF-219) in participants with Idiopathic Pulmonary Fibrosis (IPF) with persistent cough. Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Idiopathic Pulmonary Fibrosis, 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
- 51 participants
- Where
- No sites listed yet
- Study dates
- 26 Aug 2015to 14 Jul 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 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Idiopathic pulmonary fibrosis diagnosis based upon the American Thoracic Society (ATS)/ European Respiratory Society (ERS)/Japanese Respiratory Society (JRS)/ Latin American Thoracic Society (ALAT) IPF 2011 guideline
- Life expectancy of greater than 6 months
- Stable medical condition (IPF) for at least 4 weeks
- Self-reported history of troublesome daily cough for more than 8 weeks
- Score of ≥ 40mm on the Cough Severity Visual Analogue Scale (VAS) at Screening
- Women of child-bearing potential must use 2 forms of acceptable birth control method from Screening through the Follow-Up Visit
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- Male subjects and their partners of child-bearing potential must use 2 methods of acceptable birth control from Screening until 3 months after the last dose of study drug
- Written informed consent
- Willing and able to comply with all aspects of the protocol
Who cannot join
- Current smoker (i.e., within the last 30 days).
- Initiation of treatment with an ACE-inhibitor within 4 weeks prior to the Baseline Visit (Day 0) or during the study
- History of upper and/or lower respiratory tract infection within 4 weeks of the Baseline Visit (Day 0)
- History of opioid use for treatment of cough within 1 week of the Baseline Visit (Day 0)
- Requiring prohibited medications
- Body mass index (BMI) <18 kg/m^2 or ≥ 40 kg/m^2
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- History or symptoms of renal disease or renal obstructive disease
- History of concurrent malignancy or recurrence of malignancy within 2 years prior to Screening (not including subjects with <3 excised basal cell carcinomas)
- History of a diagnosis of drug or alcohol dependency or abuse within approximately the last 3 years
- Any condition possibly affecting drug absorption (e.g., gastrectomy, gastroplasty, any type of bariatric surgery, vagotomy, or bowel resection)
- Recent history of stroke or transient ischemic attack (within 6 months prior to Screening) not due to trauma, repaired vascular malformation, or aneurysm
- Screening systolic blood pressure (SBP) >160 mm Hg or a diastolic blood pressure (DBP) >90 mm Hg
- QTc interval >450 milliseconds in males, >470 milliseconds in females
- Significantly abnormal laboratory tests at Screening
- Breastfeeding
- Treatment with an investigational drug or biologic within 30 days preceding the first dose of study medication or plans to take another investigational drug or biologic within 30 days of study completion
- Blood donation within 56 days or plasma donation within 7 days prior to dosing
- 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
About this study
Official title: A Randomized Placebo-Controlled Study to Assess the Efficacy and Safety of AF-219, a P2X3 Receptor Antagonist, in Subjects With Idiopathic Pulmonary Fibrosis (IPF) With Persistent Cough
A randomized, double-blind, placebo-controlled, crossover, dose escalation study of gefapixant (AF-219) in participants with Idiopathic Pulmonary Fibrosis (IPF) with persistent cough.
Read the detailed description
Prior to Amendment 3, participants were randomized to receive either placebo twice daily (BID) for 14 days during Period 1 followed by gefapixant 50 mg BID for 10 days then gefapixant 150 mg BID for 4 days BID during Period 2; or gefapixant 50 mg BID for 10 days then gefapixant 150 mg BID for 4 days during Period 1, followed by placebo BID for 14 days during Period 2. Each period was separated by a 14 to 21-day washout period.
During Amendment 3, participants were randomized to receive either placebo BID for 14 days during Period 1 followed by gefapixant 50 mg BID for 14 days during Period 2; or gefapixant 50 mg BID for 14 days during Period 1, followed by placebo BID for 14 days during Period 2. Each period was separated by a 14 to 21-day washout period.
- Conditions
- Idiopathic Pulmonary Fibrosis, Cough
- Being tested
- Gefapixant, Placebo
- Medical subject headings
- Idiopathic Pulmonary Fibrosis, 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 50 mg tablet, administered by mouth
PlaceboOther
Matching placebo to gefapixant, tablet administered by mouth
| Study group | Role | What they receive |
|---|---|---|
| Gefapixant>Placebo Pre-Amendment 3 | Experimental | Gefapixant 50 mg twice daily (BID) for 10 days, then 150 mg BID for 4 days in Period 1, followed by a 14-21 day washout period, then placebo BID for 14 days in Period 2 Receives: Drug: Gefapixant; Other: Placebo |
| Placebo>Gefapixant Pre-Amendment 3 | Experimental | Placebo BID for 14 days in Period 1, followed by a 14-21 day washout period, then gefapixant 50 mg BID for 10 days, then 150 mg for 4 days in Period 2 Receives: Drug: Gefapixant; Other: Placebo |
| Gefapixant>Placebo Post-Amendment 3 | Experimental | Gefapixant 50 mg twice daily (BID) for 14 days in Period 1, followed by a 14-21 day washout period, then placebo BID for 14 days in Period 2 Receives: Drug: Gefapixant; Other: Placebo |
| Placebo>Gefapixant Post-Amendment 3 | Experimental | Placebo BID for 14 days in Period 1, followed by a 14-21 day washout period, then gefapixant 50 mg BID for 14 days in Period 2 Receives: Drug: Gefapixant; Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mixed Model of Repeated Measures (MMRM) Change From Baseline in Awake Objective Cough Frequency (Periods 1 & 2 Combined)
Cough monitoring was conducted for 24 hours while awake, at pre-dose on Day 0 (baseline), and after administration of the study drug on Day 7 and Day 14 in Periods 1 and 2. The cough frequency is the coughs/hour over each 24-hour period. Awake objective cough frequency was analyzed using Mixed Effect Model for Repeated Measures (MMRM) to evaluate the results of the 2-period cross-over study. Baseline cough frequency was derived from the cough monitoring performed at the beginning of each treatment period while the post-treatment cough frequency was derived from the cough monitoring performed at the end of the dosing period. A negative change indicates a decrease in cough frequency, while a positive change indicates an increase in cough frequency.
Measured: Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2)
Awake Objective Cough Frequency (Periods 1 & 2 Combined)
Cough monitoring was conducted for 24 hours while awake, at pre-dose on Day 0 (baseline), and after administration of the study drug on Day 7 and Day 14 in Periods 1 and 2. The cough frequency is the coughs/hour over each 24-hour period. Awake objective cough frequency was defined as the total number of cough events during the monitoring period the participant was awake divided by the total duration for the monitoring period the participant was awake. Baseline cough frequency was derived from the cough monitoring performed at the beginning of each treatment period while the post-treatment cough frequency was derived from the cough monitoring performed at the end of the dosing period.
Measured: Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2)
Change From Baseline of Awake Objective Cough Frequency (Periods 1 & 2 Combined)
Cough monitoring was conducted for 24 hours while awake, at pre-dose on Day 0 (baseline), and after administration of the study drug on Day 7 and Day 14 in Periods 1 and 2. The cough frequency is the coughs/hour over each 24-hour period. Awake objective cough frequency was defined as the total number of cough events during the monitoring period the participant was awake divided by the total duration for the monitoring period the participant was awake. Baseline cough frequency was derived from the cough monitoring performed at the beginning of each treatment period while the post-treatment cough frequency was derived from the cough monitoring performed at the end of the dosing period. A negative value indicates a decrease in cough frequency.
Measured: Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2)
Percent Change From Baseline of Awake Objective Cough Frequency (Periods 1 & 2 Combined)
Awake objective cough frequency was defined as the total number of cough events during the monitoring period the participant was awake divided by the total duration for the monitoring period the participant was awake. Percent change from baseline in awake objective cough frequency (0-6 hours after the morning dose) was reported at each dosing interval. Percent change in awake cough frequency = 100 X (post treatment cough frequency - baseline cough frequency) divided by the baseline cough frequency. A negative value indicates a decrease in cough frequency.
Measured: Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2)
Secondary outcomes (22)
MMRM Analysis of Change From Baseline in Awake Objective Cough Frequency (Period 1)
Awake objective cough frequency was defined as the total number of cough events during the monitoring period the participant was awake divided by the total duration for the monitoring period the participant was awake. Change from Baseline in awake cough frequency = post-treatment awake cough frequency - Baseline awake cough frequency. A negative value indicates a decrease in cough frequency. A positive value indicates an increase in cough frequency. Baseline cough frequency was derived from the cough monitoring performed at the beginning of each treatment period while the post-treatment cough frequency was derived from the cough monitoring performed at the end of the dosing period. Awake objective cough frequency for Period 1 was analyzed for using MMRM to evaluate the results of the 2-period cross-over study. The derived change measured at each dose were the repeated measures.
Measured: Baseline (Day 0), Day 7, and Day 14 (Period 1)
MMRM Analysis of Change From Baseline in Awake Objective Cough Frequency (Period 2)
Awake objective cough frequency was defined as the total number of cough events during the monitoring period the participant was awake divided by the total duration for the monitoring period the participant was awake. Change from baseline in awake cough frequency = post-treatment awake cough frequency - Baseline awake cough frequency. A negative value indicates a decrease in cough frequency. A positive value indicates an increase in cough frequency. Baseline cough frequency was derived from the cough monitoring performed at the beginning of each treatment period while the post-treatment cough frequency was derived from the cough monitoring performed at the at the end of the dosing period. Awake objective cough frequency for Period 2 was analyzed using MMRM to evaluate the results of the 2-period cross-over study. The derived change measured at each dose were the repeated measures.
Measured: Baseline (Day 0), Day 7, and Day 14 (Period 2)
Responder Analysis of Awake Cough Frequency at Day 7 (Periods 1 & 2 Combined)
Awake objective cough frequency was defined as the total number of cough events during the monitoring period the participant was awake divided by the total duration for the monitoring period the participant was awake. The number of participants that met responder criteria for ≥70%, ≥50%, ≥30%, and ≥20% change (reduction) from baseline levels in 24-hour awake cough frequency was reported (Period 1 and Period 2 combined) at Day 7.
Measured: Day 7 (Period 1 and Period 2)
Responder Analysis of Awake Cough Frequency at Day 14 (Periods 1 & 2 Combined)
Awake objective cough frequency was defined as the total number of cough events during the monitoring period the participant was awake divided by the total duration for the monitoring period the participant was awake. The number of participants that met responder criteria for ≥70%, ≥50%, ≥30%, and ≥20% change (reduction) from baseline levels in 24-hour awake cough frequency was reported (Period 1 and Period 2 combined) at Day 14.
Measured: Day 14 (Period 1 and Period 2)
MMRM Analysis of Change From Baseline 24-hour Objective Cough Frequency (Periods 1 & 2 Combined)
24-hour objective cough frequency = total number of coughs during the monitoring period divided by the total duration for the monitoring period. A negative value indicates a decrease in cough frequency. A positive value indicates an increase in cough frequency. 24-hour objective cough frequency was analyzed using MMRM to evaluate the results of the 2-period cross-over study. The derived change measured at each dose were the repeated measures.
Measured: Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2)
MMRM Analysis of Change From Baseline in 24-hour Objective Cough Frequency (Period 1)
24-hour objective cough frequency = total number of coughs during the monitoring period divided by the total duration for the monitoring period. A negative value indicates a decrease in cough frequency. A positive value indicates an increase in cough frequency. 24-hour objective cough frequency for Period 1 was analyzed using MMRM to evaluate the results of the 2-period cross-over study. The derived change measured at each dose were the repeated measures.
Measured: Baseline (Day 0), Day 7, and Day 14 (Period 1)
MMRM Analysis of Change From Baseline in 24-hour Objective Cough Frequency (Period 2)
24-hour objective cough frequency = total number of coughs during the monitoring period divided by the total duration for the monitoring period. A negative value indicates a decrease in cough frequency. A positive value indicates an increase in cough frequency. 24-hour objective cough frequency for Period 2 was analyzed using MMRM to evaluate the results of the 2-period cross-over study. The derived change measured at each dose were the repeated measures.
Measured: Baseline (Day 0), Day 7, and Day 14 (Period 2)
24-hour Objective Cough Frequency (Periods 1 & 2 Combined)
24-hour objective cough frequency = total number of coughs during the monitoring period divided by the total duration for the monitoring period.
Measured: Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2)
Change From Baseline of 24-hour Cough Frequency (Periods 1 & 2 Combined)
24-hour objective cough frequency = total number of coughs during the monitoring period divided by the total duration for the monitoring period. A negative value indicates a decrease in cough frequency. A positive value indicates an increase in cough frequency. 24-hour objective cough frequency was analyzed using MMRM to evaluate the results of the 2-period cross-over study. The derived change measured at each dose were the repeated measures.
Measured: Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2)
Percent Change From Baseline of 24-hour Cough Frequency (Periods 1 & 2 Combined)
24-hour objective cough frequency = total number of coughs during the monitoring period divided by the total duration for the monitoring period. Percent change in cough frequency = 100 X (post treatment cough frequency - baseline cough frequency) divided by the baseline cough frequency. A negative value indicates a decrease in cough frequency. A positive value indicates an increase in cough frequency.
Measured: Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2)
MMRM Analysis of Change From Baseline in Sleep Cough Frequency (Periods 1 & 2 Combined)
Sleep Objective Cough Frequency = Total number of cough events during the monitoring period the participant is asleep divided by the total duration (in hours) for the monitoring period the participant is asleep. 24-hour sound recordings were collected with a digital recording device. A negative result indicates a decrease in cough frequency, while a positive result indicates an increase in cough frequency. Sleep cough frequency was analyzed using MMRM to evaluate the results of the 2-period cross-over study. The derived change measured at each dose were the repeated measures.
Measured: Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2)
MMRM Analysis of Change From Baseline in Cough Visual Analog Scale (VAS) (Periods 1 & 2 Combined)
Cough VAS is scored from 0 to 100 using a 10 mm visual analogue scale with 0 at 0mm and 100 at 10mm with 0 (no cough) and 100 (most severe cough). Baseline cough VAS is defined as average of screening and baseline cough VAS. A negative result indicates a decrease in cough frequency, while a positive result indicates an increase in cough frequency. Cough VAS was analyzed using MMRM to evaluate the results of the 2-period cross-over study. The derived change measured at each dose were the repeated measures.
Measured: Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2)
MMRM Analysis of Change From Baseline in Cough Quality of Life Questionnaire (CQLQ) (Periods 1 & 2 Combined)
CQLQ is a 28-item scale that has 4 possible responses: 1 = strongly disagree; 2 = disagree; 3 = agree; 4 = strongly agree. Subjects were instructed to circle only 1 response. The total CQLQ score is the sum of the individual item scores; the lowest possible score is 28 and the highest 112. Low CQLQ scores for both total and the 6 domains indicate less impact of cough on health-related quality of life. A negative result indicates a decrease in cough impact on quality of life. CQLQ was analyzed using MMRM to evaluate the results of the 2-period cross-over study. The derived change measured at each dose were the repeated measures.
Measured: Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2)
MMRM Analysis of Change From Baseline in Total Daily Cough Severity Diary (CSD) Score (Periods 1 & 2 Combined)
The 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 sleep 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). Baseline CSD score = average of CSD scores at screening and baseline. A negative result indicates a decrease in cough severity, while a positive result indicates an increase in cough severity. CSD was analyzed using MMRM to evaluate the results of the 2-period cross-over study. The derived change measured at each dose were the repeated measures.
Measured: Baseline (Day 0), Week 1, and Week 2 (Period 1 and Period 2)
MMRM Analysis of Change From Baseline in University of California San Diego Shortness of Breath Questionnaire (UCSD SOBQ) (Periods 1 & 2 Combined)
UCSD SOBQ is a 24-point item scale to assess shortness of breath questionnaire that has a 6-point scale ranging from 0 to 5 (0 = "not at all", to 5 = "maximal or unable to do because of breathlessness". Lowest possible score is 0 and the highest possible score is 120. The higher the score the more out of breath the participant is reporting. A negative value indicates less breathlessness. UCSD SOBQ was analyzed using MMRM to evaluate the results of the 2-period cross-over study. The derived change measured at each dose were the repeated measures.
Measured: Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2)
MMRM Analysis of Change From Baseline in Cough Borg CR10 Scale Score (Periods 1 & 2 Combined)
The Borg 10 scale assesses post-treatment breathlessness during perceived exertion while exercising. The scale ranges from 0 to 10 where 0 = nothing at all, 1 = very weak, 3 = moderate, 5 = strong, 7 = very strong, 10 = extremely strong. The lowest possible score is 0 and the highest possible score is 10. A negative value indicates less breathlessness. Cough Borg CR10 was analyzed using MMRM to evaluate the results of the 2-period cross-over study. The derived change measured at each dose were the repeated measures.
Measured: Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2)
Percentage of Participants With Borg CR10 Perception of Breathless Value ≥5 (Periods 1 & 2 Combined)
The Borg 10 scale assesses post-treatment breathlessness during perceived exertion while exercising. The scale ranges from 0 to 10 where 0 = nothing at all, 1 = very weak, 3 = moderate, 5 = strong, 7 = very strong, 10 = extremely strong. The lowest possible score is 0 and the highest possible score is 10. The percentage of participants with Borg CR10 perception of breathless value ≥5 was assessed.
Measured: Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2)
Patient's Global Impression of Change (PGIC) Day 7 (Periods 1 & 2 Combined)
PGIC is the participant self-reported overall improvement of cough following administration of study drug. The PGIC has a 7-point rating scale of "very much improved", "much improved", 'minimally improved", "no change", "minimally worse", "much worse" and "very much worse".
Measured: Day 7 (Period 1 and Period 2)
Patient's Global Impression of Change (PGIC) Day 15 (Periods 1 & 2 Combined)
PGIC is the participant self-reported overall improvement of cough following administration of study drug. The PGIC has a 7-point rating scale of "very much improved", "much improved", 'minimally improved", "no change", "minimally worse", "much worse" and "very much worse".
Measured: Day 15 (Period 1 and Period 2)
Clinician's Global Impression of Change (CGIC) Day 15 (Periods 1 & 2 Combined)
CGIC is the clinician's-reported overall improvement of participant's cough following administration of study drug. The CGIC has a 7-point rating scale of "very much improved", "much improved", 'minimally improved", "no change", "minimally worse", "much worse" and "very much worse".
Measured: Day 15 (Period 1 and Period 2)
Taste Acceptability Questionnaire: Number of Participants That Were Likely to Take Study Medication For At Least Six Months
At the end of the treatment period, participants were asked "How likely would you be to take this medication for at least 6 months?" The degree of taste acceptability was measured on a scale of "extremely unlikely", "unlikely", "neither", "likely" and "extremely likely."
Measured: After last treatment, up to Day 15 (Period 1 and Period 2)
Taste Acceptability Questionnaire: Number of Participants That Were Likely to Take Study Medication For At Least One Year
At the end of the treatment period, the participant was asked "How likely would you be to take this medication for at least one year?" The degree of taste acceptability was measured on a scale of "extremely unlikely", "unlikely", "neither", "likely" and "extremely likely."
Measured: After last treatment, up to Day 15 (Period 1 and Period 2)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jul 2015 (estimated)
- Study start26 Aug 2015
- Primary completion1 Jul 2016
- Study completion14 Jul 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 (1)Papers the sponsor has linked to this study.
- Other trials for Idiopathic Pulmonary FibrosisStudies 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
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 51 participants (actual)
Sponsor and investigators
- Lead sponsor
- Afferent Pharmaceuticals, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02502097
- Sponsor's protocol ID
- 7264-016
- Other IDs
- AF-219-016, MK-7264-016
- Status last verified
- Apr 2021
- First submitted
- 16 Jul 2015
- Last updated
- 26 May 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
Publications
Martinez FJ, Afzal AS, Smith JA, Ford AP, Li JJ, Li Y, Kitt MM; Chronic Cough in IPF Study Group. Treatment of Persistent Cough in Subjects with Idiopathic Pulmonary Fibrosis (IPF) with Gefapixant, a P2X3 Antagonist, in a Randomized, Placebo-Controlled Clinical Trial. Pulm Ther. 2021 Dec;7(2):471-486. doi: 10.1007/s41030-021-00162-9. Epub 2021 Jun 21.
PubMed 34152585
Study at a glance
From the registry record, last updated by the sponsor on 26 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Placebo-Controlled Study to Assess the Efficacy and Safety of AF-219, a P2X3 Receptor Antagonist, in Subjects With Idiopathic Pulmonary Fibrosis (IPF) With Persistent Cough
- ClinicalTrials.gov ID
- NCT02502097
- Acronym / sponsor ID
- 7264-016
- Conditions
- Idiopathic Pulmonary Fibrosis, Cough
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 51 participants (actual)
- Lead sponsor
- Afferent Pharmaceuticals, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)Industry (pharma, biotech, devices)
- Study start
- 26 Aug 2015 (actual)
- Primary completion
- 1 Jul 2016 (actual)
- Study completion
- 14 Jul 2016 (actual)
- First posted
- 20 Jul 2015 (estimated)
- Results
- Posted 26 May 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A randomized, double-blind, placebo-controlled, crossover, dose escalation study of gefapixant (AF-219) in participants with Idiopathic Pulmonary Fibrosis (IPF) with persistent cough.
Detailed description
Prior to Amendment 3, participants were randomized to receive either placebo twice daily (BID) for 14 days during Period 1 followed by gefapixant 50 mg BID for 10 days then gefapixant 150 mg BID for 4 days BID during Period 2; or gefapixant 50 mg BID for 10 days then gefapixant 150 mg BID for 4 days during Period 1, followed by placebo BID for 14 days during Period 2. Each period was separated by a 14 to 21-day washout period.
During Amendment 3, participants were randomized to receive either placebo BID for 14 days during Period 1 followed by gefapixant 50 mg BID for 14 days during Period 2; or gefapixant 50 mg BID for 14 days during Period 1, followed by placebo BID for 14 days during Period 2. Each period was separated by a 14 to 21-day washout period.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Gefapixant>Placebo Pre-Amendment 3 | Experimental | Drug: Gefapixant, Other: PlaceboGefapixant 50 mg twice daily (BID) for 10 days, then 150 mg BID for 4 days in Period 1, followed by a 14-21 day washout period, then placebo BID for 14 days in Period 2 |
| Placebo>Gefapixant Pre-Amendment 3 | Experimental | Drug: Gefapixant, Other: PlaceboPlacebo BID for 14 days in Period 1, followed by a 14-21 day washout period, then gefapixant 50 mg BID for 10 days, then 150 mg for 4 days in Period 2 |
| Gefapixant>Placebo Post-Amendment 3 | Experimental | Drug: Gefapixant, Other: PlaceboGefapixant 50 mg twice daily (BID) for 14 days in Period 1, followed by a 14-21 day washout period, then placebo BID for 14 days in Period 2 |
| Placebo>Gefapixant Post-Amendment 3 | Experimental | Drug: Gefapixant, Other: PlaceboPlacebo BID for 14 days in Period 1, followed by a 14-21 day washout period, then gefapixant 50 mg BID for 14 days in Period 2 |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Idiopathic pulmonary fibrosis diagnosis based upon the American Thoracic Society (ATS)/ European Respiratory Society (ERS)/Japanese Respiratory Society (JRS)/ Latin American Thoracic Society (ALAT) IPF 2011 guideline
- Life expectancy of greater than 6 months
- Stable medical condition (IPF) for at least 4 weeks
- Self-reported history of troublesome daily cough for more than 8 weeks
- Score of ≥ 40mm on the Cough Severity Visual Analogue Scale (VAS) at Screening
Key exclusion criteria (18 listed)
- Current smoker (i.e., within the last 30 days).
- Initiation of treatment with an ACE-inhibitor within 4 weeks prior to the Baseline Visit (Day 0) or during the study
- History of upper and/or lower respiratory tract infection within 4 weeks of the Baseline Visit (Day 0)
- History of opioid use for treatment of cough within 1 week of the Baseline Visit (Day 0)
- Requiring prohibited medications
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 50 mg tablet, administered by mouth | Drug | Gefapixant>Placebo Post-Amendment 3, Gefapixant>Placebo Pre-Amendment 3, Placebo>Gefapixant Post-Amendment 3, Placebo>Gefapixant Pre-Amendment 3 |
| PlaceboMatching placebo to gefapixant, tablet administered by mouth | Other | Gefapixant>Placebo Post-Amendment 3, Gefapixant>Placebo Pre-Amendment 3, Placebo>Gefapixant Post-Amendment 3, Placebo>Gefapixant Pre-Amendment 3 |
Primary outcome
Mixed Model of Repeated Measures (MMRM) Change From Baseline in Awake Objective Cough Frequency (Periods 1 & 2 Combined)
Time frame: Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2)
Cough monitoring was conducted for 24 hours while awake, at pre-dose on Day 0 (baseline), and after administration of the study drug on Day 7 and Day 14 in Periods 1 and 2. The cough frequency is the coughs/hour over each 24-hour period. Awake objective cough frequency was analyzed using Mixed Effect Model for Repeated Measures (MMRM) to evaluate the results of the 2-period cross-over study. Baseline cough frequency was derived from the cough monitoring performed at the beginning of each treatment period while the post-treatment cough frequency was derived from the cough monitoring performed at the end of the dosing period. A negative change indicates a decrease in cough frequency, while a positive change indicates an increase in cough frequency.
Awake Objective Cough Frequency (Periods 1 & 2 Combined)
Time frame: Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2)
Cough monitoring was conducted for 24 hours while awake, at pre-dose on Day 0 (baseline), and after administration of the study drug on Day 7 and Day 14 in Periods 1 and 2. The cough frequency is the coughs/hour over each 24-hour period. Awake objective cough frequency was defined as the total number of cough events during the monitoring period the participant was awake divided by the total duration for the monitoring period the participant was awake. Baseline cough frequency was derived from the cough monitoring performed at the beginning of each treatment period while the post-treatment cough frequency was derived from the cough monitoring performed at the end of the dosing period.
Change From Baseline of Awake Objective Cough Frequency (Periods 1 & 2 Combined)
Time frame: Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2)
Cough monitoring was conducted for 24 hours while awake, at pre-dose on Day 0 (baseline), and after administration of the study drug on Day 7 and Day 14 in Periods 1 and 2. The cough frequency is the coughs/hour over each 24-hour period. Awake objective cough frequency was defined as the total number of cough events during the monitoring period the participant was awake divided by the total duration for the monitoring period the participant was awake. Baseline cough frequency was derived from the cough monitoring performed at the beginning of each treatment period while the post-treatment cough frequency was derived from the cough monitoring performed at the end of the dosing period. A negative value indicates a decrease in cough frequency.
Percent Change From Baseline of Awake Objective Cough Frequency (Periods 1 & 2 Combined)
Time frame: Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2)
Awake objective cough frequency was defined as the total number of cough events during the monitoring period the participant was awake divided by the total duration for the monitoring period the participant was awake. Percent change from baseline in awake objective cough frequency (0-6 hours after the morning dose) was reported at each dosing interval. Percent change in awake cough frequency = 100 X (post treatment cough frequency - baseline cough frequency) divided by the baseline cough frequency. A negative value indicates a decrease in cough frequency.
22 secondary outcomes
MMRM Analysis of Change From Baseline in Awake Objective Cough Frequency (Period 1)
Time frame: Baseline (Day 0), Day 7, and Day 14 (Period 1)
MMRM Analysis of Change From Baseline in Awake Objective Cough Frequency (Period 2)
Time frame: Baseline (Day 0), Day 7, and Day 14 (Period 2)
Responder Analysis of Awake Cough Frequency at Day 7 (Periods 1 & 2 Combined)
Time frame: Day 7 (Period 1 and Period 2)
Responder Analysis of Awake Cough Frequency at Day 14 (Periods 1 & 2 Combined)
Time frame: Day 14 (Period 1 and Period 2)
MMRM Analysis of Change From Baseline 24-hour Objective Cough Frequency (Periods 1 & 2 Combined)
Time frame: Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2)
MMRM Analysis of Change From Baseline in 24-hour Objective Cough Frequency (Period 1)
Time frame: Baseline (Day 0), Day 7, and Day 14 (Period 1)
MMRM Analysis of Change From Baseline in 24-hour Objective Cough Frequency (Period 2)
Time frame: Baseline (Day 0), Day 7, and Day 14 (Period 2)
24-hour Objective Cough Frequency (Periods 1 & 2 Combined)
Time frame: Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2)
Change From Baseline of 24-hour Cough Frequency (Periods 1 & 2 Combined)
Time frame: Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2)
Percent Change From Baseline of 24-hour Cough Frequency (Periods 1 & 2 Combined)
Time frame: Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2)
MMRM Analysis of Change From Baseline in Sleep Cough Frequency (Periods 1 & 2 Combined)
Time frame: Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2)
MMRM Analysis of Change From Baseline in Cough Visual Analog Scale (VAS) (Periods 1 & 2 Combined)
Time frame: Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2)
MMRM Analysis of Change From Baseline in Cough Quality of Life Questionnaire (CQLQ) (Periods 1 & 2 Combined)
Time frame: Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2)
MMRM Analysis of Change From Baseline in Total Daily Cough Severity Diary (CSD) Score (Periods 1 & 2 Combined)
Time frame: Baseline (Day 0), Week 1, and Week 2 (Period 1 and Period 2)
MMRM Analysis of Change From Baseline in University of California San Diego Shortness of Breath Questionnaire (UCSD SOBQ) (Periods 1 & 2 Combined)
Time frame: Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2)
MMRM Analysis of Change From Baseline in Cough Borg CR10 Scale Score (Periods 1 & 2 Combined)
Time frame: Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2)
Percentage of Participants With Borg CR10 Perception of Breathless Value ≥5 (Periods 1 & 2 Combined)
Time frame: Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2)
Patient's Global Impression of Change (PGIC) Day 7 (Periods 1 & 2 Combined)
Time frame: Day 7 (Period 1 and Period 2)
Patient's Global Impression of Change (PGIC) Day 15 (Periods 1 & 2 Combined)
Time frame: Day 15 (Period 1 and Period 2)
Clinician's Global Impression of Change (CGIC) Day 15 (Periods 1 & 2 Combined)
Time frame: Day 15 (Period 1 and Period 2)
Taste Acceptability Questionnaire: Number of Participants That Were Likely to Take Study Medication For At Least Six Months
Time frame: After last treatment, up to Day 15 (Period 1 and Period 2)
Taste Acceptability Questionnaire: Number of Participants That Were Likely to Take Study Medication For At Least One Year
Time frame: After last treatment, up to Day 15 (Period 1 and Period 2)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 May 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34152585Martinez FJ, Afzal AS, Smith JA, Ford AP, Li JJ, Li Y, Kitt MM; Chronic Cough in IPF Study Group. Treatment of Persistent Cough in Subjects with Idiopathic Pulmonary Fibrosis (IPF) with Gefapixant, a P2X3 Antagonist, in a Randomized, Placebo-Controlled Clinical Trial. Pulm Ther. 2021 Dec;7(2):471-486. doi: 10.1007/s41030-021-00162-9. Epub 2021 Jun 21.
- Individual participant dataSharing planned: Yes. http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
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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.
Medical Director study director
Merck Sharp & Dohme LLC
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Gefapixant in people with Idiopathic Pulmonary Fibrosis and 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 9 inclusion and 18 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 26 May 2021. 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. 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 26 May 2021). 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?
Mixed Model of Repeated Measures (MMRM) Change From Baseline in Awake Objective Cough Frequency (Periods 1 & 2 Combined) (time frame: Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2)). The study lists 4 primary outcomes in all. 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 NCT02502097, which also lists 1 linked publication.
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 26 May 2021.