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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 51
- 主要终点
- Change From Baseline of Awake Objective Cough Frequency (Periods 1 & 2 Combined)
研究概览
简要总结
A randomized, double-blind, placebo-controlled, crossover, dose escalation study of gefapixant (AF-219) in participants with Idiopathic Pulmonary Fibrosis (IPF) with persistent cough.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •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
排除标准
- •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
- •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
研究组 & 干预措施
Gefapixant>Placebo Pre-Amendment 3
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
干预措施: Gefapixant (Drug)
Gefapixant>Placebo Pre-Amendment 3
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
干预措施: Placebo (Other)
Placebo>Gefapixant Pre-Amendment 3
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
干预措施: Gefapixant (Drug)
Placebo>Gefapixant Pre-Amendment 3
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
干预措施: Placebo (Other)
Gefapixant>Placebo Post-Amendment 3
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
干预措施: Gefapixant (Drug)
Gefapixant>Placebo Post-Amendment 3
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
干预措施: Placebo (Other)
Placebo>Gefapixant Post-Amendment 3
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
干预措施: Gefapixant (Drug)
Placebo>Gefapixant Post-Amendment 3
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
干预措施: Placebo (Other)
结局指标
主要结局
Change From Baseline of Awake Objective Cough Frequency (Periods 1 & 2 Combined)
时间窗: 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.
Mixed Model of Repeated Measures (MMRM) Change From Baseline in Awake Objective Cough Frequency (Periods 1 & 2 Combined)
时间窗: 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.
Percent Change From Baseline of Awake Objective Cough Frequency (Periods 1 & 2 Combined)
时间窗: 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.
Awake Objective Cough Frequency (Periods 1 & 2 Combined)
时间窗: 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.
次要结局
- MMRM Analysis of Change From Baseline 24-hour Objective Cough Frequency (Periods 1 & 2 Combined)(Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2))
- MMRM Analysis of Change From Baseline in Awake Objective Cough Frequency (Period 1)(Baseline (Day 0), Day 7, and Day 14 (Period 1))
- Responder Analysis of Awake Cough Frequency at Day 7 (Periods 1 & 2 Combined)(Day 7 (Period 1 and Period 2))
- 24-hour Objective Cough Frequency (Periods 1 & 2 Combined)(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)(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)(Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2))
- Responder Analysis of Awake Cough Frequency at Day 14 (Periods 1 & 2 Combined)(Day 14 (Period 1 and Period 2))
- MMRM Analysis of Change From Baseline in Sleep Cough Frequency (Periods 1 & 2 Combined)(Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2))
- MMRM Analysis of Change From Baseline in Awake Objective Cough Frequency (Period 2)(Baseline (Day 0), Day 7, and Day 14 (Period 2))
- MMRM Analysis of Change From Baseline in 24-hour Objective Cough Frequency (Period 1)(Baseline (Day 0), Day 7, and Day 14 (Period 1))
- MMRM Analysis of Change From Baseline in 24-hour Objective Cough Frequency (Period 2)(Baseline (Day 0), Day 7, and Day 14 (Period 2))
- Percent Change From Baseline of 24-hour Cough Frequency (Periods 1 & 2 Combined)(Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2))
- Patient's Global Impression of Change (PGIC) Day 15 (Periods 1 & 2 Combined)(Day 15 (Period 1 and Period 2))
- Clinician's Global Impression of Change (CGIC) Day 15 (Periods 1 & 2 Combined)(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(After last treatment, up to Day 15 (Period 1 and Period 2))
- Change From Baseline of 24-hour Cough Frequency (Periods 1 & 2 Combined)(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)(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)(Baseline (Day 0), Week 1, and Week 2 (Period 1 and Period 2))
- Taste Acceptability Questionnaire: Number of Participants That Were Likely to Take Study Medication For At Least Six Months(After last treatment, up to Day 15 (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)(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)(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)(Day 7 (Period 1 and Period 2))