A Phase 3, Randomized, Double-Blind, Placebo-Controlled, 12-Month Study to Evaluate the Efficacy and Safety of MK-7264 in Adult Participants With Chronic Cough (PN030)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,317
- 试验地点
- 171
- 主要终点
- Model-Based Geometric Mean Ratio (GMR) of 24-Hour Coughs Per Hour at Week 24/Baseline
研究概览
简要总结
The primary objectives of this study are to evaluate the efficacy of gefapixant (MK-7264) in reducing cough frequency as measured over a 24-hour period, and to determine the safety and tolerability of gefapixant. The primary hypothesis is that at least one dose of gefapixant is superior to placebo in reducing coughs per hour (over 24 hours) at Week 24.
详细描述
This study will have a main 24-week treatment period and a 28-week extension period of treatment (total treatment period of 52 weeks). Participants at selected sites and countries who complete the main and extension study periods may consent to participate in an observational, 12-week, Off-treatment Durability Study Period. Any assessments conducted in the observational period will be exploratory.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Chest radiograph or computed tomography scan of the thorax (within 5 years of Screening/Visit 1 and after the onset of chronic cough) not demonstrating any abnormality considered to be significantly contributing to the chronic cough or any other clinically significant lung disease in the opinion of the principal investigator or the sub-investigator
- •Has had chronic cough for at least 1 year with a diagnosis of refractory chronic cough or unexplained chronic cough
- •Is a female who is not pregnant, not breastfeeding, not of childbearing potential, or agrees to follow contraceptive guidance
- •Provides written informed consent and is willing and able to comply with the study protocol (including use of the digital cough recording device and completion of study questionnaires)
排除标准
- •Is a current smoker or has given up smoking within 12 months of Screening, or is a former smoker with greater than 20 pack-years
- •Has a history of respiratory tract infection or recent clinically significant change in pulmonary status
- •Has a history of chronic bronchitis
- •Is currently taking an angiotensin converting enzyme inhibitor (ACEI), or has used an ACEI within 3 months of Screening
- •Has an estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m^2 at Screening OR an eGFR ≥30 mL/min/1.73 m^2 and <50 mL/min/1.73 m^2 at Screening with unstable renal function
- •Has a history of malignancy ≤5 years
- •Is a user of recreational or illicit drugs or has had a recent history of drug or alcohol abuse or dependence
- •Has a history of anaphylaxis or cutaneous adverse drug reaction (with or without systemic symptoms) to sulfonamide antibiotics or other sulfonamide-containing drugs
- •Has a known allergy/sensitivity or contraindication to gefapixant
- •Has donated or lost ≥1 unit of blood within 8 weeks prior to the first dose of gefapixant
- •Has previously received gefapixant
- •Currently participating in or has participated in an interventional clinical study within 30 days of screening
研究组 & 干预措施
Placebo
Participants will receive a matching placebo tablet BID during the 24-week main study period and the 28-week extension period.
干预措施: Placebo (Drug)
Gefapixant 15 mg BID
Participants will receive a gefapixant 15 mg tablet BID and placebo tablet to match gefapixant 45 mg BID during the 24-week main study period and the 28-week extension period.
干预措施: Placebo (Drug)
Gefapixant 15 mg BID
Participants will receive a gefapixant 15 mg tablet BID and placebo tablet to match gefapixant 45 mg BID during the 24-week main study period and the 28-week extension period.
干预措施: Gefapixant 15 mg BID (Drug)
Gefapixant 45 mg BID
Participants will receive a gefapixant 45 mg tablet BID and placebo tablet to match gefapixant 15 mg BID during the 24-week main study period and during the 28-week extension period.
干预措施: Placebo (Drug)
Gefapixant 45 mg BID
Participants will receive a gefapixant 45 mg tablet BID and placebo tablet to match gefapixant 15 mg BID during the 24-week main study period and during the 28-week extension period.
干预措施: Gefapixant 45 mg BID (Drug)
结局指标
主要结局
Model-Based Geometric Mean Ratio (GMR) of 24-Hour Coughs Per Hour at Week 24/Baseline
时间窗: Baseline, Week 24
24-hour coughs per hour was defined as the average hourly cough frequency based on 24-hour sound recordings using a digital recording device (cough monitor). A longitudinal analysis of covariance (ANCOVA) model was applied to log-transformed cough data to determine geometric mean (GM) 24-hour coughs per hour at baseline and week 24. The GMR (Week 24 GM 24-hour coughs per hour divided by Baseline GM 24-hour coughs per hour) is reported.
Number of Participants Who Experienced At Least One Adverse Event (AE) During Treatment and Follow-up
时间窗: Up to 54 Weeks
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.
Number of Participants Who Discontinued a Study Drug Due to an AE
时间窗: Up to 52 weeks
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.
次要结局
- Percentage of Participants With a ≥1.3 Point Change From Baseline in the Leicester Questionnaire (LCQ) Total Score at Week 24(Baseline, Week 24)
- Model-Based GMR of Awake Coughs Per Hour at Week 24/Baseline(Baseline, Week 24)
- Percentage of Participants With a ≤-30% Change From Baseline in 24-hour Coughs Per Hour at Week 24(Baseline, Week 24)
- Percentage of Participants With ≤-1.3 Point Change From Baseline of Mean Weekly Cough Severity Diary (CSD) Total Score at Week 24(Baseline, Week 24)
- Percentage of Participants With ≤-2.7 Point Change From Baseline of Mean Weekly CSD Total Score at Week 24(Baseline, Week 24)
- Percentage of Participants With a ≤-30 Millimeter (mm) Change From Baseline in Cough Severity Visual Analog Scale (VAS) Score at Week 24(Baseline, Week 24)