A Randomized, Double-Blind, Placebo-Controlled Dose-Ranging Study to Evaluate the Efficacy and Safety of Nalbuphine Extended-Release Tablets for the Treatment of Participants With Refractory Chronic Cough
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 100
- 试验地点
- 10
- 主要终点
- Relative Change From Baseline in 24-hour Cough Frequency at Week 6
研究概览
简要总结
The purpose of this study is to evaluate the efficacy and safety of Nalbuphine ER Extended-release tablets for the treatment of participants with RCC.
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
- •Meets society guideline-based criteria for a diagnosis of RCC defined as:
- •Insufficient improvement in cough after treatment for any identified cough-associated conditions.
- •Unexplained cough for which an underlying condition has not been determined despite adequate investigation with diagnostic tests and trials of therapy.
- •Persistent and chronic cough for at least one year prior to Screening.
- •Chest computed tomography (CT) or chest radiograph of the thorax performed within the last 24 months and after the onset of chronic cough OR the procedure completed by the Investigator during the Screening period, that does not show any abnormality considered to be significantly contributing to the RCC in the opinion of the Principal Investigator.
- •24-hour objective cough frequency ≥10 coughs/hour based on VitaloJAK® cough monitor recording performed during the Screening and Placebo Run-in Periods as well as a minimum recording duration of 20 hours suitable for analysis during the placebo Run-in assessment.
- •Forced expiratory volume in 1 second (FEV1) /forced vital capacity (FVC) ratio ≥ 60% as determined by spirometry adhering to American Thoracic Society (ATS)/European Respiratory Society (ERS) guidelines.
排除标准
- •Clinical diagnosis of sleep apnea and/or use of continuous positive airway pressure (CPAP).
- •Upper or lower respiratory tract infection or change in pulmonary status in the 4 weeks prior to the Screening visit or during the Screening or PBO Run-in periods.
- •History of bronchiectasis, chronic obstructive pulmonary disease (COPD) or idiopathic pulmonary fibrosis (IPF), or other significant respiratory disorder that might affect cough.
- •History of uncontrolled asthma defined as one of the following:
- •≥1 clinically significant exacerbation in the last 6 months, OR
- •≥2 clinically significant exacerbations in the past 12 months (a clinically significant asthma exacerbation is defined as requiring the use of systemic corticosteroids).
- •Current smoker or vaper or current use of tobacco smoke, cannabis smoke, or nicotine vaper.
- •Individuals who have stopped smoking or vaping within the past 6 months, or those with >20 pack-year smoking history.
- •Current active tuberculosis or nontuberculous mycobacterial infection, a history of latent untreated tuberculosis, or a history of incompletely treated tuberculosis.
- •Speech therapy/physiotherapy for RCC starting within 4 weeks of Baseline or during the study. Speech therapy/physiotherapy is acceptable if the participant has started the therapy more than 4 weeks prior to the Baseline visit AND plans to continue the therapy through the Titration and Fixed-dose Treatment Period.
- •Known intolerance [gastrointestinal, central nervous system (CNS) symptoms], hypersensitivity, or drug allergy considered to be related to an opioid drug or known hypersensitivity to nalbuphine or to NAL ER excipients.
- •Note: Other protocol-defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
NAL ER 27 mg BID
Participants will receive NAL ER during the titration period, starting at 27 mg QD to 27 mg BID from Day 1 to Day 14. Participants will receive NAL ER 27 mg BID during the fixed-dose treatment period from Day 15 to Day 42.
干预措施: Placebo (Drug)
Placebo
Participants will receive matching placebo during the titration period from Day 1 to Day 14 and the fixed-dose treatment period from Day 15 to Day 42.
干预措施: Placebo (Drug)
NAL ER 54 mg BID
Participants will receive NAL ER during the titration period, with dose titration starting at 27 milligrams (mg) once daily (QD) and increasing up to 54 mg twice daily (BID) from Day 1 to Day 14. Participants will receive NAL ER 54 mg BID during the fixed-dose treatment period from Day 15 to Day 42.
干预措施: NAL ER (Drug)
NAL ER 27 mg QD
Participants will receive NAL ER 27 mg QD during the titration period from Day 1 to Day 14. Participants will continue to receive NAL ER 27 mg QD during the fixed-dose treatment period from Day 15 to Day 42.
干预措施: NAL ER (Drug)
NAL ER 54 mg BID
Participants will receive NAL ER during the titration period, with dose titration starting at 27 milligrams (mg) once daily (QD) and increasing up to 54 mg twice daily (BID) from Day 1 to Day 14. Participants will receive NAL ER 54 mg BID during the fixed-dose treatment period from Day 15 to Day 42.
干预措施: Placebo (Drug)
NAL ER 27 mg BID
Participants will receive NAL ER during the titration period, starting at 27 mg QD to 27 mg BID from Day 1 to Day 14. Participants will receive NAL ER 27 mg BID during the fixed-dose treatment period from Day 15 to Day 42.
干预措施: NAL ER (Drug)
NAL ER 27 mg QD
Participants will receive NAL ER 27 mg QD during the titration period from Day 1 to Day 14. Participants will continue to receive NAL ER 27 mg QD during the fixed-dose treatment period from Day 15 to Day 42.
干预措施: Placebo (Drug)
结局指标
主要结局
Relative Change From Baseline in 24-hour Cough Frequency at Week 6
时间窗: Baseline, Week 6
次要结局
- Relative Change From Baseline in 24-hour Cough Frequency(Baseline up to Week 6)
- Percentage of Participants Achieving ≥30%, ≥50% and ≥75% Reduction in 24-hour Cough Frequency(Baseline up to Week 6)
- Change From Baseline in Patient Reported Cough Frequency (PR-CF)(Baseline up to Week 6)
- Change From Baseline in Cough Severity Visual Analog Scale (CS-VAS)(Baseline up to Week 6)
- Percentage of Participants Achieving a 30 Millimeter (mm) Improvement in CS-VAS Total Score(Baseline up to Week 6)
- Change From Baseline in Cough Severity Numerical Rating Scale (CS-NRS)(Baseline up to Week 6)
- Change From Baseline in McMaster Cough Severity Questionnaire (MCSQ) Total Score(Baseline up to Week 6)
- Change From Baseline in MCSQ Domains (Intensity and Frequency)(Baseline up to Week 6)
- Change From Baseline in Leicester Cough Questionnaire (LCQ) Total Score at Week 6(Baseline, Week 6)
- Change From Baseline in Each LCQ Domain Score (Physical, Psychological, Social) at Week 6(Baseline, Week 6)
- Percentage of Participants Achieving a 1.3- Point Increase From Baseline in LCQ Total Score at Week 6(Baseline, Week 6)
- Relative Change From Baseline in Awake Cough Frequency(Baseline up to Week 6)
- Relative Change From Baseline in Sleep Cough Frequency(Baseline up to Week 6)
- Change From Baseline in Patient Global Impression of Severity (PGI-S) Cough Score(Baseline up to Week 6)
- Mean Patient Global Impression of Change for Cough (PGI-C) Cough Score(Up to Week 6)
- Change From Baseline in International Consultation on Incontinence Questionnaire - Urinary Incontinence Short Form (ICIQ-UI SF) Score at Week 6(Baseline, Week 6)
- Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs)(Up to Day 63)