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临床试验/NCT05964335
NCT05964335已完成2 期

A Randomized, Double-Blind, Placebo-Controlled, Parallel, 4-Arm Dose Ranging Study of the Safety and Efficacy of Nalbuphine Extended-Release Tablets (NAL ER) for the Treatment of Cough in Idiopathic Pulmonary Fibrosis (IPF)

Trevi Therapeutics107 个研究点 分布在 10 个国家目标入组 165 人开始时间: 2024年2月6日最近更新:
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适应症
干预措施
相关药物

试验速览

阶段
2 期
状态
已完成
入组人数
165
试验地点
107
主要终点
Relative Change From Baseline in 24-hour Cough Frequency at Week 6
研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验相关资讯

研究概览

简要总结

The main purpose of the study is to evaluate the effect of NAL ER on 24-hour cough frequency using objective digital cough monitoring and to assess safety and tolerability of NAL ER.

详细描述

This is a multi-center randomized, double-blind, placebo-controlled, parallel, 4-arm study.

After meeting eligibility during the Screening Period, subjects will be randomized (1:1:1:1) to one of four treatment arms.

  • Arm 1: Placebo
  • Arm 2: 27 mg nalbuphine ER
  • Arm 3: 54 mg nalbuphine ER
  • Arm 4: 108 mg nalbuphine ER

Each arm will be titrated to their fixed dose during the blinded 2-week Titration period according to Table: Dosing Scheme, followed by the 4-week Fixed Dose Period for a total of 6 weeks on drug.

Subjects will be taken off study drug at the end of the Fixed Dose Period and followed off treatment for an additional 2 weeks.

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

  • •Diagnosis of IPF as determined by the Principal Investigator based on ATS/ERS/JRS/ALAT guidelines.
  • •Cough Severity Score ≥ 4 on CS-NRS (Cough Severity Numerical Rating Scale) during the Screening period and Baseline.
  • •History of chronic cough for at least 8 weeks before screening.
  • •SpO2 ≥ 92%, taken after at least 5 minutes in a sitting position, undisturbed and non-stimulated (Saturation of Hemoglobin with Oxygen as Measured by Pulse Oximetry).
  • •FVC ≥ 40% predicted of normal - Forced Vital Capacity, as determined by spirometry adhering to ATS/ERS guidelines.
  • •DLCO ≥ 25% predicted of normal - Diffusing capacity of the lung for carbon monoxide corrected for hemoglobin, assessed within the last 12 weeks, or at the time of screening.

排除标准

  • •Currently on continuous oxygen therapy for longer than 16 hours at any level or delivered by any modality. Intermittent oxygen use of any duration over any given 24-hour period is allowed.
  • •Inadequate swallow reflex as assessed by the ability to sip 3 fluid oz (or 89 mL) of water without coughing or choking.
  • •Upper or lower respiratory tract infection in the last 8 weeks prior to the baseline visit.
  • •Clinical history of aspiration pneumonitis.
  • •Diagnosis of sleep apnea.
  • •Abnormal kidney or liver functions based on Screening lab results.
  • •Known hypersensitivity to nalbuphine or to NAL ER excipients
  • •History of major psychiatric disorder.
  • •History of substance abuse.
  • •Significant medical condition or other factors that may interfere with the participant's ability to successfully complete the study.
  • •Pregnant or lactating female participant.
  • •Known intolerance (gastrointestinal, central nervous system symptoms), hypersensitivity, drug allergy following the use of an opioid drug.
  • •Use of opiates is prohibited within 14 days prior to the baseline visit.
  • •Use of benzodiazepines are prohibited within 14 days prior to the baseline visit and for the duration of the study.
  • •Monoamine oxidase inhibitors (MAOIs) including methylene blue (methylthioninium chloride) and the antibiotic linezolid are prohibited within 14 days prior to the baseline visit and for the duration of the study.
  • •Use of oral corticosteroid cough treatment is prohibited within 4 weeks prior to the baseline visit and for the duration of the study.
  • •Exposure to any investigational medication, including placebo, is prohibited within 4 weeks prior to the baseline visit and for the duration of the study.
  • •Medications prescribed as cough suppressants are prohibited unless on a stable dose 14-days prior to the baseline visit and are expected to remain on that dose for the duration of the study.
  • •Use of medications that affect serotonergic neurotransmission and that when used concomitantly with opioids can increase the risk of serotonin syndrome are prohibited unless on a stable dose 14-days prior to the baseline visit and are expected to remain on that dose for the duration of the study.
  • •Anti-fibrotic medications are prohibited unless on a stable dose for 8 weeks prior to the baseline visit and are expected to remain on that dose for the duration of the study.
  • •Strong inhibitors/inducers of the P450 Isozymes are prohibited unless on a stable dose for 14-days prior to baseline visit and are expected to remain on that dose for the duration of the study.
  • •Use of a medication having a "known risk" of Torsade de Pointes (categorized as "KR" on the Credible Meds® website.) 4 weeks prior to Baseline.
  • •Use of unstable doses of medications associated with a potential risk of QT prolongation but not clearly associated with Torsade de Pointes within 4 weeks of screening.
  • •Other protocol defined inclusion/exclusion criteria may apply.

研究组 & 干预措施

NAL ER 27 mg

Experimental

Participants were titrated over 2 weeks to NAL ER 27 mg BID, then maintained at the fixed dose for 4 weeks (total 6 weeks of treatment).

干预措施: NAL ER (Drug)

Placebo

Placebo Comparator

Participants received a matching placebo BID, using the same 2-week blinded titration schedule and 4-week fixed-dose period as the active treatment arms (6 weeks total).

干预措施: Placebo (Drug)

NAL ER 54 mg

Experimental

Participants were titrated over 2 weeks to NAL ER 54 mg BID, then maintained at the fixed dose for 4 weeks (total 6 weeks of treatment).

干预措施: NAL ER (Drug)

NAL ER 108 mg

Experimental

Participants were titrated over 2 weeks to NAL ER 108 mg BID, then maintained at the fixed dose for 4 weeks (total 6 weeks of treatment).

干预措施: NAL ER (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

Relative change in 24-hour (combined daytime and nighttime) cough frequency (coughs per hour) from baseline was assessed. Assessment was done using objective digital cough monitoring. The relative change from baseline = \[ (Post-baseline - Baseline) / Baseline\] × 100. The baseline value was defined as the last non-missing observation prior to the date of the first dose of study.

次要结局

  • Relative Change From Baseline in Evaluating Respiratory Symptoms in Idiopathic Pulmonary Fibrosis (E-RS:IPF) Cough Subscale at Week 6(Baseline, Week 6)
  • Number of Participants Who Experienced at Least One Treatment Emergent Adverse Events (TEAEs)(Up to Week 12)
  • Relative Change From Baseline in 24-hour Cough Frequency at Week 6(Baseline, Weeks 6)
  • Percentage of Responders With ≥30%, ≥50% and ≥75% Reduction in the 24-Hour Cough Frequency at Week 6(At Week 6)
  • Relative Change From Baseline in Awake Cough Frequency at Week 6(Baseline, Week 6)
  • Relative Change From Baseline in Sleep Cough Frequency at Week 6(Baseline, Week 6)
  • Relative Change From Baseline in E-RS: IPF Cough Subscale at Week 6(Baseline, Week 6)
  • Percentage of E-RS: IPF Cough Subscale Responders With At Least One Category Improvement at Week 6(At Week 6)
  • Change From Baseline in E-RS:IPF Total Score at Week 6(Baseline, Week 6)
  • Change From Baseline in IPF-Breathlessness Subdomain Score at Week 6(Baseline, Week 6)
  • Change From Baseline in IPF-Cough Subdomain Score at Week 6(Baseline, Week 6)
  • Change From Baseline in IPF-Sputum Subdomain Score at Week 6(Baseline, Week 6)
  • Change From Baseline in L-IPF Symptoms Domain Scores at Week 6(Baseline, Week 6)
  • Change From Baseline in IPF-Chest Subdomain Score at Week 6(Baseline, Week 6)
  • Change From Baseline in Cough Severity Numerical Rating Scale (CS-NRS) at Week 6(Baseline, Week 6)
  • Change From Baseline in LCQ Domains at Week 6(Baseline, Week 6)
  • Change From Baseline in Living With Pulmonary Fibrosis Impacts Questionnaire (L-IPF©) Impacts Raw Sum Score at Week 6(Baseline, Week 6)
  • Number of Participants With Shift From Baseline in European Quality of Life 5 Dimensions 5 Level (EQ-5D-5L™) at Week 6(Baseline, Week 6)
  • Change From Baseline in Patient Global Impression of Severity (PGI-S) Cough Score at Week 6(Baseline, Week 6)
  • Patient Global Impression of Change (PGI-C) Cough Score at Week 6(At Week 6)
  • Percentage of Participants With Improvement by ≥1 and ≥ 2 on PGI-C Cough(At Week 6)
  • Percentage of Participants With Worsening by ≥1 and ≥2 on PGI-C Cough(At Week 6)
  • Percentage of Participants With no Change on PGI-C Cough(At Week 6)
  • Percentage of Participants With Improvement by ≥1 and ≥2 on PGI-S Cough(At Week 6)
  • Percentage of Participants With Worsening by ≥1 and ≥2 and PGI-S Cough(At Week 6)
  • Percentage of Participants With no Change on PGI-S Cough(At Week 6)
  • Change From Baseline in PGI-S IPF at Week 6(Baseline, Week 6)
  • PGI-C IPF Score at Week 6(At Week 6)
  • Percentage of Participants With Improvement by ≥1 and ≥2 on PGI-C IPF(At Week 6)
  • Percentage of Participants With Worsening by ≥1 and ≥2 on PGI-C IPF(At Week 6)
  • Percentage of Participants With no Change on PGI-C IPF(At Week 6)
  • Percentage of Participants With Improvement by ≥1 and ≥2 on PGI-S-IPF(At Week 6)
  • Percentage of Participants With Worsening by ≥1 and ≥2 on PGI-S-IPF(At Week 6)
  • Percentage of Participants With no Change on PGI-S-IPF(At Week 6)
  • Change From Baseline in Clinicians Global Impression of Severity (CGI-S) Score at Week 6(Baseline, Week 6)
  • CGI-C IPF Score at Week 6(At Week 6)
  • Percentage of Participants With Improvement by ≥1 and ≥2 on the Clinicians Global Impression of Change (CGI-C) at Week 6(At Week 6)
  • Percentage of Participants With Worsening by ≥1 and ≥2 on the CGI-C at Week 6(At Week 6)
  • Percentage of Participants With no Change on the CGI-C at Week 6(At Week 6)
  • Percentage of Participants With Improvement by ≥1 and ≥2 on the Clinicians Global Impression of Severity (CGI-S) at Week 6(At Week 6)
  • Percentage of Participants With Worsening by ≥1 and ≥2 on the CGI-S at Week 6(At Week 6)
  • Percentage of Participants With no Change on the CGI-S at Week 6(At Week 6)
  • Percentage of Participants With Improvement by ≥1 and ≥2 Categories, Worsening by ≥1 and ≥2 Categories, and no Change on the PGI-C and PGI-S IPF at Weeks 2, 4, and 6(At Weeks 2, 4, and 6)
  • Change From Baseline in Clinicians Global Impression of Severity (CGI-S) score at Week 6(Baseline, Week 6)
  • Absolute Values for CGI-C IPF Score at Week 6(At Week 6)
  • Percentage of Participants With Improvement by ≥1 and ≥2 Categories, Worsening by ≥1 and ≥2 Categories, and no Change on the CGI-C and CGI-S at Week 6(At Week 6)
  • Change From Baseline in Evaluating Respiratory Symptoms in Idiopathic Pulmonary Fibrosis (E-RS:IPF) Cough subscale at Week 6(Baseline, Week 6)
  • Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs)(Up to Week 12)
  • Relative Change From Baseline in 24-hour Cough Frequency at Weeks 2,4, and 6(Baseline, Weeks 2, 4, and 6)
  • Percentage of Responders With ≥30%, ≥50% and ≥75% Reduction in the 24-Hour Cough Frequency at Week 2, 4, and 6(At Weeks 2, 4, and 6)
  • Relative Change From Baseline in Awake Cough Frequency at Week 2, 4, and 6(Baseline, Weeks 2, 4, and 6)
  • Relative Change From Baseline in Sleep Cough Frequency at Week 2, 4, and 6(Baseline, Weeks 2, 4, and 6)
  • Change From Baseline in E-RS: IPF Cough Subscale at Weeks 1, 2, 3, 4, 5, and 6(Baseline, Weeks 1, 2, 3, 4, 5, 6)
  • Percentage of E-RS: IPF Cough Subscale Responders With At least one Category Improvement at Weeks 1, 2, 3, 4, 5, and 6(At Weeks 1, 2, 3, 4, 5, and 6)
  • Change From Baseline in E-RS: IPF Total Score, Subdomain Scores (IPF-Breathlessness, IPF-Cough, IPF-Sputum, and IPF-Chest Symptoms) and Individual Items at Weeks 1, 2, 3, 4, 5, and 6(Baseline, Weeks 1, 2, 3, 4, 5, and 6)
  • Change From Baseline in Cough Severity Numerical Rating Scale (CS-NRS) at Weeks 1, 2, 3, 4, 5, and 6(Baseline, Weeks 1, 2, 3, 4, 5, and 6)
  • Change From Baseline in LCQ Domains and Individual Items at Week 6(Baseline, Week 6)
  • Change From Baseline in Living With Pulmonary Fibrosis Impacts Questionnaire (L-IPF©) at Week 6(Baseline, Week 6)
  • Change From Baseline in Living With Pulmonary Fibrosis Symptoms Questionnaire (L-IPF) and its Domains at Week 6(Baseline, Week 6)
  • Change from Baseline in EuroQol 5-Dimension 5-Level (EQ-5D-5L™) at Week 6(Baseline, Week 6)
  • Change From Baseline in Patient Global Impression of Severity (PGI-S) Cough at Weeks 2, 4, and 6(Baseline, Weeks 2, 4, and 6)
  • Absolute Values of PGI-C Cough Score at Weeks 2, 4, and 6(At Weeks 2, 4, and 6)
  • Percentage of Participants With Improvement by ≥1 and ≥2 Categories, Worsening by ≥1 and ≥2 Categories, and no Change on PGI-C and PGI-S Cough at Each Post-Baseline Timepoint(At Weeks 2, 4, and 6)
  • Change from Baseline in PGI-S IPF at Weeks 2, 4, and 6(Baseline, Weeks 2, 4, and 6)
  • Absolute Values of PGI-C IPF at Weeks 2, 4, and 6(At Weeks 2, 4, and 6)
  • Change From Baseline in Leicester Cough Questionnaire (LCQ) Total Score at Week 6(Baseline, Week 6)
  • Percentage of LCQ Total Score Responders With 1.3-Point Increase Response at Week 6(At Week 6)

研究者

申办方类型
Industry
责任方
Sponsor

研究点 (107)

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