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临床试验/2023-505296-72-00
2023-505296-72-00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 Therapeutics Inc.23 个研究点 分布在 5 个国家目标入组 90 人开始时间: 2023年11月29日最近更新:
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试验速览

阶段
2 期
状态
已完成
发起方
入组人数
90
试验地点
23
主要终点
Relative change from Baseline in 24-hour cough frequency (coughs per hour) at Week 6 for NAL ER compared with placebo.
研究概览入排标准结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

Effect of NAL ER on 24-hour cough frequency (coughs per hour) at Week 6 using objective digital cough monitoring.

入排标准

年龄范围
18 years 至 65+ years（65+ Years, 18-64 Years）
接受健康志愿者
是

入选标准

  • •Diagnosis of IPF as determined by the 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 – Force Vital Capacity, as determined by spirometry adhering to ATS/ERS guidelines.
  • •DLCO ≥ 25% predicted of normal - Diffusing capacity of the lungs for carbon monoxide corrected for hemoglobin, assessed within the last 12 weeks, or at the time of screening.
  • •Males or females ages 18 years and older at the time of consent.
  • •Willing and able to provide written informed consent, comply with study requirements and restrictions, and agree to the confidential use and storage of all data and use of all anonymized data for publication including scientific publication.

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.
  • •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 prescribed as cough treatment is prohibited within 4 weeks prior to the baseline visit and for the duration of the study.
  • •Inadequate swallow reflex as assessed by the ability to sip 3 fluid oz (or 90 mL) of water without coughing or choking.
  • •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.
  • •Upper or lower respiratory tract infection in the last 8 weeks prior to the baseline visit.
  • •Clinical history of aspiration pneumonitis.
  • •History of major psychiatric disorder, which in the opinion of the Investigator, could interfere with the assessment of anti-cough efficacy and/or safety events during the study or with the ability of the subject to cooperate with study requirements.
  • •Diagnosis of sleep apnea.
  • •Cardiac Safety: Mean QTcF value of 3 centrally read screening electrocardiograms (ECGs) calculated as: a) ≥470ms if QRS <120ms or b) ≥500ms in the presence of either a Right Bundle Branch Block (RBBB) or QRS ≥120ms.
  • •Heart Rate: <50 bpm or >100 bpm, as determined by vital signs pulse over 30-60 seconds. a) Subjects with a resting heart rate of <50 bpm will have it repeated once after 5 minutes in the supine position, and if it remains <50 bpm during the repeat, they will be considered a screen failure. b) Subjects with a rate >100 bpm should be considered a screen failure. Rescreening may be possible with the approval of the medical monitor, after medical or alternative management of the atrial fibrillation.
  • •Kidney Function: Estimated glomerular filtration rate ≤44 mL/min/1.73 m2 at screening.
  • •Liver Function: Total Bilirubin >3mg/dL [>50umol/L] and Serum Albumin <2.8g/dL at screening.
  • •Known hypersensitivity to nalbuphine or to NAL ER excipients.
  • •Use of a medication having a “known risk” of Torsade de Pointes (TdP) categorized as “KR” on the Credible Meds® website, is prohibited within 4 weeks prior to the baseline visit and for the duration of the study. Medications associated with a potential risk of QT prolongation, but not clearly associated with TdP, are permitted at study entry if the following criteria are met: • Subject has been given medication at stable doses for a full 4 weeks prior to baseline. • Medication dose will not be increased after baseline, or during the study, and it is anticipated that the subject will receive the medication for the entirety of the study.
  • •History of substance abuse, including excessive alcohol consumption, that in the opinion of the investigator, may interfere with the conduct of the study. Alcohol consumption should be limited for the duration of study treatment.
  • •Significant medical condition or other factors as assessed by the investigator that may interfere with the subject’s ability to successfully complete the study.
  • •Pregnant or lactating female subject. Women of childbearing potential (WOCBP) must use an acceptable method of birth control and have a negative pregnancy test at the screening and baseline visits. WOCBP and acceptable methods of birth control are defined in the protocol.
  • •Known intolerance (gastrointestinal, central nervous system symptoms), hypersensitivity, drug allergy following the use of an opioid drug.
  • •Concurrent or anticipated enrollment in an ongoing interventional clinical trial. Observational or long-term safety follow-up studies (e.g., in a vaccine study) may be allowed upon medical monitor approval.
  • •Use of opiates is prohibited within 14 days prior to the baseline visit. This includes opiate containing anti-cough agents, and naltrexone. Subjects are prohibited from using opioids for the duration of the study.
  • •Use of benzodiazepines are prohibited within 14 days prior to the baseline visit and for the duration of the study.

结局指标

主要结局

Relative change from Baseline in 24-hour cough frequency (coughs per hour) at Week 6 for NAL ER compared with placebo.

Relative change from Baseline in 24-hour cough frequency (coughs per hour) at Week 6 for NAL ER compared with placebo.

次要结局

  • Relative change from Baseline in the E-RS:IPF Cough subscale at Week 6 for NAL ER compared with placebo.
  • Adverse events, clinical laboratory assessments, vital signs, spirometry and physical examination summaries.
  • Electrocardiogram (ECG) summaries [ECGs will be analyzed in a separate report].
  • Subjective Opiate Withdrawal Scale (SOWS) daily summaries for the 14 days following the last dose of investigational product.
  • Relative change from Baseline in 24-hour cough frequency (coughs per hour) at Week 2, 4, and 6, for NAL ER compared with placebo.
  • Proportion of responders with ≥30%, ≥50% and ≥75% reduction in the 24-hour cough frequency at Week 2, 4, and 6, for NAL ER compared with placebo.
  • Relative change from Baseline in awake cough frequency (coughs per hour) Week 2, 4, and 6, for NAL ER compared with placebo.
  • Relative change from Baseline in sleep cough frequency (coughs per hour) at Week 2, 4, and 6, for NAL ER compared with placebo.
  • Change from Baseline in the E-RS:IPF Cough subscale at Week 1, 2, 3, 4, 5, and 6, for NAL ER compared with placebo.
  • Proportion of E-RS:IPF Cough subscale responders, with response defined as at least a one category improvement at Week 1, 2, 3, 4, 5, and 6 for NAL ER compared with placebo.
  • Change from Baseline in the E-RS:IPF total score, subdomain scores (IPF-Breathlessness, IPF-Cough, IPF-Sputum, and IPF-Chest Symptoms), and individual items at Week 1, 2, 3, 4, 5, and 6, for NAL ER compared with placebo.
  • Change from Baseline in the CS-NRS at Week 1, 2, 3, 4, 5, and 6, for NAL ER compared with placebo.
  • Change from Baseline in the LCQ total scores at Week 6, for NAL ER compared with placebo.
  • Proportion of LCQ total score responders, with response defined as 1.3-point increase at Week 6 for NAL ER compared with placebo.
  • Change from Baseline in the L-IPF at Week 6, for NAL ER compared with placebo (Impacts).
  • Change from Baseline in the EQ-5D-5L at Week 6, for NAL ER compared with placebo.
  • Change from Baseline in the PGI-S Cough at Week 2, 4, and 6, for NAL ER compared with placebo.
  • Change from Baseline in the PGI-S IPF at Week 2, 4, and 6, for NAL ER compared with placebo.
  • Change from Baseline in the CGI-S at Week 6, for NAL ER compared with placebo.
  • Change from Baseline in the L-IPF and its domains at Week 6, for NAL ER compared with placebo (Symptoms).
  • Change from Baseline in the LCQ domains and individual items at Week 6, for NAL ER compared with placebo.
  • PGI-C Cough score at Week 2, 4, and 6 for NAL ER compared with placebo.
  • Proportion of subjects with improvement by ≥1 and ≥2 categories, worsening by ≥1 and ≥2 categories, and no change on the PGI-C and PGI-S cough at each post-baseline timepoint for NAL ER compared with placebo.
  • PGI-C IPF score at Week 2, 4, and 6 for NAL ER compared with placebo.
  • Proportion of subjects 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 each post-baseline timepoint for NAL ER compared with placebo.
  • CGI-C IPF score at Week 6 for NAL ER compared with placebo.
  • Proportion of subjects: improvement by ≥1 and ≥2 categories, worsening by ≥1 and ≥2 categories, and no change on the CGI-C and CGI-S at each post-baseline timepoint for NAL ER compared with placebo.

研究者

发起方
Trevi Therapeutics Inc.
申办方类型
Pharmaceutical company
责任方
Principal Investigator
主要研究者

Trevi Therapeutics

Scientific

Trevi Therapeutics Inc.

研究点 (23)

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