The Effect of Nalbuphine Extended-Release (NAL ER) on Cough in Participants With Refractory Chronic Cough (RCC)

Official title

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

Overview

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.

Interventions

• Drug NAL ER
  Oral tablets
• Drug Placebo
  Oral tablets

Primary outcome measures

• Relative Change From Baseline in 24-hour Cough Frequency at Week 6 [Time frame: Baseline, Week 6]

Secondary outcome measures (12)

• Relative Change From Baseline in 24-hour Cough Frequency [Time frame: Baseline up to Week 6]
• Percentage of Participants Achieving ≥30%, ≥50% and ≥75% Reduction in 24-hour Cough Frequency [Time frame: Baseline up to Week 6]
• Change From Baseline in Patient Reported Cough Frequency (PR-CF) [Time frame: Baseline up to Week 6]
• Change From Baseline in Cough Severity Visual Analog Scale (CS-VAS) [Time frame: Baseline up to Week 6]
• Percentage of Participants Achieving a 30 Millimeter (mm) Improvement in CS-VAS Total Score [Time frame: Baseline up to Week 6]
• Change From Baseline in Cough Severity Numerical Rating Scale (CS-NRS) [Time frame: Baseline up to Week 6]
• Change From Baseline in McMaster Cough Severity Questionnaire (MCSQ) Total Score [Time frame: Baseline up to Week 6]
• Change From Baseline in MCSQ Domains (Intensity and Frequency) [Time frame: Baseline up to Week 6]
• Change From Baseline in Leicester Cough Questionnaire (LCQ) Total Score at Week 6 [Time frame: Baseline, Week 6]
• Change From Baseline in Each LCQ Domain Score (Physical, Psychological, Social) at Week 6 [Time frame: Baseline, Week 6]
• Percentage of Participants Achieving a 1.3- Point Increase From Baseline in LCQ Total Score at Week 6 [Time frame: Baseline, Week 6]
• Relative Change From Baseline in Awake Cough Frequency [Time frame: Baseline up to Week 6]

Eligibility criteria

Inclusion criteria

• 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.

Exclusion criteria

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

Canada · 5 centers

• BLC Clinical Research — Burlington
• Diex Recherche - Quebec — Québec
• Clinique Specialisee En Allergie De La Capitale — Québec
• Centre D'Investigation Clinique Mauricie Inc (CIC Mauricie) — Trois-Rivières
• Diex Recherche-Victoriaville — Victoriaville

Identifiers

NCT: NCT07671924 · NAL04-202 · 2026-526087-20-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗