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

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

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.

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.