Refractory Chronic Cough Improvement Via NAL ER (RIVER)

Key Inclusion Criteria

• Diagnosis of refractory chronic cough (RCC) for at least one year
• Chest radiograph or CT of thorax within 24 months or during screening not demonstrating any significant abnormalities contributing to RCC

Exclusion Criteria

• Diagnosis of sleep apnea
• Respiratory tract infection within 6 weeks of Baseline
• History of bronchiectasis, COPD, or IPF
• History of uncontrolled asthma
• Current smokers/vapers, quit smoking with =20 pack years
• History of major psychiatric disorder
• History of substance abuse
• Pregnant or lactating females
• Known intolerance to opioids
• Abnormal kidney or liver functions based on Screening lab results.
• Known hypersensitivity to nalbuphine or to NAL ER excipients
• Previous participation in a nalbuphine ER clinical study
• Use of opiates, benzodiazepines, or MAOIs within 14 days of Baseline
• Use of pregabalin, gabapentin, thalidomide for treatment of cough within 14 days of Baseline
• Use of ACE inhibitors within 12 weeks of Baseline
• 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.
• Use of unstable doses of cough suppressants within 14 days of Baseline
• Use of unstable doses of medications that affect serotonergic neurotransmission that may cause serotonin syndrome with opioids within14 days of Baseline
• Use of unstable doses of P450 isozyme inhibitors/inducers within 14 days of Baseline

Other protocol defined inclusion/exclusion criteria applied.