Refractory Chronic Cough Improvement Via NAL ER (RIVER)

Trevi Therapeutics

Status and phase: Completed; Phase 2

Conditions: Refractory Chronic Cough

Treatments: Drug: Placebo; Drug: NAL ER

Study type: Interventional

Funder types: Industry

Identifiers

NCT05962151

NAL04-201

Details and patient eligibility

About

The main purpose of this study is to evaluate the effect of NAL ER on 24-hour cough frequency and to assess safety and tolerability of NAL-ER for treatment of refractory chronic cough.

Enrollment: 66 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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 <=12 months, using nicotine supplements, or history of >=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 may apply.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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66 participants in 2 patient groups

First NAL ER, then Placebo

Experimental group

Description:

Participants will receive NAL ER at escalating doses (27 mg QD to BID, 54 mg BID, and 108 mg BID) in Treatment Period 1, followed by placebo matched to NAL ER in Treatment Period 2.

Treatment:

Drug: NAL ER

Drug: Placebo

First Placebo then NAL ER

Experimental group

Description:

Participants will receive placebo matched to NAL ER in Treatment Period 1, followed by NAL ER at escalating doses (27 mg QD to BID, 54 mg BID, and 108 mg BID) in Treatment Period 2.

Treatment:

Drug: NAL ER

Drug: Placebo