cough reduction in ipf with nalbuphine er

Conditions: Idiopathic Pulmonary Fibrosis

Summary: this is a multi-center randomized, double-blind, placebo-controlled, parallel, 4-arm study of nalbuphine er (nal er). after meeting eligibility during the screening period, subjects will be randomized (1:1:1:1) to one of four treatment arms with placebo and increasing doses of nalbuphine er. each arm will be titrated to their fixed dose during the blinded 2-week titration period followed by the 4-week fixed dose period for a total of 6 weeks on drug. for more information see the country specific approved websites: germany, netherlands, poland, spain, italy, chile: thecoraltrial.com united kingdom, australia, canada: coralcoughtrial.com turkey: please refer to the list of locations and reach out to the site directly

this is a multi-center randomized, double-blind, placebo-controlled, parallel, 4-arm study. after meeting eligibility during the screening period, subjects will be randomized (1:1:1:1) to one of four treatment arms. * arm 1: placebo * arm 2: 27 mg nalbuphine er * arm 3: 54 mg nalbuphine er * arm 4: 108 mg nalbuphine er each arm will be titrated to their fixed dose during the blinded 2-week titration period according to table: dosing scheme, followed by the 4-week fixed dose period for a total of 6 weeks on drug. subjects will be taken off study drug at the end of the fixed dose period and followed off treatment for an additional 2 weeks.

Eligibility criteria:
inclusion criteria: * diagnosis of ipf as determined by the principal 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 - forced vital capacity, as determined by spirometry adhering to ats/ers guidelines. * dlco ≥ 25% predicted of normal - diffusing capacity of the lung for carbon monoxide corrected for hemoglobin, assessed within the last 12 weeks, or at the time of screening. exclusion criteria: * 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. * inadequate swallow reflex as assessed by the ability to sip 3 fluid oz (or 89 ml) of water without coughing or choking. * upper or lower respiratory tract infection in the last 8 weeks prior to the baseline visit. * clinical history of aspiration pneumonitis. * diagnosis of sleep apnea. * abnormal kidney or liver functions based on screening lab results. * known hypersensitivity to nalbuphine or to nal er excipients * history of major psychiatric disorder. * history of substance abuse. * significant medical condition or other factors that may interfere with the subject's ability to successfully complete the study. * pregnant or lactating female subject. * known intolerance (gastrointestinal, central nervous system symptoms), hypersensitivity, drug allergy following the use of an opioid drug. * use of opiates is prohibited within 14 days prior to the baseline visit. * use of benzodiazepines are prohibited within 14 days prior to the baseline visit and for the duration of the study. * 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 cough treatment is prohibited within 4 weeks prior to the baseline visit and for the duration of the study. * 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. * 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.

Keywords: cough nalbuphine