A Phase 2, Double-Blind, Randomized, Placebo-Controlled, Two-Treatment, Two-Period Crossover Efficacy and Safety Study in Idiopathic Pulmonary Fibrosis With Nalbuphine ER Tablets for the Treatment of Cough

INTERVENTION: Product Name: Nalbuphine Extended‐Realease (ER) Tablets Product Code: TR0311 Pharmaceutical Form: Prolonged‐release tablet INN or Proposed INN: Nalbuphine CAS Number: 23277‐43‐2 Current Sponsor code: 3360 Other descriptive name: NALBUPHINE HYDROCHLORIDE Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 27‐ Pharmaceutical form of the placebo: Tablet Route of administration of the placebo: Oral use Product Name: Nalbuphine Extended‐Release (ER) Tablets Product Code: TR0311 Pharmaceutical Form: Prolonged‐release tablet INN or Proposed INN: Nalbuphine CAS Number: 23277‐43‐2 Current Sponsor code: 3360 Other descriptive name: NALBUPHINE HYDROCHLORIDE Concentration unit: mg/g milligram(s)/gram Concentration type: equal Concentration number: 54‐ Pharmaceutical form of the placebo: Tablet Route of administration of the placebo: Oral use CONDITION: Therapeutic area: Body processes [G] ‐ Circulatory and Respiratory Physiological Phenomena [G09] Treatment of Cough in Idiopathic Pulmonary Fibrosis SECONDARY OUTCOME: ; Secondary end point(s): • Relative change in daytime cough frequency (coughs per hour) from baseline at day 9 (dose 54 mg BID), day 16 (dose 108 mg BID), and day 22 (dose 162 mg BID) by treatment. ; • Relative change in 24‐hour (combined daytime and nighttime) cough frequency (coughs per hour) from baseline at Day 9 (dose: 54 mg BID), Day 16 (dose: 108 mg BID), and Day 22 (dose: 162 mg BID) by treatment. ; • Relative change in nighttime cough frequency (coughs per hour) from baseline at Day 9 (dose: 54 mg BID), Day 16 (dose: 108 mg BID), and Day 22 (dose: 162 mg BID) by treatment. ; • Percentage of E‐RS diary cough subscale (E‐RS diary question number 2) responders, with response defined as at least a one category improvement from baseline, at days 9, 16, and 22 by treatment. ; • Mean change in the Cough Severity Numerical Rating Scale at days 8, 15, and 21 by treatment. ; • Mean change in the E‐RS diary breathlessness subscale (E‐RS diary questions 7, 8, 9, 10, and 11) from baseline at days 9, 16, and 22 by treatment. ; • Mean change in the 14‐item EXACT v1.1 e‐diary tool total score from baseline at days 9, 16, and 22 by treatment. ; • Mean change in the PROMIS Item Bank v1.0 Fatigue Short Form 7a scale from baseline at days 8, 15, and 21 by treatment. ; • Mean change in the CGI‐C over time measured at days 8, 15, and 21 by treatment. ; Timepoint(s) of evaluation of this end point: Days 8, 9, 15, 16, 21 and 22 INCLUSION CRITERIA: 1. Diagnosis of “definiteâ€� or “probableâ€� IPF based on ATS/ERS/JRS/ALAT criteria. 2. Forced vital capacity (FVC) > 40% predicted of normal. 3. Diffusing capacity of the lung for carbon monoxide corrected for hemoglobin [DLCO] > 25% predicted of normal. 4. Chronic cough > 8 weeks. 5. Adequate swallow reflex as assessed by the ability to sip 3 fluid oz (or 89 ml) of water without coughing or choking. 6. Daytime cough severity score = 4 on Cough Severity Numerical Rating Scale at screening. 7. Males or females age 18 years and older at the time of consent. 9. Willing and PRIMARY OUTCOME: ; Main Objective: • To evaluate the safety and tolerability of nalbuphine ER tablets in the study population.; • To evaluate the effect of NAL ER tablets on the mean daytime cough frequency (coughs per hour) at Day 22 (dose 162 mg BID) as compared to placebo tablets. Assessment is done using objective digital cough monitoring. Daytime is defined as the time the subject is awake in the 24 hours after the digital cough monitor is applied for use.; ; Secondary Objective: To evaluate the; • Effect of escalating doses of NAL ER on mean relative change from baseline in daytime cough frequency at Day 9, 16 & 22; • Effect of escalating doses of NAL ER on mean relative change from baseline in 24‐hr cough frequency at Day 9, 16 & 22; • Effect of escalating doses of NAL ER on mean relative change from baseline in nighttime cough frequency at Day 9, 16 & 22; • Percentage of responders on E‐RS diary cough scale (Q2) by treatment at Day 9, 16 & 22, with response defined as at least one category improvement from baseline; • Mean change from baseline in Cough Severity Numerical Rating Scale at Day 8, 15 & 21; • Mean change from baseline in E‐RS diary breathlessness scale (Qs 7, 8, 9, 10 and 11) at Day 9, 16 & 22; • Mean change from baseline in 14‐item EXACT version 1.1 e‐diary tool total score at Day 9, 16 & 22; • Mean change from baseline in PROMIS Item Bank v1.0 Fatigue Short Form 7a scale at Day 8, 15 & 21; • Change in CGI‐C over time at Day 8, 15 & 21; Primary end point(s): Percent change in daytime cough frequency (coughs per hour) from baseline as assessed by objective digital cough monitoring at Day 22 by treatment. Daytime is defined as the time the subject is awake in the 24 hours after the digital cough monitor is applied for use. Timepoint(s) of evaluation of this end point: Day 22 8. Females of childbearing potential must use an acceptable method of birth control (if sexually active). All females of childbearing potential must have a negative pregnancy test at the screening and baseline visits.