A Study of Nalbuphine (Extended Release) ER in Idiopathic Pulmonary Fibrosis (IPF) for Treatment of Cough (CANAL)

Phase 2, Double-blind, Randomized, Placebo-controlled, Two-Treatment, Two-Period Crossover Efficacy and Safety Study in Idiopathic Pulmonary Fibrosis (IPF) With Nalbuphine ER Tablets for the Treatment of Cough

To investigate the efficacy and safety of Nalbuphine ER (NAL ER) tablets in subjects diagnosed with Idiopathic Pulmonary Fibrosis (IPF) and evaluate it's treatment of cough in these patients. This is a two-treatment, 2-period crossover study. Subjects will be randomized in Treatment Period 1 to either NAL ER or matching placebo and evaluated for approximately 21 days. After completion of the first phase, subjects who received NAL ER will crossover to placebo and subjects who received placebo will crossover to NAL ER to complete Treatment Period 2.

Study Overview

• Status: Completed
• Conditions: Cough; Idiopathic Pulmonary Fibrosis; Nalbuphine
• Intervention / Treatment: Drug: NAL ER; Drug: Placebo

Detailed Description

This is a double-blind, randomized, placebo-controlled, 2-treatment, 2-period crossover efficacy and safety study in IPF subjects with NAL ER tablets for the treatment of cough. The study consists of 2 treatment periods of 3 weeks, each followed by a washout period of 2 weeks.

Treatment Period 1: During Treatment Period 1, eligible subjects will be randomized (1:1) to one of the following treatment arms:

• Arm 1: Active NAL ER followed by crossover Placebo in Treatment Period 2
• Arm 2: Placebo followed by crossover NAL ER in Treatment Period 2

Following 3 weeks of dosing in Treatment Period 1, subjects will complete a 2-week washout period before entering Treatment Period 2. Subjects assigned to Arm 1 will receive placebo and subjects assigned to Arm 2 will receive NAL ER during Treatment Period 2. A final 2-week washout period will occur at the completion of Treatment Period 2.

NAL ER Dosing Subjects on NAL ER will have the dose titrated from 27 mg once daily (QD) to 54 mg twice a day (BID) over a 5-day period and then maintained at 54 mg twice a day (BID) for approximately 4 days. Doses will be subsequently escalated and maintained at 108 mg twice a day (BID) over 1 week and then to 162 mg twice a day (BID) over 6 days.

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • Birmingham, United Kingdom, DD1 9SY
    • 16
  • Cambridge, United Kingdom, CB23 3RE
    • 09
  • Cottingham, United Kingdom, HU16 5JQ
    • 08
  • Dundee, United Kingdom, DD1 9SY
    • 17
  • Edinburgh, United Kingdom
    • 13
  • London, United Kingdom, NW1 2BU
    • 04
  • London, United Kingdom, SW3 6NP
    • 01
  • Manchester, United Kingdom, M23 9LT
    • 02
  • Newcastle Upon Tyne, United Kingdom, NE1 4LP
    • 10
  • North Shields, United Kingdom, NE29 8NH
    • 15
  • Norwich, United Kingdom, NR4 7UY
    • 07
  • Nottingham, United Kingdom, NG5 1PB
    • 06
  • Oxford, United Kingdom
    • 14
  • Southampton, United Kingdom, SO16 6YD
    • 03
  • Northern Ireland
    • Antrim, Northern Ireland, United Kingdom, BT9 7AB
      • 11

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Individuals diagnosed with Idiopathic Pulmonary Fibrosis
2. Chronic cough > 8 weeks.
3. Daytime cough severity score ≥ 4 on Cough Severity Numerical Rating Scale at screening

Exclusion Criteria:

1. The following conditions are excluded:

   1. Interstitial lung disease (ILD) known to be caused by domestic and occupational environmental exposures.
   2. Interstitial lung disease (ILD) known to be caused by connective tissue disease.

   3. Interstitial lung disease (ILD) known to be caused by drug related toxicity.

      2. Currently on continuous oxygen therapy.

      3. History of substance abuse that, as determined by the Investigator, may interfere with the conduct of the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NAL ER then placebo; Participants will receive NAL ER 27 mg QD, 27 mg BID, 54 mg BID, 108 mg BID, 162 mg BID over a 3 week period, followed by a 2 week washout. They will then receive Placebo tablet (matching NAL ER BID) for 3 weeks.	Drug: NAL ER; Participants will receive NAL ER 27 mg QD, 27 mg BID, 54 mg BID, 108 mg BID, 162 mg BID over a 3 week period.; Other Names: Nalbuphine; Drug: Placebo; Participants will receive Placebo tablet (matching NAL ER BID) over a 3 week period.; Other Names: Nalbuphine
Experimental: Placebo then NAL ER; Participants will receive Placebo tablet (matching NAL ER BID) for 3 weeks, followed by a 2 week washout. They will then receive NAL ER 27 mg QD, 27 mg BID, 54 mg BID, 108 mg BID, 162 mg BID over a 3 week period .	Drug: NAL ER; Participants will receive NAL ER 27 mg QD, 27 mg BID, 54 mg BID, 108 mg BID, 162 mg BID over a 3 week period.; Other Names: Nalbuphine; Drug: Placebo; Participants will receive Placebo tablet (matching NAL ER BID) over a 3 week period.; Other Names: Nalbuphine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of percentage of responders by Treatment	To evaluate the effect of Nalbuphine ER tablets on the mean daytime cough frequency (coughs per hour) at day 22 (dose 162 mg twice daily [BID]) as compared to placebo. Daytime is defined as the period between the time the subject reported being awake and the time the subject went to bed. Assessment is done using objective digital cough monitoring.	Up to 3 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline daytime cough frequency effect of escalating doses of Nalbuphine ER	To evaluate the effect of escalating doses of Nalbuphine ER on the mean relative change from baseline in daytime cough frequency (coughs per hour) at day 9 (dose: 54 mg BID), day 16 (dose: 108 mg BID) and day 22 (dose: 162 mg BID).	Up to 3 weeks
Comparison of percentage of responders on the Evaluating Respiratory Symptoms (E-RS™) diary cough scale	The E-RS will be used to look at the percentage of responders with response defined as at least one category improvement from baseline.	Up to 3 weeks

Collaborators and Investigators

• Sponsor: Trevi Therapeutics
• Collaborators: Parexel
• Investigators: Study Director: Thomas Sciascia, Trevi Therapeutics, Inc

Study record dates

Study Major Dates

• Study Start (Actual): August 8, 2019
• Primary Completion (Actual): May 27, 2022
• Study Completion (Actual): May 27, 2022

Study Registration Dates

• First Submitted: July 11, 2019
• First Submitted That Met QC Criteria: July 22, 2019
• First Posted (Actual): July 23, 2019

Study Record Updates

• Last Update Posted (Actual): May 25, 2023
• Last Update Submitted That Met QC Criteria: May 23, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Cough; Idiopathic Pulmonary Fibrosis; Nalbuphine
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Signs and Symptoms, Respiratory; Lung Diseases, Interstitial; Fibrosis; Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis; Cough; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Nalbuphine
• Other Study ID Numbers: TR12; 2018-004744-31 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No