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

• ClinicalTrials.gov Identifier: NCT04030026
• Recruitment Status: Completed
• First Posted: July 23, 2019
• Last Update Posted: October 5, 2022
• Sponsor: Trevi Therapeutics
• Collaborator: Parexel
• Information provided by (Responsible Party): Trevi Therapeutics

Study Description

Brief Summary:

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 evaluate 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.

Condition or disease	Intervention/treatment	Phase
Nalbuphine; Idiopathic Pulmonary Fibrosis; Cough	Drug: Nalbuphine ER; Drug: Placebo oral tablet	Phase 2

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 BID over a 5-day period and then maintained at 54 mg BID for approximately 4 days. Doses will be subsequently escalated and maintained at 108 mg BID over 1 week and then to 162 mg BID over 6 days.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 42 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: Randomized, double-blinded, placebo-controlled, 2-Treatment, 2-Period Crossover Study
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Matching Placebo
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: August 8, 2019
• Actual Primary Completion Date: May 27, 2022
• Actual Study Completion Date: May 27, 2022

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Arm 1a: Nalbuphine ER; Active tablets containing the study drug being tested (NAL ER) twice a day for Treatment Period 1	Drug: Nalbuphine ER; Subjects on NAL ER will have the dose titrated from 27 mg once daily (QD) to 54 mg BID over a 5-day period and then maintained at 54 mg BID for approximately 4 days. Doses will be subsequently escalated and maintained at 108 mg BID over 1 week and then to 162 mg BID over 6 days.; Other Name: NAL ER
Placebo Comparator: Arm 2a: Placebo; Placebo twice a day for Treatment Period 1	Drug: Placebo oral tablet; Placebo Comparative will be given in Arm 1b and again in Arm 2a; Other Name: Placebo
Placebo Comparator: Arm 1b: Placebo; Placebo twice a day for Treatment Period 1	Drug: Placebo oral tablet; Placebo Comparative will be given in Arm 1b and again in Arm 2a; Other Name: Placebo
Active Comparator: Arm 2b: Nalbuphine ER; Active tablets containing the study drug being tested (NAL ER) twice a day for Treatment Period 2	Drug: Nalbuphine ER; Subjects on NAL ER will have the dose titrated from 27 mg once daily (QD) to 54 mg BID over a 5-day period and then maintained at 54 mg BID for approximately 4 days. Doses will be subsequently escalated and maintained at 108 mg BID over 1 week and then to 162 mg BID over 6 days.; Other Name: NAL ER

Outcome Measures

Primary Outcome Measures :

1. Comparison of percentage of responders by Treatment [ Time Frame: Up to 3 weeks ]
   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.

Secondary Outcome Measures :

1. Change from baseline daytime cough frequency effect of escalating doses of Nalbuphine ER [ Time Frame: Up to 3 weeks ]
   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).
2. Comparison of percentage of responders on the Evaluating Respiratory Symptoms (E-RS™) diary cough scale [ Time Frame: Up to 3 weeks ]
   The E-RS will be used to look at the percentage of responders with response defined as at least one category improvement from baseline.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United Kingdom

11

Antrim, Northern Ireland, United Kingdom, BT9 7AB

16

Birmingham, United Kingdom, DD1 9SY

09

Cambridge, United Kingdom, CB23 3RE

08

Cottingham, United Kingdom, HU16 5JQ

17

Dundee, United Kingdom, DD1 9SY

13

Edinburgh, United Kingdom

04

London, United Kingdom, NW1 2BU

01

London, United Kingdom, SW3 6NP

02

Manchester, United Kingdom, M23 9LT

10

Newcastle Upon Tyne, United Kingdom, NE1 4LP

15

North Shields, United Kingdom, NE29 8NH

07

Norwich, United Kingdom, NR4 7UY

06

Nottingham, United Kingdom, NG5 1PB

14

Oxford, United Kingdom

03

Southampton, United Kingdom, SO16 6YD

Sponsors and Collaborators

Trevi Therapeutics

Parexel

Investigators

• Study Director: Thomas Sciascia; Trevi Therapeutics, Inc

More Information

• Responsible Party: Trevi Therapeutics
• ClinicalTrials.gov Identifier: NCT04030026
• Other Study ID Numbers: TR12; 2018-004744-31 ( EudraCT Number )
• First Posted: July 23, 2019
• Last Update Posted: October 5, 2022
• Last Verified: October 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Trevi Therapeutics:

Nalbuphine; Cough; Idiopathic Pulmonary Fibrosis; Pharmacokinetics

Additional relevant MeSH terms:

Nalbuphine; Pulmonary Fibrosis; Cough; Idiopathic Pulmonary Fibrosis; Fibrosis; Pathologic Processes; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Analgesics, Opioid; Narcotics; Central Nervous System Depressants; Physiological Effects of Drugs; Analgesics; Sensory System Agents; Peripheral Nervous System Agents