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

Sponsor

Trevi Therapeutics (Industry)

Overall Status

Completed

CT.gov ID

NCT04030026

Collaborator

Parexel (Industry)

Enrollment

Locations

Arms

33.6

Actual Duration (Months)

2.8

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

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

Actual Enrollment :

42 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Intervention Model Description:

Randomized, double-blinded, placebo-controlled, 2-Treatment, 2-Period Crossover StudyRandomized, 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 :

Aug 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 Names: 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 Names: 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 Names: 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 Names: NAL ER

Outcome Measures

Primary Outcome Measures

Comparison of percentage of responders by Treatment [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

Change from baseline daytime cough frequency effect of escalating doses of Nalbuphine ER [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).
Comparison of percentage of responders on the Evaluating Respiratory Symptoms (E-RS™) diary cough scale [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

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

The following conditions are excluded:
Interstitial lung disease (ILD) known to be caused by domestic and occupational environmental exposures.
Interstitial lung disease (ILD) known to be caused by connective tissue disease.
Interstitial lung disease (ILD) known to be caused by drug related toxicity.
Currently on continuous oxygen therapy.
History of substance abuse that, as determined by the Investigator, may interfere with the conduct of the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	11	Antrim	Northern Ireland	United Kingdom	BT9 7AB
2	16	Birmingham		United Kingdom	DD1 9SY
3	09	Cambridge		United Kingdom	CB23 3RE
4	08	Cottingham		United Kingdom	HU16 5JQ
5	17	Dundee		United Kingdom	DD1 9SY
6	13	Edinburgh		United Kingdom
7	04	London		United Kingdom	NW1 2BU
8	01	London		United Kingdom	SW3 6NP
9	02	Manchester		United Kingdom	M23 9LT
10	10	Newcastle Upon Tyne		United Kingdom	NE1 4LP
11	15	North Shields		United Kingdom	NE29 8NH
12	07	Norwich		United Kingdom	NR4 7UY
13	06	Nottingham		United Kingdom	NG5 1PB
14	14	Oxford		United Kingdom
15	03	Southampton		United Kingdom	SO16 6YD