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

NCT04030026 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: TR122018-004744-31
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 11

Brief Summary

To evaluate the safety and tolerability of nalbuphine ER tablets in the study population and 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.

Conditions

Idiopathic Pulmonary Fibrosis

Keywords

Nalbuphine; Cough; Idiopathic Pulmonary Fibrosis; Pharmacokinetics

Outcome Measures

Primary Outcomes (9)

• Number of Participants Who Experienced at Least One Treatment Emergent Adverse Events (TEAEs)

  An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A TEAE was defined as any AE that occurs after the first dose of study drug. TEAEs included both serious and non-serious TEAEs.

  Up to Day 72

• Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters

  The clinical laboratory parameters included the urinalysis, hematology, serum chemistry, coagulation and liver function parameters. Clinical significance was determined by the investigator.

  Up to Day 72

• Number of Participants With Clinically Significant Changes in Vital Sign Parameters

  Vital signs measurements included blood pressure, heart rate, and respiration rate, body temperature, pulse oximetry, and weight. Clinical significance was determined by the investigator.

  Up to Day 72

• Number of Participants With Clinically Significant Changes in Physical Examination Parameters

  Physical examination included examination of the following body systems: general appearance, eyes, ears, nose, throat, head and neck, chest and lungs, cardiovascular, abdomen, musculoskeletal, lymphatic, dermatological, neurological, and extremities. Clinical significance was determined by the investigator.

  Up to Day 72

• Number of Participants With Clinically Significant Abnormalities in 12-Lead Electrocardiogram (ECG)

  Changes in ECG data such as heart rate, rhythm, and other clinically significant abnormalities (left ventricular hypertrophy, pathological Q-waves) were measured. Clinical significance was determined by the investigator.

  Up to Day 72

• Change From Baseline in Forced Vital Capacity (FVC) at Day 21

  Spirometry was used to assess FVC. It was used to assess pulmonary breathing mechanics.

  Baseline, Day 21

• Subjective Opiate Withdrawal (SOWS) Total Raw Score

  The SOWS is a self-administered scale for grading opioid withdrawal symptoms and was collected via the study issued e-diary. It consisted of 16 symptoms related to how the participant felt. Each symptom was scored between 0 to 4. The total score ranges between 0 to 64, higher score indicates more severe symptoms.

  Up to Day 72

• Daytime Cough Frequency at Baseline

  Daytime cough was defined as cough that occurs between the time that the participant is a wake in the 24 hours after the digital cough monitor was applied for use. Assessment was done using objective digital cough monitoring. Baseline was defined as the last available assessment prior to the first Treatment Period 1 IP intake.

  At Baseline

• Percent Change From Baseline in Daytime Cough Frequency at Day 22

  Daytime cough was defined as cough that occurs between the time that the participant is a wake in the 24 hours after the digital cough monitor was applied for use. Assessment was done using objective digital cough monitoring. Percent change in daytime cough frequency (coughs per hour) from baseline was assessed. Baseline was defined as the last available assessment prior to the first Treatment Period 1 IP intake.

  Baseline, Day 22

Secondary Outcomes (9)

• Change From Baseline in Daytime Cough Frequency at Day 22

  Baseline, Day 22

• Percent Change From Baseline in 24-Hour Cough Frequency at Day 22

  Baseline, Day 22

• Percent Change From Baseline in Nighttime Cough Frequency at Day 22

  Baseline, Day 22

• Mean Change From Baseline in the Evaluating Respiratory Symptoms (E-RS) Diary Cough Subscale at Days 9, 16, and 22

  Baseline, Days 9, 16, and 22

• Mean Change From Baseline in E-RS Breathlessness Score at Days 9, 16, and 22

  Baseline, Days 9, 16, and 22

Study Arms (2)

NAL ER then placebo

EXPERIMENTAL

Participants received NAL ER in treatment period 1 at dose 27 mg once daily (QD) to 54 mg twice daily (BID) over a 5-day period and then maintained at 54 mg BID for 4 days. Dose was increased to 108 mg BID for 1 week then to 162 mg BID for 6 days, followed by placebo matching NAL ER for 3 weeks in treatment period 2. Both the treatment periods were separated by 2 weeks of washout period.

Drug: NAL ER; Drug: Placebo

Placebo then NAL ER

EXPERIMENTAL

Participants received placebo matching NAL ER for 3 weeks in treatment period 1 followed by NAL ER in treatment period 2 at dose 27 mg QD to 54 mg BID over a 5-day period and then maintained at 54 mg BID for 4 days. Dose was increased to 108 mg BID for 1 week then to 162 mg BID for 6 days. Both the treatment periods were separated by 2 weeks of washout period.

Drug: NAL ER; Drug: Placebo

Interventions

NAL ER DRUG

Participants received NAL ER 27 mg QD, 27 mg BID, 54 mg BID, 108 mg BID, 162 mg BID.

Also known as: Nalbuphine

NAL ER then placebo; Placebo then NAL ER

Placebo DRUG

Participants received Placebo tablet (matching NAL ER ).

Also known as: Placebo matched to NAL ER

NAL ER then placebo; Placebo then NAL ER

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Trevi Therapeutics: lead
• Parexel: collaborator

Study Sites (11)

09

Cambridge, CB23 3RE, United Kingdom

Location

08

Cottingham, HU16 5JQ, United Kingdom

Location

17

Dundee, DD1 9SY, United Kingdom

Location

13

Edinburgh, United Kingdom

Location

04

London, NW1 2BU, United Kingdom

Location

01

London, SW3 6NP, United Kingdom

Location

02

Manchester, M23 9LT, United Kingdom

Location

10

Newcastle upon Tyne, NE1 4LP, United Kingdom

Location

06

Nottingham, NG5 1PB, United Kingdom

Location

14

Oxford, United Kingdom

Location

03

Southampton, SO16 6YD, United Kingdom

Location

Related Publications (1)

• Maher TM, Avram C, Bortey E, Hart SP, Hirani N, Molyneux PL, Porter JC, Smith JA, Sciascia T. Nalbuphine Tablets for Cough in Patients with Idiopathic Pulmonary Fibrosis. NEJM Evid. 2023 Aug;2(8):EVIDoa2300083. doi: 10.1056/EVIDoa2300083. Epub 2023 May 22.

  PMID: 38320144 DERIVED

MeSH Terms

Conditions

Idiopathic Pulmonary Fibrosis; Cough

Interventions

Nalbuphine

Condition Hierarchy (Ancestors)

Pulmonary Fibrosis; Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Results Point of Contact

• Title: Thomas Sciascia, MD, Chief Scientific Officer
• Organization: Trevi Therapeutics, Inc.

info@trevitherapeutics.com

203-304-2499

Study Officials

• Thomas Sciascia

  Trevi Therapeutics, Inc

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized, double-blinded, placebo-controlled, 2-Treatment, 2-Period Crossover Study

Study Record Dates

• First Submitted: July 11, 2019
• First Posted: July 23, 2019
• Study Start: October 29, 2019
• Primary Completion: May 27, 2022
• Study Completion: May 27, 2022
• Last Updated: May 29, 2025
• Results First Posted: May 29, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

GB (11)