Nalbuphine ER for Pulmonary Fibrosis

(CORAL Trial)

Recruiting in Palo Alto (17 mi)

+67 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Trevi Therapeutics

Must not be taking: Opiates, Benzodiazepines, MAOIs, others

Disqualifiers: Sleep apnea, Psychiatric disorder, Substance abuse, others

Prior Safety Data

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

This is a multi-center randomized, double-blind, placebo-controlled, parallel, 4-arm study of nalbuphine ER (NAL ER). After meeting eligibility during the Screening Period, subjects will be randomized (1:1:1:1) to one of four treatment arms with placebo and increasing doses of nalbuphine ER. Each arm will be titrated to their fixed dose during the blinded 2-week Titration period followed by the 4-week Fixed Dose Period for a total of 6 weeks on drug. For more information see the country specific approved websites: Germany, Netherlands, Poland, Spain, Italy, Chile: TheCoralTrial.com United Kingdom, Australia, Canada: CoralCoughTrial.com Turkey: please refer to the list of locations and reach out to the site directly

Will I have to stop taking my current medications?

You may need to stop taking certain medications before joining the trial. Opiates, benzodiazepines, MAOIs, oral corticosteroid cough treatments, and some other medications are not allowed within 14 days to 4 weeks before the trial and during the study. If you're on stable doses of certain medications, you might be able to continue them, but it's best to discuss with the trial team.

How does the drug Nalbuphine ER differ from other treatments for pulmonary fibrosis?

Nalbuphine ER is unique because it is an extended-release formulation, which means it is designed to release the drug slowly over time, potentially offering more consistent symptom control compared to other treatments that may require more frequent dosing.

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Eligibility Criteria

This trial is for adults with Idiopathic Pulmonary Fibrosis (IPF) who have a chronic cough and meet specific lung function criteria, including a Cough Severity Score of at least 4, oxygen saturation levels above 92%, and certain capacities in diffusing carbon monoxide and forced vital capacity. It's not suitable for those who don't meet these lung function thresholds.

Inclusion Criteria

My lung function test shows at least 40% of normal capacity.

I have been diagnosed with IPF according to specific lung disease guidelines.

My cough is severe, scoring 4 or more on a scale.

Exclusion Criteria

History of substance abuse

Known intolerance (gastrointestinal, central nervous system symptoms), hypersensitivity, drug allergy following the use of an opioid drug

I haven't changed my medication doses that could affect my heart's rhythm in the last month.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Titration

Participants are titrated to their fixed dose during the blinded 2-week Titration period

2 weeks

2 visits (in-person)

Fixed Dose

Participants receive a fixed dose of the study drug or placebo for 4 weeks

4 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

1 visit (in-person)

Participant Groups

The study tests the effectiveness of three different doses of nalbuphine ER (27 mg, 54 mg, and 108 mg) compared to a placebo in reducing cough due to IPF. Participants are randomly assigned to one of four groups and will take their assigned treatment over six weeks after an initial titration period.

Group I: NAL ER 54 mg Experimental Treatment 1 Intervention

BID

Group II: NAL ER 27 mg Experimental Treatment 1 Intervention

BID

Group III: NAL ER 108 mg Experimental Treatment 1 Intervention

BID

Group IV: Placebo Placebo Group 1 Intervention

Placebo, tablets BID

Nalbuphine ER is already approved in United States, European Union, Canada for the following indications:

🇺🇸 Approved in United States as Nubain for:

• Moderate to severe pain
• Preoperative and postoperative analgesia
• Obstetrical analgesia during labor and delivery

🇪🇺 Approved in European Union as Nalbuphine for:

• Moderate to severe pain
• Preoperative and postoperative analgesia
• Obstetrical analgesia during labor and delivery

🇨🇦 Approved in Canada as Nalbuphine for:

• Moderate to severe pain
• Preoperative and postoperative analgesia
• Obstetrical analgesia during labor and delivery

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Office of Dr. Syed Anees MD Windsor, Canada

CIC Mauricie Inc. Trois-Rivieres, Canada

Centre for Lung Health Clinic Vancouver, Canada

The Pacific Lung Health Centre - St. Pauls Hospital Vancouver, Canada

More Trial Locations

Who Is Running the Clinical Trial?

Trevi Therapeutics Lead Sponsor

References

1. England pubmed.ncbi.nlm.nih.gov

Inhaled nintentanib, pirfenidone and macitentan for pulmonary fibrosis: a laboratory experiment. [2023] Aim: Idiopathic pulmonary fibrosis is a rare disease with few efficient drugs in the market. The consequences of this disease are mainly respiratory failure and pulmonary hypertension. Materials & methods: In our experiment we used the drugs pirfenidone, nintetanib and macitentan. We performed nebulization experiments with three jet nebulizers and three ultrasound nebulizers with different combinations of residual cup designs, and residual cup loadings in order to identify which combination produces droplets of less than 5 μm in mass median aerodynamic diameter. Results: Pirfenidone versus nintetanib had smaller droplet size formation at both inhaled technologies (1.37 < 2.23 and 1.92 < 3.11, jet and ultrasound respectively). Discussion: Pirfenidone and nintetanib can be administered as aerosol in any type of nebulization system.

2. Italy pubmed.ncbi.nlm.nih.gov

Nintedanib (BIBF 1120) for IPF: a tomorrow therapy? [2021] Idiopathic pulmonary fibrosis is a rare, life threatening disease characterized by an anarchic fibrogenesis, limited survival and few therapeutic options. Its pathogenesis is complex and involves the interaction among various pathways driven by proinflammatory/profibrogenetic mediators such as platelet -derived growth factor, vascular endothelial growth factor or basic fibroblast growth factor. Given their prominent pathogenic roles in this disease such growth factor might be suitable therapeutic targets.In fact, the existing preclinical and clinical data demonstrated that their therapeutic inhibition results in a delayed progression of the pulmonary fibrosis and in the improvement of the disease outcome. BIBF 1120 is a potent triple blocker of the receptors of these growth factors which is currently evaluated as a potential therapy in the idiopathic pulmonary fibrosis. This review discusses the existing data supporting its potential use in this disease.

3. Iran pubmed.ncbi.nlm.nih.gov

Vinpocetine's immunomodulating, anti-oxidant, anti-inflammatory, ant-ifibrotic, and PDE inhibiting potencies ameliorate bleomycin-induced pulmonary fibrosis. [2023] Pulmonary fibrosis (PF) is a global health problem with a high economic burden. Intratracheal administration of bleomycin is the best model that resembles the pathogenesis of PF in humans. Recently, vinpocetine proved to have neuroprotective, cardioprotective, hepatoprotective, anti-aging, and antifibrotic effects through its anti-oxidant, immunomodulating, and anti-inflammatory activities. The present study investigated the antifibrotic potentiality of vinpocetine in a rat model of PF induced by intratracheal bleomycin administration.

4. England pubmed.ncbi.nlm.nih.gov

Evaluation of bosentan for idiopathic pulmonary fibrosis. [2010] Idiopathic pulmonary fibrosis (IPF) is a quality-of-life-altering and life-shortening lung disease manifested by physiologic restriction, hypoxemia and progressive shortness of breath. Despite nearly 30 years of investigation, the median survival for patients with this disease remains dismal at approximately 3 years from the time of diagnosis. Recent investigations have identified a number of potential molecular therapeutic targets for IPF that include endothelin-1 and other fibrogenic cytokines. Bosentan, a nonselective endothelin receptor antagonist approved in the USA and Europe for the treatment of patients with pulmonary arterial hypertension, is currently undergoing evaluation as a potential therapy for IPF. A recently completed multinational, placebo-controlled trial failed to show a beneficial impact of bosentan on the primary end point, but results from a hypothesis-generating, post hoc analysis of data from this trial have prompted an assessment of the drug for efficacy in a selected subgroup of IPF patients - those with biopsy-proven IPF and little radiographic honeycombing. Results from this trial are anticipated in 2009.

5. United States pubmed.ncbi.nlm.nih.gov

BUILD-3: a randomized, controlled trial of bosentan in idiopathic pulmonary fibrosis. [2022] A previous trial of bosentan in idiopathic pulmonary fibrosis (IPF) showed a trend to delayed IPF worsening or death. Also, improvements in some measures of dyspnea and health-related quality of life were observed.