Nalbuphine ER for Pulmonary Fibrosis

(CORAL Trial)

Recruiting at 67 trial locations

Overseen By Catherine Weenink

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Trevi Therapeutics

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

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

160 Participants Needed

Trial Summary

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. ^{1 2 3 4 5}

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

Research Team

Chief Development Officer

Principal Investigator

Trevi Therapeutics

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.

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)

Treatment Details

Interventions

• Nalbuphine ER

Trial Overview 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.

Participant Groups

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

Who Is Running the Clinical Trial?

Trevi Therapeutics

Lead Sponsor

Trials

11

Recruited

1,400+

Findings from Research

In experiments comparing nebulization technologies, pirfenidone produced smaller droplet sizes than nintetanib, indicating potentially better delivery efficiency for inhalation therapy.

Both pirfenidone and nintetanib can be effectively administered as aerosols using various nebulization systems, which may enhance treatment options for patients with idiopathic pulmonary fibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhaled nintentanib, pirfenidone and macitentan for pulmonary fibrosis: a laboratory experiment. Zarogoulidis, P., Petridis, D., Huang, H., et al.[2023]

Idiopathic pulmonary fibrosis is a serious disease with limited treatment options, and it involves complex interactions among various proinflammatory and profibrogenetic growth factors.

BIBF 1120, a potent triple blocker of these growth factor receptors, has shown promise in preclinical and clinical studies by delaying disease progression and improving outcomes for patients with idiopathic pulmonary fibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nintedanib (BIBF 1120) for IPF: a tomorrow therapy? Antoniu, SA.[2021]

In a rat model of pulmonary fibrosis induced by bleomycin, vinpocetine demonstrated a dose-dependent ability to improve lung function and structure over 21 days, indicating its potential as an antifibrotic treatment.

Vinpocetine effectively reduced inflammatory markers and fibrosis scores while restoring normal lung tissue characteristics, suggesting it works through antioxidant and anti-inflammatory mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vinpocetine's immunomodulating, anti-oxidant, anti-inflammatory, ant-ifibrotic, and PDE inhibiting potencies ameliorate bleomycin-induced pulmonary fibrosis. Balaha, M., Alahmari, A., Kandeel, S., et al.[2023]

Idiopathic pulmonary fibrosis (IPF) is a severe lung disease with a median survival of only about 3 years after diagnosis, highlighting the urgent need for effective treatments.

Bosentan, an endothelin receptor antagonist, did not show overall benefit in a recent trial for IPF, but a post hoc analysis suggests it may be effective in a specific subgroup of patients with biopsy-proven IPF and minimal honeycombing, warranting further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of bosentan for idiopathic pulmonary fibrosis. Swigris, JJ., Brown, KK.[2010]

In a study involving 616 patients with idiopathic pulmonary fibrosis (IPF), bosentan did not significantly delay disease worsening or death compared to placebo, indicating it may not be effective for this purpose.

Despite the lack of primary endpoint success, bosentan was well tolerated and showed some positive effects on lung function measures over one year, suggesting it may have a safety profile similar to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BUILD-3: a randomized, controlled trial of bosentan in idiopathic pulmonary fibrosis. King, TE., Brown, KK., Raghu, G., et al.[2022]

References

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

Inhaled nintentanib, pirfenidone and macitentan for pulmonary fibrosis: a laboratory experiment. [2023]

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

Nintedanib (BIBF 1120) for IPF: a tomorrow therapy? [2021]

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]

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

Evaluation of bosentan for idiopathic pulmonary fibrosis. [2010]

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

BUILD-3: a randomized, controlled trial of bosentan in idiopathic pulmonary fibrosis. [2022]