Nalbuphine ER for Pulmonary Fibrosis

(CORAL Trial)

No longer recruiting at 81 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether Nalbuphine ER (an extended-release medication) can reduce coughing in people with pulmonary fibrosis, a lung disease that causes scarring and breathing problems. Researchers aim to determine if this medication can lower cough frequency over 24 hours and assess its safety. Participants will be randomly assigned to different groups, with some receiving various doses of Nalbuphine ER and others a placebo (a substance with no active medication). Ideal participants have experienced a chronic cough for at least 8 weeks and maintain adequate oxygen levels without needing continuous oxygen therapy. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that Nalbuphine ER is likely to be safe for humans?

Studies have shown that nalbuphine ER (Extended Release) has been tested for safety in people with similar health conditions. Most patients in these studies tolerated the treatment well. Some experienced side effects like nausea and constipation, which were more common compared to treatments like morphine. Overall, most found the side effects manageable.

Nalbuphine ER is also under study for its effect on reducing cough in conditions like pulmonary fibrosis. Previous research suggests it can significantly lessen coughing, offering promise for those with this condition. While side effects can occur, past studies generally consider the treatment safe. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for pulmonary fibrosis?

Unlike the standard of care for pulmonary fibrosis, which typically includes antifibrotic medications like pirfenidone or nintedanib, Nalbuphine ER offers a unique approach by acting on the opioid receptors in the body. This is significant because it may help manage symptoms and improve lung function through a different mechanism than existing treatments. Researchers are excited about Nalbuphine ER because it could provide a novel therapeutic option that potentially enhances quality of life for patients with pulmonary fibrosis, addressing aspects of the disease that current treatments do not.

What evidence suggests that Nalbuphine ER might be an effective treatment for pulmonary fibrosis?

Research has shown that nalbuphine ER, a long-lasting tablet, may help reduce coughing in people with pulmonary fibrosis. In earlier studies, patients who took nalbuphine ER experienced fewer coughs over 24 hours compared to those who did not take the drug. This trial will evaluate different doses of nalbuphine ER—27 mg, 54 mg, and 108 mg—to assess their effectiveness in managing chronic cough linked to this condition. Although more research is needed, these findings suggest that nalbuphine ER could be a promising option for those dealing with cough due to pulmonary fibrosis. ^{1 3 6 7 8}

Who Is on the Research Team?

Chief Development Officer

Principal Investigator

Trevi Therapeutics

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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, 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+

Published Research Related to This Trial

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]

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]

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]

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]

Citations

1. evidence.nejm.org evidence.nejm.org/doi/full/10.1056/EVIDoa2300083

Nalbuphine Tablets for Cough in Patients with Idiopathic ... In this small crossover trial we administered nalbuphine extended-release tablets (NAL ER) as a potential cough therapy for such patients.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04030026

NCT04030026 | A Study of Nalbuphine (Extended Release ... 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 ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38320144/

Nalbuphine Tablets for Cough in Patients with Idiopathic ... In this small crossover trial we administered nalbuphine extended-release tablets (NAL ER) as a potential cough therapy for such patients.

4. trevitherapeutics.com trevitherapeutics.com/wp-content/uploads/2024/05/BTS-2022-Molyneaux-et-al-Efficacy-of-oral-nalbuphine-extended-release-for-the-treatment-of-chronic-cough-.pdf

Efficacy of oral nalbuphine extended release for the ... Efficacy of oral nalbuphine extended release for the treatment of chronic cough in idiopathic pulmonary fibrosis: data analysis of a phase 2 study. Philip L ...

5. ir.trevitherapeutics.com ir.trevitherapeutics.com/2025-06-02-Trevi-Therapeutics-Announces-Positive-Topline-Results-from-the-Phase-2b-CORAL-Trial-of-Haduvio-in-Patients-with-Idiopathic-Pulmonary-Fibrosis-Chronic-Cough

Trevi Therapeutics Announces Positive Topline Results ... The primary endpoint in the CORAL trial was achieved, demonstrating statistically significant reductions in 24-hour cough frequency across all dose groups at ...

6. trevitherapeutics.com trevitherapeutics.com/previous-clinical-trials/

Previous Clinical Trial Results Haduvio™ (oral nalbuphine ER) achieved statistically significant reductions in cough frequency in patients with idiopathic pulmonary fibrosis (IPF) and in ...

7. publications.ersnet.org publications.ersnet.org/content/breathe/21/2/240176.full.pdf

Cough in idiopathic pulmonary fibrosis: what is new However, adverse events were significantly higher in the morphine group compared to placebo and were mainly nausea (14%) and constipation (21%) [28]. Nalbuphine ...

8. ir.trevitherapeutics.com ir.trevitherapeutics.com/2025-09-18-Trevi-Therapeutics-Announces-Two-Posters-from-the-Phase-2a-RIVER-Trial-Data-Will-be-Featured-at-the-European-Respiratory-Society-ERS-Congress-2025

Sep 18, 2025 This consistent cough, and any associated damage, may lead to a higher risk of morbidity and mortality, including worsening disease, a higher ...