Nalmefene vs Naloxone for Opioid Overdose

Overseen By Silas Bussman

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: University of New Mexico

Must not be taking: Buprenorphine

Disqualifiers: Age <18, Non-English, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 2

Duration: 8 hours

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial compares two medicines, naloxone and nalmefene, to determine which is more effective for treating opioid overdoses in adults. Naloxone (also known as Narcan) is commonly used but may require multiple doses. In contrast, nalmefene (Nalmefene Hydrochloride Injection) lasts longer and could reduce the need for additional doses. The trial seeks to determine if nalmefene can lower the chances of needing extra medical help, such as hospital admission or a breathing tube. Adults who have experienced an opioid overdose and received naloxone might be suitable candidates for this trial. Participants will be monitored in the emergency department and receive a follow-up call a week later to check on their progress. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Do I have to stop taking my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are given buprenorphine during your emergency department visit, you cannot participate in the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that both nalmefene and naloxone are generally safe and well-tolerated for treating opioid overdoses. Many people know naloxone as Narcan, and it has proven safe in various situations.

Studies have found that nalmefene works quickly to reverse breathing problems caused by opioids, usually within 2 to 5 minutes after administration. In trials with over a thousand participants, researchers monitored side effects, and while some were noted, the treatment was considered safe. Both nalmefene and naloxone are already approved for treating opioid overdoses, indicating that their safety is well understood.

These treatments are used in emergencies to save lives, and safety data suggests they do this effectively with manageable risks. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Nalmefene is unique because it offers a potentially longer-lasting effect compared to the current standard treatment, naloxone, for reversing opioid overdoses. While naloxone is effective at quickly reversing opioid effects, its shorter duration can lead to the re-emergence of overdose symptoms, requiring multiple doses. Nalmefene, on the other hand, may provide extended relief, reducing the need for repeated dosing and continuous medical supervision. Researchers are excited about nalmefene because it could improve patient outcomes by maintaining stability longer after an overdose.

What evidence suggests that this trial's treatments could be effective for opioid overdose?

This trial will compare the effectiveness of nalmefene and naloxone for opioid overdose. Research has shown that nalmefene, which participants in this trial may receive, effectively reverses opioid overdoses, similar to naloxone. Studies have found that nalmefene can restore breathing problems caused by opioids within 2 to 5 minutes. Its effects last longer than naloxone, possibly up to four hours, potentially reducing the need for additional doses. This extended effect could help maintain breathing until the opioids leave the system. Both nalmefene and naloxone are approved for treating opioid overdoses and work by blocking the effects of opioids to restart breathing. ^{2 5 6 7 8}

Who Is on the Research Team?

Caitlin Bonney, MD

Principal Investigator

University of New Mexico Health Sciences Center

Are You a Good Fit for This Trial?

Adults who have experienced an opioid overdose and are brought to the emergency department can participate. They must stay for observation for 8 hours after treatment and be available for a follow-up call after 7 days.

Inclusion Criteria

I am an adult who received naloxone for an opioid overdose.

Exclusion Criteria

Allergy to naloxone

Allergy to nalmefene

Non-English speaking

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

Not specified

Treatment

Participants receive either nalmefene or naloxone in the emergency department and are observed for 8 hours

8 hours

1 visit (in-person)

Follow-up

Participants are contacted by phone to assess for recurrence of opioid overdose symptoms and adverse events

7 days

1 visit (virtual)

What Are the Treatments Tested in This Trial?

Interventions

• Nalmefene
• Naloxone

Trial Overview The trial is testing if nalmefene, which lasts longer than naloxone, reduces the need for multiple doses in treating opioid overdoses. It also examines whether nalmefene leads to fewer complications like hospital admission or intubation compared to naloxone.

How Is the Trial Designed?

Group I: Nalmefene Experimental Treatment 1 Intervention

Nalmefene Rescue Study Arm Treatment: Subjects will receive study drug if they exhibit respiratory depression (defined as respiratory rate less than 8 breaths per minute and/or end-tidal carbon dioxide measurement of greater than 50 mm Hg) lasting for longer than 10 seconds. Respiratory support with bag-valve mask and/or supplemental oxygen will be provided while the study drug is being prepared. Nalmefene will be administered as per intervention description.

Group II: Naloxone Active Control 1 Intervention

Naloxone Rescue Arm Treatment: Subjects will receive study drug if they exhibit respiratory depression (defined as respiratory rate less than 8 breaths per minute and/or end-tidal carbon dioxide measurement of greater than 50 mm Hg) lasting for longer than 10 seconds. Respiratory support with bag-valve mask and/or supplemental oxygen will be provided while the study drug is being prepared. Naloxone will be administered as per intervention description.

Nalmefene is already approved in United States for the following indications:

Approved in United States as Opvee for:

• Complete or partial reversal of opioid drug effects, including respiratory depression, induced by either natural or synthetic opioids
• Management of known or suspected opioid overdose

Who Is Running the Clinical Trial?

University of New Mexico

Lead Sponsor

Trials

393

Recruited

3,526,000+

Published Research Related to This Trial

Naltrexone, a long-acting opioid antagonist, may provide an alternative treatment option for opioid use disorder (OUD) that can be initiated immediately after an emergency department visit for opioid overdose, addressing the need for diverse treatment options.

The review highlights the pharmacology and history of naltrexone, emphasizing its potential effectiveness as medication for addiction treatment (MAT) compared to traditional opioid agonist therapies like methadone and buprenorphine, which can be difficult to access.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential uses of naltrexone in emergency department patients with opioid use disorder. Bradley, ES., Liss, D., Carreiro, SP., et al.[2023]

In a study involving emergency department patients with suspected narcotic overdose, both nalmefene (1 mg and 2 mg) and naloxone (2 mg) were found to be equally effective in improving respiratory rates and consciousness levels, with no significant differences in outcomes between the treatments.

The safety profiles were similar, with adverse events occurring in about 15-30% of patients across all treatment groups, but none were serious or led to morbidity, indicating that both nalmefene and naloxone are safe options for treating opioid overdoses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Double-blind, randomized study of nalmefene and naloxone in emergency department patients with suspected narcotic overdose. Kaplan, JL., Marx, JA., Calabro, JJ., et al.[2019]

Current opioid overdose treatment relies on naloxone, which has limitations, especially in mass casualty situations involving synthetic opioids, prompting the need for new alternatives.

Emerging treatments discussed at a 2019 scientific meeting include intranasal nalmefene, which has a longer action than naloxone, and novel strategies like covalent naloxone nanoparticles and detoxifying nanosponge decoy receptors, which could enhance the effectiveness of opioid overdose interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Countermeasures for Preventing and Treating Opioid Overdose. France, CP., Ahern, GP., Averick, S., et al.[2021]

Nalmefene, an investigational narcotic antagonist, was found to be effective in reversing opiate overdose in a study of 53 patients, with a rapid complete response observed in 80% of opiate-positive cases.

The study indicated that nalmefene is safe, with no serious adverse events related to its use, even in cases involving other narcotics like methadone and codeine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of intravenous nalmefene for emergency department patients with suspected narcotic overdose: a pilot study. Kaplan, JL., Marx, JA.[2019]

In a study involving 42 healthy participants, the naloxone auto-injector (NAI) was significantly more effective than the intranasal delivery system (NXN) for administering naloxone during a simulated opioid overdose, with 90.5% success for NAI compared to 0% for NXN before training.

After training, 100% of participants successfully used NAI, while only 57.1% could use NXN, highlighting that NAI is easier to use and requires less training for effective administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Usability Study of a Novel Auto-Injector and an Intranasal System for Naloxone Delivery. Edwards, ET., Edwards, ES., Davis, E., et al.[2020]

Intranasal (IN) nalmefene delivers significantly higher plasma concentrations and reaches peak levels faster than the intramuscular (IM) formulation, making it a potentially more effective option for emergency treatment of opioid overdose.

Both IN and IM nalmefene have similar plasma half-lives, but the rapid delivery of IN nalmefene could be crucial in reducing opioid overdose morbidity and mortality, especially given the rise in high-potency synthetic opioids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic Properties of an FDA-approved Intranasal Nalmefene Formulation for the Treatment of Opioid Overdose. Crystal, R., Ellison, M., Purdon, C., et al.[2023]

Naloxone infusion may be an effective treatment for opiate overdose, as demonstrated in two successful cases, suggesting it can help prevent patients from relapsing into narcosis after an overdose.

The extreme safety profile of naloxone makes it a favorable option for continuous infusion, particularly for treating overdoses from longer-acting narcotics like methadone, warranting further clinical trials to confirm its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Continuous infusion of naloxone in the treatment of narcotic overdose. Bradberry, JC., Raebel, MA.[2019]

Citations

1. purduepharma.com purduepharma.com/news/2024/09/30/study-examining-use-of-nalmefene-hci-injection-for-opioid-overdose-reversal-in-emergency-departments-concludes-observational-period/

Study Examining Use of Nalmefene HCI Injection for Opioid ... Preclinical studies have shown that nalmefene at doses up to 10 mg/kg (437 times the maximum recommended human dose) produced incomplete ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05808881

NCT05808881 | Clinical Outcomes From Nalmefene The purpose of this study is to assess the effectiveness of nalmefene relative to naloxone for the reversal of opioid intoxication in emergency department (ED) ...

3. ascpt.onlinelibrary.wiley.com ascpt.onlinelibrary.wiley.com/doi/10.1002/cpt.3514?af=R

FDA Approval Summary: Nalmefene Nasal Spray for the ... Following administration of IV nalmefene HCl, doses of 0.5–1.0 mg effectively reversed opioid-induced respiratory depression within 2–5 minutes, ...

4. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2025/218590Orig1s000MedR.pdf

218590Orig1s000 CLINICAL REVIEW(S) - accessdata.fda.gov While nalmefene hydrochloride administration has only mild effects in opioid-naïve persons, it can cause opioid withdrawal in persons with ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0955395924000082

Stronger, longer, better opioid antagonists? Nalmefene is ... In this article, we explore the medical need and ramifications of the introduction of longer-acting opioid antagonists in the current opioid overdose landscape.

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2023/217470Orig1s000.pdf

OPVEE nasal spray device - accessdata.fda.gov Adverse reaction information was obtained following administration of nalmefene injection to. 152 normal volunteers and in controlled clinical trials to 1127 ...

7. acmt.net acmt.net/news/acmt-aact-joint-position-statement-on-nalmefene-should-not-replace-naloxone-as-the-primary-opioid-antidote-at-this-time/

ACMT & AACT Joint Position Statement on Nalmefene ... We do not have clinical data for nalmefene in patients with synthetic opioid overdose. Moreover, the current standard opioid antidote, naloxone, has a ...

8. nalmefenehcl.com nalmefenehcl.com/overdose-crisis/

Opioid Overdose Crisis - Nalmefene HCl injection Preclinical studies have shown that nalmefene at doses up to 10 mg/kg (437 times the maximum recommended human dose) produced incomplete reversal of ...