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: Unknown

Trial Summary

What is the purpose of this trial?

The goal of this clinical trial is to compare naloxone to nalmefene for the treatment of opioid overdose in adults. The main questions it aims to answer are: * Does nalmefene lower the number of doses of medicine participants need to treat opioid overdose? * When participants are given nalmefene instead of naloxone, do they have fewer complications of opioid overdose such as being admitted to the hospital or having a breathing tube inserted? Researchers will compare nalmefene to naloxone for the treatment of opioid overdose. Nalmefene and naloxone are both approved medicines to treat opioid overdose. Participants who are brought to the emergency department after an opioid overdose will be given a dose of either nalmefene or naloxone if their breathing slows down again after an opioid overdose. Participants will: * Stay in the emergency department for 8 hours after receiving a dose of nalmefene or naloxone. * Receive a phone call 7 days after their emergency department to check on how they are doing. Background information: Naloxone (also known as Narcan) and nalmefene are opioid blocking medicines. When someone overdoses on an opioid, such as heroin or fentanyl, their breathing slows down or stops and they can die. By giving naloxone or nalmefene, the effect of the opioid can be blocked and the person can start breathing again. Naloxone is the most commonly used medicine to reverse an opioid overdose. The effect of naloxone lasts about an hour, and patients may need more than one dose of naloxone to keep them breathing. Sometimes patients overdose, get a dose of naloxone and wake up, and then some time later their breathing slows down again and they need another dose of naloxone. This can happen because the effect of the opioid they took lasts longer than the effect of the naloxone. The effect of nalmefene lasts longer than naloxone, about four hours. If a person gets nalmefene, their opioid may wear off before the nalmefene wears off and they might not need any more doses of a reversal medicine. Both naloxone and nalmefene are approved medicines for treating opioid overdose. Often, when a person overdoses on an opioid, someone gives them naloxone right away and then they are brought to the emergency department. In the emergency department, they are watched for several hours to make sure they don't stop breathing again when their naloxone wears off. If they do stop breathing again, they are given another dose of naloxone. In this study, participants will be given either nalmefene or naloxone if their breathing slows down while they are in the emergency department.

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.

What data supports the idea that Nalmefene vs Naloxone for Opioid Overdose is an effective drug?

The available research shows that Nalmefene has a longer duration of action, lasting 4 to 10 hours, compared to Naloxone. This means it can potentially provide longer-lasting protection against opioid overdose. Additionally, an intranasal formulation of Nalmefene was found to reach higher concentrations in the blood more quickly than an intramuscular dose, which could be crucial in emergency situations. These properties suggest that Nalmefene could be an effective option for treating opioid overdoses, especially with high-potency synthetic opioids. ^{1 2 3 4 5}

What safety data exists for Nalmefene and Naloxone in treating opioid overdose?

Nalmefene and Naloxone have been studied for safety in treating opioid overdose. Nalmefene, with a longer duration of action, has been evaluated in emergency department settings and shown to have a safety profile comparable to Naloxone. Nalmefene was approved as an injection in 1995 but withdrawn in 2008 for reasons unrelated to safety. Recent studies have developed an intranasal formulation, showing similar safety profiles to the intramuscular version. Naloxone, approved by the FDA nearly 50 years ago, is the standard treatment for opioid overdose, with various delivery methods like auto-injectors and intranasal systems being studied for usability and effectiveness. ^{1 2 3 4 6}

Is the drug Nalmefene a promising treatment for opioid overdose?

Yes, Nalmefene is a promising drug for treating opioid overdose because it has a longer duration of action compared to Naloxone, which means it can work for a longer time to reverse the effects of an overdose. This can be especially helpful in emergency situations where quick and lasting action is needed. ^{1 2 3 4 7}

Research Team

Caitlin Bonney, MD

Principal Investigator

University of New Mexico Health Sciences Center

Eligibility Criteria

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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]

References

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

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

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

Double-blind, randomized study of nalmefene and naloxone in emergency department patients with suspected narcotic overdose. [2019]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Comparative Usability Study of a Novel Auto-Injector and an Intranasal System for Naloxone Delivery. [2020]

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

Pharmacokinetic Properties of an FDA-approved Intranasal Nalmefene Formulation for the Treatment of Opioid Overdose. [2023]

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

Continuous infusion of naloxone in the treatment of narcotic overdose. [2019]

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

Countermeasures for Preventing and Treating Opioid Overdose. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Potential uses of naltrexone in emergency department patients with opioid use disorder. [2023]