Naloxone + Buprenorphine Induction for Opioid Use Disorder

(NBIM Trial)

Overseen By Anjalee Sharma, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Johns Hopkins University

Must not be taking: OUD medications

Disqualifiers: Cognitive impairment, Pregnancy, Hypertension, 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

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

Compensation: Varies

Number of Visits: 2

Duration: 2-3 days

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to find a quick and safe way to start buprenorphine treatment for people using fentanyl. Researchers will test whether using naloxone (also known as Narcan or Evzio) first can make the switch to buprenorphine smoother and more comfortable. Participants will receive different doses of buprenorphine after naloxone to determine which works best. Suitable candidates for this trial have a moderate to severe opioid use disorder and test positive for fentanyl. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are currently taking medications for opioid use disorder or any medication that is contraindicated (not recommended) with the study medication.

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

Research shows that naloxone effectively reverses opioid overdoses, including those involving fentanyl. It is generally safe for emergency use to counteract opioid effects. Some individuals might experience withdrawal symptoms after receiving naloxone, especially with regular opioid use.

Buprenorphine often treats opioid addiction by reducing cravings and withdrawal symptoms. Studies have shown that most patients tolerate it well. However, starting buprenorphine can be challenging because it might cause uncomfortable withdrawal symptoms if opioids remain in the body.

Combining naloxone with buprenorphine aims to ease the transition. Previous patients using these medications have demonstrated that this approach can be effective. While naloxone can trigger withdrawal, it helps clear opioids from the body, allowing buprenorphine to work better without causing additional discomfort.

Overall, both naloxone and buprenorphine have been used safely in many patients. This trial seeks to ensure this combination is well-tolerated and effective for people using fentanyl. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard opioid use disorder treatments, which typically start with buprenorphine alone, this approach uses naloxone nasal spray combined with varying doses of buprenorphine. Researchers are excited because this combination could potentially induce the treatment more effectively by rapidly reversing opioid effects with naloxone and then stabilizing withdrawal symptoms with buprenorphine. This method could offer a faster, smoother transition for people beginning treatment, making it easier for them to stick with it and ultimately improve recovery outcomes.

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

Research has shown that naloxone effectively reverses opioid overdoses, including those from fentanyl. It often aids individuals in beginning treatment with buprenorphine, a medication for opioid addiction. Buprenorphine attaches to the same brain areas as other opioids, reducing cravings and withdrawal symptoms. In this trial, participants will receive different dosages of buprenorphine (4mg, 8mg, 16mg, or 24mg) immediately after naloxone administration. Studies have found that using naloxone with buprenorphine does not cause harmful effects. This combination may help individuals who use fentanyl start buprenorphine treatment more safely. ^{1 2 3 5 6}

Who Is on the Research Team?

Cecilia Bergeria, PhD

Principal Investigator

Johns Hopkins School of Medicine

Are You a Good Fit for This Trial?

This trial is for adults over 18 who speak English, have a moderate to severe opioid use disorder with fentanyl present in their urine, and are medically cleared to take the study medication. They must be willing to follow the study protocol but not currently on medications for OUD or pregnant/breastfeeding.

Inclusion Criteria

You are currently suffering from a moderate to severe opioid use disorder.

My urine test was positive for fentanyl.

My doctor has approved me to take the study medication.

Exclusion Criteria

I have not had a serious heart problem in the last 3 years.

Deemed by the principal investigator or medical team to not be a good fit for the study protocol

Unable to read or understand study questions with assistance from the research staff

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Treatment

Participants undergo naloxone-facilitated buprenorphine induction with ascending doses to assess tolerability

2-3 days

Residential stay at clinical research unit

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

1 visit (in-person or virtual)

Extension

Participants are connected to a medical provider for continued buprenorphine prescribing

What Are the Treatments Tested in This Trial?

Interventions

• Naloxone Nasal Spray

Trial Overview The trial tests a new method of starting buprenorphine treatment using naloxone nasal spray among individuals who use fentanyl. It aims to see if this approach can safely and quickly transition patients without prolonged withdrawal by gradually increasing buprenorphine doses.

How Is the Trial Designed?

Group I: 8mg buprenorphine Experimental Treatment 1 Intervention

8mg of buprenorphine will be given to a subset of participants immediately after naloxone administration.

Group II: 4mg buprenorphine Experimental Treatment 1 Intervention

4mg of buprenorphine will be given to a subset of participants immediately after naloxone administration.

Group III: 24mg buprenorphine Experimental Treatment 1 Intervention

24mg of buprenorphine will be given to a subset of participants immediately after naloxone administration.

Group IV: 16mg buprenorphine Experimental Treatment 1 Intervention

16mg of buprenorphine will be given to a subset of participants immediately after naloxone administration.

Naloxone Nasal Spray is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Narcan for:

• Reversal of opioid overdose

Approved in European Union as Naloxone for:

• Reversal of opioid overdose

Approved in Canada as Naloxone for:

• Reversal of opioid overdose

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

Cure Addiction Now

Collaborator

Trials

1

Recruited

30+

Published Research Related to This Trial

Initiating buprenorphine treatment for Opioid Use Disorder (OUD) by paramedics in the prehospital setting shows promise as a potential intervention for patients at high risk of overdose, especially those who refuse transport to medical facilities.

The preliminary cases suggest that starting buprenorphine during emergency medical services (EMS) responses can help engage patients in long-term treatment services, contributing to a broader strategy to address the opioid epidemic.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prehospital Initiation of Buprenorphine Treatment for Opioid Use Disorder by Paramedics. Hern, HG., Goldstein, D., Kalmin, M., et al.[2022]

Training patients in their homes on how to recognize opioid overdose symptoms and use the Naloxone auto-injector significantly improved their knowledge and response skills, with a statistically significant increase in correct identification of overdose response steps (p = 0.03).

The study faced challenges in feasibility due to insurance coverage issues, as 20 out of 40 enrolled patients withdrew because their insurance did not cover the cost of the Naloxone auto-injector.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The feasibility of employing a home healthcare model for education and treatment of opioid overdose using a naloxone auto-injector in a private practice pain medicine clinic. Dragovich, A., Brason, F., Beltran, T., et al.[2019]

NARCAN® Nasal Spray is easier to use than a naloxone prefilled syringe with nasal atomizer (PFS-NA), requiring fewer steps for administration, which is crucial in high-stress opioid overdose situations.

Inexperienced users, such as bystanders or nonmedical first responders, are more likely to make mistakes with the more complex PFS-NA, highlighting the importance of using NARCAN® Nasal Spray to improve the chances of timely and correct naloxone delivery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Human Factors Evaluation of Two Nasal Naloxone Administration Devices: NARCAN® Nasal Spray and Naloxone Prefilled Syringe with Nasal Atomizer. Tippey, KG., Yovanoff, M., McGrath, LS., et al.[2020]

In a case series of three patients from a Vancouver addiction clinic, unexpected precipitated withdrawal occurred during the initiation of buprenorphine/naloxone (BUP/NX) after periods of fentanyl abstention, highlighting a challenge in treating opioid use disorder.

The findings suggest that fentanyl may have a longer-lasting effect in the body than previously thought, complicating the BUP/NX induction process and indicating a need for revised strategies when treating individuals with a history of fentanyl use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Challenges with buprenorphine inductions in the context of the fentanyl overdose crisis: A case series. Shearer, D., Young, S., Fairbairn, N., et al.[2023]

This study is the first randomized controlled trial comparing rapid micro-induction to standard induction of buprenorphine/naloxone in treating opioid use disorder, involving 50 participants to assess safety and effectiveness.

Rapid micro-induction could potentially eliminate the need for patients to experience withdrawal symptoms before starting treatment, addressing a significant barrier to accessing care for opioid use disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparing rapid micro-induction and standard induction of buprenorphine/naloxone for treatment of opioid use disorder: protocol for an open-label, parallel-group, superiority, randomized controlled trial. Wong, JSH., Nikoo, M., Westenberg, JN., et al.[2023]

The study will involve 280 adults with opioid use disorder and aims to improve adherence to buprenorphine-naloxone treatment through two psychological interventions: contingency management (CM) and brief motivational interviewing plus substance-free activities and mindfulness (BSM).

The primary goal is to assess which intervention is more effective in promoting medication adherence, measured by attendance at physician appointments and the presence of buprenorphine in urine toxicology, with follow-up occurring 8 months after randomization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of a sequential multiple assignment randomized trial to test contingency management and an integrated behavioral economic and mindfulness intervention for buprenorphine-naloxone medication adherence for opioid use disorder. Peter, SC., Murphy, JG., Witkiewitz, K., et al.[2023]

Buprenorphine-naloxone (Suboxone) was found to be safe and well tolerated for short-term opioid detoxification in a study involving 234 opioid-dependent patients across twelve community-based treatment programs.

The treatment showed high medication compliance (81% of doses ingested) and successful induction, with 90% of patients reaching the target dose within three days, indicating its efficacy and practicality in diverse settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bringing buprenorphine-naloxone detoxification to community treatment providers: the NIDA Clinical Trials Network field experience. Amass, L., Ling, W., Freese, TE., et al.[2022]

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]

The use of the naloxone autoinjector (NAI) Evzio significantly increased from 218 prescriptions in Year 1 to 2,527 in Year 3, leading to a reduction in fatal opioid overdoses, with 2.5 deaths avoided in Year 3 compared to matched controls.

Despite rising acquisition costs of the NAI, which reached nearly $1.5 million in Year 3, the medical resource savings associated with its use offset these costs, resulting in a net cost of $481,000, demonstrating the economic benefit of timely access to naloxone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Economic impact of a novel naloxone autoinjector on third-party payers. Weiss, RC., Bazalo, GR., Thomson, H., et al.[2015]

Narcan, a nasal-spray form of naloxone, is FDA-approved and provides an easy-to-use method for reversing opioid overdoses, making it a critical tool for saving lives.

As overdose deaths rise in hospitals, health systems are considering equipping police and security officers with naloxone and training them in its use to enhance emergency response capabilities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Equipping an urban hospital police and security team with Narcan. Driscoli, J., Michelman, B.[2018]

A survey of intravenous drug users in Helsinki revealed that 73% used buprenorphine as their primary drug, primarily for self-treating addiction or withdrawal symptoms.

The combination of buprenorphine and naloxone (Suboxone) was tried by 68% of respondents, but 80% reported negative experiences, suggesting that while it may help reduce buprenorphine abuse, its acceptance among users is low.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abuse liability of buprenorphine-naloxone tablets in untreated IV drug users. Alho, H., Sinclair, D., Vuori, E., et al.[2015]

Buprenorphine/naloxone has a unique pharmacology that provides a ceiling effect on its cardio-respiratory depressant properties, making it potentially safer than other opioids, especially at higher doses.

Data from various safety monitoring systems indicate that buprenorphine/naloxone has a favorable safety profile compared to other opioids and psychotropic drugs, suggesting it may reduce the risk of overdose-related morbidity and mortality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Question About the Safety of Buprenorphine/Naloxone and Benzodiazepine Drugs. Howland, RH.[2015]

Citations

1. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK441910/

Naloxone - StatPearls - NCBI Bookshelf Naloxone is indicated for the treatment of opioid toxicity, specifically to reverse respiratory depression from opioid use.

2. hhs.texas.gov hhs.texas.gov/sites/default/files/documents/october-2024-durb-agenda-item3z.pdf

Gainwell Technologies - Therapeutic Class Review These results support the effectiveness of naloxone in treating fentanyl overdoses and suggest that it may require fewer doses compared to ...

3. 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.

4. acog.org acog.org/clinical/clinical-guidance/committee-opinion/articles/2017/08/opioid-use-and-opioid-use-disorder-in-pregnancy

Opioid Use and Opioid Use Disorder in Pregnancy However, recent studies that evaluated the use of the combination product buprenorphine with naloxone found no adverse effects, and outcomes were similar when ...

5. fda.gov fda.gov/media/189037/download?attachment

Naloxone Hydrochloride These results demonstrate that the proposed naloxone nasal spray product achieves comparable or greater systemic naloxone exposures as compared ...

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK603725/

Buprenorphine and Naloxone - StatPearls - NCBI Bookshelf The combination medication buprenorphine-naloxone is not an appropriate treatment for opioid-induced respiratory depression. Go to: Enhancing ...