Buprenorphine/Naloxone for Opioid Use Disorder

Overseen By James Wong, MSc

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of British Columbia

Must not be taking: Methadone, Buprenorphine

Disqualifiers: Severe medical, psychiatric conditions, others

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

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method for initiating treatment for opioid use disorder (OUD) using buprenorphine/naloxone, a common medication for this condition. The study compares the standard method, which requires patients to stop using opioids and undergo withdrawal first, with a new approach called rapid micro-induction. This new method involves taking small, frequent doses of the medication, allowing patients to start treatment without experiencing withdrawal. Individuals dealing with opioid use disorder and seeking treatment might be suitable candidates for this trial. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in OUD treatment.

Will I have to stop taking my current medications?

The trial does not specify if you must stop all current medications, but you cannot have used methadone or buprenorphine in the past 5 days. If your current medications are contraindicated (not recommended) with buprenorphine/naloxone, you may need to stop them.

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

Research has shown that buprenorphine/naloxone (bup/nx) is generally safe for treating opioid use disorder. Studies have gathered safety data from thousands of patients. For instance, one study collected safety information from 3,214 people using buprenorphine at doses similar to those for opioid addiction treatment. Another study examined 538 people using buprenorphine/naloxone tablets, providing additional safety insights.

Side effects can include mild issues like nausea and headache. More serious side effects, such as trouble breathing, are rare at low to moderate doses. This combination of medications is widely used and generally well-tolerated.

Hydromorphone, also part of the trial, is another opioid medication often used for pain relief. It is considered safe when used properly, but it can cause unwanted effects, especially in people not accustomed to strong painkillers. Side effects might include dizziness or sleepiness, with serious risks like overdose if misused.

Both treatments have been extensively studied and are generally regarded as well-tolerated when used correctly. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for opioid use disorder because they offer innovative approaches to managing withdrawal symptoms. The Standard Induction method uses a flexible dosing schedule based on the Clinical Opiate Withdrawal Scale, allowing tailored treatment to the patient's needs. Meanwhile, the Rapid Micro-Induction method introduces a fast-track approach, starting with small, frequent doses to ease withdrawal symptoms, reducing the uncomfortable waiting period typically associated with traditional methods. Both approaches aim for faster stabilization and more comfortable transitions, potentially improving patient outcomes compared to conventional treatment strategies.

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

Research shows that combining buprenorphine and naloxone effectively treats opioid use disorder (OUD). Studies have found that this treatment significantly reduces the risk of death and aids recovery from OUD. It also poses a lower overdose risk compared to some other treatments. In this trial, participants may receive buprenorphine/naloxone through either a standard induction method or a rapid micro-induction method. Starting with smaller, more frequent doses of buprenorphine/naloxone, known as rapid micro-induction, can ease the initiation of treatment by preventing withdrawal symptoms. Additionally, in the rapid micro-induction arm, hydromorphone is initially used alongside buprenorphine/naloxone, and it has proven as effective as other strong opioids for individuals with severe OUD. ^{6 7 8 9 10}

Who Is on the Research Team?

Pouya Azar, MD, FRCPC, DABAM

Principal Investigator

University of British Columbia

Nickie Mathew, MD, MSc, FRCPC, ABPN, ABPM

Principal Investigator

University of British Columbia

Are You a Good Fit for This Trial?

This trial is for adults over 19 with Opioid Use Disorder who are seeking treatment and can follow the study plan. They must not have used methadone or buprenorphine in the past 5 days, have no severe health conditions that conflict with treatments, and if female and able to have children, agree to use approved birth control.

Inclusion Criteria

You have an addiction to opioids, as defined by mental health professionals.

Individuals seeking Opioid Agonist Treatment (OAT);

Be willing and able to adhere to the study protocol and follow-up schedule;

Exclusion Criteria

I am allergic to buprenorphine/naloxone or hydromorphone.

There is a possibility that you may need to take medication during the trial that could be unsafe or prevent you from completing the study.

I don't have severe health or mental health conditions that make buprenorphine/naloxone or hydromorphone unsafe for me.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Induction

Participants undergo either rapid micro-induction or standard induction of buprenorphine/naloxone

3 days

Daily visits for monitoring and dose adjustments

Treatment

Participants continue receiving buprenorphine/naloxone with consolidated dosing

4 weeks

Weekly visits for monitoring and prescription pick-up

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Bi-weekly visits for follow-up assessments

What Are the Treatments Tested in This Trial?

Interventions

• Buprenorphine/naloxone
• Hydromorphone

Trial Overview The study compares two ways of starting treatment for opioid addiction: 'Rapid Micro-Induction' which doesn't require withdrawal before beginning therapy, versus the 'Standard Induction' where patients must first go through withdrawal. It tests safety and effectiveness.

How Is the Trial Designed?

Group I: Rapid Micro-Induction Experimental Treatment 2 Interventions

On Day 1, participants will receive 0.5mg bup/nx sublingually (SL) every 3 hours (Q3H) - total daily dose of 4mg. On Day 2, they will receive 1mg bup/nx SL Q3H - total daily dose of 8mg. On Day 3, they will receive 8mg bup/nx SL once and 1-4mg bup/nx SL Q3H as needed (PRN) for withdrawal symptoms and/or craving and/or pain - maximum daily dose of 32mg. Afterwards, their day 3 total dose will be consolidated to once daily dosing - maximum daily dose of 32mg. On Days 1 and 2, participants will concurrently receive 1-48mg hydromorphone orally, intravenously, subcutaneously, or intramuscularly (PO/IV/SC/IM) Q1 to 3H PRN for withdrawal symptoms and/or craving and/or pain, titrated to effect (start at lower end of dosing range). Hydromorphone will be discontinued on Days 3 onwards.

Group II: Standard Induction Active Control 1 Intervention

Day 1 is initiated when participants score 11 or above on the Clinical Opiate Withdrawal Scale (COWS), and when they have been abstinent from short-acting opioids for at least 6-12 hours or from long-acting opioids for 24-72 hours. On Day 1, participants will start with 2 or 4mg bup/nx SL. If their COWS score increases, bup/nx will be held. If their COWS score remains the same or decreases, additional dosing can be done in increments of 2mg bup/nx SL every 2 hours (Q2H) as needed (PRN). On Day 2, dosing will be consolidated to once daily dosing. The maximum total daily dose for Day 1 and 2 is 32mg.

Buprenorphine/naloxone is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Suboxone for:

• Opioid dependence
• Opioid use disorder

Approved in United States as Suboxone for:

• Opioid dependence
• Opioid use disorder

Approved in Canada as Suboxone for:

• Opioid dependence
• Opioid use disorder

Who Is Running the Clinical Trial?

University of British Columbia

Lead Sponsor

Trials

1,506

Recruited

2,528,000+

Vancouver Coastal Health

Collaborator

Trials

41

Recruited

717,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11610725/

Buprenorphine-Naloxone for Opioid Use Disorder Buprenorphine-naloxone was associated with significantly reduced mortality and increased remission rates for patients with opioid use disorder.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6585403/

Buprenorphine Treatment for Opioid Use Disorder Among all randomized patients, buprenorphine was modestly superior to XR-naltrexone on the primary outcome of relapse, and on the number of opioid positive ...

3. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/2825088

Buprenorphine/Naloxone vs Methadone for the Treatment ... The risk of treatment discontinuation was higher among recipients of buprenorphine/naloxone compared with methadone (88.8% vs 81.5% within 24 months).

4. cdc.gov cdc.gov/mmwr/volumes/73/wr/mm7325a1.htm

Treatment for Opioid Use Disorder: Population Estimates Medications for opioid use disorder (OUD), particularly buprenorphine and methadone, substantially reduce overdose-related and overall mortality ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2949875923002606

Evaluation of opioid use disorder treatment outcomes in ... In this study, patients receiving once daily buprenorphine-naloxone had similar treatment outcomes to patients receiving split dosing.

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2016/204242s009lbl.pdf

ZUBSOLV (buprenorphine and naloxone) sublingual tablets In total, safety data were available from 3214 opioid-dependent subjects exposed to buprenorphine at doses in the range used in treatment of opioid addiction.

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2022/204242s021s023lbl.pdf

prescribing information - accessdata.fda.gov In total, safety data were available for 538 opioid-dependent subjects exposed to ZUBSOLV. (buprenorphine/naloxone) sublingual tablets when used for initial ...

8. samhsa.gov samhsa.gov/substance-use/treatment/options/buprenorphine

What is Buprenorphine? Side Effects, Treatment & Use Buprenorphine is an opioid partial agonist. It produces effects such as euphoria or respiratory depression at low to moderate doses. With ...

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

Buprenorphine and Naloxone - StatPearls - NCBI Bookshelf Buprenorphine-naloxone is an effective and commonly prescribed combination medication created to treat opioid use disorder. Mechanism.

10. mayoclinic.org mayoclinic.org/drugs-supplements/buprenorphine-naloxone-oromucosal-route-sublingual-route/description/drg-20074097

Buprenorphine/naloxone (oromucosal route, sublingual ... Buprenorphine and naloxone sublingual tablet is used to treat opioid (narcotic) dependence or addiction.