Opioid Medications for Opioid Use Disorder

Overseen By JOSHUA LILE, Ph.D.

Age: 18 - 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: Joshua A. Lile, Ph.D.

Must not be taking: Alcohol, Benzodiazepines, Barbiturates

Disqualifiers: Respiratory disease, Cardiovascular issues, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 9 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how opioid use and withdrawal affect decision-making and the brain. Researchers are testing two treatments—oxycodone and remifentanil, both opioid medications—to understand their effects on individuals with opioid use disorder. Participants will complete tasks after taking either an active medication or a placebo (a harmless pill with no effect) to compare results. This trial is best suited for individuals who have been using opioids and experience withdrawal symptoms. As an Early Phase 1 trial, this research focuses on understanding how these treatments work in people, offering participants a unique opportunity to contribute to groundbreaking research.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you have a substance use disorder for substances other than opioids or nicotine that requires detoxification, you may not be eligible to participate.

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

Research has shown that oxycodone is a strong painkiller with serious side effects, particularly for those unaccustomed to such medications. It is approved for managing pain, indicating safety when used correctly. However, misuse can lead to overdose and other unwanted effects.

Studies have indicated that remifentanil is effective and generally well-tolerated in medical settings, such as during surgery. It appears safe for mothers and babies during labor pain relief and may even reduce time on machines like ventilators. However, like other opioids, improper use carries a risk of overdose and other issues.

Both drugs have demonstrated safety in certain medical situations, but they require careful management due to associated risks. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these treatments for opioid use disorder because they explore the nuanced effects of oxycodone and remifentanil in managing addiction. Unlike the standard treatments such as methadone or buprenorphine that primarily focus on opioid replacement therapy, oxycodone and remifentanil are being studied for their unique effects on decision-making and behavior through a controlled gambling task. This approach could uncover new insights into how these medications affect cognitive processes linked to addiction, potentially leading to more targeted therapies in the future. Additionally, the inclusion of a remifentanil dose-ranging session offers a fresh perspective on individualized dosing strategies, which could improve treatment outcomes.

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

Research shows that oxycodone, a common painkiller, primarily relieves pain. However, its addictive nature complicates its use in treating opioid use disorder (OUD). Limited evidence supports its effectiveness for OUD treatment. In this trial, participants will receive oxycodone in one of the treatment arms to assess its effects during a gambling task.

Studies have found that remifentanil acts quickly and has a short duration. Its rapid action makes it suitable for hospital use. While there is limited information on its direct effectiveness in treating OUD, its quick effect proves useful in controlled settings. Participants with a history of IV opioid use in this trial can choose to complete a final remifentanil dose-ranging session. More research is needed to understand its potential in managing OUD. ^{1 6 7 8 9}

Who Is on the Research Team?

JOSHUA LILE, Ph.D.

Principal Investigator

University of Kentucky

Are You a Good Fit for This Trial?

This trial is for adults with moderate to severe opioid use disorder who have used opioids recently or are in withdrawal. They must speak English and, if female, use effective birth control. It excludes those with other substance disorders needing detox (except nicotine), MRI contraindications, respiratory risks, seeking SUD treatment, poor veins (for remifentanil session), significant diseases or psychiatric disorders affecting compliance.

Inclusion Criteria

I am using an effective form of birth control.

Able to speak and read English

Must meet moderate/severe criteria for moderate/severe opioid use disorder, report recent prescription or illicit opioid use, and be opioid dependent, as evidenced by either a urine sample positive for recent opioid use or being in frank withdrawal during screening.

Exclusion Criteria

At risk for respiratory complications and have predictors of difficult bag mask ventilation (e.g., dentures, very full beard), in case emergency respiratory intervention is needed.

I don't have any major health or mental issues that would stop me from following the study's requirements.

Contraindications for MRI scanning (e.g., pacemaker, metal implants, claustrophobia, or any other implanted medical device).

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants complete a gambling task during oxycodone and placebo administration, with an optional remifentanil dose-ranging session for those with a history of IV opioid use

9 days

Inpatient enrollment

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Oxycodone
• Remifentanil

Trial Overview The study tests how opioid dependency and withdrawal affect decision-making using tasks and brain imaging. It aims to understand the related neurobehavioral processes and find a suitable dose of intravenous remifentanil for future research on individuals dependent on opioids.

How Is the Trial Designed?

Group I: Placebo treatment followed by active treatment Experimental Treatment 2 Interventions

Participants complete a gambling task during placebo administration and then complete the same gambling task during oxycodone administration. Participants with a history of IV opioid use can opt to complete a final remifentanil dose-ranging session.

Group II: Active treatment followed by placebo treatment Experimental Treatment 2 Interventions

Participants complete a gambling task during oxycodone administration and then complete the same gambling task during placebo administration. Participants with a history of IV opioid use can opt to complete a final remifentanil dose-ranging session.

Who Is Running the Clinical Trial?

Joshua A. Lile, Ph.D.

Lead Sponsor

Trials

6

Recruited

120+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Published Research Related to This Trial

Over 2 million Americans have opioid use disorder, which is partly due to overprescribing, highlighting the need for better opioid stewardship and management strategies by physicians.

Three FDA-approved medications—methadone, buprenorphine, and naltrexone—are effective for treating opioid use disorder, but successful outcomes are best achieved through comprehensive, interprofessional management plans rather than relying solely on medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prescription Drug and Alcohol Use Disorders: Opioid Use Disorder. Witt, L., Butler, F.[2019]

Methadone and buprenorphine-naloxone are effective long-term maintenance medications for opioid use disorders (OUDs), positively impacting the health of individuals with opioid addiction.

Despite their effectiveness, the use of buprenorphine and naltrexone is limited due to stigma and barriers in access to treatment, highlighting the need for improved education and resources in the medical community.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current status of opioid addiction treatment and related preclinical research. Kreek, MJ., Reed, B., Butelman, ER.[2023]

Xtampza® ER (oxycodone DETERx®) is an extended-release opioid formulation designed to deter abuse, and studies show that even when physically manipulated (crushed or chewed), it maintains its extended-release pharmacokinetic profile, making it less likely to be abused compared to immediate-release formulations.

In contrast, when OxyContin is crushed, it loses its extended-release properties and behaves like immediate-release oxycodone, highlighting Xtampza ER's potential as a safer option for patients needing chronic pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of physical manipulation on the oral pharmacokinetic profile of Xtampza&#174; ER (oxycodone DETERx&#174; formulation): A review of published studies. Gudin, J.[2020]

The abuse-deterrent formulation OxyM-ER (oxycodone myristate extended-release) may not provide effective pain management for cancer patients with low-calorie or low-fat diets, as its efficacy can be influenced by dietary intake.

An interdisciplinary approach, including dietary modifications, can enhance pain control for patients switched to OxyM-ER, demonstrating the importance of considering individual patient circumstances in opioid management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Impact of Food on Bioavailability of Oxycodone Myristate: A Case Report. Nguyen, TP., Hagiwara, Y., Pies, C., et al.[2022]

Physicians perceive methadone and buprenorphine as more effective than extended-release naltrexone for treating opioid use disorder, especially in patients with co-occurring mental health disorders, highlighting a need for better education on the efficacy of all treatment options.

Insurance obstacles, particularly prior authorization requirements, are the most significant barriers to prescribing buprenorphine and naltrexone, suggesting that policy changes are necessary to improve access to these effective treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A mixed-method comparison of physician-reported beliefs about and barriers to treatment with medications for opioid use disorder. Haffajee, RL., Andraka-Christou, B., Attermann, J., et al.[2021]

A significant increase in reports of abuse, misuse, and dependence related to prescription opioids was observed from 2003 to 2018, with 16,506 reports in EudraVigilance and 130,293 in the FDA Adverse Events Reporting System.

Fentanyl and oxycodone were particularly associated with abuse concerns, while tramadol and oxycodone showed stronger links to drug dependence and withdrawal, highlighting the need for careful monitoring by healthcare providers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacovigilance Signals of the Opioid Epidemic over 10 Years: Data Mining Methods in the Analysis of Pharmacovigilance Datasets Collecting Adverse Drug Reactions (ADRs) Reported to EudraVigilance (EV) and the FDA Adverse Event Reporting System (FAERS). Chiappini, S., Vickers-Smith, R., Guirguis, A., et al.[2022]

Oxycodone consumption has significantly increased over the past two decades, surpassing morphine in 2008, yet much of its pharmacokinetic data is outdated, primarily from the 1990s.

Recent studies have provided crucial information on oxycodone's effects in special populations (like neonates and the elderly) and highlighted important drug interactions, particularly with CYP450 enzymes, which can affect its safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Updated Clinical Pharmacokinetics and Pharmacodynamics of Oxycodone. Kinnunen, M., Piirainen, P., Kokki, H., et al.[2020]

Methadone is the most effective medication for treating opioid use disorder (OUD), as it helps suppress withdrawal symptoms and has strong evidence supporting its efficacy, especially with longer treatment durations leading to better social outcomes.

New formulations of buprenorphine and naltrexone, along with take-home naloxone programs, aim to improve safety and adherence in OUD treatment, addressing issues like relapse and overdose risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Medication Treatment of Opioid Use Disorder. Bell, J., Strang, J.[2021]

The review of 18 studies indicates that treating ADHD in patients with opioid use disorder (OUD) can lead to better retention in OUD treatment programs and improvements in ADHD severity.

While the specific medications for OUD treatment could not be prioritized, the findings suggest that addressing ADHD symptoms is important for reducing illicit substance abuse in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gaps in Evidence-based Treatment of Concurrent Attention Deficit Hyperactivity Disorder and Opioid Use Disorder: A Scoping Review. Ramey, OL., Bonny, AE., Silva Almodóvar, A., et al.[2023]

Xtampza ER, an abuse-deterrent formulation of extended-release oxycodone, demonstrated significant pain relief in patients with chronic low back pain, showing a mean reduction in pain intensity of -1.56 compared to placebo over 12 weeks.

The study, involving 740 participants, found that Xtampza ER was well tolerated with an adverse event profile similar to other opioids, and it resulted in fewer patients needing rescue medication compared to the placebo group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 3, multicenter, randomized, double-blind, placebo-controlled, safety, tolerability, and efficacy study of Xtampza ER in patients with moderate-to-severe chronic low back pain. Katz, N., Kopecky, EA., O'Connor, M., et al.[2022]

Citations

1. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK458653/

Evidence on Strategies for Addressing the Opioid Epidemic The purpose of this chapter is to review available evidence on strategies that have been used to address the problems of opioid misuse, OUD, and related deaths.

2. xtampzaer.com xtampzaer.com/hcp/clinical-studies/

Clinical Studies | XTAMPZA® ER (oxycodone), CII Oral abuse: XTAMPZA ER demonstrated a statistically significant reduction in oral abuse potential vs oxycodone immediate-release (IR)1. The oral abuse potential ...

3. fda.gov fda.gov/media/140805/download

Report on Abuse-Deterrent Opioid Formulations and ... In contrast, Oxycontin was available to about 30% of Medicare beneficiaries but accounted for over 70% of ADF opioid analgesic PDEs.

4. psychiatry.org psychiatry.org/patients-families/opioid-use-disorder

Psychiatry.org - Opioid Use Disorder An estimated 3-12% of people treated with opioids for chronic pain will develop an addiction or abuse with negative consequences.(12) Approximately 8.6 million ...

5. cdc.gov cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm

CDC Clinical Practice Guideline for Prescribing Opioids ... The systematic review addressed the effectiveness of long-term opioid therapy for outcomes related to pain, function, and quality of life; the ...

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK482226/

Oxycodone - StatPearls - NCBI Bookshelf - NIH Oxycodone is a potent semisynthetic opioid agonist prescription medication with agonistic properties on mu-, kappa-, and delta-type opioid receptors.

7. academic.oup.com academic.oup.com/painmedicine/article/21/12/3660/5936096

Postmarketing Analysis of Misuse, Abuse, and Diversion of ... Nonoral abuse cases involving Xtampza ER were infrequent; Web monitoring data support findings that Xtampza ER is difficult to abuse nonorally.

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2016/208090s003lbl.pdf

XTAMPZA ER (oxycodone) extended-release capsules As extended-release products such as XTAMPZA ER deliver the opioid over an extended period of time, there is a greater risk for overdose and death due to the ...

9. mayoclinic.org mayoclinic.org/drugs-supplements/oxycodone-oral-route/description/drg-20074193

Oxycodone (oral route) - Side effects & dosage Oxycodone can cause serious unwanted effects if taken by adults who are not used to strong opioid pain medicines, children, or pets. Make sure ...