New Opioid Packaging for Opioid Use Disorder

Overseen By Nathaniel M Rickles, PharmD, PhD, BCPP, FAPhA

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: UConn Health

Must be taking: Opioids

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

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

Compensation: Varies

Number of Visits: 2

Duration: 3 months

352 Participants Needed

Trial Summary

What is the purpose of this trial?

The overall objective of this clinical trial is to identify the impact of selected package features, known as the Opioid Package Prototype (OPP), on the safe and effective use of opioids. Our specific aims are: (Aim 1) to evaluate the effectiveness of OPP on prescribing, dispensing, and patient use of oxycodone among orthopaedic surgery patients receiving post-operative outpatient oxycodone for post-surgical pain management, and (Aim 2) to determine the feasibility of OPP for orthopaedic surgery prescribers, pharmacists, and orthopaedic surgery patients. Such data can be used to further optimize packaging and labeling design, help patients and caregivers utilize their medication and packaging correctly, and improve prescribing and dispensing habits. The central hypothesis is that the OPP will be more effective than the amber vial in efforts to reduce oxycodone prescribing among patients over 18 receiving short-term management of post orthopedic surgery pain.

Do I have to stop taking my current medications for this trial?

The trial information does not specify whether you need to stop taking your current medications. It focuses on the use of oxycodone for post-surgical pain management.

What data supports the effectiveness of the drug Opioid Package Prototype (OPP) for opioid use disorder?

Research shows that reformulated OxyContin, which is part of the OPP, is effective in reducing nonoral abuse, such as snorting and injecting, due to its abuse-deterrent properties. This suggests that the OPP may help reduce misuse and abuse of opioids. ^{1 2 3 4 5}

Is the new opioid packaging generally safe for humans?

The reformulated OxyContin, designed to deter tampering and abuse, has been studied for its potential to reduce misuse. While these studies focus on reducing abuse rather than direct safety, they suggest that the reformulated version is less likely to be tampered with, which could indirectly enhance safety by reducing misuse. ^{1 2 5 6 7}

How is the drug Opioid Package Prototype (OPP) different from other drugs for opioid use disorder?

The Opioid Package Prototype (OPP) is unique because it includes reformulated versions of oxycodone products like OxyContin, which are designed to deter tampering and abuse. These formulations make it harder to misuse the drug by crushing or dissolving it, reducing the risk of nonoral abuse such as snorting or injecting. ^{1 2 3 5 8}

Research Team

Nathaniel M Rickles, PharmD, PhD, BCPP, FAPhA

Principal Investigator

University of Connecticut

Eligibility Criteria

This trial is for adults over 18 who are undergoing outpatient orthopaedic surgery and need opioids like oxycodone for post-surgery pain. Participants must be able to use a MyChart account, understand English, and agree to get their medication from UConn Health Specialty Pharmacy.

Inclusion Criteria

The patient is able to read and understand English

I am willing to take oxycodone for my condition.

The patient is willing and able to use a MyChart account

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oxycodone 5mg tablets dispensed in the Opioid Package Prototype (OPP) or standard amber vial for post-operative pain management

3 months

Baseline, 1 week, 1 month, and 3 months after surgery

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of anxiety, depression, pain, and medication use

3 months

1 week, 1 month, and 3 months after surgery

Feasibility Assessment

Interviews conducted to assess the feasibility of the Opioid Package Prototype (OPP) for prescribers, pharmacists, and patients

1-3 months after surgery

Treatment Details

Interventions

• Opioid Package Prototype (OPP)
• Usual Care (standard amber vial)

Trial Overview The study is testing the Opioid Package Prototype (OPP), which aims to improve how patients receive and manage their opioid medications after surgery. It will compare OPP's effectiveness with usual care using standard amber vials in prescribing, dispensing, and patient usage.

Participant Groups

Group I: Opioid Package Prototype (OPP) Experimental Treatment 1 Intervention

Oxycodone 5mg tablets dispensed in the Opioid Package Prototype (OPP) with frequency and quantities varying, depending on the type of surgical procedure performed, surgeon, and individual patient

Group II: Usual Care (standard amber vial) Active Control 1 Intervention

Oxycodone 5mg tablets dispensed in the standard amber vial (usual care) with frequency and quantities varying, depending on the type of surgical procedure performed, surgeon, and individual patient

Opioid Package Prototype (OPP) is already approved in United States, European Union, Canada for the following indications:

Approved in United States as OxyContin for:

• Moderate to severe pain
• Chronic pain

Approved in European Union as OxyNorm for:

• Moderate to severe pain
• Chronic pain

Approved in Canada as OxyContin for:

• Moderate to severe pain
• Chronic pain

Who Is Running the Clinical Trial?

UConn Health

Lead Sponsor

Trials

218

Recruited

59,100+

Food and Drug Administration (FDA)

Collaborator

Trials

184

Recruited

1,553,000+

University of Connecticut

Collaborator

Trials

194

Recruited

162,000+

Findings from Research

In a study with 30 recreational opioid users, participants found the reformulated OxyContin® (ORF) to be significantly less attractive and less likely to be tampered with compared to the original OxyContin (OC), indicating its effectiveness as a tamper-deterrent product.

Participants rated the original OxyContin as the most desirable and valuable opioid product, suggesting that the reformulated ORF successfully reduces the appeal for misuse among users.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Attractiveness of reformulated OxyContin(R) tablets: assessing comparative preferences and tampering potential. Sellers, EM., Perrino, PJ., Colucci, SV., et al.[2013]

The abuse-deterrent formulation (ADF) of OxyContin significantly reduced nonoral abuse rates from 91.4% to 47.9%, particularly for methods like insufflation and intravenous injection, indicating its effectiveness in curbing misuse.

In contrast, while the Opana ER ADF also reduced nonoral abuse rates, it did not show a significant decrease over time, suggesting that the effectiveness of ADFs may vary by drug, even when using the same technology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A tale of 2 ADFs: differences in the effectiveness of abuse-deterrent formulations of oxymorphone and oxycodone extended-release drugs. Cicero, TJ., Ellis, MS., Kasper, ZA.[2021]

In a study involving 40 nondependent recreational opioid users, the new formulation of immediate release oxycodone (IRO-A) resulted in significantly lower subjective ratings of 'drug liking' and 'overall drug liking' compared to the standard immediate release oxycodone (IRO) when both were crushed and administered intranasally.

While both formulations caused common opioid-related side effects, IRO-A was associated with more nasal-related symptoms, suggesting that although it may be less appealing for recreational use, it still carries risks of adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessing subjective and physiologic effects following intranasal administration of a new formulation of immediate release oxycodone HCl (Oxecta™) tablets in nondependent recreational opioid users. Schoedel, KA., Rolleri, RL., Faulknor, JY., et al.[2019]

In a study of 243 patients over 5 weeks, oxycodone/naloxone prolonged-release (OXN PR) significantly improved bowel function compared to oxycodone prolonged-release (OxyPR), with greater reductions in opioid-induced constipation as measured by the bowel function index.

Both treatments provided similar levels of pain relief, but patients on OXN PR required less laxative rescue medication and experienced a doubling in complete spontaneous bowel movements, indicating that OXN PR can effectively manage pain without compromising bowel health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase III randomized controlled study on the efficacy and improved bowel function of prolonged-release (PR) oxycodone-naloxone (up to 160/80 mg daily) vs oxycodone PR. Dupoiron, D., Stachowiak, A., Loewenstein, O., et al.[2018]

The introduction of the abuse-deterrent formulation of OxyContin(®) in April 2014 led to an 80% decline in pharmacy sales of the 80mg version, which was commonly misused by people who inject drugs (PWID).

Post-introduction, there was a significant drop in the use of OxyContin(®) among PWID, with visits to the Sydney Medically Supervised Injecting Centre for OxyContin(®) injection decreasing from 62% to just 5%, indicating that the reformulated product was less attractive for tampering.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The introduction of a potentially abuse deterrent oxycodone formulation: Early findings from the Australian National Opioid Medications Abuse Deterrence (NOMAD) study. Degenhardt, L., Bruno, R., Ali, R., et al.[2018]

The NOMAD study aims to evaluate the effectiveness of the new tamper-resistant formulation of OxyContin® in reducing extra-medical use and tampering, using a comprehensive approach that includes routine data analysis and a cohort of 606 individuals who misuse opioids.

This study is significant as it is one of the most thorough investigations into the impact of an opioid medication on misuse and diversion, which could provide valuable insights for policymakers and healthcare providers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluating the potential impact of a reformulated version of oxycodone upon tampering, non-adherence and diversion of opioids: the National Opioid Medications Abuse Deterrence (NOMAD) study protocol. Degenhardt, L., Larance, B., Bruno, R., et al.[2019]

After the reformulation of OxyContin® in 2010, over half of the 4,098 New York City residents studied changed their prescription filling patterns, with 14% discontinuing opioid prescriptions, 46% continuing with oxycodone 80 mg, and 40% switching to lower doses like oxycodone 30 mg.

The median morphine milligram equivalents (MME) significantly decreased across all groups post-reformulation, suggesting that the reformulation may have led some individuals to seek alternative sources, such as heroin, to manage withdrawal symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reformulation of oxycodone 80 mg to prevent misuse: A cohort study assessing the impact of a supply-side intervention. Nolan, ML., Harocopos, A., Allen, B., et al.[2021]

The reformulated extended-release oxycodone (ERO) showed significantly lower rates of abuse (33% prevalence) compared to the original ERO and immediate-release oxycodone (IR oxycodone), indicating its effectiveness in reducing misuse among individuals with a history of opioid abuse.

After the reformulation, the prevalence of original ERO abuse declined significantly, and there was no evidence that the reformulated ERO became a substitute for the original, suggesting that the new formulation successfully deterred abuse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The impact of a reformulation of extended-release oxycodone designed to deter abuse in a sample of prescription opioid abusers. Havens, JR., Leukefeld, CG., DeVeaugh-Geiss, AM., et al.[2014]

References

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

Attractiveness of reformulated OxyContin(R) tablets: assessing comparative preferences and tampering potential. [2013]

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

A tale of 2 ADFs: differences in the effectiveness of abuse-deterrent formulations of oxymorphone and oxycodone extended-release drugs. [2021]

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

Assessing subjective and physiologic effects following intranasal administration of a new formulation of immediate release oxycodone HCl (Oxecta™) tablets in nondependent recreational opioid users. [2019]

4. England pubmed.ncbi.nlm.nih.gov

A phase III randomized controlled study on the efficacy and improved bowel function of prolonged-release (PR) oxycodone-naloxone (up to 160/80 mg daily) vs oxycodone PR. [2018]

5. Ireland pubmed.ncbi.nlm.nih.gov

The introduction of a potentially abuse deterrent oxycodone formulation: Early findings from the Australian National Opioid Medications Abuse Deterrence (NOMAD) study. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Evaluating the potential impact of a reformulated version of oxycodone upon tampering, non-adherence and diversion of opioids: the National Opioid Medications Abuse Deterrence (NOMAD) study protocol. [2019]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Reformulation of oxycodone 80 mg to prevent misuse: A cohort study assessing the impact of a supply-side intervention. [2021]

8. Ireland pubmed.ncbi.nlm.nih.gov

The impact of a reformulation of extended-release oxycodone designed to deter abuse in a sample of prescription opioid abusers. [2014]