Cabotegravir + Buprenorphine for Opioid Use Disorder

(NOTRE Trial)

Overseen By Hannah Camp, MPH, MSW

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Duke University

Must be taking: Buprenorphine, PrEP

Must not be taking: Antidepressants, Antipsychotics

Disqualifiers: Liver issues, Heart disease, 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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatments for people with opioid use disorder (OUD) who also seek to prevent HIV. Participants will either take daily oral pills or receive long-acting injections. The trial aims to evaluate the effectiveness of these treatments and their implementation in real-world settings. Individuals with a history of opioid use disorder, who are HIV-negative, and soon to be released from certain correctional facilities may qualify for this study. As a Phase 4 trial, the treatment has already received FDA approval and proven effective, offering participants the opportunity to contribute to understanding its benefits for more patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on medications that may cause QTc prolongation (a heart rhythm condition), you might need to stop those.

What is the safety track record for Cabotegravir and Buprenorphine?

Research shows that both cabotegravir and buprenorphine, when administered as long-lasting injections, are generally well-tolerated. Studies have found that cabotegravir, used to prevent HIV, is safe and effective when injected every 1-2 months. No major safety issues have been reported, and people usually handle the injections well, experiencing only mild side effects like soreness at the injection site.

For buprenorphine, which aids in treating opioid addiction, research indicates it is safe and effective in reducing cravings and withdrawal symptoms. Long-lasting injections of buprenorphine have helped people manage daily activities better, with no major safety concerns reported.

Both treatments have received FDA approval for their specific uses, indicating a strong safety record based on extensive research. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments because they offer a new approach to managing opioid use disorder and HIV prevention. Unlike standard treatments, which often rely on daily oral medications, this trial explores long-acting injectable forms of cabotegravir and buprenorphine. The long-acting injectables are administered every 1-2 months, potentially improving adherence and convenience for patients who struggle with daily dosing. This could significantly enhance treatment outcomes by providing consistent medication levels without the daily hassle, making it a promising alternative to existing options.

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

Research has shown that Cabotegravir, when administered as a long-lasting injection, effectively controls the HIV virus. Approximately 70% of patients received all their injections, demonstrating good adherence to the treatment. In this trial, participants in the Long Acting Injectable Arm will receive Cabotegravir in a long-acting injectable formulation. Similarly, Buprenorphine, also administered as a long-lasting injection, has been linked to improved rates of opioid abstinence. Studies indicate that between 50% and 73% of individuals adhere to this treatment. Participants in the Long Acting Injectable Arm will also receive Buprenorphine in this form. Additionally, after about a year of using injectable Buprenorphine, improvements in health and social situations were observed. Both treatments have shown promising results in their respective areas. ^{2 6 7 8 9}

Who Is on the Research Team?

Lauren Brinkley-Rubinstein, PhD

Principal Investigator

Duke University

Are You a Good Fit for This Trial?

This trial is for individuals with opioid use disorder, at risk of HIV infection or have a prescription drug abuse history. It's also open to those who may develop cataracts as a result of their condition or treatment. Participants must meet certain health criteria not specified here.

Inclusion Criteria

HIV negative as confirmed by a HIV rapid test

Eligible for release within 120 days (sentenced and/or pretrial) excluding individuals who might be sentenced to federal prison

History of OUD meeting DSM-5 criteria of moderate or severe opioid use disorder at the time of incarceration or treated in an opioid agonist treatment program during the year before incarceration or met OUD criteria in the year prior to incarceration

Exclusion Criteria

Untreated psychiatric disorder that may make participation hazardous such as untreated psychosis (treated psychiatric disorders allowed)

Suicidal ideation

I do not have any severe illnesses like unstable diabetes, heart disease, or liver problems.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

R61 Phase

Development of the intervention protocol for delivery of LAI PrEP + XR-B through interviews with stakeholders and incarcerated individuals

1 year

R33 Phase

Implementation evaluation and randomized control trial comparing LAI PrEP + XR-B to oral PrEP + SL-B

4 years

Follow-up

Participants are monitored for safety and effectiveness after treatment with monthly follow-ups for 7 months and a final long-term follow-up visit at 12 months

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Buprenorphine
• Cabotegravir

Trial Overview The study tests long-acting pre-exposure prophylaxis (PrEP) and medications for opioid use disorder in carceral settings. It compares injections and pills of Cabotegravir and Buprenorphine over five years, including an initial one-year exploratory phase followed by a four-year randomized control trial.

How Is the Trial Designed?

Group I: Long Acting Injectable Arm Experimental Treatment 2 Interventions

Participants assigned to this arm will be administered the-long acting injectable formulation of pre-exposure prophylaxis every 1-2 months, as well as the long-acting injectable formulation of buprenorphine, at the same clinic visit.

Group II: Daily Oral Pill Arm Active Control 2 Interventions

Participants assigned to this arm will be administered daily oral pre-exposure prophylaxis for HIV prevention, as well as daily oral buprenorphine for opioid use disorder

Who Is Running the Clinical Trial?

Duke University

Lead Sponsor

Trials

2,495

Recruited

5,912,000+

Friends Research Institute, Inc.

Collaborator

Trials

60

Recruited

22,500+

The Miriam Hospital

Collaborator

Trials

252

Recruited

39,200+

University of Arkansas

Collaborator

Trials

500

Recruited

153,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Published Research Related to This Trial

Cabotegravir long-acting injectable (CAB LA) was found to be well tolerated among participants, with a high completion rate of injections (80% in Cohort 1 and 92% in Cohort 2), despite common injection site reactions (ISRs) that were mostly mild to moderate.

The study demonstrated that CAB LA 600 mg administered every 8 weeks successfully maintained drug levels above effective thresholds in 95% of participants, supporting its potential for HIV prevention and treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, tolerability, and pharmacokinetics of long-acting injectable cabotegravir in low-risk HIV-uninfected individuals: HPTN 077, a phase 2a randomized controlled trial. Landovitz, RJ., Li, S., Grinsztejn, B., et al.[2023]

Buprenorphine, particularly the brand-name formulations like Suboxone, has been significantly more utilized and reimbursed in Medicaid compared to other formulations, with brand-name versions dispensed 2.7 times more and costing 4.4 times more than all other formulations combined from 2002 to 2018.

Delays in the availability of generic buprenorphine formulations due to market and regulatory factors contributed to increased costs and may have hindered access to treatment for opioid use disorder during the opioid crisis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Factors Affecting Buprenorphine Utilization and Spending in Medicaid, 2002-2018. Barenie, RE., Sinha, MS., Kesselheim, AS.[2021]

From 2010 to 2014, the prevalence of opioid use disorder (OUD) diagnoses increased fourfold among commercially insured individuals, yet the proportion of those receiving medication for OUD decreased significantly from 25% to 16%.

Discontinuation rates for OUD medications were notably high, with over 50% of patients discontinuing injectable and oral naltrexone within 30 days, indicating a need for improved strategies to maintain treatment adherence, especially compared to sublingual buprenorphine/naloxone, which had lower discontinuation rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Injectable naltrexone, oral naltrexone, and buprenorphine utilization and discontinuation among individuals treated for opioid use disorder in a United States commercially insured population. Morgan, JR., Schackman, BR., Leff, JA., et al.[2023]

Veterans receiving buprenorphine for opioid use disorder had a significantly lower risk of death by suicide or overdose, being 4.33 times less likely to die compared to those not on the medication, based on a study of Veterans from 2008 to 2017.

The risk of suicide or overdose was particularly high shortly after discontinuing buprenorphine treatment, indicating that ongoing pharmacotherapy is crucial for reducing mortality risks in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association Between Buprenorphine for Opioid Use Disorder and Mortality Risk. Vakkalanka, P., Lund, BC., Arndt, S., et al.[2022]

In the LATTE study, after 6 years of treatment, 66% of participants maintained undetectable HIV-1 levels (RNA <50 copies/mL), indicating the long-term efficacy of oral cabotegravir + rilpivirine as maintenance therapy for HIV-1.

The treatment showed an acceptable safety profile, with only 1% of participants experiencing serious drug-related adverse events and a low rate of treatment-emergent resistance, suggesting it is a durable option for ART-naive adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Efficacy, Safety, and Durability of Cabotegravir and Rilpivirine as 2-Drug Oral Maintenance Therapy After 6 Years of Study. Sutton, KC., De Vente, J., Leblanc, R., et al.[2022]

Buprenorphine is an effective treatment for opioid use disorder, supported by numerous studies, yet many patients do not receive it or any other medical treatment.

New long-acting injectable formulations of buprenorphine may enhance treatment adherence and reduce the risk of misuse, addressing some of the barriers to effective treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Buprenorphine Treatment for Opioid Use Disorder: An Overview. Shulman, M., Wai, JM., Nunes, EV.[2022]

In the LATTE trial involving 243 antiretroviral-naive HIV-1-infected adults, cabotegravir combined with rilpivirine maintained viral suppression effectively, with 82% of patients achieving fewer than 50 copies of HIV-1 RNA at week 48, compared to 71% in the efavirenz group.

Cabotegravir was well tolerated, with fewer treatment-related adverse events leading to withdrawal (3%) compared to efavirenz (15%), suggesting a favorable safety profile for cabotegravir in long-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabotegravir plus rilpivirine, once a day, after induction with cabotegravir plus nucleoside reverse transcriptase inhibitors in antiretroviral-naive adults with HIV-1 infection (LATTE): a randomised, phase 2b, dose-ranging trial. Margolis, DA., Brinson, CC., Smith, GHR., et al.[2020]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39470393/

Effectiveness of long-acting buprenorphine - A systematic ... LAI-B was positively associated with improvements in abstinence rates and patient-centred outcomes. There was limited data on the long-term ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0740547222000587

Long-acting injectable buprenorphine for opioid use disorder Four studies explored retention as an outcome of LAIB treatment and found it to range between 50 and 73% in those receiving LAIB (Frost et al., 2019; Haight et ...

3. pcssnow.org pcssnow.org/wp-content/uploads/2020/01/mrl_PCSS-Lofwall-LongActingBup-v5-2.11.2020-AAAP.pdf

Long-acting Buprenorphine Treatment for Opioid Use Disorder Most common side effects were: nausea, vomiting, headache, constipation, increased LFTs, tiredness, injection site itching and pain. Uncommon: need for surgical ...

4. recoveryanswers.org recoveryanswers.org/research-post/injectable-buprenorphine-1-year-outcomes/

Injectable buprenorphine for opioid use disorder: Effects on ... Medical problems, employment status, drug use, legal status, family/social status, and psychiatric problems all improved after ~12 months of injectable ...

5. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/2814255

Availability of Long-Acting Injectable Buprenorphine at ... This study assesses the proportion of US substance use and mental health care facilities that offered any medications for opioid use ...

6. nice.org.uk nice.org.uk/advice/es19/evidence/evidence-review-pdf-6666819661

buprenorphine prolonged- release injection (Buvidal) There are no safety data for people younger than 18 years or older than 66 years. Buprenorphine prolonged-release injection is indicated for maintenance ...

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

What is Buprenorphine? Side Effects, Treatment & Use When taken as prescribed, buprenorphine is safe and effective. Buprenorphine has unique pharmacological properties that: Diminish the effects of ...

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2024/210136Orig1s000SumR.pdf

210136Orig1s000 - accessdata.fda.gov The efficacy and safety of BRIXADI for the treatment of opioid use disorder ... Weekly and Once-Monthly, Long-Acting Subcutaneous Injectable Depot ...

9. aetna.com aetna.com/cpb/medical/data/900_999/0910.html

Buprenorphine Implant and Extended-Release ... The safety and efficacy of Sublocade were evaluated in two clinical studies (one phase 3 double-blind efficacy and safety study (13-0001, NCT02357901) and an ...