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

300 Participants Needed

Trial Summary

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 data supports the effectiveness of the drug Cabotegravir for treating opioid use disorder?

Cabotegravir has been shown to be effective in treating HIV, as it is a potent inhibitor of the HIV integrase enzyme and has been used successfully in combination with other drugs for maintaining viral suppression in HIV patients. However, there is no direct evidence from the provided research about its effectiveness for opioid use disorder. ^{1 2 3 4 5}

How does the drug Cabotegravir + Buprenorphine differ from other treatments for opioid use disorder?

The combination of Cabotegravir and Buprenorphine for opioid use disorder is unique because it potentially offers a new approach by combining an antiretroviral drug (Cabotegravir) with a partial opioid agonist (Buprenorphine), which may enhance treatment adherence and effectiveness compared to existing options that typically involve only opioid agonists or antagonists. ^{6 7 8 9 10}

What is the purpose of this trial?

The investigators plan to conduct an R61/33 hybrid type 2 implementation-effectiveness trial that includes 1) a one-year exploratory R61 phase that will enable the development of the intervention protocol needed for the R33 trial phase including concrete R61 phase milestones; 2) a four-year R33 phase that will include a concurrent implementation evaluation and a randomized control trial.

Research Team

Lauren Brinkley-Rubinstein, PhD

Principal Investigator

Duke University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

References

1. United States 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. [2020]

2. United States 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. [2023]

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

Effectiveness and Safety of Bictegravir/Emtricitabine/Tenofovir Alafenamide in Patients With HIV-1 Infection and Ongoing Substance Use Disorder: The BASE Study. [2023]

4. United States 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. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Comparative Clinical Pharmacokinetics and Pharmacodynamics of HIV-1 Integrase Strand Transfer Inhibitors: An Updated Review. [2021]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Buprenorphine Treatment for Opioid Use Disorder: An Overview. [2022]

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

The New Kid on the Block--Incorporating Buprenorphine into a Medical Toxicology Practice. [2018]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Association Between Buprenorphine for Opioid Use Disorder and Mortality Risk. [2022]

9. United States 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. [2023]

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

Factors Affecting Buprenorphine Utilization and Spending in Medicaid, 2002-2018. [2021]