Oritavancin + Medication for Infections and Opioid Use Disorder

(AIM-STOP Trial)

Overseen By Lisa Anderson

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Maryland, Baltimore

Must be taking: Medication for opioid use disorder

Must not be taking: Prohibited concomitant medications

Disqualifiers: Hypersensitivity, Liver disease, Kidney 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

2 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, but it mentions that you cannot be on prohibited concomitant medications. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

What data supports the effectiveness of the drug Oritavancin for infections and opioid use disorder?

Oritavancin is effective for treating skin infections, as it was shown to work as well as vancomycin, a common antibiotic, in clinical trials. However, there is no direct evidence from the provided research that supports its effectiveness for opioid use disorder. ^{1 2 3 4 5}

What makes the drug Oritavancin unique for treating infections and opioid use disorder?

Oritavancin is unique because it combines its antibacterial properties with potential benefits for opioid use disorder, leveraging its dual-acting mechanism on kappa and mu opioid receptors, which are involved in pain and addiction pathways. ^{6 7 8 9 10}

What is the purpose of this trial?

Standard of care for patients with opioid use disorder and complicated infections is discharge to subacute nursing facilities on IV antibiotics until completion of treatment course. We aim to determine the efficacy of an alternative strategy using intermittent outpatient oritavancin therapy dosed weekly combined with initiation and continuation of medication assisted treatment for opioid use disorder for completion of antimicrobial therapy in a 12 week prospective, open-label study. Patients hospitalized for a drug use related infection and thought to need prolonged parenteral antimicrobial therapy will be assessed by a substance use consultant and Infectious Diseases service. If they are not on Medication for Opioid Use Disorder (MOUD), they will be assessed for initiation of MOUD. A collaborative multidisciplinary discharge planning process will be initiated and will involve linkage to care. If they have an infection with a gram positive organism, and are thought to be clinically stable for hospital discharge, they will be assessed for appropriateness for oritavancin and first dose will be administered prior to discharge. They will have an intake into an opioid treatment program where they can access collocated services and will be discharged with linkage to care through a peer recovery coach. They will be assessed in this collocated clinic post discharge for optimization of MOUD and progress of infection and subsequent dose/s of oritavancin will be administered. Patients will be followed for 12 weeks for cure/completion of therapy and MOUD outcomes.

Eligibility Criteria

This trial is for adults over 18 with opioid use disorder who have infections from drug use, need long-term IV antibiotics, and are stable enough to leave the hospital. They must not be on opioid therapy but willing to start MOUD (like methadone/suboxone), follow up at a clinic, and if female, agree to effective birth control or be postmenopausal/sterilized.

Inclusion Criteria

I have an infection from drug use requiring long-term IV antibiotics.

Able and willing to sign consent

I have used opioids not prescribed to me in the last 3 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intermittent outpatient oritavancin therapy dosed weekly combined with initiation and continuation of medication assisted treatment for opioid use disorder

12 weeks

Weekly visits for oritavancin administration and MOUD optimization

Follow-up

Participants are monitored for cure/completion of therapy and MOUD outcomes

4 weeks

Treatment Details

Interventions

• Oritavancin

Trial Overview The study tests weekly doses of an antibiotic called Oritavancin in outpatient settings combined with MOUD for treating serious infections related to drug use. It's a 12-week open-label study where patients also receive care coordination and support from peer recovery coaches.

Participant Groups

Group I: Historical outcomes with standard of care treatment Experimental Treatment 1 Intervention

Historical outcomes with standard of care treatment involving IV antibiotics administered in a skilled nursing facility will be compared

Oritavancin is already approved in United States, European Union for the following indications:

Approved in United States as Orbactiv/Kimyrsa for:

• Acute bacterial skin and skin structure infections

Approved in European Union as Orbactiv/Kimyrsa for:

• Acute bacterial skin and skin structure infections

Who Is Running the Clinical Trial?

University of Maryland, Baltimore

Lead Sponsor

Trials

729

Recruited

540,000+

Findings from Research

Kimyrsa, a new formulation of oritavancin, offers a shorter infusion time and greater flexibility with solution compatibility while maintaining a similar pharmacokinetic and microbiologic profile to the original formulation.

Despite these advantages, Kimyrsa currently lacks significant real-world experience compared to other lipoglycopeptides, making its exact role in treatment uncertain but likely similar to that of the original formulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Kimyrsa and Orbactiv - A Tale of Two Formulations. Jackson, BT., Cluck, DB., Henao-Martínez, AF., et al.[2023]

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]

Oritavancin is a new lipoglycopeptide antibiotic that is as effective as vancomycin for treating acute bacterial skin infections, based on phase 3 trials involving adult patients, with results assessed 48-72 hours after treatment initiation.

It is well tolerated with mostly mild side effects, and its single-dose administration offers advantages like reduced hospital stays and no need for dosage adjustments in patients with liver or kidney issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oritavancin: a review in acute bacterial skin and skin structure infections. Syed, YY., Scott, LJ.[2018]

An integrated drug repurposing strategy identified five candidate medications (tramadol, olanzapine, mirtazapine, bupropion, and atomoxetine) that significantly increase the odds of remission from opioid use disorder (OUD), based on analysis of electronic health records from over 72.9 million patients.

These candidate drugs target multiple genes and pathways associated with OUD, suggesting they may effectively address both OUD and related comorbid conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug repurposing for opioid use disorders: integration of computational prediction, clinical corroboration, and mechanism of action analyses. Zhou, M., Wang, Q., Zheng, C., et al.[2023]

In a study of 336 patients treated with elbasvir/grazoprevir (EBR/GZR), an impressive 318 (95%) achieved sustained virologic response at 12 weeks (SVR12), indicating high efficacy in real-world settings.

However, people who injected drugs (PWID) with recent drug use had significantly lower SVR rates (69%) compared to those without recent drug use (97%), highlighting the need for targeted interventions for this group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of recent drug use on the efficacy of elbasvir/grazoprevir for HCV-infected people on opioid agonist therapy. Macías, J., Téllez, F., de Los Santos, I., et al.[2022]

A new compound, 2-(tert-butylthio)-5-chloro-6-[(2R)-4-(2-hydroxyethyl)-2-methylpiperazin-1-yl]-1H-benzimidazole, was developed as a highly potent and selective antagonist for the ORL1 receptor, showing promise for oral administration and effective brain penetration.

The optimization process involved modifying the piperazine ring, which enhanced the compound's selectivity and potency, while also allowing for control over its activity on other opioid receptors through stereochemistry adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel ORL1-selective antagonists with oral bioavailability and brain penetrability. Okamoto, O., Kobayashi, K., Kawamoto, H., et al.[2022]

The newly discovered compound, identified as 10, is a potent antagonist of the opioid receptor-like 1 (ORL1) with strong selectivity, meaning it effectively targets ORL1 without significantly affecting other opioid receptors.

Compound 10 has demonstrated in vivo efficacy after oral administration, and it is currently undergoing clinical trials, indicating its potential as a therapeutic option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of an orally active opioid receptor-like 1 (ORL1) receptor antagonist 4-{3-[(2R)-2,3-dihydroxypropyl]-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl}-1-[(1S,3S,4R)-spiro[bicyclo[2.2.1]heptane-2,1'-cyclopropan]-3-ylmethyl]piperidine as clinical candidate. Satoh, A., Sagara, T., Sakoh, H., et al.[2022]

The compound 1d, a phenyl ring analogue of buprenorphine, shows high affinity for μ, κ, and δ opioid receptors while also having moderate affinity for nociceptin opioid peptide receptors, making it a promising candidate for preventing relapse in drug abuse.

In vivo studies confirmed that 1d does not exhibit opioid agonist activity, effectively acting as an antagonist to both morphine and ethylketocyclazocine, which supports its potential as a safe treatment option without the risk of opioid-like effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selectively promiscuous opioid ligands: discovery of high affinity/low efficacy opioid ligands with substantial nociceptin opioid peptide receptor affinity. Kumar, V., Ridzwan, IE., Grivas, K., et al.[2022]

The study developed a predictive model for the efficacy of dual-acting kappa opioid receptor (KOR) agonist and mu opioid receptor (MOR) partial agonist ligands, showing that modifications to the chemical structure can influence receptor activity.

In vivo tests of two selected ligands confirmed their KOR activity and some MOR activity, indicating that in vitro efficacy measures can reliably predict how these compounds will perform in living organisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Orvinols with mixed kappa/mu opioid receptor agonist activity. Greedy, BM., Bradbury, F., Thomas, MP., et al.[2023]

Compound 39 (MK-1925) was identified as a selective and orally available antagonist for the opioid receptor-like 1 (ORL1), demonstrating the potential for effective brain penetration.

In vivo studies showed that MK-1925 is effective after oral dosing, making it a promising candidate for further clinical development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of MK-1925: a selective, orally active and brain-penetrable opioid receptor-like 1 (ORL1) antagonist. Kobayashi, K., Tsujita, T., Ito, H., et al.[2022]

References

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

Kimyrsa and Orbactiv - A Tale of Two Formulations. [2023]

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

Gaps in Evidence-based Treatment of Concurrent Attention Deficit Hyperactivity Disorder and Opioid Use Disorder: A Scoping Review. [2023]

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

Oritavancin: a review in acute bacterial skin and skin structure infections. [2018]

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

Drug repurposing for opioid use disorders: integration of computational prediction, clinical corroboration, and mechanism of action analyses. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Impact of recent drug use on the efficacy of elbasvir/grazoprevir for HCV-infected people on opioid agonist therapy. [2022]

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

Novel ORL1-selective antagonists with oral bioavailability and brain penetrability. [2022]

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

Identification of an orally active opioid receptor-like 1 (ORL1) receptor antagonist 4-{3-[(2R)-2,3-dihydroxypropyl]-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl}-1-[(1S,3S,4R)-spiro[bicyclo[2.2.1]heptane-2,1'-cyclopropan]-3-ylmethyl]piperidine as clinical candidate. [2022]

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

Selectively promiscuous opioid ligands: discovery of high affinity/low efficacy opioid ligands with substantial nociceptin opioid peptide receptor affinity. [2022]

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

Orvinols with mixed kappa/mu opioid receptor agonist activity. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Identification of MK-1925: a selective, orally active and brain-penetrable opioid receptor-like 1 (ORL1) antagonist. [2022]