Virginia Opioid Overdose Treatment InitiatVE

The study will assess subjects that receive acute administration of SUBOXONE sublingual film
in the Emergency Department (ED) followed by SUBLOCADE administration in the ED and referral
to an affiliated outpatient treatment clinic, compared to historical control data from VCU
electronic health records. The affiliated clinic will agree to see the subject on arrival at
the clinic during normal clinic hours.

Patients presenting to the ED for an opioid overdose (OD) who received treatment with an
opioid antagonist and are considered clinically stable and alert will be approached regarding
interest in study participation. Written informed consent will only be obtained if the
patient's judgement is intact as determined clinically by the investigator or a medically
qualified sub-investigator or research nurse. This OD will be considered the index OD.

Subjects will be given the opportunity to participate in an optional pharmacogenetics (PGx)
sub-study.

The subject will receive referral to an outpatient treatment clinic affiliated with the
hospital system in which the ED resides.

Once subjects arrive at the treatment clinic, they will continue to receive SUBLOCADE for 6
months. All subjects will receive site standard psychosocial therapy at least weekly during
the first 3 months of treatment, and twice monthly thereafter if clinically stable.

All subjects will complete an End of Treatment (EOT) / Early Termination (ET) visit 28 days
after their last injection of SUBLOCADE. Within 3 months prior to or at the EOT visit, the
investigator or a medically qualified sub-investigator will discuss the subject's available
treatment options and arrange referral. All subjects will receive a safety follow-up
telephone call, 30 days after their EOT/ET visit to assess AEs, SAEs, pregnancy status (if
applicable) and concomitant medications. Subjects who decline to continue in medication
assisted treatment (MAT) will receive monthly safety follow-up phone calls for an additional
5 months (6 months total) to assess SAEs, pregnancy status (if applicable) and concomitant
medications.

Inclusion Criteria:

- Signed the informed consent form (ICF) and have the ability to comply with the
requirements and restrictions listed therein.

- Age: ≥ 18 years at time of executing the ICF.

- Currently meets DSM-5 criteria for moderate to severe opioid use disorder.

- Must have Clinical Opioid Withdrawal Scale (COWS) score of >8 to be eligible for
SUBOXONE dose.

- Is clinically stable (respiratory rate [RR] ≥ 12, pulse oximetry > 95%, Glasgow Coma
Scale [GCS] score of 15) and suitable for the trial in investigator or designee's
judgement.

- Agrees not to take any buprenorphine products other than those administered during the
current study throughout participation in the study.

- Negative urine pregnancy test for females.

- Vital signs (blood pressure, heart rate, temperature) considered within normal limits
or non-clinically significant elevation, as assessed by treating physician.

Exclusion Criteria:

- Current diagnosis, other than opioid use disorder, requiring chronic opioid treatment.

- Active suicidal ideation in opinion of investigator or designee.

- Female subject that is lactating, pregnant or planning to become pregnant during their
participation in the study.

- Uncontrolled intercurrent illness including, but not limited to, psychiatric
illness/social situations that would limit compliance with study requirements or
compromise the ability of the subject to provide written informed consent, signs of
opioid toxicity more than 2 hours from naloxone administration or subjects with
evidence of pulmonary edema.

- Known allergy or hypersensitivity to SUBOXONE.

- Any condition that, in the opinion of the investigator would interfere with
interpretation of subject safety or study results.

- Currently receiving medication assisted treatment (MAT) for opioid use disorder (OUD)
(e.g. methadone, buprenorphine) or received MAT as a treatment for OUD within 30 days
prior to consent.

- Concurrent treatment with another investigational agent.

- Concurrent enrolment in another clinical study, or observational study that includes
MAT.

- Treatment for opioid use disorder required by court order.

- Current or pending incarceration/ legal action that could affect participation or
compliance in the study.

- Subjects who are unable, in the opinion of the investigator, to comply fully with the
study requirements.

- Less than 48-72 hours since last use of long acting opioids (e.g., methadone), by
self-report.

- Current intoxication with benzodiazepines or alcohol.

- Meet current DSM-5 diagnosis for severe Benzodiazepine or Alcohol Use Disorder, or
endorse benzodiazepine or alcohol withdrawal symptoms.

- Current illicit opioid users who endorse regular use of long acting opioids (e.g.
methadone).

- Total bilirubin ≥ 1.5x the upper limit of normal (ULN), alanine aminotransferase (ALT)
≥3xULN, aspartate aminotransferase (AST) ≥ 3xULN, serum creatinine > 2xULN,
international normalized ratio (INR) >1.5xULN

- Patients with a history of Long QT Syndrome or an immediate family member with this
condition or those taking Class lA antiarrhythmic medications (e.g., quinidine,
procainamide, disopyramide) or Class Ill antiarrhythmic medications (e.g., sotalol,
amiodarone, or other mediations that prolong the QT interval.