Virginia Opioid Overdose Treatment InitiatVE (VOTIVE)

This is a Phase 3b, open-label study in patients that present to the ED for an opioid OD and receive treatment with an opioid antagonist. The study is designed to determine effect of SUBLOCADE on repeat overdose and death compared to historical control data.

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 electronic health records.

Study Overview

• Status: Terminated
• Conditions: Opioid Use Disorder
• Intervention / Treatment: Drug: SUBLOCADE

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: overdose patients; subjects that receive acute administration of SUBOXONE sublingual film in the ED followed by SUBLOCADE administration in the ED and referral to an affiliated outpatient treatment clinic, and receive monthly SUBLOCADE injections for 6 months in the context of outpatient treatment.	Drug: SUBLOCADE; SUBLOCADE (buprenorphine extended-release) injection is a colorless to amber sterile solution for SC injection designed to deliver buprenorphine at doses of 100 mg or 300 mg at a controlled rate over a one-month period.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Repeat OD or Opioid-related Death	Repeat OD or opioid-related death will be measured from electronic medical records and state death registries	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment Engagement	Treatment engagement as measured by number of outpatient clinic visits (attendance), receipt of SUBLOCADE injections (buprenorphine treatment) at 3 and 6 months.	3 and 6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Opioid Craving	Opioid craving in subjects as measured by Craving Visual Analog Scale (VAS), a 3-item scale in which individuals rate their cravings for opioids on a scale from 0 (NOT AT ALL) to 10 (EXTREMELY)	6 months
Illicit Opioid Use	Illicit opioid use as measured by urine drug screen (UDS) results.	6 months
Genetic Predictors of Treatment Response	Number of participants with mu opioid receptor polymorphisms associated with repeat overdose and death history of OD in subjects	6 months
Healthcare Resource Utilization	Healthcare resource utilization (measured by number of outpatient clinic and emergency department visits, and number of inpatient admissions) as compared to the historical controls	6 months
Treatment Effectiveness and Employment	Treatment effectiveness as measured by Treatment Effectiveness Assessment (TEA)	6 months
Medication Satisfaction	measured by the Medication Satisfaction Questionnaire (MSQ)	6 months
Employment, Presentism and Absenteeism	assessed by the Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP)	6 months

Collaborators and Investigators

• Sponsor: Virginia Commonwealth University
• Collaborators: Indivior, PLC.

Study record dates

Study Major Dates

• Study Start (Actual): January 4, 2019
• Primary Completion (Actual): February 24, 2021
• Study Completion (Actual): February 24, 2021

Study Registration Dates

• First Submitted: January 4, 2019
• First Submitted That Met QC Criteria: January 24, 2019
• First Posted (Actual): January 28, 2019

Study Record Updates

• Last Update Posted (Actual): May 5, 2022
• Last Update Submitted That Met QC Criteria: April 8, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Narcotic-Related Disorders; Drug Overdose; Opioid-Related Disorders; Opiate Overdose; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Narcotic Antagonists; Buprenorphine
• Other Study ID Numbers: HM20015109

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No