Opioid Use Disorder
Conditions
Brief summary
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.
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.
Interventions
DRUGSUBLOCADE
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.
Sponsors
Indivior, PLC.
Virginia Commonwealth University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
The study is designed to determine effect of SUBLOCADE on repeat overdose and death compared to historical control data.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Repeat OD or Opioid-related Death | 6 months | Repeat OD or opioid-related death will be measured from electronic medical records and state death registries |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Treatment Engagement | 3 and 6 months | Treatment engagement as measured by number of outpatient clinic visits (attendance), receipt of SUBLOCADE injections (buprenorphine treatment) at 3 and 6 months. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Genetic Predictors of Treatment Response | 6 months | Number of participants with mu opioid receptor polymorphisms associated with repeat overdose and death history of OD in subjects |
| Healthcare Resource Utilization | 6 months | Healthcare resource utilization (measured by number of outpatient clinic and emergency department visits, and number of inpatient admissions) as compared to the historical controls |
| Opioid Craving | 6 months | 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) |
| Medication Satisfaction | 6 months | measured by the Medication Satisfaction Questionnaire (MSQ) |
| Employment, Presentism and Absenteeism | 6 months | assessed by the Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP) |
| Treatment Effectiveness and Employment | 6 months | Treatment effectiveness as measured by Treatment Effectiveness Assessment (TEA) |
| Illicit Opioid Use | 6 months | Illicit opioid use as measured by urine drug screen (UDS) results. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
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. | 19 |
| Total | 19 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 11 |
| Overall Study | Protocol Violation | 2 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Overdose Patients |
|---|---|
| Age, Continuous | 46.4 years STANDARD_DEVIATION 12.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 17 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 18 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Region of Enrollment United States | 19 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 19 |
| other Total, other adverse events | 11 / 19 |
| serious Total, serious adverse events | 2 / 19 |
Outcome results
Primary
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
Time frame: 6 months
Population: Because repeat OD or opioid-related death is measured from electronic medical records and state death registries, data was collected on all participants even if they did not complete the study
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Overdose Patients | Number of Repeat OD or Opioid-related Death | Prevalence of repeat opioid-related overdose | 0 Participants |
| Overdose Patients | Number of Repeat OD or Opioid-related Death | Prevalence opioid-related death | 0 Participants |
Secondary
Treatment Engagement
Treatment engagement as measured by number of outpatient clinic visits (attendance), receipt of SUBLOCADE injections (buprenorphine treatment) at 3 and 6 months.
Time frame: 3 and 6 months
Population: An intent to treat model was used so data from all participants, even those who did not complete, was analyzed
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Overdose Patients | Treatment Engagement | 3 months | 8.1 visits | Standard Deviation 7.72 |
| Overdose Patients | Treatment Engagement | 6 months | 13.3 visits | Standard Deviation 9.8 |
Other Pre-specified
Employment, Presentism and Absenteeism
assessed by the Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP)
Time frame: 6 months
Other Pre-specified
Genetic Predictors of Treatment Response
Number of participants with mu opioid receptor polymorphisms associated with repeat overdose and death history of OD in subjects
Time frame: 6 months
Other Pre-specified
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
Time frame: 6 months
Other Pre-specified
Illicit Opioid Use
Illicit opioid use as measured by urine drug screen (UDS) results.
Time frame: 6 months
Other Pre-specified
Medication Satisfaction
measured by the Medication Satisfaction Questionnaire (MSQ)
Time frame: 6 months
Other Pre-specified
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)
Time frame: 6 months
Other Pre-specified
Treatment Effectiveness and Employment
Treatment effectiveness as measured by Treatment Effectiveness Assessment (TEA)
Time frame: 6 months