Clinical trial NCT03993392: SUBLOCADE Rapid Initiation Study
Official title: An Open-label, Rapid Initiation Study for Extended-Release Buprenorphine Subcutaneous Injection (SUBLOCADE)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Opioid-use Disorder
Lead sponsor: Indivior Inc.
Sponsor class: INDUSTRY
First posted: 2019-06-20
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study is to evaluate the safety and tolerability of initiating SUBLOCADE™ treatment following a shorter period of transmucosal (TM) buprenorphine treatment.

Detailed description: Currently patients who are appropriate candidates for SUBLOCADE™ injection for subcutaneous (SC) use must initiate treatment with TM buprenorphine for a minimum of 7 days before receiving their first injection. This study is to evaluate the safety and tolerability of starting SUBLOCADE treatment following a shorter period.

Adults with moderate to severe opioid use disorder (OUD) not currently receiving medication assisted treatment will be recruited to participate. Prior to receiving TM buprenorphine, subjects will report their last opioid use and be experiencing at least mild withdrawal. Subjects will receive at least one dose of TM buprenorphine to ensure tolerability and that they show no evidence of precipitated withdrawal. If no evidence of intolerability or no precipitated withdrawal occurs, subjects will receive a single injection of SUBLOCADE and remain in the clinic for approximately 48 hours after the injection to assess for safety and tolerability.

Eligibility criteria: Inclusion Criteria:

* Signed the informed consent form (ICF) and have the ability to comply with the requirements and restrictions listed therein.
* Documented history of moderate or severe opioid use disorder (OUD) as defined by Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5).
* Seeking buprenorphine-assisted treatment for OUD and is an appropriate candidate in the opinion of the Investigator or medically qualified sub-Investigator.
* A female subject is eligible to participate if she is not pregnant (as confirmed by a negative urine human chorionic gonadotrophin test), is not lactating and, if of childbearing potential, agrees not to become pregnant while on the study and use medically acceptable means of contraception while on the study.

Exclusion Criteria:

* Current diagnosis, other than OUD, requiring chronic opioid treatment.
* Meet DSM-5 criteria for severe alcohol-use disorder.
* Has received any medication assisted treatment within 2 weeks.
* Concurrent or prior treatment with any long-acting depot form of buprenorphine containing products.
* Concurrent treatment with another investigational agent or enrolment in another clinical study (except for an observational study) or treatment with another investigational agent within 30 days prior to screening.
* Concurrent treatment with medications contraindicated for use with buprenorphine as per local prescribing information, including benzodiazepines or any other central nervous system depressants.
* Significant traumatic injury, major surgical procedure (as defined by the Investigator) within 30 days prior to Day 1 or still recovering from prior surgery.
* Any other active medical condition, organ disease or concurrent medication or treatment that may either compromise subject safety or interfere with study endpoints.
* Congenital long QT syndrome, history of prolonged QT in the 3 months prior to screening, or a corrected QT interval (Fridericia's - QTcF) \>450 msec (male) or \>470 msec (female), or history of risk factors for Torsades de Pointes. Known personal and/or family history of congenital QT prolongation, or taking Class IA antiarrhythmic medications (e.g., quinidine, procainamide, disopyramide) or Class III antiarrhythmic medications (e.g., sotalol, amiodarone) or other mediations that prolong the QT interval. Known family history of sudden unexplained death.
* Total bilirubin ≥1.5\*upper limit of normal (ULN), alanine aminotransferase (ALT) ≥3\*ULN, aspartate aminotransferase (AST) ≥5\*ULN, serum creatinine \>2\*ULN at screening.
* Abdominal area unsuitable for SC injections.
* Uncontrolled intercurrent illness including, but not limited to, a medical or psychiatric illness/social situation that would limit compliance with study requirements or compromise the ability of the subject to provide written informed consent.
* Known allergy or hypersensitivity to buprenorphine, ATRIGEL or their excipients.
* Subject to court order requiring treatment for OUD.
* Subjects who are unable, in the opinion of the Investigator or Indivior, to comply fully with the study requirements including those who are currently incarcerated or pending incarceration/legal action.
* Clinic staff and/or subjects who have a financial interest in the study or who have an immediate family member of either the clinic staff and/or Indivior employees directly involved in the study.

Primary outcomes:
measure: Participants Who Experienced Any Precipitated Withdrawal Within One Hour After SUBLOCADE Administration
timeFrame: Day 1: Pre-SUBLOCADE evaluation taken after TM buprenorphine treatment and prior to injection: SUBLOCADE evaluation taken within one hour of SUBLOCADE injection
Secondary outcomes:
measure: Participants With Treatment-Emergent Adverse Events (TEAE)
timeFrame: Day 1 to Day 28
measure: Participants With Treatment-Emergent Adverse Events (TEAE) Within 48 Hours Post-SUBLOCADE Injection
timeFrame: Day 1 SUBLOCADE injection up to 48 hours later
measure: Cumulative Number of Participants Who Experienced a >=6 Point Clinical Opiate Withdrawal Scale (COWS) Total Score Increase After SUBLOCADE Administration From the Pre-SUBLOCADE Value at Key Timepoints
timeFrame: Day 1: Pre-SUBLOCADE evaluation taken after TM buprenorphine treatment and prior to injection: SUBLOCADE evaluations taken 1, 6, 12, 24 and 48 hours after SUBLOCADE injection.
measure: COWS Total Score Normalized Area Under the Curve (AUC) Through Key Timepoints Post SUBLOCADE Injection
timeFrame: SUBLOCADE injection on Day 1 through 1, 6, 12, 24 and 48 hours after SUBLOCADE injection
measure: Total Score on COWS At Timepoints During the Treatment Period
timeFrame: Day 1 to Day 29
measure: Total Score on Opioid Craving Visual Analogue Scale (OC-VAS) At Timepoints During the Treatment Period
timeFrame: Day 1 to Day 29
Other outcomes:
Locations:
city: Berlin
country: United States
facility: Hassman Research Institute
state: New Jersey
Study officials:
affiliation: Hassman Research Institute
name: Howard Hassman
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hassman H, Strafford S, Shinde SN, Heath A, Boyett B, Dobbins RL. Open-label, rapid initiation pilot study for extended-release buprenorphine subcutaneous injection. Am J Drug Alcohol Abuse. 2023 Jan 2;49(1):43-52. doi: 10.1080/00952990.2022.2106574. Epub 2022 Aug 24.
citation: Mariani JJ, Dobbins RL, Heath A, Gray F, Hassman H. Open-label investigation of rapid initiation of extended-release buprenorphine in patients using fentanyl and fentanyl analogs. Am J Addict. 2024 Jan;33(1):8-14. doi: 10.1111/ajad.13484. Epub 2023 Nov 8.