SUBLOCADE Rapid Initiation Study | NCT03993392

NCT03993392

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
TM buprenorphine followed by SUBLOCADE 300 mg	Experimental	Participants with a diagnosis of OUD stopped use of their current opioid prior to coming to the clinic to be assessed for withdrawal symptoms. If confirmed to be in withdrawal, participants were administered 4 mg transmucosal (TM) buprenorphine. If tolerated without sensitivity, clinical signs of sedation, or precipitated withdrawal, 300 mg SUBLOCADE was administered. Following SUBLOCADE administration, participants remained in the clinic for approximately 48 hours and were assessed for safety and tolerability, as well as for any signs of precipitated withdrawal. Participants returned to the clinic weekly, until the end-of-treatment (EOT) visit (28 days after SUBLOCADE administration).	Drug: TM buprenorphine Drug: SUBLOCADE

Name	Type	Description	Arm Group Labels	Other Names
TM buprenorphine	Drug	4mg TM buprenorphine, investigator choice as to brand	TM buprenorphine followed by SUBLOCADE 300 mg

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Participants Who Experienced Any Precipitated Withdrawal Within One Hour After SUBLOCADE Administration	Clinical Opiate Withdrawal Scale (COWS) is an 11-item instrument used to assess signs and symptoms of opioid withdrawal. The score is the sum of the responses for a total range of 0-48. The COWS is commonly used by clinicians treating patients with buprenorphine to monitor the severity of withdrawal. COWS scores below 5 are considered not indicative of withdrawal. Scores from 5 to 12 are considered mild withdrawal; from 13 to 24 moderate withdrawal; 25 to 36 moderately severe withdrawal, and 37-48 severe withdrawal. Precipitated withdrawal was defined as in increase in Clinical Opioid Withdrawal Scale (COWS) score by ≥6 from the pre-SUBLOCADE value within 1 hour SUBLOCADE injection.	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	Description	Time Frame
Participants With Treatment-Emergent Adverse Events (TEAE)	A TEAE was an AE that started after the administration of TM buprenorphine for induction on Day 1. TEAE=any untoward medical occurrence that develops or worsens in severity after dispensation of the study drug and does not necessarily have a causal relationship to the study drug. Severity was rated by the investigator as mild, moderate and severe, with severe= a marked limitation in activity. Relation of AE to treatment was determined by the investigator. Serious AEs include death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, OR an important medical event that jeopardized the patient and required medical or surgical intervention to prevent one of the outcomes listed in this definition. AEs of special interest include SUBOCADE depot removal, occurrences of alanine aminotransferase (ALT) >3upper limit of normal (ULN) and bilirubin >2ULN.

Eligibility Module

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.

Name	Affiliation	Role
Howard Hassman	Hassman Research Institute	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Hassman Research Institute		Berlin	New Jersey	08009	United States

PubMed Identifier	Type	Citation	Retractions
36001871	Result	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.
37936553	Result	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.

Arm/Group Information

ID	Title	Description
FG000	TM Buprenorphine Followed by SUBLOCADE 300 mg	Participants with a diagnosis of opioid use disorder (OUD) stopped use of their current opioid prior to coming to the clinic to be assessed for withdrawal symptoms. If confirmed in withdrawal, participants were administered 4 mg transmucosal (TM) buprenorphine. If tolerated without sensitivity, clinical signs of sedation, or precipitated withdrawal, 300 mg SUBLOCADE was administered. Following SUBLOCADE administration, participants remained in the clinic for approximately 48 hours and were assessed for safety and tolerability, as well as for any signs of precipitated withdrawal. Participants returned to the clinic weekly, until the end-of-treatment (EOT) visit (28 days after SUBLOCADE administration).

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	TM Buprenorphine Followed by SUBLOCADE 300 mg	Participants with a diagnosis of OUD stopped use of their current opioid prior to coming to the clinic to be assessed for withdrawal symptoms. If confirmed to be in withdrawal, participants were administered 4 mg transmucosal (TM) buprenorphine. If tolerated without sensitivity, clinical signs of sedation, or precipitated withdrawal, 300 mg SUBLOCADE was administered. Following SUBLOCADE administration, participants remained in the clinic for approximately 48 hours and were assessed for safety and tolerability, as well as for any signs of precipitated withdrawal. Participants returned to the clinic weekly, until the end-of-treatment (EOT) visit (28 days after SUBLOCADE administration).

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type	Title	Description	Population Description	Reporting Status	Anticipated Posting Date	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Time Frame	Units Analyzed	Denominator Units Selected	Arm/Group Information	Denominators	Classes	Analyses
Primary	Participants Who Experienced Any Precipitated Withdrawal Within One Hour After SUBLOCADE Administration	Clinical Opiate Withdrawal Scale (COWS) is an 11-item instrument used to assess signs and symptoms of opioid withdrawal. The score is the sum of the responses for a total range of 0-48. The COWS is commonly used by clinicians treating patients with buprenorphine to monitor the severity of withdrawal. COWS scores below 5 are considered not indicative of withdrawal. Scores from 5 to 12 are considered mild withdrawal; from 13 to 24 moderate withdrawal; 25 to 36 moderately severe withdrawal, and 37-48 severe withdrawal. Precipitated withdrawal was defined as in increase in Clinical Opioid Withdrawal Scale (COWS) score by ≥6 from the pre-SUBLOCADE value within 1 hour SUBLOCADE injection.	Full analysis set (FAS): Participants who receive a SUBLOCADE injection and have data for >=1 COWS assessment at the Pre-SUBLOCADE timepoint just before the SUBLOCADE injection and a COWS assessment within one hour after the SUBLOCADE injection. One participant did not have a COWS score at one hour so is not included.	Posted		Count of Participants		Participants		Day 1: Pre-SUBLOCADE evaluation taken after TM buprenorphine treatment and prior to injection: SUBLOCADE evaluation taken within one hour of SUBLOCADE injection

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Induction Phase	Treatment-emergent adverse events (TEAEs) where the start date/time of the event is on or after the date/time of the administration of transmucosal (TM) buprenorphine (BUP) for induction but prior to the date/time of the SUBLOCADE injection.

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Irritability	Psychiatric disorders	MedDRA 21.1	Systematic Assessment

Title	Organization	Phone	Extension	Email
Global Director, Clinical Development	Indivior, Inc	804-379-1090		Robert.Dobbins@Indivior.com

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Aug 14, 2019	Nov 13, 2020	Prot_000.pdf
SAP	No	Yes	No	Statistical Analysis Plan	Feb 20, 2020	Nov 13, 2020	SAP_001.pdf

ID	Term
D009293	Opioid-Related Disorders

ID	Term
D000079524	Narcotic-Related Disorders
D019966	Substance-Related Disorders
D064419	Chemically-Induced Disorders
D001523	Mental Disorders

ID	Term
D000069479	Buprenorphine, Naloxone Drug Combination
D002047	Buprenorphine
C000627685	Sublocade

ID	Term
D009019	Morphinans
D053610	Opiate Alkaloids
D000470	Alkaloids
D006571	Heterocyclic Compounds

ID	Title	Description
OG000	TM Buprenorphine Followed by SUBLOCADE 300 mg	Participants with a diagnosis of OUD stopped use of their current opioid prior to coming to the clinic to be assessed for withdrawal symptoms. If confirmed to be in withdrawal, participants were administered 4 mg transmucosal (TM) buprenorphine. If tolerated without sensitivity, clinical signs of sedation, or precipitated withdrawal, 300 mg SUBLOCADE was administered. Following SUBLOCADE administration, participants remained in the clinic for approximately 48 hours and were assessed for safety and tolerability, as well as for any signs of precipitated withdrawal. Participants returned to the clinic weekly, until the end-of-treatment (EOT) visit (28 days after SUBLOCADE administration).