SUBLOCADE Rapid Initiation Study

• Sponsor: Indivior Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03993392
• Collaborator: (none)
• Enrollment: 26
• Location: 1
• Arm: 1
• Actual Duration (Months): 3.9
• Patients Per Site Per Month: 6.7

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Opioid-use Disorder	Drug: TM buprenorphine; Drug: SUBLOCADE	Phase 4

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 26 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label, Rapid Initiation Study for Extended-Release Buprenorphine Subcutaneous Injection (SUBLOCADE)
• Actual Study Start Date: Aug 29, 2019
• Actual Primary Completion Date: Dec 26, 2019
• Actual Study Completion Date: Dec 26, 2019

Arms and Interventions

Arm

Intervention/Treatment

Experimental: 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).

Drug: TM buprenorphine; 4mg TM buprenorphine, investigator choice as to brand; Other Names: suboxone subutex belbuca zubsolv bunavail generic buprenorphine ; Drug: SUBLOCADE; 300mg subcutaneous injection; Other Names: extended release buprenorphine

Outcome Measures

Primary Outcome Measures

1. Participants Who Experienced Any Precipitated Withdrawal Within One Hour After SUBLOCADE Administration [Day 1: Pre-SUBLOCADE evaluation taken after TM buprenorphine treatment and prior to injection: SUBLOCADE evaluation taken within one hour of SUBLOCADE injection]

   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.

Secondary Outcome Measures

1. Participants With Treatment-Emergent Adverse Events (TEAE) [Day 1 to Day 28]

   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) >3*upper limit of normal (ULN) and bilirubin >2*ULN.

2. Participants With Treatment-Emergent Adverse Events (TEAE) Within 48 Hours Post-SUBLOCADE Injection [Day 1 SUBLOCADE injection up to 48 hours later]

   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) >3*upper limit of normal (ULN) and bilirubin >2*ULN.

3. 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 [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.]

   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. Cumulative number of participants in key timepoints who had a COWS total score increase of ≥6 points from the pre-SUBLOCADE value.

4. COWS Total Score Normalized Area Under the Curve (AUC) Through Key Timepoints Post SUBLOCADE Injection [SUBLOCADE injection on Day 1 through 1, 6, 12, 24 and 48 hours after SUBLOCADE injection]

   The area under the curve (AUC) for COWS total score from the pre-SUBLOCADE value to a later time point were calculated using the linear trapezoidal method. For each analysis time interval (AUC0-1hr, AUC0-6hrs, AUC0-12hrs, AUC0-24hrs, AUC0-48hrs) the AUC value was normalized across participants for the actual duration (in hours) of the time interval. The normalized AUC for COWS can be interpreted as the averaged AUC per hour or the averaged COWS over a time interval, as if the COWS was measured hourly during that time interval. Participants were included in a given interval if they had a pre-SUBLOCADE COWS assessment and a COWS assessment at the terminal timepoint for the interval.

5. Total Score on COWS At Timepoints During the Treatment Period [Day 1 to Day 29]

   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.

6. Total Score on Opioid Craving Visual Analogue Scale (OC-VAS) At Timepoints During the Treatment Period [Day 1 to Day 29]

   Participants indicated their level of craving for opioids by marking a 100mm visual analogue scale where 0 = no craving and 100 = maximal craving.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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 ≥1.5upper limit of normal (ULN), alanine aminotransferase (ALT) ≥3ULN, aspartate aminotransferase (AST) ≥5ULN, serum creatinine >2ULN 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hassman Research Institute	Berlin	New Jersey	United States	08009

Sponsors and Collaborators

• Indivior Inc.

Investigators

• Principal Investigator: Howard Hassman, Hassman Research Institute

Study Documents (Full-Text)

• Study Protocol - Aug 14, 2019
• Statistical Analysis Plan - Feb 20, 2020

More Information

Publications

None provided.

• Responsible Party: Indivior Inc.
• ClinicalTrials.gov Identifier: NCT03993392
• Other Study ID Numbers: INDV-6000-403
• First Posted: Jun 20, 2019
• Last Update Posted: Apr 15, 2021
• Last Verified: Mar 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Opioid-Related Disorders; Buprenorphine

Study Results

Participant Flow

Recruitment Details	A total of 49 participants were screened and a total of 26 (53.1%) were enrolled into the study (i.e., were administered TM buprenorphine in the induction phase).
Pre-assignment Detail	Reasons not enrolled: 10 patients did not meet inclusion/exclusion criteria; 3 did not meet Day 1 check-in criteria; 3 withdrew consent; 3 were not entered because the study was closed to enrolment; 4 patients were for other reasons

Arm/Group Title	TM Buprenorphine Followed by SUBLOCADE 300 mg
Arm/Group Description	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).
Period Title: Overall Study
STARTED	26
Treated With SUBLOCADE	24
COMPLETED	20
NOT COMPLETED	6

Baseline Characteristics

Arm/Group Title	TM Buprenorphine Followed by SUBLOCADE 300 mg
Arm/Group Description	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).
Overall Participants	24
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	40.0 (13.45)
Sex: Female, Male (Count of Participants)
Female	12 50%
Male	12 50%
Race/Ethnicity, Customized (Count of Participants)
Asian	1 4.2%
Black or African American	9 37.5%
White	13 54.2%
Other	1 4.2%
Age Group (Count of Participants)
>=18 to <30 years	7 29.2%
>=30 to <45 years	8 33.3%
>=45 to < 60 years	6 25%
>=60 to < 65 years	3 12.5%
>= 65 years	0 0%
Ethnicity (Count of Participants)
Not Hispanic or Latino	22 91.7%
Not Reported	2 8.3%
Screening Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	22.60 (4.058)
Screening BMI Group (Count of Participants)
0 to <18.5 (underweight)	2 8.3%
>=18.5 and <25 (normal)	18 75%
>=25 and <30 (overweight)	1 4.2%
>=30 (obesity)	3 12.5%
Tobacco Use (Count of Participants)
Never	2 8.3%
Current	22 91.7%
Caffeine Use (Count of Participants)
Never	2 8.3%
Current	22 91.7%
Clinical Opiate Withdrawal Scale (COWS) Total Score at Screening (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	4.7 (4.63)
Opioid Craving Visual Analog Scale (OC-VAS) at Screening (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	58.3 (23.97)
Urine Drug Screen (UDS) for Opioids at Screening (Count of Participants)
Positive	18 75%
Negative	6 25%
Opioid Drug Use History - Lifetime Use (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	13.88 (13.542)
Opioid Drug Use History - Last 30 Days Use (days) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [days]	28.88 (3.837)
Opioid Drug Use History - Participants Use Intravenously in Last 30 Days (Count of Participants)
Count of Participants [Participants]	6 25%
Day 1 Urine Drug Screen: Participants with Positive Opioid Tests (Count of Participants)
Morphine	5 20.8%
Methadone	1 4.2%
Fentanyl	17 70.8%
Oxycodone	3 12.5%

Outcome Measures

1. Primary Outcome

Title	Participants Who Experienced Any Precipitated Withdrawal Within One Hour After SUBLOCADE Administration
Description	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.
Time Frame	Day 1: Pre-SUBLOCADE evaluation taken after TM buprenorphine treatment and prior to injection: SUBLOCADE evaluation taken within one hour of SUBLOCADE injection

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	TM Buprenorphine Followed by SUBLOCADE 300 mg
Arm/Group Description	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).
Measure Participants	23
Count of Participants [Participants]	1 4.2%

2. Secondary Outcome

Title	Participants With Treatment-Emergent Adverse Events (TEAE)
Description	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) >3*upper limit of normal (ULN) and bilirubin >2*ULN.
Time Frame	Day 1 to Day 28

Outcome Measure Data

Analysis Population Description

The safety population was used for the safety analysis, and consisted of all participants who received at least 1 dose of SUBLOCADE

Arm/Group Title	TM Buprenorphine Followed by SUBLOCADE 300 mg
Arm/Group Description	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).
Measure Participants	24
Any TEAE	20 83.3%
Study Drug-related TEAE	5 20.8%
Serious TEAE	0 0%
Related and Serious TEAE	0 0%
Severe TEAE	5 20.8%
TEAE leading to death	0 0%
TEAE leading to discontinuation of drug	0 0%
TEAE leading to interruption of drug	0 0%
Serious TEAEs - discontinuation of drug	0 0%
Serious TEAEs - interruption of drug	0 0%
AE of Special Interest	0 0%

3. Secondary Outcome

Title	Participants With Treatment-Emergent Adverse Events (TEAE) Within 48 Hours Post-SUBLOCADE Injection
Description	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) >3*upper limit of normal (ULN) and bilirubin >2*ULN.
Time Frame	Day 1 SUBLOCADE injection up to 48 hours later

Outcome Measure Data

Analysis Population Description

The safety population was used for the safety analysis, and consisted of all participants who received at least 1 dose of SUBLOCADE

Arm/Group Title	TM Buprenorphine Followed by SUBLOCADE 300 mg
Arm/Group Description	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).
Measure Participants	24
Any TEAE	19 79.2%
Study Drug-related TEAE	4 16.7%
Serious TEAE	0 0%
Related and Serious TEAE	0 0%
Severe TEAE	5 20.8%
TEAE leading to death	0 0%
TEAE leading to discontinuation of drug	0 0%
TEAE leading to interruption of drug	0 0%
Serious TEAEs - discontinuation of drug	0 0%
Serious TEAEs - interruption of drug	0 0%
AE of Special Interest	0 0%

4. Secondary Outcome

Title	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
Description	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. Cumulative number of participants in key timepoints who had a COWS total score increase of ≥6 points from the pre-SUBLOCADE value.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) of participants 'at risk' at the start of the time interval. A participant was at risk if they had a pre-SUBLOCADE COWs assessment and COWS assessments at the current and all prior key timepoints and did not have the event in a previous timepoint. One participant did not have a COWS score at one hour so is not included.

Arm/Group Title	TM Buprenorphine Followed by SUBLOCADE 300 mg
Arm/Group Description	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).
Measure Participants	23
>0 to 1 hour	1 4.2%
> 1 to 6 hours	2 8.3%
>6 to 12 hours	2 8.3%
>12 to 24 hours	2 8.3%
>24 to 48 hours	2 8.3%

5. Secondary Outcome

Title	COWS Total Score Normalized Area Under the Curve (AUC) Through Key Timepoints Post SUBLOCADE Injection
Description	The area under the curve (AUC) for COWS total score from the pre-SUBLOCADE value to a later time point were calculated using the linear trapezoidal method. For each analysis time interval (AUC0-1hr, AUC0-6hrs, AUC0-12hrs, AUC0-24hrs, AUC0-48hrs) the AUC value was normalized across participants for the actual duration (in hours) of the time interval. The normalized AUC for COWS can be interpreted as the averaged AUC per hour or the averaged COWS over a time interval, as if the COWS was measured hourly during that time interval. Participants were included in a given interval if they had a pre-SUBLOCADE COWS assessment and a COWS assessment at the terminal timepoint for the interval.
Time Frame	SUBLOCADE injection on Day 1 through 1, 6, 12, 24 and 48 hours after SUBLOCADE injection

Outcome Measure Data

Analysis Population Description

Full analysis set. Participants were included in a given interval if they had a pre-SUBLOCADE COWS assessment and a COWS assessment at the terminal timepoint for the interval.

Arm/Group Title	TM Buprenorphine Followed by SUBLOCADE 300 mg
Arm/Group Description	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).
Measure Participants	24
Through 1 hour post SUBLOCADE	11.91 (3.700)
Through 6 hours post SUBLOCADE	9.27 (3.939)
Through 12 hours post SUBLOCADE	7.91 (3.772)
Through 24 hours post SUBLOCADE	6.59 (3.021)
Through 48 hours post SUBLOCADE	5.03 (2.566)

6. Secondary Outcome

Title	Total Score on COWS At Timepoints During the Treatment Period
Description	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.
Time Frame	Day 1 to Day 29

Outcome Measure Data

Analysis Population Description

Full analysis set of participants with data at each timepoint.

Arm/Group Title	TM Buprenorphine Followed by SUBLOCADE 300 mg
Arm/Group Description	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).
Measure Participants	24
Day 1 Check-in	12.5 (3.74)
Pre TM Buprenephrine	14.6 (4.13)
Pre-SUBLOCADE	12.6 (4.05)
1 hour post-SUBLOCADE dose	11.1 (4.51)
2 hours post-SUBLOCADE dose	10.1 (4.99)
3 hours post-SUBLOCADE dose	9.1 (5.32)
4 hours post-SUBLOCADE dose	8.0 (3.93)
6 hours post-SUBLOCADE dose	6.9 (4.06)
8 hours post-SUBLOCADE dose	6.6 (3.83)
12 hours post-SUBLOCADE dose	6.6 (3.69)
16 hours post-SUBLOCADE dose	6.0 (2.65)
20 hours post-SUBLOCADE dose	5.0 (2.90)
24 hours post-SUBLOCADE dose	4.2 (3.16)
30 hours post-SUBLOCADE dose	3.9 (3.00)
36 hours post-SUBLOCADE dose	3.5 (2.65)
48 hours post-SUBLOCADE dose	2.8 (2.54)
Day 8	1.9 (1.64)
Day 15	2.0 (1.99)
Day 22	2.0 (2.58)
End of Treatment Day 29	1.8 (2.12)

7. Secondary Outcome

Title	Total Score on Opioid Craving Visual Analogue Scale (OC-VAS) At Timepoints During the Treatment Period
Description	Participants indicated their level of craving for opioids by marking a 100mm visual analogue scale where 0 = no craving and 100 = maximal craving.
Time Frame	Day 1 to Day 29

Outcome Measure Data

Analysis Population Description

Full analysis set of participants with data at each timepoint.

Arm/Group Title	TM Buprenorphine Followed by SUBLOCADE 300 mg
Arm/Group Description	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).
Measure Participants	24
Day 1 Check-in	66.0 (22.03)
Pre TM Buprenephrine	65.0 (31.06)
Pre-SUBLOCADE	57.0 (28.91)
1 hour post-SUBLOCADE dose	56.5 (26.52)
2 hours post-SUBLOCADE dose	52.8 (29.99)
3 hours post-SUBLOCADE dose	53.9 (30.22)
4 hours post-SUBLOCADE dose	44.5 (29.75)
6 hours post-SUBLOCADE dose	42.6 (26.98)
8 hours post-SUBLOCADE dose	43.1 (27.20)
12 hours post-SUBLOCADE dose	39.3 (31.19)
16 hours post-SUBLOCADE dose	29.7 (38.48)
20 hours post-SUBLOCADE dose	33.5 (20.79)
24 hours post-SUBLOCADE dose	27.3 (20.77)
30 hours post-SUBLOCADE dose	16.7 (12.37)
36 hours post-SUBLOCADE dose	13.8 (13.74)
48 hours post-SUBLOCADE dose	12.1 (12.09)
Day 8	7.6 (11.00)
Day 15	6.4 (9.54)
Day 22	13.1 (20.32)
End of Treatment Day 29	7.3 (9.24)

Adverse Events

Time Frame	Day 1 to Day 29
Arm/Group Title	Induction Phase		Safety Population (Post -SUBLOCADE)
Arm/Group Description	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.		Treatment-emergent adverse events (TEAEs) where the start date/time of the event is post-SUBLOCADE injection.
All Cause Mortality
	Induction Phase		Safety Population (Post -SUBLOCADE)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/26 (0%)		0/24 (0%)
Serious Adverse Events
	Induction Phase		Safety Population (Post -SUBLOCADE)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/26 (0%)		0/24 (0%)
Other (Not Including Serious) Adverse Events
	Induction Phase		Safety Population (Post -SUBLOCADE)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/26 (15.4%)		20/24 (83.3%)
Gastrointestinal disorders
Nausea	0/26 (0%)		10/24 (41.7%)
Diarrhoea	0/26 (0%)		4/24 (16.7%)
Vomiting	1/26 (3.8%)		3/24 (12.5%)
General disorders
Pain	2/26 (7.7%)		8/24 (33.3%)
Chills	0/26 (0%)		3/24 (12.5%)
Injection site bruising	0/26 (0%)		3/24 (12.5%)
Injection site erythema	0/26 (0%)		1/24 (4.2%)
Drug withdrawal syndrome	1/26 (3.8%)		0/24 (0%)
Infections and infestations
Gastroenteritis viral	0/26 (0%)		1/24 (4.2%)
Herpes zoster	0/26 (0%)		1/24 (4.2%)
Infusion site cellulitis	0/26 (0%)		1/24 (4.2%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/26 (0%)		1/24 (4.2%)
Myalgia	0/26 (0%)		1/24 (4.2%)
Nervous system disorders
Headache	0/26 (0%)		1/24 (4.2%)
Psychiatric disorders
Irritability	0/26 (0%)		12/24 (50%)
Anxiety	2/26 (7.7%)		9/24 (37.5%)
Insomnia	0/26 (0%)		6/24 (25%)
Agitation	0/26 (0%)		1/24 (4.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Proposed publications shall be submitted to Sponsor 30 days prior to submission for publication, and may be withheld for an additional period, up to 90 days, to allow Sponsor to file patent applications. If a multicenter publication isn't submitted for publication within 12 months of the conclusion of the Study at all sites, or is published in a shorter period, the results from the institution's site may be published individually.