Opioid-use Disorder
Conditions
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.
Interventions
DRUGTM buprenorphine
4mg TM buprenorphine, investigator choice as to brand
DRUGSUBLOCADE
300mg subcutaneous injection
Sponsors
Indivior Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
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. * 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
United States
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 details
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
Participants by arm
| Arm | Count |
|---|---|
| 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). | 24 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Did not meet Day 1 check-in criteria | 1 |
| Overall Study | Lost to Follow-up | 2 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | TM Buprenorphine Followed by SUBLOCADE 300 mg |
|---|---|
| Age, Continuous | 40.0 years STANDARD_DEVIATION 13.45 |
| Age Group >=18 to <30 years | 7 Participants |
| Age Group >=30 to <45 years | 8 Participants |
| Age Group >=45 to < 60 years | 6 Participants |
| Age Group >=60 to < 65 years | 3 Participants |
| Age Group >= 65 years | 0 Participants |
| Caffeine Use Current | 22 Participants |
| Caffeine Use Never | 2 Participants |
| Clinical Opiate Withdrawal Scale (COWS) Total Score at Screening | 4.7 units on a scale STANDARD_DEVIATION 4.63 |
| Day 1 Urine Drug Screen: Participants with Positive Opioid Tests Fentanyl | 17 Participants |
| Day 1 Urine Drug Screen: Participants with Positive Opioid Tests Methadone | 1 Participants |
| Day 1 Urine Drug Screen: Participants with Positive Opioid Tests Morphine | 5 Participants |
| Day 1 Urine Drug Screen: Participants with Positive Opioid Tests Oxycodone | 3 Participants |
| Ethnicity Not Hispanic or Latino | 22 Participants |
| Ethnicity Not Reported | 2 Participants |
| Opioid Craving Visual Analog Scale (OC-VAS) at Screening | 58.3 units on a scale STANDARD_DEVIATION 23.97 |
| Opioid Drug Use History - Last 30 Days Use | 28.88 days STANDARD_DEVIATION 3.837 |
| Opioid Drug Use History - Lifetime Use | 13.88 years STANDARD_DEVIATION 13.542 |
| Opioid Drug Use History - Participants Use Intravenously in Last 30 Days | 6 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 9 Participants |
| Race/Ethnicity, Customized Other | 1 Participants |
| Race/Ethnicity, Customized White | 13 Participants |
| Screening BMI Group 0 to <18.5 (underweight) | 2 Participants |
| Screening BMI Group >=18.5 and <25 (normal) | 18 Participants |
| Screening BMI Group >=25 and <30 (overweight) | 1 Participants |
| Screening BMI Group >=30 (obesity) | 3 Participants |
| Screening Body Mass Index (BMI) | 22.60 kg/m^2 STANDARD_DEVIATION 4.058 |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 12 Participants |
| Tobacco Use Current | 22 Participants |
| Tobacco Use Never | 2 Participants |
| Urine Drug Screen (UDS) for Opioids at Screening Negative | 6 Participants |
| Urine Drug Screen (UDS) for Opioids at Screening Positive | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 26 | 0 / 24 |
| other Total, other adverse events | 4 / 26 | 20 / 24 |
| serious Total, serious adverse events | 0 / 26 | 0 / 24 |
Outcome results
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.
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
Population: 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 | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TM Buprenorphine Followed by SUBLOCADE 300 mg | Participants Who Experienced Any Precipitated Withdrawal Within One Hour After SUBLOCADE Administration | 1 Participants |
Secondary
COWS Total Score Normalized Area Under the Curve (AUC) Through Key Timepoints Post 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.
Time frame: SUBLOCADE injection on Day 1 through 1, 6, 12, 24 and 48 hours after SUBLOCADE injection
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TM Buprenorphine Followed by SUBLOCADE 300 mg | COWS Total Score Normalized Area Under the Curve (AUC) Through Key Timepoints Post SUBLOCADE Injection | Through 1 hour post SUBLOCADE | 11.91 hours*units on a scale | Standard Deviation 3.7 |
| TM Buprenorphine Followed by SUBLOCADE 300 mg | COWS Total Score Normalized Area Under the Curve (AUC) Through Key Timepoints Post SUBLOCADE Injection | Through 6 hours post SUBLOCADE | 9.27 hours*units on a scale | Standard Deviation 3.939 |
| TM Buprenorphine Followed by SUBLOCADE 300 mg | COWS Total Score Normalized Area Under the Curve (AUC) Through Key Timepoints Post SUBLOCADE Injection | Through 12 hours post SUBLOCADE | 7.91 hours*units on a scale | Standard Deviation 3.772 |
| TM Buprenorphine Followed by SUBLOCADE 300 mg | COWS Total Score Normalized Area Under the Curve (AUC) Through Key Timepoints Post SUBLOCADE Injection | Through 24 hours post SUBLOCADE | 6.59 hours*units on a scale | Standard Deviation 3.021 |
| TM Buprenorphine Followed by SUBLOCADE 300 mg | COWS Total Score Normalized Area Under the Curve (AUC) Through Key Timepoints Post SUBLOCADE Injection | Through 48 hours post SUBLOCADE | 5.03 hours*units on a scale | Standard Deviation 2.566 |
Secondary
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
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.
Population: 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 | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| TM Buprenorphine Followed by SUBLOCADE 300 mg | 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 | >6 to 12 hours | 2 Participants |
| TM Buprenorphine Followed by SUBLOCADE 300 mg | 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 | >12 to 24 hours | 2 Participants |
| TM Buprenorphine Followed by SUBLOCADE 300 mg | 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 | >24 to 48 hours | 2 Participants |
| TM Buprenorphine Followed by SUBLOCADE 300 mg | 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 | >0 to 1 hour | 1 Participants |
| TM Buprenorphine Followed by SUBLOCADE 300 mg | 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 | > 1 to 6 hours | 2 Participants |
Secondary
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) \>3\*upper limit of normal (ULN) and bilirubin \>2\*ULN.
Time frame: Day 1 to Day 28
Population: The safety population was used for the safety analysis, and consisted of all participants who received at least 1 dose of SUBLOCADE
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| TM Buprenorphine Followed by SUBLOCADE 300 mg | Participants With Treatment-Emergent Adverse Events (TEAE) | Any TEAE | 20 Participants |
| TM Buprenorphine Followed by SUBLOCADE 300 mg | Participants With Treatment-Emergent Adverse Events (TEAE) | Study Drug-related TEAE | 5 Participants |
| TM Buprenorphine Followed by SUBLOCADE 300 mg | Participants With Treatment-Emergent Adverse Events (TEAE) | Serious TEAE | 0 Participants |
| TM Buprenorphine Followed by SUBLOCADE 300 mg | Participants With Treatment-Emergent Adverse Events (TEAE) | Related and Serious TEAE | 0 Participants |
| TM Buprenorphine Followed by SUBLOCADE 300 mg | Participants With Treatment-Emergent Adverse Events (TEAE) | Severe TEAE | 5 Participants |
| TM Buprenorphine Followed by SUBLOCADE 300 mg | Participants With Treatment-Emergent Adverse Events (TEAE) | TEAE leading to death | 0 Participants |
| TM Buprenorphine Followed by SUBLOCADE 300 mg | Participants With Treatment-Emergent Adverse Events (TEAE) | TEAE leading to discontinuation of drug | 0 Participants |
| TM Buprenorphine Followed by SUBLOCADE 300 mg | Participants With Treatment-Emergent Adverse Events (TEAE) | TEAE leading to interruption of drug | 0 Participants |
| TM Buprenorphine Followed by SUBLOCADE 300 mg | Participants With Treatment-Emergent Adverse Events (TEAE) | Serious TEAEs - discontinuation of drug | 0 Participants |
| TM Buprenorphine Followed by SUBLOCADE 300 mg | Participants With Treatment-Emergent Adverse Events (TEAE) | Serious TEAEs - interruption of drug | 0 Participants |
| TM Buprenorphine Followed by SUBLOCADE 300 mg | Participants With Treatment-Emergent Adverse Events (TEAE) | AE of Special Interest | 0 Participants |
Secondary
Participants With Treatment-Emergent Adverse Events (TEAE) Within 48 Hours Post-SUBLOCADE Injection
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
Population: The safety population was used for the safety analysis, and consisted of all participants who received at least 1 dose of SUBLOCADE
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| TM Buprenorphine Followed by SUBLOCADE 300 mg | Participants With Treatment-Emergent Adverse Events (TEAE) Within 48 Hours Post-SUBLOCADE Injection | Any TEAE | 19 Participants |
| TM Buprenorphine Followed by SUBLOCADE 300 mg | Participants With Treatment-Emergent Adverse Events (TEAE) Within 48 Hours Post-SUBLOCADE Injection | Related and Serious TEAE | 0 Participants |
| TM Buprenorphine Followed by SUBLOCADE 300 mg | Participants With Treatment-Emergent Adverse Events (TEAE) Within 48 Hours Post-SUBLOCADE Injection | Severe TEAE | 5 Participants |
| TM Buprenorphine Followed by SUBLOCADE 300 mg | Participants With Treatment-Emergent Adverse Events (TEAE) Within 48 Hours Post-SUBLOCADE Injection | TEAE leading to death | 0 Participants |
| TM Buprenorphine Followed by SUBLOCADE 300 mg | Participants With Treatment-Emergent Adverse Events (TEAE) Within 48 Hours Post-SUBLOCADE Injection | TEAE leading to discontinuation of drug | 0 Participants |
| TM Buprenorphine Followed by SUBLOCADE 300 mg | Participants With Treatment-Emergent Adverse Events (TEAE) Within 48 Hours Post-SUBLOCADE Injection | Serious TEAEs - discontinuation of drug | 0 Participants |
| TM Buprenorphine Followed by SUBLOCADE 300 mg | Participants With Treatment-Emergent Adverse Events (TEAE) Within 48 Hours Post-SUBLOCADE Injection | Serious TEAEs - interruption of drug | 0 Participants |
| TM Buprenorphine Followed by SUBLOCADE 300 mg | Participants With Treatment-Emergent Adverse Events (TEAE) Within 48 Hours Post-SUBLOCADE Injection | AE of Special Interest | 0 Participants |
| TM Buprenorphine Followed by SUBLOCADE 300 mg | Participants With Treatment-Emergent Adverse Events (TEAE) Within 48 Hours Post-SUBLOCADE Injection | Study Drug-related TEAE | 4 Participants |
| TM Buprenorphine Followed by SUBLOCADE 300 mg | Participants With Treatment-Emergent Adverse Events (TEAE) Within 48 Hours Post-SUBLOCADE Injection | Serious TEAE | 0 Participants |
| TM Buprenorphine Followed by SUBLOCADE 300 mg | Participants With Treatment-Emergent Adverse Events (TEAE) Within 48 Hours Post-SUBLOCADE Injection | TEAE leading to interruption of drug | 0 Participants |
Secondary
Total Score on COWS At Timepoints During the Treatment Period
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
Population: Full analysis set of participants with data at each timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TM Buprenorphine Followed by SUBLOCADE 300 mg | Total Score on COWS At Timepoints During the Treatment Period | Day 1 Check-in | 12.5 units on a scale | Standard Deviation 3.74 |
| TM Buprenorphine Followed by SUBLOCADE 300 mg | Total Score on COWS At Timepoints During the Treatment Period | Pre TM Buprenephrine | 14.6 units on a scale | Standard Deviation 4.13 |
| TM Buprenorphine Followed by SUBLOCADE 300 mg | Total Score on COWS At Timepoints During the Treatment Period | 1 hour post-SUBLOCADE dose | 11.1 units on a scale | Standard Deviation 4.51 |
| TM Buprenorphine Followed by SUBLOCADE 300 mg | Total Score on COWS At Timepoints During the Treatment Period | 2 hours post-SUBLOCADE dose | 10.1 units on a scale | Standard Deviation 4.99 |
| TM Buprenorphine Followed by SUBLOCADE 300 mg | Total Score on COWS At Timepoints During the Treatment Period | 8 hours post-SUBLOCADE dose | 6.6 units on a scale | Standard Deviation 3.83 |
| TM Buprenorphine Followed by SUBLOCADE 300 mg | Total Score on COWS At Timepoints During the Treatment Period | 12 hours post-SUBLOCADE dose | 6.6 units on a scale | Standard Deviation 3.69 |
| TM Buprenorphine Followed by SUBLOCADE 300 mg | Total Score on COWS At Timepoints During the Treatment Period | 20 hours post-SUBLOCADE dose | 5.0 units on a scale | Standard Deviation 2.9 |
| TM Buprenorphine Followed by SUBLOCADE 300 mg | Total Score on COWS At Timepoints During the Treatment Period | 36 hours post-SUBLOCADE dose | 3.5 units on a scale | Standard Deviation 2.65 |
| TM Buprenorphine Followed by SUBLOCADE 300 mg | Total Score on COWS At Timepoints During the Treatment Period | 48 hours post-SUBLOCADE dose | 2.8 units on a scale | Standard Deviation 2.54 |
| TM Buprenorphine Followed by SUBLOCADE 300 mg | Total Score on COWS At Timepoints During the Treatment Period | Day 15 | 2.0 units on a scale | Standard Deviation 1.99 |
| TM Buprenorphine Followed by SUBLOCADE 300 mg | Total Score on COWS At Timepoints During the Treatment Period | End of Treatment Day 29 | 1.8 units on a scale | Standard Deviation 2.12 |
| TM Buprenorphine Followed by SUBLOCADE 300 mg | Total Score on COWS At Timepoints During the Treatment Period | Pre-SUBLOCADE | 12.6 units on a scale | Standard Deviation 4.05 |
| TM Buprenorphine Followed by SUBLOCADE 300 mg | Total Score on COWS At Timepoints During the Treatment Period | 3 hours post-SUBLOCADE dose | 9.1 units on a scale | Standard Deviation 5.32 |
| TM Buprenorphine Followed by SUBLOCADE 300 mg | Total Score on COWS At Timepoints During the Treatment Period | 4 hours post-SUBLOCADE dose | 8.0 units on a scale | Standard Deviation 3.93 |
| TM Buprenorphine Followed by SUBLOCADE 300 mg | Total Score on COWS At Timepoints During the Treatment Period | 6 hours post-SUBLOCADE dose | 6.9 units on a scale | Standard Deviation 4.06 |
| TM Buprenorphine Followed by SUBLOCADE 300 mg | Total Score on COWS At Timepoints During the Treatment Period | 16 hours post-SUBLOCADE dose | 6.0 units on a scale | Standard Deviation 2.65 |
| TM Buprenorphine Followed by SUBLOCADE 300 mg | Total Score on COWS At Timepoints During the Treatment Period | 24 hours post-SUBLOCADE dose | 4.2 units on a scale | Standard Deviation 3.16 |
| TM Buprenorphine Followed by SUBLOCADE 300 mg | Total Score on COWS At Timepoints During the Treatment Period | 30 hours post-SUBLOCADE dose | 3.9 units on a scale | Standard Deviation 3 |
| TM Buprenorphine Followed by SUBLOCADE 300 mg | Total Score on COWS At Timepoints During the Treatment Period | Day 8 | 1.9 units on a scale | Standard Deviation 1.64 |
| TM Buprenorphine Followed by SUBLOCADE 300 mg | Total Score on COWS At Timepoints During the Treatment Period | Day 22 | 2.0 units on a scale | Standard Deviation 2.58 |
Secondary
Total Score on Opioid Craving Visual Analogue Scale (OC-VAS) At Timepoints During the Treatment Period
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
Population: Full analysis set of participants with data at each timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TM Buprenorphine Followed by SUBLOCADE 300 mg | Total Score on Opioid Craving Visual Analogue Scale (OC-VAS) At Timepoints During the Treatment Period | Day 1 Check-in | 66.0 units on a scale | Standard Deviation 22.03 |
| TM Buprenorphine Followed by SUBLOCADE 300 mg | Total Score on Opioid Craving Visual Analogue Scale (OC-VAS) At Timepoints During the Treatment Period | 16 hours post-SUBLOCADE dose | 29.7 units on a scale | Standard Deviation 38.48 |
| TM Buprenorphine Followed by SUBLOCADE 300 mg | Total Score on Opioid Craving Visual Analogue Scale (OC-VAS) At Timepoints During the Treatment Period | 20 hours post-SUBLOCADE dose | 33.5 units on a scale | Standard Deviation 20.79 |
| TM Buprenorphine Followed by SUBLOCADE 300 mg | Total Score on Opioid Craving Visual Analogue Scale (OC-VAS) At Timepoints During the Treatment Period | 24 hours post-SUBLOCADE dose | 27.3 units on a scale | Standard Deviation 20.77 |
| TM Buprenorphine Followed by SUBLOCADE 300 mg | Total Score on Opioid Craving Visual Analogue Scale (OC-VAS) At Timepoints During the Treatment Period | Pre TM Buprenephrine | 65.0 units on a scale | Standard Deviation 31.06 |
| TM Buprenorphine Followed by SUBLOCADE 300 mg | Total Score on Opioid Craving Visual Analogue Scale (OC-VAS) At Timepoints During the Treatment Period | Pre-SUBLOCADE | 57.0 units on a scale | Standard Deviation 28.91 |
| TM Buprenorphine Followed by SUBLOCADE 300 mg | Total Score on Opioid Craving Visual Analogue Scale (OC-VAS) At Timepoints During the Treatment Period | 1 hour post-SUBLOCADE dose | 56.5 units on a scale | Standard Deviation 26.52 |
| TM Buprenorphine Followed by SUBLOCADE 300 mg | Total Score on Opioid Craving Visual Analogue Scale (OC-VAS) At Timepoints During the Treatment Period | 2 hours post-SUBLOCADE dose | 52.8 units on a scale | Standard Deviation 29.99 |
| TM Buprenorphine Followed by SUBLOCADE 300 mg | Total Score on Opioid Craving Visual Analogue Scale (OC-VAS) At Timepoints During the Treatment Period | 3 hours post-SUBLOCADE dose | 53.9 units on a scale | Standard Deviation 30.22 |
| TM Buprenorphine Followed by SUBLOCADE 300 mg | Total Score on Opioid Craving Visual Analogue Scale (OC-VAS) At Timepoints During the Treatment Period | 4 hours post-SUBLOCADE dose | 44.5 units on a scale | Standard Deviation 29.75 |
| TM Buprenorphine Followed by SUBLOCADE 300 mg | Total Score on Opioid Craving Visual Analogue Scale (OC-VAS) At Timepoints During the Treatment Period | 6 hours post-SUBLOCADE dose | 42.6 units on a scale | Standard Deviation 26.98 |
| TM Buprenorphine Followed by SUBLOCADE 300 mg | Total Score on Opioid Craving Visual Analogue Scale (OC-VAS) At Timepoints During the Treatment Period | 8 hours post-SUBLOCADE dose | 43.1 units on a scale | Standard Deviation 27.2 |
| TM Buprenorphine Followed by SUBLOCADE 300 mg | Total Score on Opioid Craving Visual Analogue Scale (OC-VAS) At Timepoints During the Treatment Period | 12 hours post-SUBLOCADE dose | 39.3 units on a scale | Standard Deviation 31.19 |
| TM Buprenorphine Followed by SUBLOCADE 300 mg | Total Score on Opioid Craving Visual Analogue Scale (OC-VAS) At Timepoints During the Treatment Period | 30 hours post-SUBLOCADE dose | 16.7 units on a scale | Standard Deviation 12.37 |
| TM Buprenorphine Followed by SUBLOCADE 300 mg | Total Score on Opioid Craving Visual Analogue Scale (OC-VAS) At Timepoints During the Treatment Period | 36 hours post-SUBLOCADE dose | 13.8 units on a scale | Standard Deviation 13.74 |
| TM Buprenorphine Followed by SUBLOCADE 300 mg | Total Score on Opioid Craving Visual Analogue Scale (OC-VAS) At Timepoints During the Treatment Period | 48 hours post-SUBLOCADE dose | 12.1 units on a scale | Standard Deviation 12.09 |
| TM Buprenorphine Followed by SUBLOCADE 300 mg | Total Score on Opioid Craving Visual Analogue Scale (OC-VAS) At Timepoints During the Treatment Period | Day 8 | 7.6 units on a scale | Standard Deviation 11 |
| TM Buprenorphine Followed by SUBLOCADE 300 mg | Total Score on Opioid Craving Visual Analogue Scale (OC-VAS) At Timepoints During the Treatment Period | Day 15 | 6.4 units on a scale | Standard Deviation 9.54 |
| TM Buprenorphine Followed by SUBLOCADE 300 mg | Total Score on Opioid Craving Visual Analogue Scale (OC-VAS) At Timepoints During the Treatment Period | Day 22 | 13.1 units on a scale | Standard Deviation 20.32 |
| TM Buprenorphine Followed by SUBLOCADE 300 mg | Total Score on Opioid Craving Visual Analogue Scale (OC-VAS) At Timepoints During the Treatment Period | End of Treatment Day 29 | 7.3 units on a scale | Standard Deviation 9.24 |