Treatment Seeking Participants With Opioid Use Disorders Assessing Tolerability of Depot Injections of Buprenorphine

Data represent the count of participants at various percentage abstinence levels. Abstinence was defined as urine samples being negative for opioids AND negative self-reports (obtained from Timeline Followback (TLFB) interviews) for illicit opioid use. The primary endpoint was based on visits in which paired urine samples and self-reports were expected for each subject as specified in the schedule of events. Missing urine drug screen(s) (UDS) samples and/or self-reports were considered as non-negative.

Time frame: Weekly from Weeks 5-24

Population: Full analysis set

The CGI-I was used to rate the change in clinical status since the start of the treatment on an ordinal scale ranging from 1 (very much improved; nearly all better; good level of functioning; minimal symptoms; represents a very substantial change) to 7 (very much worse; severe exacerbation of symptoms and loss of functioning). Baseline was defined as the last non-missing value prior to subcutaneous injection on Day 1. Measurements taken during the treatment period were taken at the end of each 28 day treatment and prior to dosing of the next treatment. Negative change from baseline values indicate an improved clinical global impression. Change from baseline was analyzed using a mixed model for repeated measures (MMRM) with terms for treatment, visit, and treatment-by-visit interaction as factors and baseline value as a covariate. Center was included in the model as a random effect.

Time frame: Baseline: Day 1 (prior to dosing), Days 29, 57, 85, 113, 141, 169

Population: Full analysis set of participants who had available data on baseline score and change from baseline in any visit through week 24.

The CGI-S was an assessment completed by the clinician to rate the severity of symptoms on an ordinal scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill subjects; pathology drastically interferes in many life functions). Baseline was defined as the last non-missing value prior to subcutaneous injection on Day 1. Measurements taken during the treatment period were taken at the end of each 28 day treatment and prior to dosing of the next treatment. Negative change from baseline values indicate an improvement in the severity of symptoms. Change from baseline was analyzed using a mixed model for repeated measures (MMRM) with terms for treatment, visit, and treatment-by-visit interaction as factors and baseline value as a covariate. Center was included in the model as a random effect.

Time frame: Baseline: Day 1 (prior to dosing), Days 29, 57, 85, 113, 141, 169

Population: Full analysis set of participants who had available data on baseline score and change from baseline in any visit through week 24.

COWS is an 11-item instrument used to assess signs and symptoms of opioid withdrawal (Wesson et al., 1999). 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. Negative change from baseline values indicate a lessening of withdrawal symptoms. Baseline was defined as the last non-missing value prior to subcutaneous injection on Day 1. The COWS was completed each week; measurements were taken prior to dosing on weeks 5, 9, 13, 17 and 21. Change from baseline was analyzed using a mixed model for repeated measures (MMRM) with terms for treatment, visit, and treatment-by-visit interaction as factors and baseline value as a covariate.

Time frame: Baseline: Day 1 (prior to dosing), Baseline: Day 1 (prior to dosing), Days 2, 8, 5, 22, 29, 30, 36, 43, 50, 57, 58, 64, 71, 78, 85, 86, 92, 99, 106, 113, 114, 120, 127, 134, 141, 142, 148, 155, 162, 169

Population: Full analysis set of participants who had available data on baseline score and change from baseline in any visit through week 24.

The opioid craving scale was a 100 mm scale with 0= 'no craving' on the left end and 100= 'strongest craving ever' on the right end of the scale. Participants marked where along the scale reflected their craving for opioids. The full range of the change from baseline scale was therefore 100 (no craving at baseline, strongest craving during study) to -100 (strongest craving at baseline, no craving during study). Baseline was defined as the last non-missing value prior to subcutaneous injection on Day 1. The opioid craving VAS was completed each week; measurements were taken prior to dosing on weeks 5, 9, 13, 17 and 21. Negative change from baseline values indicate a lessening of craving symptoms. Change from baseline was analyzed using a mixed model for repeated measures (MMRM) with terms for treatment, visit, and treatment-by-visit interaction as factors and baseline value as a covariate. Center was included in the model as a random effect.

Time frame: Baseline: Day 1 (prior to dosing), Weeks 5-24

Population: Full analysis set of participants who had available data on baseline score and change from baseline in any visit through week 24.

The Subjective Opiate Withdrawal Scale (SOWS) contains 16 symptoms whose intensity the participant rates on a scale of 0 (not at all) to 4 (extremely) for a full scale of 0 (no withdrawal symptoms) to 64 (extreme withdrawal symptoms). Negative change from baseline values indicate a lessening of withdrawal symptoms. Baseline was defined as the last non-missing value prior to subcutaneous injection on Day 1. The SOWS was completed each week; measurements were taken prior to dosing on weeks 5, 9, 13, 17 and 21. Change from baseline was analyzed using a mixed model for repeated measures (MMRM) with terms for treatment, visit, and treatment-by-visit interaction as factors and baseline value as a covariate.

Time frame: Baseline: Day 1 (prior to dosing), Baseline: Day 1 (prior to dosing), Days 2, 8, 5, 22, 29, 30, 36, 43, 50, 57, 58, 64, 71, 78, 85, 86, 92, 99, 106, 113, 114, 120, 127, 134, 141, 142, 148, 155, 162, 169

Population: Full analysis set of participants who had available data on baseline score and change from baseline in any visit through week 24.

Data represent the count of participants at various percentage levels in which self-reports were negative for illicit use of opioids. Self-reports were obtained from Timeline Followback (TLFB) interviews. All missing self-reports were considered non-negative.

Time frame: Weekly from Weeks 5-24

Population: Full analysis set

Data represent the count of participants at various percentage levels in which urine samples tested negative for opioids. All missing reports for urine samples were considered non-negative.

Time frame: Weekly from Weeks 5-24

Population: Full analysis set

Participants with both a negative urine sample and negative self-report for illicit opioid use at Week 24.

Time frame: Week 24

Population: Full analysis set

A completer was defined as a participant who completed either the urine drug screen (UDS) or Timeline Followback (TLFB) assessment at the Week 24 visit.

Time frame: Week 24

Population: Full analysis set

Treatment-emergent adverse event (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 on a scale of 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 adverse event, 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 intervention to prevent one of the outcomes listed in this definition.

Time frame: Day 1 through Week 24

Population: Safety analysis set

Treatment success is defined as a participant having ≥80% of urine samples negative for opioids combined with self-reports negative for illicit opioid use between weeks 5-24.

Time frame: Weeks 5-24

Population: Full analysis set

The C-SSRS asks questions of study participants regarding whether they had suicidal ideation and/or suicidal behavior since the last visit using the electronic version of the scale. The C-SSRS was completed each week; measurements were taken prior to dosing on weeks 5, 9, 13, 17 and 21.

Time frame: Weekly - Week 2 through Week 24

Population: Safety analysis set of participants who completed a C-SSRS during the treatment period.

The total number of weeks of abstinence was assessed from urine samples negative for opioids combined with self-reports negative for illicit opioid use collected from week 5 through week 24. All missing reports for opioids were considered non-negative.

Time frame: Weeks 5 through 24

Population: Full analysis set

Injection site pain as measured by participant-reported VAS The participant-reported VAS for injection site pain was measured on a 100 mm scale with 'no pain' on the left end and 'strongest pain ever' on the right end of the scale (total scale of 0-100). Participants marked where along the scale reflected their localized injection pain. The injection site pain VAS scores were obtained (after the completion of the injection) within 1 minute and at 5, 10, 15, 30, 60 and 120 minutes (+- 5 minutes). The timing of the injection site pain VAS should have been measured from the end of the injection. Data represents the worst pain recorded for each participant across all 6 injections and all VAS records. The mean value is presented.

Time frame: Days 1, 29, 57, 85, 113, 141

Population: Safety population