Opioid Use Disorder, Opioid-related Disorders
Conditions
Brief summary
A multi-center, open-label, long-term safety study in which approximately 600 subjects diagnosed with opioid use disorder will be enrolled. Following a screening period, all subjects will receive run in SUBOXONE sublingual film followed by an initial injection of open-label high dose (300 mg) RBP-6000. The RBP-6000 monthly injection dose can be adjusted to low dose (100 mg), and back to high dose, based on the medical judgment of the Investigator. Subjects will participate in the study for either 6 or 12 months.
Detailed description
Approximately 600 subjects diagnosed with opioid use disorder will be enrolled; approximately 300 subjects who completed the randomized,double-blind, placebo-controlled study NCT02357901 (RB-US-13-0001) ('roll-over' participants), and approximately 300 subjects who did not participate in study RB-US-13-0001 ('de novo' participants). Following informed consent and completion of screening procedures, all subjects will receive SUBOXONE sublingual film, titrated to response. After 4-14 days of SUBOXONE sublingual film treatment, subjects will be evaluated for enrollment into the study. Eligible subjects will receive 300 mg RBP-6000 as an initial dose, followed by monthly injections of 100 mg or 300 mg RBP-6000, based on the medical judgment of the investigator. Subjects who participated in study RB-US-13-0001 ('roll-over' participants) will receive monthly injections for up to 6 months. Subjects who did not participate in study RB-US-13-0001 ('de novo' participants) will receive monthly injections for up to12 months. At all injection visits continuous electrocardiogram recordings and pulse oximetry will be collected prior to injection and at least 4 hours after injection. Subjects will return to the clinic every 1-4 weeks for laboratory tests, complete study questionnaires, adverse event and injection site assessments.
Interventions
SUBOXONE (buprenorphine sublingual film) is used for induction therapy on Days -14 to -12. Participants then complete a 4-to-11 day sublingual film dose adjustment at doses ranging from 8 mg to 24 mg sublingual film prior to starting the Treatment Period.
DRUGRBP-6000
Injections administered subcutaneously every 28 days on alternate sides of participant's abdomen starting at 300 mg. Subsequent doses of RBP-6000 could be adjusted down to 100 mg with the possibility of adjusting back up to 300 mg based on the medical judgment of the investigator. De novo subjects receive up to 12 injections and roll-over subjects receive up to 6 injections.
Sponsors
Indivior Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
De novo subjects: * Seeking treatment for opioid use disorder (OUD) and for the previous 3 months meet the Diagnostic and Statistical Manual 5 (DSM-5) criteria for moderate or severe OUD * Appropriate candidate for opioid partial-agonist treatment * BMI between 18 and 35, inclusive Roll-over subjects: * Completed RB-US-13-0001
Exclusion criteria
De novo subjects: * Current diagnosis, other than OUD, requiring chronic opioid treatment * Current substance use disorder with regard to substances other than opioids, cocaine, cannabis, tobacco or alcohol * Received medication-assisted treatment for OUD in the 90 days prior to informed consent * Use (within past 30 days prior to informed consent) or positive urine drug screen (UDS) at screening for barbiturates, benzodiazepines,methadone or buprenorphine * Treatment for OUD required by court order * History of recent suicidal ideation or attempt Roll over subjects: * Experienced major protocol deviations or adverse events in RB-US-13-0001 which could potentially compromise subject safety * Discontinued early from study RB-US-13-0001
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Worst Local Injection Site Pain From Injections as Measured by Participant-Reported Visual Analog Scale (VAS) | De Novo Subjects: Days 1, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281 and 309 Roll-over Subjects: Days 1, 29, 57, 85, 113, 141 | 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' at 0 mm and 'strongest pain ever' at 100 mm (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 and 60 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 injections and all VAS records. The mean value is presented. De Novo subjects were given injections on Days 1, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281 and 309. Roll-over subjects were given injections on Days 1, 29, 57, 85, 113, 141. |
| Participants With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period | Day 1 to Week 49 (De novo arm); Day 1 to Week 25 (Roll-over arm) | 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. |
| Percentage Change From Baseline to End of Study (Weeks 25 and 49) in Vital Signs | Baseline (Day 1 predose) End of Study: Week 49 (De novo arm); Week 25 (Roll-over arm) | Vital signs include * systolic blood pressure (mmHg) * diastolic blood pressure (mmHg) * respiratory rate (breaths/minute) * weight (kg) * body mass index (kg/m\^2) * waist-to-hip ratio Baseline is defined as the last non-missing value prior to subcutaneous injection of RBP-6000 on Day 1. |
| Shifts in Suicidality Using the Columbia Suicide Severity Rating Scale (C-SSRS) From Baseline to Most Severe Assessment During the Treatment Period | Baseline (Screening visit, days -21 to -15), End of Study: Week 49 (De novo arm); Week 25 (Roll-over arm) | 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. Only the most severe assessment is reported in this summary. Participants who experienced suicidal ideation and suicidal behavior are only summarized in the suicidal behavior since behavior is more severe than ideation. C-SSRS baseline version was completed during the screening visit. C-SSRS 'since-last-visit' version was completed weekly for the first month and at least every month until the end of the study. Shift table category titles are structured as: baseline category/treatment category. The category 'No Suicidal Ideation or Behaviour' has been abbreviated as 'No Suicidal I or B'. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Clinical Opiate Withdrawal Scale (COWS) at End of Study (Weeks 25 and 49) | Baseline (Day 1 predose), End of Study: Week 49 (De novo arm); Week 25 (Roll-over arm) | 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. 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. Baseline value is reported as an observed actual value. Weeks 25 and 49 represent change from baseline values. |
| Change From Baseline in the Subjective Opiate Withdrawal Scale (SOWS) at End of Study (Weeks 25 and 49) | Baseline (Day 1 predose), End of Study: Week 49 (De novo arm); Week 25 (Roll-over arm) | 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. Baseline value is reported as an observed actual value. Weeks 25 and 49 represent change from baseline values. |
| Change From Baseline in the Opioid Craving Visual Analog Scale (VAS) at End of Study (Weeks 25 and 49) | Baseline (Day 1 predose), End of Study: Week 49 (De novo arm); Week 25 (Roll-over arm) | The opioid craving scale was a 100 mm scale with 'no craving' indicated by 0 mm and 'strongest craving ever' indicated by 100 mm. Participants marked where along the scale reflected their craving for opioids. Baseline was defined as the last non-missing value prior to subcutaneous injection on Day 1. Baseline value is reported as an observed actual value. Weeks 25 and 49 represent change from baseline values. |
| Cumulative Distribution Function (CDF) of the Percentage Abstinence Collected From Week 1 Through End of Study (Weeks 25 and 49) | Weekly during Month 1, Every other week from Month 2-6, Monthly from Month 7-12. De novo arm stopped at Week 49. Roll-over arm stopped at Week 25 | Participants' self-reported illicit opioid drug use from the timeline followback (TLFB) interview and results from the urine drug screens (UDS) for opioids were combined into a single endpoint. Opioids assessed included codeine, hydrocodone, hydromorphone, methadone, morphine, opiates, oxycodone, and oxymorphone (by UDS) and amphetamine/methadone, buprenorphine, methadone, and opioids in the TLFB. 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 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. All missing reports for opioids were considered nonnegative. |
Countries
United States
Participant flow
Pre-assignment details
A total of 994 subjects were screened by 39 sites, and of those, 775 subjects entered the run-in period receiving at least 1 dose of SUBOXONE (508 de novo subjects and 267 roll-over subjects).
Participants by arm
| Arm | Count |
|---|---|
| De Novo Subjects Subjects who did not participate in RB-US-13-0001 received SUBOXONE sublingual film during the Run-In period, followed by an initial open-label injection of 300 mg RBP-6000. Participants continued with monthly injections of either 300 mg or 100 mg (based on judgement of the Investigator) for a total of 12 months in the Treatment period. | 412 |
| Roll-over Subjects Subjects who completed RB-US-13-0001 received SUBOXONE sublingual film during the Run-In period, followed by an initial open-label injection of 300 mg RBP-6000. Participants continued with monthly injections of either 300 mg or 100 mg (based on judgement of the Investigator) for a total of 6 months in the Treatment period. | 257 |
| Total | 669 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Run-In Period (Days -14 to Day -1) | Adverse Event | 1 | 1 |
| Run-In Period (Days -14 to Day -1) | Lost to Follow-up | 44 | 3 |
| Run-In Period (Days -14 to Day -1) | Other | 19 | 1 |
| Run-In Period (Days -14 to Day -1) | Physician Decision | 0 | 1 |
| Run-In Period (Days -14 to Day -1) | Protocol Violation | 2 | 0 |
| Run-In Period (Days -14 to Day -1) | Withdrawal by Subject | 22 | 3 |
| Run-In Period (Days -14 to Day -1) | Withdrawal symptoms | 1 | 0 |
| Run-In Period (Days -14 to Day -1) | Withdrawn by the investigator | 7 | 1 |
| Treatment Period | Adverse Event | 11 | 4 |
| Treatment Period | Incarceration, pregnancy, misc | 29 | 5 |
| Treatment Period | Lost to Follow-up | 80 | 19 |
| Treatment Period | Physician Decision | 5 | 0 |
| Treatment Period | Protocol Violation | 4 | 4 |
| Treatment Period | Withdrawal by Subject | 67 | 24 |
| Treatment Period | Withdrawal symptoms | 3 | 0 |
| Treatment Period | Withdrawn by the investigator | 7 | 1 |
Baseline characteristics
| Characteristic | Roll-over Subjects | De Novo Subjects | Total |
|---|---|---|---|
| Age, Continuous | 41.6 years STANDARD_DEVIATION 11.07 | 38.4 years STANDARD_DEVIATION 12.1 | 39.6 years STANDARD_DEVIATION 11.81 |
| Age, Customized >=18 to <30 years | 40 Participants | 122 Participants | 162 Participants |
| Age, Customized >=30 to <45 years | 114 Participants | 157 Participants | 271 Participants |
| Age, Customized >=45 to <60 years | 89 Participants | 107 Participants | 196 Participants |
| Age, Customized >= 60 to < 65 years | 14 Participants | 25 Participants | 39 Participants |
| Age, Customized >=65 years | 0 Participants | 1 Participants | 1 Participants |
| Alcohol use Current | 144 Participants | 193 Participants | 337 Participants |
| Alcohol use Former | 65 Participants | 97 Participants | 162 Participants |
| Alcohol use Never | 48 Participants | 122 Participants | 170 Participants |
| Body Mass Index | 26.14 kg/m^2 STANDARD_DEVIATION 5.067 | 25.38 kg/m^2 STANDARD_DEVIATION 4.286 | 25.67 kg/m^2 STANDARD_DEVIATION 4.613 |
| Caffeine use Current | 229 Participants | 365 Participants | 594 Participants |
| Caffeine use Former | 7 Participants | 13 Participants | 20 Participants |
| Caffeine use Missing data | 0 Participants | 1 Participants | 1 Participants |
| Caffeine use Never | 21 Participants | 33 Participants | 54 Participants |
| Race American Indian or Alaska Native | 2 Participants | 2 Participants | 4 Participants |
| Race Asian | 0 Participants | 2 Participants | 2 Participants |
| Race Black or African American | 85 Participants | 107 Participants | 192 Participants |
| Race Multiple | 2 Participants | 2 Participants | 4 Participants |
| Race Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race Other | 0 Participants | 4 Participants | 4 Participants |
| Race White | 167 Participants | 295 Participants | 462 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 16 Participants | 43 Participants | 59 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 241 Participants | 369 Participants | 610 Participants |
| Sex: Female, Male Female | 88 Participants | 149 Participants | 237 Participants |
| Sex: Female, Male Male | 169 Participants | 263 Participants | 432 Participants |
| Tobacco use Current | 222 Participants | 354 Participants | 576 Participants |
| Tobacco use Former | 12 Participants | 18 Participants | 30 Participants |
| Tobacco use Never | 23 Participants | 40 Participants | 63 Participants |
| Waist-to-Hip Ratio | 0.90 ratio STANDARD_DEVIATION 0.083 | 0.91 ratio STANDARD_DEVIATION 0.086 | 0.90 ratio STANDARD_DEVIATION 0.085 |
| Weight | 78.43 kg STANDARD_DEVIATION 18.097 | 75.49 kg STANDARD_DEVIATION 14.658 | 76.62 kg STANDARD_DEVIATION 16.117 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 412 | 0 / 257 |
| other Total, other adverse events | 146 / 412 | 42 / 257 |
| serious Total, serious adverse events | 16 / 412 | 9 / 257 |
Outcome results
Primary
Participants With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period
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 to Week 49 (De novo arm); Day 1 to Week 25 (Roll-over arm)
Population: Safety analysis set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| De Novo Subjects | Participants With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period | >=1 TEAE | 302 Participants |
| De Novo Subjects | Participants With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period | >=1 TEAE related to study drug | 172 Participants |
| De Novo Subjects | Participants With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period | >=1 serious TEAE | 16 Participants |
| De Novo Subjects | Participants With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period | >=1 serious study treatment-related TEAE | 0 Participants |
| De Novo Subjects | Participants With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period | Death | 0 Participants |
| De Novo Subjects | Participants With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period | >=1 severe TEAE | 36 Participants |
| De Novo Subjects | Participants With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period | TEAE leading to study treatment discontinuation | 13 Participants |
| De Novo Subjects | Participants With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period | TEAE leading to dose reduction | 29 Participants |
| Roll-over Subjects | Participants With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period | TEAE leading to dose reduction | 17 Participants |
| Roll-over Subjects | Participants With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period | >=1 TEAE | 145 Participants |
| Roll-over Subjects | Participants With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period | Death | 0 Participants |
| Roll-over Subjects | Participants With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period | >=1 TEAE related to study drug | 61 Participants |
| Roll-over Subjects | Participants With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period | TEAE leading to study treatment discontinuation | 4 Participants |
| Roll-over Subjects | Participants With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period | >=1 serious TEAE | 9 Participants |
| Roll-over Subjects | Participants With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period | >=1 severe TEAE | 7 Participants |
| Roll-over Subjects | Participants With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period | >=1 serious study treatment-related TEAE | 0 Participants |
Primary
Percentage Change From Baseline to End of Study (Weeks 25 and 49) in Vital Signs
Vital signs include * systolic blood pressure (mmHg) * diastolic blood pressure (mmHg) * respiratory rate (breaths/minute) * weight (kg) * body mass index (kg/m\^2) * waist-to-hip ratio Baseline is defined as the last non-missing value prior to subcutaneous injection of RBP-6000 on Day 1.
Time frame: Baseline (Day 1 predose) End of Study: Week 49 (De novo arm); Week 25 (Roll-over arm)
Population: Safety analysis set of participants with both a baseline and end of study reading
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| De Novo Subjects | Percentage Change From Baseline to End of Study (Weeks 25 and 49) in Vital Signs | Systolic blood pressure | 0.2 percentage change from baseline | Standard Deviation 11.69 |
| De Novo Subjects | Percentage Change From Baseline to End of Study (Weeks 25 and 49) in Vital Signs | Diastolic blood pressure | 0.1 percentage change from baseline | Standard Deviation 13.97 |
| De Novo Subjects | Percentage Change From Baseline to End of Study (Weeks 25 and 49) in Vital Signs | Respiratory rate | -1.2 percentage change from baseline | Standard Deviation 11.11 |
| De Novo Subjects | Percentage Change From Baseline to End of Study (Weeks 25 and 49) in Vital Signs | Body weight | 1.52 percentage change from baseline | Standard Deviation 10.651 |
| De Novo Subjects | Percentage Change From Baseline to End of Study (Weeks 25 and 49) in Vital Signs | Body mass index | 1.53 percentage change from baseline | Standard Deviation 10.657 |
| De Novo Subjects | Percentage Change From Baseline to End of Study (Weeks 25 and 49) in Vital Signs | Waist-to-hip ratio | 1.828 percentage change from baseline | Standard Deviation 11.1698 |
| Roll-over Subjects | Percentage Change From Baseline to End of Study (Weeks 25 and 49) in Vital Signs | Body mass index | -0.93 percentage change from baseline | Standard Deviation 6.507 |
| Roll-over Subjects | Percentage Change From Baseline to End of Study (Weeks 25 and 49) in Vital Signs | Systolic blood pressure | 1.3 percentage change from baseline | Standard Deviation 11.25 |
| Roll-over Subjects | Percentage Change From Baseline to End of Study (Weeks 25 and 49) in Vital Signs | Body weight | -0.94 percentage change from baseline | Standard Deviation 6.497 |
| Roll-over Subjects | Percentage Change From Baseline to End of Study (Weeks 25 and 49) in Vital Signs | Diastolic blood pressure | 1.6 percentage change from baseline | Standard Deviation 12.49 |
| Roll-over Subjects | Percentage Change From Baseline to End of Study (Weeks 25 and 49) in Vital Signs | Waist-to-hip ratio | 1.015 percentage change from baseline | Standard Deviation 8.115 |
| Roll-over Subjects | Percentage Change From Baseline to End of Study (Weeks 25 and 49) in Vital Signs | Respiratory rate | 1.0 percentage change from baseline | Standard Deviation 11.02 |
Primary
Shifts in Suicidality Using the Columbia Suicide Severity Rating Scale (C-SSRS) From Baseline to Most Severe Assessment During the Treatment Period
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. Only the most severe assessment is reported in this summary. Participants who experienced suicidal ideation and suicidal behavior are only summarized in the suicidal behavior since behavior is more severe than ideation. C-SSRS baseline version was completed during the screening visit. C-SSRS 'since-last-visit' version was completed weekly for the first month and at least every month until the end of the study. Shift table category titles are structured as: baseline category/treatment category. The category 'No Suicidal Ideation or Behaviour' has been abbreviated as 'No Suicidal I or B'.
Time frame: Baseline (Screening visit, days -21 to -15), End of Study: Week 49 (De novo arm); Week 25 (Roll-over arm)
Population: Safety population. Four de novo subjects and one roll-over subject are not reported because they used the C-SSRS baseline version throughout the study.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| De Novo Subjects | Shifts in Suicidality Using the Columbia Suicide Severity Rating Scale (C-SSRS) From Baseline to Most Severe Assessment During the Treatment Period | No Suicidal I or B / Suicidal Ideation | 10 Participants |
| De Novo Subjects | Shifts in Suicidality Using the Columbia Suicide Severity Rating Scale (C-SSRS) From Baseline to Most Severe Assessment During the Treatment Period | Suicidal Ideation / Suicidal Behaviour | 3 Participants |
| De Novo Subjects | Shifts in Suicidality Using the Columbia Suicide Severity Rating Scale (C-SSRS) From Baseline to Most Severe Assessment During the Treatment Period | Suicidal Ideation / No Suicidal I or B | 46 Participants |
| De Novo Subjects | Shifts in Suicidality Using the Columbia Suicide Severity Rating Scale (C-SSRS) From Baseline to Most Severe Assessment During the Treatment Period | Suicidal Behaviour / No Suicidal I or B | 28 Participants |
| De Novo Subjects | Shifts in Suicidality Using the Columbia Suicide Severity Rating Scale (C-SSRS) From Baseline to Most Severe Assessment During the Treatment Period | No Suicidal I or B / Suicidal Behaviour | 3 Participants |
| De Novo Subjects | Shifts in Suicidality Using the Columbia Suicide Severity Rating Scale (C-SSRS) From Baseline to Most Severe Assessment During the Treatment Period | Suicidal Behaviour / Suicidal Ideation | 2 Participants |
| De Novo Subjects | Shifts in Suicidality Using the Columbia Suicide Severity Rating Scale (C-SSRS) From Baseline to Most Severe Assessment During the Treatment Period | Suicidal Ideation / Suicidal Ideation | 7 Participants |
| De Novo Subjects | Shifts in Suicidality Using the Columbia Suicide Severity Rating Scale (C-SSRS) From Baseline to Most Severe Assessment During the Treatment Period | Suicidal Behaviour / Suicidal Behaviour | 2 Participants |
| De Novo Subjects | Shifts in Suicidality Using the Columbia Suicide Severity Rating Scale (C-SSRS) From Baseline to Most Severe Assessment During the Treatment Period | No Suicidal I or B / No Suicidal I or B | 307 Participants |
| Roll-over Subjects | Shifts in Suicidality Using the Columbia Suicide Severity Rating Scale (C-SSRS) From Baseline to Most Severe Assessment During the Treatment Period | Suicidal Behaviour / Suicidal Behaviour | 0 Participants |
| Roll-over Subjects | Shifts in Suicidality Using the Columbia Suicide Severity Rating Scale (C-SSRS) From Baseline to Most Severe Assessment During the Treatment Period | No Suicidal I or B / No Suicidal I or B | 252 Participants |
| Roll-over Subjects | Shifts in Suicidality Using the Columbia Suicide Severity Rating Scale (C-SSRS) From Baseline to Most Severe Assessment During the Treatment Period | No Suicidal I or B / Suicidal Ideation | 1 Participants |
| Roll-over Subjects | Shifts in Suicidality Using the Columbia Suicide Severity Rating Scale (C-SSRS) From Baseline to Most Severe Assessment During the Treatment Period | No Suicidal I or B / Suicidal Behaviour | 1 Participants |
| Roll-over Subjects | Shifts in Suicidality Using the Columbia Suicide Severity Rating Scale (C-SSRS) From Baseline to Most Severe Assessment During the Treatment Period | Suicidal Ideation / No Suicidal I or B | 1 Participants |
| Roll-over Subjects | Shifts in Suicidality Using the Columbia Suicide Severity Rating Scale (C-SSRS) From Baseline to Most Severe Assessment During the Treatment Period | Suicidal Ideation / Suicidal Ideation | 1 Participants |
| Roll-over Subjects | Shifts in Suicidality Using the Columbia Suicide Severity Rating Scale (C-SSRS) From Baseline to Most Severe Assessment During the Treatment Period | Suicidal Ideation / Suicidal Behaviour | 0 Participants |
| Roll-over Subjects | Shifts in Suicidality Using the Columbia Suicide Severity Rating Scale (C-SSRS) From Baseline to Most Severe Assessment During the Treatment Period | Suicidal Behaviour / No Suicidal I or B | 0 Participants |
| Roll-over Subjects | Shifts in Suicidality Using the Columbia Suicide Severity Rating Scale (C-SSRS) From Baseline to Most Severe Assessment During the Treatment Period | Suicidal Behaviour / Suicidal Ideation | 0 Participants |
Primary
Worst Local Injection Site Pain From Injections as Measured by Participant-Reported Visual Analog Scale (VAS)
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' at 0 mm and 'strongest pain ever' at 100 mm (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 and 60 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 injections and all VAS records. The mean value is presented. De Novo subjects were given injections on Days 1, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281 and 309. Roll-over subjects were given injections on Days 1, 29, 57, 85, 113, 141.
Time frame: De Novo Subjects: Days 1, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281 and 309 Roll-over Subjects: Days 1, 29, 57, 85, 113, 141
Population: Safety analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| De Novo Subjects | Worst Local Injection Site Pain From Injections as Measured by Participant-Reported Visual Analog Scale (VAS) | Injection 1 | 44.0 units on a scale | Standard Deviation 29.86 |
| De Novo Subjects | Worst Local Injection Site Pain From Injections as Measured by Participant-Reported Visual Analog Scale (VAS) | Injection 7 | 28.9 units on a scale | Standard Deviation 32.13 |
| De Novo Subjects | Worst Local Injection Site Pain From Injections as Measured by Participant-Reported Visual Analog Scale (VAS) | Injection 8 | 28.6 units on a scale | Standard Deviation 30.21 |
| De Novo Subjects | Worst Local Injection Site Pain From Injections as Measured by Participant-Reported Visual Analog Scale (VAS) | Injection 9 | 30.2 units on a scale | Standard Deviation 33.96 |
| De Novo Subjects | Worst Local Injection Site Pain From Injections as Measured by Participant-Reported Visual Analog Scale (VAS) | Injection 10 | 31.8 units on a scale | Standard Deviation 33.16 |
| De Novo Subjects | Worst Local Injection Site Pain From Injections as Measured by Participant-Reported Visual Analog Scale (VAS) | Injection 11 | 25.8 units on a scale | Standard Deviation 30.71 |
| De Novo Subjects | Worst Local Injection Site Pain From Injections as Measured by Participant-Reported Visual Analog Scale (VAS) | Injection 12 | 24.7 units on a scale | Standard Deviation 28.22 |
| De Novo Subjects | Worst Local Injection Site Pain From Injections as Measured by Participant-Reported Visual Analog Scale (VAS) | Injection 2 | 39.8 units on a scale | Standard Deviation 31.98 |
| De Novo Subjects | Worst Local Injection Site Pain From Injections as Measured by Participant-Reported Visual Analog Scale (VAS) | Injection 3 | 38.9 units on a scale | Standard Deviation 32.14 |
| De Novo Subjects | Worst Local Injection Site Pain From Injections as Measured by Participant-Reported Visual Analog Scale (VAS) | Injection 4 | 33.6 units on a scale | Standard Deviation 32.86 |
| De Novo Subjects | Worst Local Injection Site Pain From Injections as Measured by Participant-Reported Visual Analog Scale (VAS) | Injection 5 | 30.6 units on a scale | Standard Deviation 30.96 |
| De Novo Subjects | Worst Local Injection Site Pain From Injections as Measured by Participant-Reported Visual Analog Scale (VAS) | Injection 6 | 30.5 units on a scale | Standard Deviation 31.89 |
| Roll-over Subjects | Worst Local Injection Site Pain From Injections as Measured by Participant-Reported Visual Analog Scale (VAS) | Injection 1 | 33.5 units on a scale | Standard Deviation 31.5 |
| Roll-over Subjects | Worst Local Injection Site Pain From Injections as Measured by Participant-Reported Visual Analog Scale (VAS) | Injection 4 | 31.3 units on a scale | Standard Deviation 31.72 |
| Roll-over Subjects | Worst Local Injection Site Pain From Injections as Measured by Participant-Reported Visual Analog Scale (VAS) | Injection 2 | 32.7 units on a scale | Standard Deviation 31.59 |
| Roll-over Subjects | Worst Local Injection Site Pain From Injections as Measured by Participant-Reported Visual Analog Scale (VAS) | Injection 6 | 30.5 units on a scale | Standard Deviation 30.88 |
| Roll-over Subjects | Worst Local Injection Site Pain From Injections as Measured by Participant-Reported Visual Analog Scale (VAS) | Injection 3 | 30.2 units on a scale | Standard Deviation 32.09 |
| Roll-over Subjects | Worst Local Injection Site Pain From Injections as Measured by Participant-Reported Visual Analog Scale (VAS) | Injection 5 | 32.2 units on a scale | Standard Deviation 31.25 |
Secondary
Change From Baseline in the Clinical Opiate Withdrawal Scale (COWS) at End of Study (Weeks 25 and 49)
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. 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. Baseline value is reported as an observed actual value. Weeks 25 and 49 represent change from baseline values.
Time frame: Baseline (Day 1 predose), End of Study: Week 49 (De novo arm); Week 25 (Roll-over arm)
Population: Safety analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| De Novo Subjects | Change From Baseline in the Clinical Opiate Withdrawal Scale (COWS) at End of Study (Weeks 25 and 49) | Baseline (actual value) | 2.1 units on a scale | Standard Deviation 2.43 |
| De Novo Subjects | Change From Baseline in the Clinical Opiate Withdrawal Scale (COWS) at End of Study (Weeks 25 and 49) | Change from baseline: Week 25 | -1.0 units on a scale | Standard Deviation 2.61 |
| De Novo Subjects | Change From Baseline in the Clinical Opiate Withdrawal Scale (COWS) at End of Study (Weeks 25 and 49) | Change from baseline: Week 49 | -1.0 units on a scale | Standard Deviation 2.41 |
| Roll-over Subjects | Change From Baseline in the Clinical Opiate Withdrawal Scale (COWS) at End of Study (Weeks 25 and 49) | Baseline (actual value) | 1.5 units on a scale | Standard Deviation 1.98 |
| Roll-over Subjects | Change From Baseline in the Clinical Opiate Withdrawal Scale (COWS) at End of Study (Weeks 25 and 49) | Change from baseline: Week 25 | -0.3 units on a scale | Standard Deviation 2.37 |
Secondary
Change From Baseline in the Opioid Craving Visual Analog Scale (VAS) at End of Study (Weeks 25 and 49)
The opioid craving scale was a 100 mm scale with 'no craving' indicated by 0 mm and 'strongest craving ever' indicated by 100 mm. Participants marked where along the scale reflected their craving for opioids. Baseline was defined as the last non-missing value prior to subcutaneous injection on Day 1. Baseline value is reported as an observed actual value. Weeks 25 and 49 represent change from baseline values.
Time frame: Baseline (Day 1 predose), End of Study: Week 49 (De novo arm); Week 25 (Roll-over arm)
Population: Safety analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| De Novo Subjects | Change From Baseline in the Opioid Craving Visual Analog Scale (VAS) at End of Study (Weeks 25 and 49) | Baseline (actual value) | 5.9 units on a scale | Standard Deviation 10.59 |
| De Novo Subjects | Change From Baseline in the Opioid Craving Visual Analog Scale (VAS) at End of Study (Weeks 25 and 49) | Change from baseline: Week 25 | -0.2 units on a scale | Standard Deviation 16.19 |
| De Novo Subjects | Change From Baseline in the Opioid Craving Visual Analog Scale (VAS) at End of Study (Weeks 25 and 49) | Change from baseline: Week 49 | -2.0 units on a scale | Standard Deviation 10.83 |
| Roll-over Subjects | Change From Baseline in the Opioid Craving Visual Analog Scale (VAS) at End of Study (Weeks 25 and 49) | Baseline (actual value) | 4.4 units on a scale | Standard Deviation 9.62 |
| Roll-over Subjects | Change From Baseline in the Opioid Craving Visual Analog Scale (VAS) at End of Study (Weeks 25 and 49) | Change from baseline: Week 25 | 4.2 units on a scale | Standard Deviation 16.77 |
Secondary
Change From Baseline in the Subjective Opiate Withdrawal Scale (SOWS) at End of Study (Weeks 25 and 49)
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. Baseline value is reported as an observed actual value. Weeks 25 and 49 represent change from baseline values.
Time frame: Baseline (Day 1 predose), End of Study: Week 49 (De novo arm); Week 25 (Roll-over arm)
Population: Safety analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| De Novo Subjects | Change From Baseline in the Subjective Opiate Withdrawal Scale (SOWS) at End of Study (Weeks 25 and 49) | Baseline (actual value) | 3.8 units on a scale | Standard Deviation 5.27 |
| De Novo Subjects | Change From Baseline in the Subjective Opiate Withdrawal Scale (SOWS) at End of Study (Weeks 25 and 49) | Change from baseline: Week 25 | -1.1 units on a scale | Standard Deviation 6.63 |
| De Novo Subjects | Change From Baseline in the Subjective Opiate Withdrawal Scale (SOWS) at End of Study (Weeks 25 and 49) | Change from baseline: Week 49 | -1.6 units on a scale | Standard Deviation 5.05 |
| Roll-over Subjects | Change From Baseline in the Subjective Opiate Withdrawal Scale (SOWS) at End of Study (Weeks 25 and 49) | Baseline (actual value) | 2.8 units on a scale | Standard Deviation 5.44 |
| Roll-over Subjects | Change From Baseline in the Subjective Opiate Withdrawal Scale (SOWS) at End of Study (Weeks 25 and 49) | Change from baseline: Week 25 | 1.1 units on a scale | Standard Deviation 7.17 |
Secondary
Cumulative Distribution Function (CDF) of the Percentage Abstinence Collected From Week 1 Through End of Study (Weeks 25 and 49)
Participants' self-reported illicit opioid drug use from the timeline followback (TLFB) interview and results from the urine drug screens (UDS) for opioids were combined into a single endpoint. Opioids assessed included codeine, hydrocodone, hydromorphone, methadone, morphine, opiates, oxycodone, and oxymorphone (by UDS) and amphetamine/methadone, buprenorphine, methadone, and opioids in the TLFB. 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 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. All missing reports for opioids were considered nonnegative.
Time frame: Weekly during Month 1, Every other week from Month 2-6, Monthly from Month 7-12. De novo arm stopped at Week 49. Roll-over arm stopped at Week 25
Population: Safety analysis set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| De Novo Subjects | Cumulative Distribution Function (CDF) of the Percentage Abstinence Collected From Week 1 Through End of Study (Weeks 25 and 49) | >=30% | 239 Participants |
| De Novo Subjects | Cumulative Distribution Function (CDF) of the Percentage Abstinence Collected From Week 1 Through End of Study (Weeks 25 and 49) | >=60% | 166 Participants |
| De Novo Subjects | Cumulative Distribution Function (CDF) of the Percentage Abstinence Collected From Week 1 Through End of Study (Weeks 25 and 49) | >=20% | 278 Participants |
| De Novo Subjects | Cumulative Distribution Function (CDF) of the Percentage Abstinence Collected From Week 1 Through End of Study (Weeks 25 and 49) | >=70% | 132 Participants |
| De Novo Subjects | Cumulative Distribution Function (CDF) of the Percentage Abstinence Collected From Week 1 Through End of Study (Weeks 25 and 49) | >=40% | 217 Participants |
| De Novo Subjects | Cumulative Distribution Function (CDF) of the Percentage Abstinence Collected From Week 1 Through End of Study (Weeks 25 and 49) | >=80% | 98 Participants |
| De Novo Subjects | Cumulative Distribution Function (CDF) of the Percentage Abstinence Collected From Week 1 Through End of Study (Weeks 25 and 49) | >=10% | 315 Participants |
| De Novo Subjects | Cumulative Distribution Function (CDF) of the Percentage Abstinence Collected From Week 1 Through End of Study (Weeks 25 and 49) | >=90% | 62 Participants |
| De Novo Subjects | Cumulative Distribution Function (CDF) of the Percentage Abstinence Collected From Week 1 Through End of Study (Weeks 25 and 49) | >=50% | 187 Participants |
| De Novo Subjects | Cumulative Distribution Function (CDF) of the Percentage Abstinence Collected From Week 1 Through End of Study (Weeks 25 and 49) | =100% | 32 Participants |
| De Novo Subjects | Cumulative Distribution Function (CDF) of the Percentage Abstinence Collected From Week 1 Through End of Study (Weeks 25 and 49) | >=0% | 412 Participants |
| Roll-over Subjects | Cumulative Distribution Function (CDF) of the Percentage Abstinence Collected From Week 1 Through End of Study (Weeks 25 and 49) | =100% | 47 Participants |
| Roll-over Subjects | Cumulative Distribution Function (CDF) of the Percentage Abstinence Collected From Week 1 Through End of Study (Weeks 25 and 49) | >=0% | 257 Participants |
| Roll-over Subjects | Cumulative Distribution Function (CDF) of the Percentage Abstinence Collected From Week 1 Through End of Study (Weeks 25 and 49) | >=10% | 206 Participants |
| Roll-over Subjects | Cumulative Distribution Function (CDF) of the Percentage Abstinence Collected From Week 1 Through End of Study (Weeks 25 and 49) | >=20% | 200 Participants |
| Roll-over Subjects | Cumulative Distribution Function (CDF) of the Percentage Abstinence Collected From Week 1 Through End of Study (Weeks 25 and 49) | >=30% | 189 Participants |
| Roll-over Subjects | Cumulative Distribution Function (CDF) of the Percentage Abstinence Collected From Week 1 Through End of Study (Weeks 25 and 49) | >=40% | 159 Participants |
| Roll-over Subjects | Cumulative Distribution Function (CDF) of the Percentage Abstinence Collected From Week 1 Through End of Study (Weeks 25 and 49) | >=50% | 150 Participants |
| Roll-over Subjects | Cumulative Distribution Function (CDF) of the Percentage Abstinence Collected From Week 1 Through End of Study (Weeks 25 and 49) | >=60% | 137 Participants |
| Roll-over Subjects | Cumulative Distribution Function (CDF) of the Percentage Abstinence Collected From Week 1 Through End of Study (Weeks 25 and 49) | >=70% | 110 Participants |
| Roll-over Subjects | Cumulative Distribution Function (CDF) of the Percentage Abstinence Collected From Week 1 Through End of Study (Weeks 25 and 49) | >=80% | 96 Participants |
| Roll-over Subjects | Cumulative Distribution Function (CDF) of the Percentage Abstinence Collected From Week 1 Through End of Study (Weeks 25 and 49) | >=90% | 74 Participants |