An Open-Label, Long-Term Safety and Tolerability Study of Depot Buprenorphine (RBP-6000) in Treatment-Seeking Subjects With Opioid Use Disorder
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 775
- 试验地点
- 42
- 主要终点
- Percentage Change From Baseline to End of Study (Weeks 25 and 49) in Vital Signs
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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.
干预措施: SUBOXONE sublingual film (Drug)
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.
干预措施: RBP-6000 (Drug)
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.
干预措施: SUBOXONE sublingual film (Drug)
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.
干预措施: RBP-6000 (Drug)
结局指标
主要结局
Percentage Change From Baseline to End of Study (Weeks 25 and 49) in Vital Signs
时间窗: 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.
Participants With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period
时间窗: 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.
Shifts in Suicidality Using the Columbia Suicide Severity Rating Scale (C-SSRS) From Baseline to Most Severe Assessment During the Treatment Period
时间窗: 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'.
Worst Local Injection Site Pain From Injections as Measured by Participant-Reported Visual Analog Scale (VAS)
时间窗: 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.
次要结局
- 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))
- 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))
- 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)
- 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))