A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study To Assess the Efficacy, Safety, and Tolerability of Multiple Subcutaneous Injections of Depot Buprenorphine (RBP-6000 [100 mg and 300 mg]) Over 24 Weeks 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
- 665
- 试验地点
- 38
- 主要终点
- Cumulative Distribution Function (CDF) of the Percentage of Urine Samples Negative for Opioids Combined With Self-Reports Negative for Illicit Opioid Use Collected From Week 5 Through Week 24
研究概览
简要总结
This is a randomized, double-blind, placebo controlled, multicenter study in male and female participants who are seeking treatment for opioid use disorder.
详细描述
After completing an up to 2-week screening period, subjects entered an open-label run-in induction phase with SUBOXONE (buprenorphine/naloxone) sublingual film for 3 days followed by a 4- to 11-day SUBOXONE sublingual film open-label run-in dose-adjustment period to achieve buprenorphine dosages ranging from 8 to 24 mg according to the SUBOXONE sublingual film prescribing information.
This is a 24-week non-residential study with participants being randomized after meeting randomization criteria. On Day 1 and Day 29 (± 2 days) participants will receive subcutaneous injections of 300 mg RBP-6000 or placebo. Thereafter, participants will receive 4 injections (once every 28 days ± 2 days) of either 300 mg or 100 mg RBP-6000 doses or placebo.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
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
- •Currently meets Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria for moderate or severe opioid use disorder
- •By medical history has met DSM-5 criteria for moderate or severe opioid use disorder for the 3 months immediately prior to signing the informed consent form
- •Is seeking medication-assisted treatment for opioid use disorder
- •Is an appropriate candidate for opioid partial-agonist medication-assisted treatment in the opinion of the investigator or medically responsible physician
- •Body mass index (BMI) of ≥ 18.0 to ≤ 35.0 kg/m^2
排除标准
- •Current diagnosis other than opioid use disorder requiring chronic opioid treatment
- •Current substance use disorder as defined by DSM-5 criteria with regard to any substances other than opioids, cocaine, cannabis, tobacco, or alcohol.
- •Positive urine drug screen (UDS) result at screening for cocaine or cannabis AND meets DSM-5 criteria for either moderate or severe cocaine or cannabis use disorder, respectively
- •Meets DSM-5 criteria for moderate or severe alcohol use disorder
- •Received medication-assisted treatment for opioid use disorder (e.g., methadone, buprenorphine) in the 90 days prior to providing written informed consent
研究组 & 干预措施
RBP-6000 300mg/100mg
During the Run-In Period, participants are inducted onto SUBOXONE sublingual film (SL) followed by a 4- to 11-day SUBOXONE sublingual film open-label run-in dose-adjustment period to achieve buprenorphine dosages ranging from 8 to 24 mg according to the SUBOXONE sublingual film prescribing information. Participants are then randomized. As of protocol Amendment 2 (21 August 2015) SUBOXONE use is tapered from 6 mg to 2 mg from Days 1-5 and then discontinued.
Participants in this treatment arm are given RBP-6000 300 mg injections on Days 1 and 29. Injections 3-6 are separated by 28 days (Day 57-Day 141) and contain RBP-6000 100 mg.
In addition, participants received individual drug counseling (IDC) at least once a week.
干预措施: SUBOXONE (Drug)
RBP-6000 300mg/100mg
During the Run-In Period, participants are inducted onto SUBOXONE sublingual film (SL) followed by a 4- to 11-day SUBOXONE sublingual film open-label run-in dose-adjustment period to achieve buprenorphine dosages ranging from 8 to 24 mg according to the SUBOXONE sublingual film prescribing information. Participants are then randomized. As of protocol Amendment 2 (21 August 2015) SUBOXONE use is tapered from 6 mg to 2 mg from Days 1-5 and then discontinued.
Participants in this treatment arm are given RBP-6000 300 mg injections on Days 1 and 29. Injections 3-6 are separated by 28 days (Day 57-Day 141) and contain RBP-6000 100 mg.
In addition, participants received individual drug counseling (IDC) at least once a week.
干预措施: RBP-6000 (Drug)
RBP-6000 300mg/300mg
During the Run-In Period, participants are inducted onto SUBOXONE sublingual film (SL) followed by a 4- to 11-day SUBOXONE sublingual film open-label run-in dose-adjustment period to achieve buprenorphine dosages ranging from 8 to 24 mg according to the SUBOXONE sublingual film prescribing information. Participants are then randomized. As of protocol Amendment 2 (21 August 2015) SUBOXONE use is tapered from 6 mg to 2 mg from Days 1-5 and then discontinued.
Participants in this treatment arm are given six RBP-6000 300 mg injections on Days 1 to 141 with injections separated by 28 days.
In addition, participants received individual drug counseling (IDC) at least once a week.
干预措施: SUBOXONE (Drug)
RBP-6000 300mg/300mg
During the Run-In Period, participants are inducted onto SUBOXONE sublingual film (SL) followed by a 4- to 11-day SUBOXONE sublingual film open-label run-in dose-adjustment period to achieve buprenorphine dosages ranging from 8 to 24 mg according to the SUBOXONE sublingual film prescribing information. Participants are then randomized. As of protocol Amendment 2 (21 August 2015) SUBOXONE use is tapered from 6 mg to 2 mg from Days 1-5 and then discontinued.
Participants in this treatment arm are given six RBP-6000 300 mg injections on Days 1 to 141 with injections separated by 28 days.
In addition, participants received individual drug counseling (IDC) at least once a week.
干预措施: RBP-6000 (Drug)
Placebo Matching 300 mg/100 mg RBP-6000
During the Run-In Period, participants are inducted onto SUBOXONE sublingual film (SL) followed by a 4- to 11-day SUBOXONE sublingual film open-label run-in dose-adjustment period to achieve buprenorphine dosages ranging from 8 to 24 mg according to the SUBOXONE sublingual film prescribing information. Participants are then randomized. As of protocol Amendment 2 (21 August 2015) SUBOXONE use is tapered from 6 mg to 2 mg from Days 1-5 and then discontinued.
Participants in this treatment arm are given placebo injections on Days 1 and 29 (matching the RBP-6000 300 mg dose volume). Injections 3-6 are separated by 28 days (Day 57-Day 141) and also contain placebo (matching the RBP-6000 100 mg volume).
In addition, participants received individual drug counseling (IDC) at least once a week.
干预措施: SUBOXONE (Drug)
Placebo Matching 300 mg/100 mg RBP-6000
During the Run-In Period, participants are inducted onto SUBOXONE sublingual film (SL) followed by a 4- to 11-day SUBOXONE sublingual film open-label run-in dose-adjustment period to achieve buprenorphine dosages ranging from 8 to 24 mg according to the SUBOXONE sublingual film prescribing information. Participants are then randomized. As of protocol Amendment 2 (21 August 2015) SUBOXONE use is tapered from 6 mg to 2 mg from Days 1-5 and then discontinued.
Participants in this treatment arm are given placebo injections on Days 1 and 29 (matching the RBP-6000 300 mg dose volume). Injections 3-6 are separated by 28 days (Day 57-Day 141) and also contain placebo (matching the RBP-6000 100 mg volume).
In addition, participants received individual drug counseling (IDC) at least once a week.
干预措施: Placebo (Drug)
Placebo Matching 300 mg RBP-6000
During the Run-In Period, participants are inducted onto SUBOXONE sublingual film (SL) followed by a 4- to 11-day SUBOXONE sublingual film open-label run-in dose-adjustment period to achieve buprenorphine dosages ranging from 8 to 24 mg according to the SUBOXONE sublingual film prescribing information. Participants are then randomized. As of protocol Amendment 2 (21 August 2015) SUBOXONE use is tapered from 6 mg to 2 mg from Days 1-5 and then discontinued.
Participants in this treatment arm are given six placebo injections (volume-matched to RBP-6000 300 mg dose) on Days 1 to 141 with injections separated by 28 days.
In addition, participants received individual drug counseling (IDC) at least once a week.
干预措施: SUBOXONE (Drug)
Placebo Matching 300 mg RBP-6000
During the Run-In Period, participants are inducted onto SUBOXONE sublingual film (SL) followed by a 4- to 11-day SUBOXONE sublingual film open-label run-in dose-adjustment period to achieve buprenorphine dosages ranging from 8 to 24 mg according to the SUBOXONE sublingual film prescribing information. Participants are then randomized. As of protocol Amendment 2 (21 August 2015) SUBOXONE use is tapered from 6 mg to 2 mg from Days 1-5 and then discontinued.
Participants in this treatment arm are given six placebo injections (volume-matched to RBP-6000 300 mg dose) on Days 1 to 141 with injections separated by 28 days.
In addition, participants received individual drug counseling (IDC) at least once a week.
干预措施: Placebo (Drug)
结局指标
主要结局
Cumulative Distribution Function (CDF) of the Percentage of Urine Samples Negative for Opioids Combined With Self-Reports Negative for Illicit Opioid Use Collected From Week 5 Through Week 24
时间窗: Weekly from Weeks 5-24
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.
次要结局
- Percentage of Participants Considered A Treatment Success(Weeks 5-24)
- Cumulative Distribution Function (CDF) of the Percentage of Urine Samples Negative for Opioids From Week 5 Through Week 24(Weekly from Weeks 5-24)
- Cumulative Distribution Function (CDF) of the Percentage of Self-Reports Negative for Illicit Opioid Use From Week 5 Through Week 24(Weekly from Weeks 5-24)
- Change From Baseline in the Opioid Craving Visual Analog Scale (VAS) Prior to Injections From Week 5 Through Week 24 Analyzed by Mixed Model for Repeated Measures(Baseline: Day 1 (prior to dosing), Weeks 5-24)
- Participants Who Complete the Week 24 Visit ("Completers")(Week 24)
- Participants Who Are Abstinent at Week 24(Week 24)
- Change From Baseline in the Clinical Global Impression - Improvement Scale (CGI-I) Prior to Injections From Week 5 Through Week 24 Analyzed by Mixed Model for Repeated Measures(Baseline: Day 1 (prior to dosing), Days 29, 57, 85, 113, 141, 169)
- Change From Baseline in the Clinical Global Impression - Severity Scale (CGI-S) Prior to Injections From Week 5 Through Week 24 Analyzed by Mixed Model for Repeated Measures(Baseline: Day 1 (prior to dosing), Days 29, 57, 85, 113, 141, 169)
- Change From Baseline in the Clinical Opiate Withdrawal Scale (COWS) Through Week 24 Analyzed by Mixed Model for Repeated Measures(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)
- Change From Baseline in the Subjective Opiate Withdrawal Scale (SOWS) Through Week 24 Analyzed by Mixed Model for Repeated Measures(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)
- Total Number of Weeks of Abstinence as Assessed From Urine Samples Negative for Opioids Combined With Self-Reports Negative for Illicit Opioid Use Collected From Week 5 Through Week 24(Weeks 5 through 24)
- Participants With Adverse Events During the Treatment Period(Day 1 through Week 24)
- Worst Injection Site Pain From Injections 1-6 as Measured by Participant-Reported Visual Analog Scale (VAS)(Days 1, 29, 57, 85, 113, 141)
- Suicidality Using the Columbia Suicide Severity Rating Scale (C-SSRS) From Week 2 - 24(Weekly - Week 2 through Week 24)