Extended-release Buprenorphine as a Novel Low-dose Induction Strategy
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 8
- 试验地点
- 1
- 主要终点
- Plasma-concentration curves (AUC) of buprenorphine.
研究概览
简要总结
This is a clinical trial to characterize the safety and pharmacokinetics of using extended-release buprenorphine (XR-BUP) as a novel low-dose buprenorphine induction strategy. Individuals with a diagnosis of Opioid Use Disorder (OUD) (n=30) will be admitted to an inpatient unit to complete study procedures over the course of 3 days. Participants will receive fentanyl to prevent the emergence of withdrawal. Each participant will then receive a single injection of XR-BUP after which study staff will monitor for any precipitated withdrawal.
详细描述
The approach is to conduct a single ascending dose trial in a controlled human laboratory setting with individuals with a diagnosis of OUD (n=30) actively using illicit fentanyl. After obtaining informed consent and establishing eligibility, 10 participants will be scheduled for an inpatient visit lasting 3 days, 2 nights and receive XR-BUP when not yet experiencing any opioid withdrawal. Participants will receive fentanyl to prevent the emergence of withdrawal, and on the following morning, receive XR-BUP 16mg in single-blind fashion. If at least 90% successfully complete induction (success defined as experiencing no precipitated withdrawal) with the 16mg dose, then we will proceed with 10 more participants to receive the 24mg dose. If at least 90% successfully complete induction the 24mg dose, then we will proceed with 10 more participants to the 32mg dose. Timed blood samples will be collected in heparinized Vacutainer tubes via a catheter in the antecubital vein at baseline, and at 0.5, 1, 2, 4, 6, 8, 12, and 24 hours after the XR-BUP injection.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Other
- 盲法
- Single (Participant)
盲法说明
Only the participant will be masked.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •English speaking adults aged 18 and above.
- •diagnosis of opioid use disorder.
- •Self-reporting use of illicit opioids in >21 days in the prior 30 days.
- •Provide urine toxicology testing positive for fentanyl at baseline.
排除标准
- •Seeking medication treatment for opioid use disorder with sublingual buprenorphine or methadone.
- •Received buprenorphine or methadone treatment in prior 30 days.
- •Current diagnosis of alcohol or sedative/hypnotic use disorder.
- •Positive urine drug screen for benzodiazepines, alcohol and or methadone.
- •Physical dependence on alcohol or sedative/hypnotics.
- •Psychotic disorder, active suicidality or homicidally or any psychiatric condition that impair ability to provide informed consent.
- •Have a history or diagnosis of Intracranial mass/bleed, seizure disorder, liver cirrhosis, renal failure, obstructive lung disease, hyperthyroidism, narrow-angle glaucoma, valvular heart disease, cardiac arrhythmias, heart failure.
- •Recent (within 6 months) head trauma, stroke, or myocardial infarction
- •Requiring treatment with opioids for acute or chronic pain.
- •History of hypersensitivity or allergy to buprenorphine or fentanyl.
- •Pregnant or breastfeeding.
- •Liver function test greater than 3 times upper normal limit.
- •Receiving medications that are strong or moderate CYP34A inducers or inhibitors (including but not limited to ketoconazole, itraconazole, clarithromycin, fluconazole, erythromycin), in the past 30 days.
研究组 & 干预措施
16mg Extended-Release Buprenorphine
The first 10 participants will receive XR-BUP 16mg in single-blind fashion.
干预措施: Extended-release Buprenorphine (Drug)
24mg Buprenorphine
After first 10 participants have been completed, the next 10 participants will receive 24mg in a single-blind fashion.
干预措施: Extended-release Buprenorphine (Drug)
32mg Buprenorphine
After the 20 participants have been completed, the next 10 participants will receive 32mg in a single-blind fashion.
干预措施: Extended-release Buprenorphine (Drug)
结局指标
主要结局
Plasma-concentration curves (AUC) of buprenorphine.
时间窗: Baseline, 0.5, 1, 2, 4, 6, 8, 12, and 24 hours after study drug administration.
The area under the plasma concentration curves (AUC) of buprenorphine will be determined. Timed blood samples will be collected in anticoagulant Vacutainer tubes via venipuncture at baseline, 0.5, 1, 2, 4, 6, 8, 12, and 24 hours after the XR-BUP injection. Samples will be centrifuged and frozen until analysis.
Safety and tolerability of XR-Buprenorphine
时间窗: For the duration of the inpatient admission, lasting 24 hours after receipt of study drug.
The primary outcome is the proportion of participants who successfully complete induction, defined as experiencing no BPOW, which will be assessed using the COWS. An increase in the COWS score by 8 or more with the total score exceeding 13, within 4 hours will be considered BPOW.
Plasma-concentration curves (AUC) of buprenorphine.
时间窗: Baseline, 0.5, 1, 2, 4, 6, 8, 12, and 24 hours after study drug administration.
The area under the plasma concentration curves (AUC) of buprenorphine will be determined. Timed blood samples will be collected in anticoagulant Vacutainer tubes via venipuncture at baseline, 0.5, 1, 2, 4, 6, 8, 12, and 24 hours after the XR-BUP injection. Samples will be centrifuged and frozen until analysis.
次要结局
- Minimum Plasma Concentration (Cmin),(Baseline, 0.5, 1, 2, 4, 6, 8, 12, and 24 hours after study drug administration.)
- Time to Maximum Plasma Concentration(Baseline, 0.5, 1, 2, 4, 6, 8, 12, and 24 hours after study drug administration.)
- Maximum Plasma Concentration(Baseline, 0.5, 1, 2, 4, 6, 8, 12, and 24 hours after study drug administration.)
- Elimination half-life(Baseline, 0.5, 1, 2, 4, 6, 8, 12, and 24 hours after study drug administration.)
- Buccal Swab(will be done once at the baseline visit.)
研究者
Joji Suzuki, MD
Director, Division of Addiction Psychiatry
Brigham and Women's Hospital