Phase 1, Double-Blind, Placebo-Controlled Assessment of Potential Interactions Between Intravenous Cocaine and Clavulanic Acid
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Changes in Blood Pressure in Response to IV Cocaine With and Without CLAV Dosing
研究概览
简要总结
The main purpose of this study is to determine if it is safe to use the study drug, clavulanic acid, in combination with cocaine. In this study, subjects will receive intravenous (i.v.) cocaine and the study drug, clavulanic acid. The safety of clavulanic acid is being studied so future studies can be done to find out if this drug is helpful in treating cocaine dependence. Currently, there is no available medication treatment for cocaine dependence.
详细描述
This is a prospective, placebo controlled inpatient crossover safety study of 3 doses (250 mg/day, 500 mg/day, 750 mg/day) of CLAV with an intravenous infusion of cocaine 40 mg. Subjects will be non-treatment seeking experienced cocaine dependent adults, ages 18-65 (N=12 completers, 21 estimated to enroll). Subjects will undergo a washout of the study drug for 5 half-lives between study drug administration sessions.
The primary objective will be to determine whether there are clinically significant adverse interactions between CLAV (250 mg/day; 500 mg/day; 750 mg/day) and intravenously administered cocaine in healthy, non-treatment seeking adults with cocaine use disorder.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Double (Participant, 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
- •Meet Diagnostic and Statistical Manual of Mental Disorders Fifth Edition criteria for cocaine use disorder, moderate to severe.
- •Be a non-treatment seeking cocaine user.
- •If female and of childbearing potential, must have a negative pregnancy test within 48 hours of beginning the study and be willing to use acceptable contraception or be abstinent for 14 days prior to study, through the entire study and 30 days after study participation.
排除标准
- •Be seeking treatment for substance abuse.
- •(For full inclusion/exclusion criteria or for more information, please contact the site directly.)
研究组 & 干预措施
Clavulanic Acid (CLAV) 250mg; CLAV 500mg then Placebo (PBO)
Clavulanic acid OR Placebo to be given in combination with intravenous cocaine; Day #2: Clavulanic Acid 250 mg (low dose); Day #3: Clavulanic Acid 500 mg; Day #4: Placebo
干预措施: Clavulanic acid (Drug)
Clavulanic Acid (CLAV) 250mg; CLAV 500mg then Placebo (PBO)
Clavulanic acid OR Placebo to be given in combination with intravenous cocaine; Day #2: Clavulanic Acid 250 mg (low dose); Day #3: Clavulanic Acid 500 mg; Day #4: Placebo
干预措施: Intravenous cocaine (Drug)
Clavulanic Acid (CLAV) 250mg; CLAV 500mg then Placebo (PBO)
Clavulanic acid OR Placebo to be given in combination with intravenous cocaine; Day #2: Clavulanic Acid 250 mg (low dose); Day #3: Clavulanic Acid 500 mg; Day #4: Placebo
干预措施: Placebo (Drug)
CLAV 250mg; PBO; then CLAV 500mg
Clavulanic acid OR Placebo to be given in combination with intravenous cocaine; Day #2: Clavulanic Acid 250 mg (low dose); Day #3: Placebo; Day #4: Clavulanic Acid 500 mg
干预措施: Clavulanic acid (Drug)
CLAV 250mg; PBO; then CLAV 500mg
Clavulanic acid OR Placebo to be given in combination with intravenous cocaine; Day #2: Clavulanic Acid 250 mg (low dose); Day #3: Placebo; Day #4: Clavulanic Acid 500 mg
干预措施: Intravenous cocaine (Drug)
CLAV 250mg; PBO; then CLAV 500mg
Clavulanic acid OR Placebo to be given in combination with intravenous cocaine; Day #2: Clavulanic Acid 250 mg (low dose); Day #3: Placebo; Day #4: Clavulanic Acid 500 mg
干预措施: Placebo (Drug)
PBO; CLAV 250mg; then CLAV 500mg
Clavulanic acid OR Placebo to be given in combination with intravenous cocaine; Day #2: Placebo; Day #3: Clavulanic Acid 250 mg (low dose); Day #4: Clavulanic Acid 500 mg
干预措施: Clavulanic acid (Drug)
PBO; CLAV 250mg; then CLAV 500mg
Clavulanic acid OR Placebo to be given in combination with intravenous cocaine; Day #2: Placebo; Day #3: Clavulanic Acid 250 mg (low dose); Day #4: Clavulanic Acid 500 mg
干预措施: Intravenous cocaine (Drug)
PBO; CLAV 250mg; then CLAV 500mg
Clavulanic acid OR Placebo to be given in combination with intravenous cocaine; Day #2: Placebo; Day #3: Clavulanic Acid 250 mg (low dose); Day #4: Clavulanic Acid 500 mg
干预措施: Placebo (Drug)
结局指标
主要结局
Changes in Blood Pressure in Response to IV Cocaine With and Without CLAV Dosing
时间窗: 4 Days (Study Days 2, 3, 4, 5)
IV cocaine was infused 1 hour following the dosing of PBO or CLAV 250mg, CLAV 500mg and CLAV 750 mg and vital signs were checked at -15min,-10min, -5 min pre-infusion of IV cocaine and then every 2 min for the first 30 minutes, then every 15min through 150 minutes post-infusion. The mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) at 2 minutes post IV cocaine infusion are reported. Also, the maximum (max) change in SBP snd DBP from baseline pre-infusion are reported (peak SBP or DBP post-infusion minus baseline SBP or DBP pre-infusion) are reported.
Number of Participants With Severe Adverse Events (AEs)
时间窗: 6 Days (Study Days 1, 2, 3, 4, 5, 10)
Rates of occurrence of serious adverse events across the different treatments: Day 1-IV cocaine only; Day 2.3 and 4 treatment with either PBO, CLAV 250mg or CLAV 500mg depending on randomization; Day 5 CLAV 750mg, Day 10 Follow-up appointment See Adverse Event section for reporting of mild-moderate AEs.
Change in Heart Rate in Response to IV Cocaine Infusion With and Without CLAV Dosing
时间窗: 4 Days (Study Days 2, 3, 4, 5)
IV cocaine was infused 1 hour following the dosing of PBO or CLAV 250mg, CLAV 500mg and CLAV 750 mg and vital signs were checked at -15min,-10min, -5 min preinfusion of IV cocaine and then every 2 min for the first 30 minutes, then every 15min through 150 minutes post-infusion. The mean heart rate (HR) at 2 minutes post IV cocaine infusion and the maximum (max) change in heart rate from baseline pre-infusion are reported (peak heart rate post-infusion minus baseline heart rate pre-infusion) are reported.
Electrocardiogram (ECG) Following IV Cocaine With and Without CLAV Dosing
时间窗: 4 Days (Study Days 2, 3, 4, 5)
ECG was done 15 min after IV cocaine infusion (following the dosing of PBO or CLAV 250mg, CLAV 500mg and CLAV 750 mg). The interval between the Q wave and the T wave, corrected (QTc) is reported.
次要结局
- Clavulanic Acid (CLAV) Concentrations Following CLAV 250mg and CLAV 500mg Doses(3 Days (Study Days 2, 3, 4))
- Pharmacokinetic (PK) Parameter of Cocaine-concentration(3 Days (Study Days 2, 3, 4))
- Difference in CLAV Concentrations Between the 250mg and 500mg CLAV Doses(3 days (Day 2, 3, 4))
- Pupil Pharmacodynamic Effects of Cocaine With Clavulanic Acid(10 minutes pre-infusion and 10, 15, 30 and 45 min after cocaine infusion on Study Days 2, 3, and 4)