Lofexidine Pharmacokinetics in the Presence of Paroxetine, a Strong CYP2D6 Inhibitor, in Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Maximum Plasma Concentration (Cmax)
研究概览
简要总结
The purpose of this study is to determine the pharmacokinetics, safety and tolerability of lofexidine HCl in the presence of paroxetine in healthy adults.
详细描述
This is a Phase 1, open-label, single-sequence study to determine the pharmacokinetics, safety and tolerability of lofexidine HCl in the presence of paroxetine in healthy adults. Lofexidine HCl is an alpha-2 adrenergic agonist under development for the treatment of acute withdrawal from short-acting opioids. Paroxetine HCl is an orally administered psychotropic drug indicated in the treatment of major depressive, obsessive compulsive, panic, social anxiety, and generalized anxiety disorders. Paroxetine is a strong CYP2D6 inhibitor.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Subject is between ages of 18 to 60 years at enrollment with a body mass index (BMI) between 18 and 35 kg/m
- •Female subjects must not be lactating, and must either a) be postmenopausal or b) agree to use an acceptable form of birth control from screening until 14 days after completion of the study.
- •Subject is in good health based on medical history, physical exam, laboratory profile, and electrocardiogram (ECG) as judged by the Investigator.
- •If subject smokes, subject agrees to limit smoking while in the study to not more than 10 cigarettes per day.
排除标准
- •History of suicidal ideations or depression requiring professional intervention including counseling or antidepressant medication over the past 12 months.
- •History or presence of allergic or adverse response to lofexidine, paroxetine, or related drugs.
- •Received any drugs capable of inhibiting CYP enzymes CYP1A2, CYP2C19, or CYP2D6 within 14 days or 5 half-lives (whichever is more) before Day
- •Consumes more than 7 drinks/week for women or 14 drinks/week for men (1 drink = 5 ounces of wine or 12 ounces of beer or 1.5 ounces of hard liquor) or has a significant history of alcohol abuse or drug/chemical abuse within the last 1 year.
- •Has a history of glucose-6-phosphate dehydrogenase (G6PD) deficiency.
研究组 & 干预措施
Lofexidine and paroxetine
Lofexidine in the presence of paroxetine
干预措施: Lofexidine (Drug)
Lofexidine and paroxetine
Lofexidine in the presence of paroxetine
干预措施: Paroxetine (Drug)
结局指标
主要结局
Maximum Plasma Concentration (Cmax)
时间窗: 0 hour (predose) and 0.25, 0.5, 1, 2, 3, 4, 5, 6.5, 8, 12, 16, 24, 32, 48 and 72 hours after lofexidine Dose 1; 0 hour (predose) and 0.25, 0.5, 1 , 2, 3, 4, 5, 6.5, 8, 12, 16, 24, 32, 48, 72, 96, 120, 144 and 168 hours after lofexidine Dose 2.
Apparent Terminal Elimination Half-life (T½)
时间窗: 0 hour (predose) and 0.25, 0.5, 1, 2, 3, 4, 5, 6.5, 8, 12, 16, 24, 32, 48 and 72 hours after lofexidine Dose 1; 0 hour (predose) and 0.25, 0.5, 1 , 2, 3, 4, 5, 6.5, 8, 12, 16, 24, 32, 48, 72, 96, 120, 144 and 168 hours after lofexidine Dose 2.
Area Under the Curve from Time Zero to Infinity (AUC 0-infinity)
时间窗: 0 hour (predose) and 0.25, 0.5, 1, 2, 3, 4, 5, 6.5, 8, 12, 16, 24, 32, 48 and 72 hours after lofexidine Dose 1; 0 hour (predose) and 0.25, 0.5, 1 , 2, 3, 4, 5, 6.5, 8, 12, 16, 24, 32, 48, 72, 96, 120, 144 and 168 hours after lofexidine Dose 2.
Apparent Clearance (CL/F)
时间窗: 0 hour (predose) and 0.25, 0.5, 1, 2, 3, 4, 5, 6.5, 8, 12, 16, 24, 32, 48 and 72 hours after lofexidine Dose 1; 0 hour (predose) and 0.25, 0.5, 1 , 2, 3, 4, 5, 6.5, 8, 12, 16, 24, 32, 48, 72, 96, 120, 144 and 168 hours after lofexidine Dose 2.
Time to Maximum Plasma Concentration (Tmax)
时间窗: 0 hour (predose) and 0.25, 0.5, 1, 2, 3, 4, 5, 6.5, 8, 12, 16, 24, 32, 48 and 72 hours after lofexidine Dose 1; 0 hour (predose) and 0.25, 0.5, 1 , 2, 3, 4, 5, 6.5, 8, 12, 16, 24, 32, 48, 72, 96, 120, 144 and 168 hours after lofexidine Dose 2.
Area Under the Concentration-Time Curve from Time Zero to Last Quantified Concentration (AUC 0-t)
时间窗: 0 hour (predose) and 0.25, 0.5, 1, 2, 3, 4, 5, 6.5, 8, 12, 16, 24, 32, 48 and 72 hours after lofexidine Dose 1; 0 hour (predose) and 0.25, 0.5, 1 , 2, 3, 4, 5, 6.5, 8, 12, 16, 24, 32, 48, 72, 96, 120, 144 and 168 hours after lofexidine Dose 2.
次要结局
- Heart rate (sitting and standing)(screening; predose and 3.5 and 7.5 hours postdose on Days 1 and 13; Day 22.)
- Laboratory Assessments(screening; Day -1, 2, 12, 14; Day 22.)
- Holter ECGs(0 (predose), and 3, 4 and 8 hours postdose on Days 1, 12, 13)
- Columbia Suicide Severity Rating Scale (C-SSRS)(screening; Days 7, 13, 22, 50.)
- 12-lead ECGs(screening; 0 and 6.5 hours postdose on Days 1, 12, 13; Day 22.)
- Blood pressure (sitting and standing)(screening; predose and 3.5 and 7.5 hours postdose on Days 1, 13; Day 22.)