Pharmacokinetics, Pharmacodynamics, and Safety of a Single Dose Intravenous Methadone in Healthy Adult Volunteers (MTH02)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 22
- 试验地点
- 1
- 主要终点
- Pharmacokinetics (PK) in Adults - Cmin
研究概览
简要总结
Single-center, open label, single-session study to evaluate methadone pharmacokinetics and pharmacodynamic in adults.
详细描述
The Adult Methadone study will be conducted at a single site, Duke Early Phase Research Unity (DEPRU), to enroll 24 participants. Participants will be treated/monitored overnight with Methadone hydrochloride IV (FDA approved and commercially available), with daily follow-up visits for 1 week total. The study aims to provide information on the disposition and clinical effects of intravenous methadone to update the drug label.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •18 to < 40 years of age at the time of enrollment
- •Provide informed consent
排除标准
- •History of cardiac dysfunction
- •History of or current QTc prolongation, defined as > 470 ms in males and > 480 ms in females
- •Known hypersensitivity to methadone hydrochloride or any other ingredient in the methadone hydrochloride injection
- •Known acute bronchial asthma or hypercarbia (known history of known PaCO2 above 45 mm HG)
- •Receipt of a serotonergic drug or buproprion within 7 days prior to study enrollment
- •Receipt of benzodiazepines, muscle relaxants, or other opioids within 7 days prior to study enrollment
- •Receipt of a moderate or strong CYP2B6 inhibitor or inducer - either prescription or non-prescription medications, herbals,34 or foods known to be metabolized by or affecting CYP2B6 - within 30 days prior to study enrollment
- •CYP2B6 inhibitors include clopidogrel, prasugrel, thioTEPA, ticlopidine, voriconazole, macrolide antibiotics, azole-antifungal agents, fluconazole, Alstonia boonei, Mangifera indica, and Picralima nitida
- •CYP2B6 inducers include artemisinin antimalarials, barbiturates, carbamazepine, cyclophosphamide, efavirenz, lopinavir, methimazole, nelfinavir, phenobarbital, phenytoin, primidone, rifampicin/rifampin, ritonavir, abacavir, amprenavir, nevirapine, telaprevir
- •Receipt of zidovudine, desipramine, or other drugs that may increase serum concentration when combined with methadone within 30 days prior to study enrollment
- •Known or suspected gastrointestinal obstruction, including paralytic ileus
- •Significant respiratory depression (respiratory rate less than 8 breaths/min or oxygen saturation (SpO2) <95%)
- •BMI ≥ 33 and BMI ≤ 17
- •Known history of moderate-to-severe liver (Child Class B or C) or kidney disease (serum creatinine > 1.5)
- •Known history of drug or alcohol addiction (prior or present addiction or treatment for addiction)
- •Females who are pregnant or nursing
研究组 & 干预措施
Single arm, Open label Methadone IV
All participants will be treated with Methadone Hydrochloride IV (over 10 minutes) and monitored overnight.
干预措施: methadone hydrochloride 0.1mg/kg (Drug)
结局指标
主要结局
Pharmacokinetics (PK) in Adults - Cmin
时间窗: 96 hours after dosing
Cmin is the observed minimum concentration post-dose.
Pharmacokinetics (PK) in Adults - Elimination Rate Constant
时间窗: 96 hours after dosing
Elimination rate constant (ke)-s a value used in pharmacokinetics to describe the rate at which a drug is removed from the human system.
Pharmacokinetics (PK) in Adults - Volume of Distribution
时间窗: 96 hours after dosing
Pharmacokinetics (PK) in Adults - Elimination Half-life
时间窗: 96 hours after dosing
Pharmacokinetics (PK) in Adults - Systemic Clearance (CL)
时间窗: 96 hours after dosing
Pharmacokinetics (PK) in Adults - Plasma AUC0-96
时间窗: 96 hours after dosing
Plasma AUC0-96 is the area under the plasma concentration versus time curve from time zero to 96 hours post-dose.
Pharmacokinetics (PK) in Adults - AUC0-inf
时间窗: 96 hours after dosing
AUC0-inf is the area under the curve from time 0 extrapolated to infinite time.
Pharmacokinetics (PK) in Adults - Cmax
时间窗: 96 hours after dosing
Cmax: A pharmacokinetic measure used to determine drug dosing. Cmax is the highest concentration of a drug in the blood, cerebrospinal fluid, or target organ after a dose is given.
Pharmacokinetics (PK) in Adults - Tmax
时间窗: 96 hours after dosing
Tmax is the time corresponding to maximum concentration post-dose.
次要结局
- Pharmacodynamics (PD) in Adults - Subjective Self-assessment of Methadone Effects - Alertness/Sedation(96 hours after dosing)
- Pharmacodynamics (PD) in Adults - Subjective Self-assessment of Methadone Effects - Clumsiness(96 hours after dosing)
- Pharmacodynamics (PD) in Adults - Subjective Self-assessment of Methadone Effects - Energy Level(96 hours after dosing)
- Pharmacodynamics (PD) in Adults - Dark-adapted Pupillometry(96 hours after dosing)
- Pharmacodynamics (PD) in Adults - Subjective Self-assessment of Methadone Effects - Nausea(96 hours after dosing)
- Pharmacodynamics (PD) in Adults - Thermal Pain Tolerance Threshold(96 hours after dosing)
- Pharmacodynamics (PD) in Adults - Subjective Self-assessment of Methadone Effects - Confusion(96 hours after dosing)
- Pharmacodynamics (PD) in Adults - Subjective Self-assessment of Methadone Effects - Anxiety(96 hours after dosing)
- Pharmacodynamics (PD) in Adults - Maximum Sedation Score(96 hours after dosing)
- Pharmacodynamics (PD) in Adults - Maximum End-expired CO2 Concentration(96 hours after dosing)
研究者
Kanecia Obie Zimmerman
Associate Professor of Pediatrics
Duke University