Mirtazapine for methamphetamine use disorder: drug-drug interaction study

米氮平治疗甲基苯丙胺使用障碍：药物相互作用研究

基本信息

批准号：
9983371
负责人：
PHILLIP O COFFIN
金额：
$ 220.56万
依托单位：
PUBLIC HEALTH FOUNDATION ENTERPRISES
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-06-01 至 2022-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9983371
关键词：
Abstinence Achievement Address Adherence Admission activity Adrenergic Agents Adult Adverse event Agonist Amphetamines Behavior Therapy Blood Pressure Bupropion Cardiac Cardiovascular system Cessation of life Clinical Trials Unit Cross-Over Studies Crossover Design Data Decision Making Development Disease Dose Double-Blind Method Double-blind trial Drug Interactions Drug Kinetics Enrollment Ensure Evaluation FDA approved General Population HIV HIV risk Heart Rate Heroin Hour Human Impulsivity Infusion procedures Inpatients Institution Intervention Laboratories Los Angeles Medicine Mental Depression Methadone Methamphetamine Mirtazapine Monitor Morbidity - disease rate Morphine Naltrexone Opioid Oral Outpatients Participant Patients Persons Pharmaceutical Preparations Pharmacological Treatment Pharmacology Pharmacotherapy Phase Phase II Clinical Trials Placebos Poisoning Process Psychological Tests Randomized Research Risk Behaviors Running Safety Sample Size San Francisco Serotonin Serotonin Syndrome Signs and Symptoms Site Speed Study Subject Subgroup Testing Toxicology United States Urine Visit addiction aripiprazole arm base comorbidity craving depressive symptoms economic cost follow-up heart rhythm illicit opioid inpatient service male medication safety men men who have sex with men methadone treatment methamphetamine effect methamphetamine use methamphetamine user morphine administration mortality opioid epidemic opioid use opioid use disorder phase I trial phase III trial prescription opioid psychologic psychostimulant response screening sex sleep quality transgender women transmission process treatment arm

项目摘要

Project Summary/Abstract Methamphetamine use is a major driver of drug-related morbidity and mortality, with intimate involvement in the national opioid crisis as well. Methamphetamine is more prevalent than many other drugs, including opioids, with 37 million users of methamphetamine and amphetamine worldwide and 1.4 million past-year users in the U.S. alone in 2016. The annual economic cost of methamphetamine use is estimated to be $23.4 billion in the United States. There are no FDA-approved pharmacotherapies for methamphetamine use disorder, a major gap in the field of addition medicine. Promising agents such as bupropion, extended-release naltrexone, aripiprazole, and selected amphetamine-based stimulants, have all shown mixed or negative results in phase 2 clinical trials. In contrast, in two separate phase 2 clinical trials mirtazapine has demonstrated a significant effect in increasing periods of abstinence from methamphetamine and decreasing related HIV risk behaviors among adults with methamphetamine use disorder who were born male and have sex with men. While testing this product in the general population, with larger samples sizes, and more intensive adherence interventions is demanded, the first step required by the FDA is now a drug-drug interaction study to evaluate pharmacokinetics of methamphetamine in the presence of mirtazapine, to evaluate for adverse events such as QT prolongation and serotonin syndrome, and to ensure the safety of these combinations in patients with co-morbid opioid use disorder who may be using illicit opioids or maintained on agonist therapy. We propose to conduct this Phase 1 human laboratory trial, also exploring mechanisms for the effect of mirtazapine with a battery of psychological testing, with 36 subjects (Group 1 with no opioid use, Group 2 with illicit opioid use, Group 3 with opioid use disorder maintained on methadone) in a within-subject crossover study. After screening, participants will be admitted to a 16-day inpatient stay, randomly assigned to mirtazapine or placebo, followed to steady state, and given placebo and a methamphetamine infusion with associated batteries of psychological testing; they will then be followed for 5 days for washout and initiated in the opposite treatment arm. Results will contribute toward further evaluation of mirtazapine for treatment of methamphetamine use disorder.

项目摘要/摘要甲基苯丙胺的使用是与药物有关的发病率和死亡率的主要驱动力，并亲密参与国家阿片类药物危机也是如此。甲基苯丙胺比许多其他药物更普遍，包括阿片类药物，全球有3700万用户的甲基苯丙胺和苯丙胺用户，过去一年有140万仅在2016年美国，甲基苯丙胺使用的年度经济成本估计为23.4美元。美国十亿。没有FDA批准的药物治疗甲基苯丙胺的使用疾病，添加医学领域的主要差距。诸如安非他酮，延长释放等有希望的代理商纳曲酮，阿立哌唑和选定的基于苯丙胺的刺激剂均显示出混合或阴性结果进行2期临床试验。相比之下，在两个单独的2阶段临床试验中在增加甲基苯丙胺的禁欲时期表现出显着影响并减少甲基苯丙胺使用障碍的成年人中相关的艾滋病毒风险行为，他们出生于男性并且患有与男人发生性关系。在一般人群中测试该产品的同时，样品尺寸较大，更多需要进行密集的依从性干预措施，FDA要求的第一步现在是毒品药物相互作用研究以评估甲基苯丙胺在米塔氮平存在下的药代动力学评估QT延长和5-羟色胺综合征等不良事件，并确保可能使用非法阿片类药物或维持激动剂治疗。我们建议进行此1阶段人类实验室试验，也探索米尔沙平对一系列心理测试的影响的机制，有36个受试者（第1组与不使用阿片类药物，第2组与阿片类药物的使用，第3组与美沙酮维持阿片类药物使用障碍）受试者内部跨界研究。筛选后，参与者将被接纳为16天的住院住宿，随机分配给Mirtazapine或安慰剂，遵循稳态，并给予安慰剂和一个甲基苯丙胺输注，并带有心理测试的相关电池；然后将跟随他们5 洗净的天数，并在相反的治疗臂中启动。结果将有助于进一步评估用于治疗甲基苯丙胺使用障碍的米氮平。