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.

项目概要/摘要甲基苯丙胺的使用是药物相关发病率和死亡率的一个主要驱动因素，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 万甲基苯丙胺和安非他明使用者，去年有 140 万使用者 2016 年仅美国的使用者。每年使用甲基苯丙胺的经济成本估计为 23.4 美元十亿在美国。目前尚无 FDA 批准的用于甲基苯丙胺使用的药物疗法障碍，加成医学领域的一个主要空白。有前途的药物，如安非他酮、缓释剂纳曲酮、阿立哌唑和某些基于安非他明的兴奋剂都显示出混合或阴性的结果 2 期临床试验结果。相比之下，在两项独立的 2 期临床试验中，米氮平已证明对增加甲基苯丙胺戒断时间和减少戒断时间有显着效果男性出生且患有甲基苯丙胺使用障碍的成年人中的相关艾滋病毒风险行为与男人发生性关系。在一般人群中测试该产品时，样本量更大，更多需要强化依从性干预，FDA 要求的第一步现在是药物-药物相互作用研究，评估米氮平存在下甲基苯丙胺的药代动力学，评估QT间期延长和血清素综合征等不良事件，并确保安全这些组合适用于患有阿片类药物使用障碍的患者，他们可能正在使用非法阿片类药物或维持激动剂治疗。我们建议进行第一阶段人体实验室试验，同时探索通过对 36 名受试者（第 1 组）进行一系列心理测试来研究米氮平的作用机制不使用阿片类药物，第 2 组非法使用阿片类药物，第 3 组有阿片类药物使用障碍，维持美沙酮治疗）受试者内交叉研究。筛选后，参与者将接受为期 16 天的住院治疗，随机分配给米氮平或安慰剂，然后进入稳定状态，并给予安慰剂和输注甲基苯丙胺并进行相关的心理测试；然后他们将被跟踪 5 冲洗天数并在相反的治疗组中开始。结果将有助于进一步评估米氮平用于治疗甲基苯丙胺使用障碍。