NDA-Enabling Phase I Lofexidine Program

NDA 启动 I 期洛非西丁项目

基本信息

批准号：
8761749
负责人：
Charles W. Gorodetzky
金额：
$ 143.85万
依托单位：
US WORLDMEDS, LLC
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-03-01 至 2016-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8761749
关键词：
Acute Adrenergic Agonists Age Analgesics Area Biological Availability Body mass index Buprenorphine Clinical Clinical Pharmacology Dose Drug Interactions Drug Kinetics Electrocardiogram End stage renal failure Ensure Equilibrium Evaluation FDA approved Fasting Fatty acid glycerol esters Feces Food Heart Hepatic Heroin Holter Electrocardiography Hydrochloride Salt Impairment Intravenous Investigational Drugs Kidney Marketing Medical Methadone Methodology Monitor Naltrexone National Institute of Drug Abuse Opiate Addiction Opiates Opioid Oral Oxycodone Patients Pharmaceutical Preparations Pharmacodynamics Pharmacology Phase Plasma Population Process Product Labeling Radiolabeled Recovery Relative (related person)Renal function Research Rural Safety Tablets Time United States National Institutes of Health United States Substance Abuse and Mental Health Services Administration Urine Withdrawal Work healthy volunteer intravenous administration liver function lofexidine named group opioid abuse opioid withdrawal prescription opiate programs public health relevance radiotracer sex suburb therapy development volunteer

项目摘要

DESCRIPTION (provided by applicant): The proposed research is aimed at characterizing the pharmacokinetic, pharmacodynamics, and clinical pharmacological profiles of lofexidine hydrochloride, an alpha-2 adrenergic agonist under development for the treatment of acute withdrawal from short acting opioids. The application revision entails an increased scope for two of the originally planned drug-drug interaction studies and adding intensive ECG monitoring and centralized analysis for the entire program. The research program consists of seven studies, each with a particular objective that will add to the overall understanding of the pharmacology of the investigational drug. The studies include evaluation of (1) absolute bioavailability and mass balance of lofexidine, (2) effect of food on lofexidine's bioavailability, (3 and 4) drug-drug pharmacodynamic interaction with a focus on heart interval interaction effects between lofexidine and methadone or buprenorphine, (5) drug-drug pharmacokinetic interaction of lofexidine and naltrexone (methadone, buprenorphine and naltrexone are drugs for related indications that may be used concurrently in a clinical setting), (6) pharmacokinetics of lofexidine in renally-impaired patients, and (7) pharmacokinetics of lofexidine in hepatically-impaired patients. The studies will be conducted in normal, healthy volunteers or special populations (as in the case of the hepatic and renal impairment studies and methadone/buprenorphine interaction studies) and employ appropriate methodology to evaluate levels of lofexidine and related compounds in urine and plasma. Holter monitoring will be used in each study to ensure quality ECG recording and centralized analysis through a specialized core lab. Quantification of lofexidine and/or its major metabolites over time in addition to observed tolerance and evaluation of other clinical parameters in each of the planned studies will add to the overall understanding of the pharmacokinetics and pharmacodynamics of lofexidine in the body. This revision application focuses on the change in studies 3 and 4 noted above and the addition of intensive ECG monitoring across the program. This information is needed to allow appropriate labeling of the product for its entrance to the US market. Furthermore, the planned research has been defined by the FDA as critical to complete the clinical pharmacology section requirements for a New Drug Application for lofexidine hydrochloride, approval of which will allow entrance of the first and only non-narcotic, non-addictive drug indicated for the treatment of opiate withdrawal to the US market.

描述（由申请人提供）：拟议的研究旨在表征洛芬盐酸洛芬氨基氨酸的药代动力学，药效学和临床药理学特征，这是一种正在开发的α-2肾上腺素能激动剂，用于治疗从短效应的阿片类药物中急性戒断急性戒断。该应用程序的修订需要增加两个原始计划的药物相互作用研究的范围，并为整个计划添加密集的ECG监测和集中分析。该研究计划由七项研究组成，每个研究都有一个特定的目标，可以增加对研究药物药理的总体理解。研究包括评估（1）绝对生物利用度和洛己定的质量平衡，（2）食物对洛己胺的生物利用度的影响，（3和4）药物 - 药物 - 药物学相互作用，重点是lofexidine和lofexidine和美匹甲酮或美甲酮或美匹胺之间的心脏间隔相互作用，（5）洛己酮和纳曲酮的药物 - 药物代动力学相互作用（美沙酮，丁丙诺啡和纳曲酮是用于在临床环境中同时使用的相关指示的药物，（6）肾脏影响的患者中洛舍氨酸的药物，以及（7））在肝损伤患者中，洛芬己定的药代动力学。这些研究将在正常，健康的志愿者或特殊人群中进行（如肝和肾脏损伤研究以及美沙酮/丁丙诺啡相互作用研究），并采用适当的方法来评估尿液和血浆中Lofexidine及其相关化合物的水平。每项研究都将使用Holter监测，以确保通过专门的核心实验室确保高质量的ECG记录和集中分析。除了观察到的每项计划研究中的耐受性和对其他临床参数的评估外，洛芬己二氨酸和/或其主要代谢产物的定量还会增加对体内洛芬己胺的药代动力学和药效学的总体理解。此修订应用程序着重于上述研究3和4的变化，并在整个计划中添加了密集的心电图监测。需要此信息以允许产品进入美国市场的适当标签。此外，计划进行的研究已被FDA定义为完成盐酸洛己烷的新药物申请的临床药理学部分的重要要求，其批准将允许进入第一种也是唯一的非麻醉性，非麻醉性药物，以鸦片撤离到美国市场的处理。