PHARMACODYNAMIC/PHARMACOKINETICS STUDY OF ZALEPLON AND ZOLPIDEM

扎来普隆和唑吡坦的药效学/药代动力学研究

• 批准号: 6245552
• 负责人: DAVID J GREENBLATT
• 金额: $ 2.82万
• 依托单位: TUFTS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-05-01 至 1997-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6245552
• 关键词: blood chemistry; clinical research; clinical trials; drug screening /evaluation; electroencephalography; human subject; neuropharmacology; pharmacokinetics; psychopharmacology; pyrazolopyrimidine; sedative /hypnotic

Zalepon (CL-284846) is a novel, pyrazolopyrimidine, sedative-hypnotic which binds weakly but differentially to the GABA brian complex. In animal models, it produced potent sedative and anticonvulsive effects similar to marketed benzodiazepines. In tests for side effect potential, zalepon, unlike most marketed sedatives, produced no hangover effect, exhibited less propensity for memory loss, reduced tolerance, (suggesting a lower potential for abuse), and at an efficacious dose showed a reduced tendency to pontentiate depressant effects with alcohol. In addition, human pharmacokinetic data predict a fast onset and elimination. Based on the medical need ofr improved sedative-hypnotics and the results of preclinical and clinical studies thus far conducted, zalepon has the potential to be an effective treatment for the symptoms of insomnia with fewer side effects than are commonly associated with most drugs currently marketed for this purpose. The primary objective of this study is to evaluate the effects of zaleplon 10 and 20mg as compared to zolidem (AMBIEN) 10 and 20mg with regard to the time course of EEG and performance test effects. A secondary objective is to relate these effects to the plasma concentration of the specific drug therapy. This study represents a double-blind, placebo-controlled, randomized 5-period crossover design. This study will be conducted at a single investigational site using a total of 10 healthy males and/or females form 18- 45 years of age. Each subject will participate for up to 31 days, including a pre-study screening to occur within 21 days of the first study drug administration, and a 10 day (10 night) confinement period. The first aftenoon prior to the confinement period (day 1) will be used to acclimate the subjects to the study center, to familiarize, them with the performance tests to be conducted (no study drug will be administered and data will be collected) and undergo pre-test article administration tests. Starting on day 1 of the confinement peroid ( and continuing every 48 hours until they have received all five treatments), subjects will be given a dose of study medication at approximately 9 am. Each dose of the study drug will be separated by a 48-hour washout period. All subjects will undergo a final evaluation immediately following the completion of the last blood sample (day 9, hour 24). Multiple venous blood samples, EEG recordings and performance tests will be collected at specified time points. Adverse events will be monitored throughout the study, and clinical laboratory tests will be performed at specified times during the study. It is anticipated that the clinical portion of the study will be complete in 5 minutes.

Zalepon（CL-284846）是一种新型吡唑并嘧啶类镇静催眠药 其与GABA脑复合体的结合微弱但有差异。 在 动物模型，它产生了强大的镇静和抗惊厥作用 类似于市售的苯二氮卓。 在潜在副作用测试中， 与大多数市售镇静剂不同，扎来朋不产生宿醉效果， 表现出较少的记忆丧失倾向，耐受性降低，（表明 滥用的可能性较低），并且在有效剂量下， 倾向于推测酒精的副作用。 此外，本发明还提供了一种方法， 人体药代动力学数据预测快速起效和消除。 基于 对改良镇静催眠药的医学需求和 迄今为止进行的临床前和临床研究，zalepon具有 可能是一种有效的治疗失眠的症状， 与目前大多数药物通常相关的副作用相比，副作用较少 为这个目的销售。 本研究的主要目的是评价扎来普隆的作用 10 mg和20 mg与唑胺（AMBIEN）10 mg和20 mg相比， EEG和性能测试效果的时间过程。 次要目标是 将这些效应与特定药物的血浆浓度联系起来 疗法 这项研究是一项双盲，安慰剂对照， 随机5阶段交叉设计。 本研究将在 单个研究中心，共使用10名健康男性和/或 18- 45岁的女性。 每例受试者将参加最多 31天，包括研究前筛选，在研究开始后21天内进行 首次研究药物给药和10天（10晚）住院 期 分娩期（第1天）前的第一个下午将用于 使受试者适应研究中心，使其熟悉 进行性能测试（不给予研究药物， 将收集数据）并进行供试品给药前试验。 从分娩期的第1天开始（每48天持续一次 小时，直到他们接受了所有五种治疗），受试者将 在大约上午9点给予一剂研究药物。 的每个剂量 研究药物给药将间隔48小时洗脱期。 所有受试者 完成后将立即进行最终评估 最后一份血样（第9天，第24小时）。 多份静脉血样， 将在指定时间收集EEG记录和性能测试 点 将在整个研究期间监测不良事件， 临床实验室检查将在治疗期间的指定时间进行。 study. 预计本研究的临床部分将 5分钟内完成。