MELATONIN ANALOG FOR JET LAG

褪黑激素类似物缓解时差反应

• 批准号: 6931369
• 负责人: Cheryle Branch Webb
• 金额: $ 35.3万
• 依托单位: P2D, INC.
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-06-01 至 2007-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6931369
• 关键词: biotherapeutic agent; circadian rhythms; clinical research; clinical trials; drug adverse effect; drug design /synthesis /production; drug screening /evaluation; electrocardiography; fatigue; hormone analog; hormone therapy; human subject; human therapy evaluation; melatonin; sleep deprivation; statistics /biometry; travel

DESCRIPTION (provided by applicant): Phase 2 Discovery is developing a synthetic melatonin analog (PD6735) for the treatment of jet lag. No medications are currently approved by the FDA for treatment of jet lag. Medications used "off-label" for jet lag possess undesired side effects. PD6735 is being developed as a safe and effective treatment for jet lag that lacks the side effects of commonly used medications. Initial clinical studies indicate that PD6735 is safe and well tolerated by humans through the maximal dose tested, 100 mg. PD6735 produced a dose-response improvement in re-adaptation to a simulated 9 hour phase shift in a double blind, placebo controlled cross over study (n=8). PD6735 also produced a dose-response improvement in sleep latency in subjects with primary insomnia in a double blind, placebo controlled cross over study (n=40). The goal of this Phase 1 application is to evaluate the feasibility of using PD6735 to reduce the symptoms of jet lag in actual air travel. Our Specific Aims are: Aim 1: Evaluate the ability of PD6735 to reduce symptoms of jet lag in long distance air travelers. Travelers (n=90) will receive PD6735 25 mg or placebo for 4 days during and after a multi-time zone flight in a randomized, placebo-controlled, double blind study. The travelers will complete the Columbia Jet Lag Scale and visual analog measures of jet lag symptom severity for 5 days during and after a multi-time zone flight; flights may be east-bound (phase advance) or west-bound (phase delay) and must cross at least 5 time zones. The rating scales will be collected, scored and statistically analyzed. Prediction: PD6735 at a dose of 25 mg for 4 days will produce a significant improvement jet lag symptoms when compared to placebo. Specific Aim 2: Evaluate the safety of PD6735 when used by long distance air travelers. Safety measures, including vital signs, electrocardiogram and clinical laboratory tests will be performed at subject enrollment and completion of the jet lag study proposed in Aim 1. Clinical adverse events, solicited and by spontaneous report, will be recorded. Prediction: PD6735 at a dose of 25 mg for 4 days will be well tolerated with a frequency of adverse events not different from placebo.

描述（由申请人提供）：第2阶段发现正在开发一种合成的褪黑激素类似物（PD6735），用于治疗喷射滞后。 FDA目前尚无药物治疗喷气滞后。用于喷射滞后的“标签外”的药物具有不希望的副作用。 PD6735正在开发为对喷气滞后的安全有效治疗，缺乏常用药物的副作用。最初的临床研究表明，PD6735是通过测试的最大剂量（100 mg）安全且耐受性良好的。 PD6735在重新适应的重新适应中产生了剂量反应改善，以在一个双盲，安慰剂控制的交叉上进行模拟的9小时相移（n = 8）。 PD6735还在双盲，安慰剂控制的杂交过度研究（n = 40）中，在主要失眠的受试者中，睡眠潜伏期的剂量反应提高（n = 40）。该第1阶段应用的目的是评估使用PD6735减少实际空气旅行中喷气滞后症状的可行性。我们的具体目的是：目标1：评估PD6735减少长途航空旅行者中喷气滞后症状的能力。旅行者（n = 90）将在多个时间内和安慰剂飞行过程中接受PD6735 25 mg或安慰剂，以随机的，安慰剂对照，双盲研究。旅行者将完成哥伦比亚喷气滞后量表和射流滞后症状严重程度的视觉模拟度量，持续5天，在多个时间区域飞行过程中和之后；航班可能是向东（阶段前进）或西部边界（相延迟），并且必须至少越过5个时区。评级量表将被收集，评分和统计分析。预测：与安慰剂相比，PD6735的剂量为25 mg 4天，将产生显着改善的喷气滞后症状。特定目标2：评估长途旅行者使用时PD6735的安全性。将记录将记录安全措施，包括生命体征，心电图和临床实验室测试，并在AIM 1中提出的JET LAG研究完成。预测：PD6735以25 mg的剂量为25 mg 4天，将耐受良好的耐受性，与安慰剂没有不同的不良事件的频率。