Melatonin Analog for Sleep Disorders

描述(由申请人提供)：第二阶段发现正在开发一种合成褪黑素类似物(PD6735)，用于治疗睡眠障碍。PD6735正在被开发为一种安全有效的睡眠障碍疗法，它没有目前一线睡眠药物的副作用。初步临床研究表明，通过测试的最大剂量20毫克，PD6735在人体内是安全和耐受性良好的。PD6735对入睡失眠症患者的睡眠潜伏期有剂量反应改善作用(双盲、安慰剂对照、交叉研究，N=19)。PD6735对睡眠潜伏期的影响在20毫克比5毫克更明显。目前的Fast Track应用程序的目标是确定PD6735对睡眠潜伏期的剂量反应效应是否会在更高的PD6735剂量下更加明显。该提案的第一阶段将确定20至100毫克剂量的PD6735的安全性和耐受性。第二阶段将确定20到100毫克剂量(或第一阶段确定的最大安全P 06735剂量)对入睡失眠症受试者睡眠潜伏期的影响。本提案第一阶段部分的具体目标是： 目的I：评价剂量达100 mg的PD6735的安全性和耐受性。口服剂量分别为20、35、50和100毫克。 目的2：测定剂量达100 mg的PD6735的药代动力学。 目的3：测定剂量达100 mg的PD6735的药效学。将评估PD6735对体温和主观嗜睡的影响。 建议的商业应用： 影响睡眠障碍的美国人超过6000万，他们在安眠药上花费超过14亿美元，由于副作用较少，与目前的一线疗法相比具有竞争优势。因此，褪黑素类似物应该会占据这个市场的很大一部分。

DESCRIPTION (PROVIDED BY APPLICANT): Phase 2 Discovery is developing a synthetic melatonin analog (PD6735) for the treatment of sleep disorders. PD6735 is being developed as a safe and effective treatment for sleep disorders that lacks the side effects of current first-line sleep medications. Initial clinical studies indicate that PD6735 is safe and well tolerated in humans through the maximal dose tested, 20 mg. PD6735 produced a dose-response improvement in sleep latency in subjects with sleep onset insomnia (double-blind, placebo controlled, crossover study, N=1 9). The PD6735 effect on sleep latency was more pronounced at 20 mg than at 5 mg. The goal of the present Fast Track application is to determine whether the dose-response effect of PD6735 on sleep latency will be more pronounced at higher PD6735 doses. Phase 1 of this proposal will establish the safety and tolerability of PD6735 at 20 to 100 mg doses. Phase 2 will determine the effect of the 20 to 100 mg doses (or the maximum safe P 06735 dose identified in Phase I) on sleep latency in subjects with sleep-onset insomnia. The Specific Aims of the Phase 1 portion of this proposal are: Aim I: Evaluate the safety and tolerability of PD6735 at doses up to 100 mg. Oral doses of 20, 35, 50 and 100 mg will be employed. Aim 2: Determine the pharmacokinetics of PD6735 at doses up to 100 mg. Aim 3: Determine the pharmacodynamics of PD6735 at doses up to 100 mg. PD6735 effects on body temperature and subjective sleepiness will be evaluated. PROPOSED COMMERCIAL APPLICATIONS: Sleep disorders affect over 60 million Americans who spend more than $1.4 billion on sleep medications would have a competitive advantage over current first line therapies by virtue of possessing fewer side effects. As such, the melatonin analog should capture a substantial portion of this market.