Melatonin Analog for Sleep Disorders

描述（由申请人提供）：第二阶段Discovery正在开发一种用于治疗睡眠障碍的合成褪黑激素类似物（PD6735）。PD6735是一种安全有效的治疗睡眠障碍的药物，没有目前一线睡眠药物的副作用。初步临床研究表明，PD6735是安全的，在人体中耐受性良好，最大剂量为20mg。PD6735对睡眠性失眠症患者的睡眠潜伏期产生剂量反应改善（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毫克时比5毫克时更为明显。目前快速通道申请的目的是确定PD6735对睡眠潜伏期的剂量反应效应是否在较高的PD6735剂量下更为明显。该提案的第一阶段将确定PD6735在20至100 mg剂量下的安全性和耐受性。第二阶段将确定20至100毫克剂量（或第一阶段确定的最大安全剂量p06735）对睡眠性失眠症受试者睡眠潜伏期的影响。本建议第一阶段部分的具体目标如下：

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.