Safety and Pharmacokinetics of PD6735 in the Elderly

描述（由申请人提供）：Phase II Discovery，Inc.正在开发一种用于治疗睡眠障碍的合成褪黑激素类似物（PD 6735），该药物没有当前一线睡眠药物的副作用。 这项I期研究计划将在健康老年受试者中检查剂量高达100 mg的PD 6735的安全性和耐受性。 在非老年人（n=40）中进行的双盲、安慰剂对照功效研究证明，在患有原发性失眠的受试者中，PD 6735剂量依赖性地减少睡眠潜伏期。与安慰剂相比，20、50或100 mg剂量的PD 6735导致客观睡眠潜伏期显著减少。这些剂量也导致感知睡眠潜伏期的减少。对于所有剂量的PD 6735，不良事件的频率和严重程度与安慰剂相似。这些结果表明，剂量高达100 mg的PD 6735对于治疗非老年人的原发性失眠是安全有效的。 PD 6735在原发性失眠老年受试者中的疗效尚不清楚。老年人是美国处方睡眠药物的最大消费者。因此，美国食品和药物管理局（FDA）要求对老年人的睡眠药物进行安全性和有效性研究。在健康老年受试者中，可获得5 mg和20 mg剂量的PD 6735的初步安全性和药代动力学数据;对于大于20 mg的剂量，没有安全性或药代动力学数据。拟定的研究将确定PD 6735在健康老年人中高达100 mg剂量的安全性，作为在老年人中进行这些剂量的疗效研究的前奏。第一阶段提案的具体目标是： 目标1：生产临床试验用品。 目的2：评估褪黑激素类似物PD 6735在健康老年人中剂量高达100 mg的安全性和耐受性。 具体目标3：确定剂量高达100 mg的PD 6735在健康老年人中的药代动力学。 目的4：在健康老年人中评价剂量高达100 mg的PD 6735的药效学。

DESCRIPTION (PROVIDED BY APPLICANT): Phase II Discovery, Inc. is developing a synthetic melatonin analog (PD6735) for treating sleep disorders that lacks the side effects of current first-line sleep medications. This Phase 1 proposal will examine the safety and tolerability of PD6735 at doses up to 100 mg in healthy elderly subjects. A double blind, placebo controlled efficacy study in non-elderly adults (n=40) demonstrated PD6735 dose dependent reductions in sleep latency in subjects with primary insomnia. PD6735 at doses of 20, 50 or 100 mg resulted in significant reductions in objective sleep latency as compared to placebo. These doses also resulted in reductions in perceived sleep latency. The frequency and severity of adverse events were similar to placebo for all doses of PD6735. These results suggest that PD6735 at doses up 100 mg is a safe and effective for the treatment of primary insomnia in non-elderly adults. The efficacy of PD6735 in elderly subjects with primary insomnia is not known. The elderly are the largest consumers of prescription sleep medications in the United States. Consequently, the US Food and Drug Administration (FDA) require safety and efficacy studies of sleep medications in the elderly. Preliminary safety and pharmacokinetic data are available for PD6735 at doses of 5 and 20 mg in healthy elderly subjects; no safety or pharmacokinetic data are available for doses greater than 20 mg. The proposed study will determine the safety of PD6735 at doses up to 100 mg in the healthy elderly as a prelude to performing efficacy studies at these doses in the elderly. The Specific Aims of this Phase 1 proposal are: Aim 1: Manufacture clinical trial supplies. Aim 2: Evaluate the safety and tolerability of the melatonin analog PD6735 in healthy elderly at doses up to 100mg. Specific Aim 3: Determine the pharmacokinetics of PD6735 in healthy elderly at doses up to 100 mg. Aim 4: Evaluate the pharmacodynamics of PD6735 in healthy elderly at doses up to 100 mg.