Ethanol Interactions of the Melatonin Agonist PD6735

描述（由申请人提供）：保密。P2D公司正在开发合成褪黑激素类似物PD6735，用于治疗失眠。失眠在美国非常普遍，影响了24%的美国人口。使用助眠剂的主要障碍是目前助眠剂的副作用。因此，对一种安全、有效且耐受性良好的睡眠药物的需求仍未得到满足。乙醇（EtOH）是最常用的助眠剂。尽管有相反的警告，但许多失眠症患者将EtOH与其他助眠药物结合使用。由于EtOH与其他药物的加性催眠作用，助眠剂经常与EtOH联合使用。然而，睡眠药物可能会加重EtOH对精神运动的损害作用。由于这些附加效应，评估新的睡眠疗法与EtOH联合使用的安全性是很重要的。该1期SBIR提案将产生PD6735和EtOH在人体中联合药效学效应的第一个数据，因此将探索将PD6735用作助眠剂而不考虑EtOH相互作用的可行性。具体目标是：具体目标1A：生产临床试验用品。准备研究所需的临床试验用品。研究药物（PD6735和匹配的安慰剂）将为拟议的临床研究生产和包装，并进行纯度、稳定性和微生物污染测试。所有的研究药物和安慰剂将在外观上相同，与双盲研究设计一致。将设计并打印病例报告表格。将为临床数据构建一个特定研究的21 CFR Part 11合规电子数据库。预测：研究药物稳定、纯净、无污染。将开发适合研究的个案报告表格和电子数据库。特异性目的1B：评估褪黑素类似物PD6735对正常志愿者EtOH产生累加性精神运动损伤的能力。一项随机、安慰剂对照的4期交叉研究将对25名年龄在21 - 50岁（含）的健康正常志愿者进行PD6735 （50 mg）、EtOH （0.6 g/kg）、PD6735 + EtOH和安慰剂的联合治疗。单独和联合治疗的药效学效果将通过一系列经过验证的精神运动和神经认知评估来评估。测试结果将作为治疗的函数进行统计比较。预测：与安慰剂/安慰剂治疗的受试者相比，安慰剂/安慰剂治疗的受试者将表现出精神运动和神经认知障碍。接受PD6735/安慰剂治疗的受试者的表现与安慰剂/安慰剂治疗的受试者相似，而接受PD6735/EtOH治疗的受试者的表现与安慰剂/EtOH治疗的受试者相似。

DESCRIPTION (provided by applicant): CONFIDENTIAL. P2D, Inc. is developing the synthetic melatonin analog PD6735 as a treatment for insomnia. Insomnia is highly prevalent in the United States, affecting 24% percent of the American population. The major barrier to sleep aid use is the side effect profile of current sleep aids. A large unmet need thus exists for a safe, effective and well tolerated sleep medication. Ethanol (EtOH) is the most commonly used sleep aid. Despite warnings to the contrary, many individuals with insomnia combine EtOH with other sleep aids. Sleep aids are often combined with EtOH due to the additive soporific effects of EtOH with other drugs. However, the psychomotor-impairing effects of EtOH may be compounded by sleep medications. Because of these additive effects, it is important to evaluate the safety of new sleep therapies in combination with EtOH. This Phase 1 SBIR proposal will produce the first data relating to the combined pharmacodynamic effects of PD6735 and EtOH in humans and thus will explore the feasibility of using PD6735 as a sleep aid without concern for EtOH interactions. The Specific Aim is: Specific Aim 1A: Manufacture clinical trial supplies. Clinical trial supplies required for the study will be prepared. Study medication (PD6735 and matching placebo) will be manufactured and packaged for the proposed clinical study and tested for purity, stability and microbial contamination. All study medication and placebos will be identical in appearance, consistent with the double-blind study design. Case report forms will be designed and printed. A study-specific 21 CFR Part 11 compliant-electronic database will be constructed for clinical data. Prediction: Study medication will be stable, pure and non-contaminated. Study-appropriate case report forms and an electronic database will be developed. Specific Aim 1B: Evaluate ability of the melatonin analog PD6735 to produce additive psychomotor impairment with EtOH in normal volunteers. A randomized, placebo-controlled 4-period crossover study will administer PD6735 (50 mg), EtOH (0.6 g/kg), a combination of PD6735 plus EtOH, and placebo to 25 healthy normal volunteers ages 21 - 50 years, inclusive. The pharmacodynamic effects of the individual and combined treatments will be evaluated using a battery of validated psychomotor and neurocognitive assessments. The test results will be compared statistically as a function of treatment. Prediction: Placebo/EtOH-treated subjects will display psychomotor and neurocognitive impairment as compared to placebo/placebo-treated subjects. Subjects who receive PD6735/placebo will perform in a manner similar to placebo/placebo-treated subjects while subjects who receive PD6735/EtOH will perform in a manner similar to placebo/EtOH-treated subjects. Project Narrative: P2D, Inc. is developing the synthetic melatonin analog PD6735 as a treatment for insomnia. Insomnia is highly prevalent in the United States, affecting 24% percent of the American population. Ethanol (EtOH) is the most commonly used sleep aid. Despite warnings to the contrary, many individuals with insomnia combine EtOH with other sleep aids. The psychomotor-impairing effects of EtOH may be compounded by sleep medications. Because of these additive effects, it is important to evaluate the safety of new sleep therapies in combination with EtOH. The proposed study will evaluate the safety of PD6735 in combination with EtOH.