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 i s:
Specific Aim 1 A: 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 1 B: 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. ? ? ?
