Safety and Pharmacokinetics of PD6735 in the Elderly

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.