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.
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.
|Zemlan, Frank P; Mulchahey, J Jeffery; Scharf, Martin B et al. (2005) The efficacy and safety of the melatonin agonist beta-methyl-6-chloromelatonin in primary insomnia: a randomized, placebo-controlled, crossover clinical trial. J Clin Psychiatry 66:384-90|