Abstract:
|
Dysregulation of the circadian system has been implicated in a number of neurodegenerative diseases, including Alzheimer's and Parkinson's Diseases. It is accompanied by disruption of core clock gene rhythmicity, and manifests physiologically by changes in the sleep-wake cycle, hormone secretion, core body temperature, and daily activity. The multifaceted structure of circadian disruption calls for development of integrated clinical and analytical approaches to help quantifying disease symptoms and the effects of treatment. Pfizer is currently developing a small molecule, casein kinase 1 delta/epsilon (CK1d/e) for the treatment of circadian related disorders. Selective inhibitors of CK1d/e enable the possibility to modulate and entrain the central circadian clock, restore rhythmicity, and have been hypothesized to alleviate downstream disease symptoms. This presentation will discuss the analysis of endpoints obtained in a Phase 1, double-blind safety, PK and tolerability study in healthy subjects who were given multiple ascending doses of a CK1d/e inhibitor for 14 consecutive days either in the morning or evening.
|