Background:
E2027 is a novel, highly selective and potent inhibitor of phosphodiesterase9 (PDE9) being evaluated as a treatment for dementia with Lewy bodies.
Methods:
Phase 1, randomized, double-blind, single ascending dose (SAD, n=96) and multiple ascending dose (MAD, n=68) studies evaluated E2027 doses (5 to 1200 mg) in healthy subjects. The impact of age, race (Japanese/non-Japanese), and food on pharmacokinetics (PK)/pharmacodynamics were evaluated. Serial cerebrospinal fluid (CSF) samples were collected to assess the target engagement.
Results:
E2027 PK profiles were biphasic (elimination half-life: ~30 hours. Approximately 3-fold accumulation was observed following multiple once-daily dosing. E2027 single doses of 50 to 400 mg resulted in mean maximum increases in CSF cyclic guanosine monophosphate ranging from 293% to 461% within 5.37 to 12.9 hours after…
