P3‐425: Safety, tolerability and efficacy of lecozotan SR in patients with mild‐to‐moderate Alzheimer's disease used as monotherapy or adjunctively with a cholinesterase inhibitor
Year: 2012
Type: article
Study design: Clinical Trial
Abstract: Lecozotan is a 5-HT 1a receptor antagonist developed for the symptomatic treatment of mild to moderate Alzheimer's disease (AD). Two randomized phase 2b studies were conducted to determine the safety, tolerability, and efficacy of lecozotan sustained release formulation (SR) in mono-therapy or adjunctively with a cholinesterase inhibitor (ChI). Three lecozotan SR doses (2, 5 and 10 mg/day) were investigated in two multicenter, randomized, double-blind, placebo-controlled studies. A total of 372 patients with mild-to-moderate AD were randomly assigned to receive one of the three lecozotan doses, donepezil or placebo in the 12-week mono-therapy study (201study) and 340 patients who were treated with a ChI were randomized to one of the three lecozotan doses or placebo in the 24-week combination therapy study (203 study). Both studies were stratified by MMSE. ADAS-Cog and ADCS-CGIC were the primary efficacy endpoints, and Disability Assessment for Dementia (DAD) was a secondary endpoint. Changes in ADAS-Cog and DAD were analyzed using an ANCOVA model and ADCS-CGIC was analyzed with the generalized CMH test. The most common treatment emergent adverse events in both studies were headache, dizziness, infection, accident injury and nausea. On the ADAS-cog scale in mITT population in study 201, subjects treated with lecozotan SR 10 mg and donepezil showed slight improvement from baseline to week 12. In these 2 groups, the adjusted mean differences from placebo at week 12 were statistically significant without multiplicity adjustment. In study 203, although there was improvement at week 24 in all lecozotan groups over the placebo group for the ADAS-Cog, none of the differences were statistically significant. On ADCS-CGIC, lecozotan groups did not show statistically significant difference from placebo in either study. On DAD, all three lecozotan doses and donepezil in 201 and lecozotan 10mg in 203 showed improvement over their corresponding placebo group, but none were statistically significant. Lecozotan SR was generally safe and well tolerated at the dosage levels tested in the populations studied when used alone or adjunctively with a ChI. The 10mg lecozotan dose showed clinical benefits in ADAS-Cog and DAD in both studies, but not for ADCS-CGIC in either study.
Source: Alzheimer s & Dementia
Institutions: Pfizer (United States), The Memory Clinic, Pfizer (France)
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2122016350