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P4‐214: Single‐ and multiple‐dose safety, tolerability and pharmacokinetics of a Novel 5HT6 receptor full antagonist (SAM‐760) for the treatment of the symptoms of Alzheimer's disease in healthy young adults and elderly subjects
Author(s) -
Bell Joanne,
BairdBellaire Susan,
Leil Tarek,
Comery Thomas,
Plotka Anna,
Antinew Jeremias,
Vandal Grace,
Chalon Stephane,
Kupiec James
Publication year - 2011
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2011.05.2237
Subject(s) - tolerability , pharmacokinetics , adverse effect , cmax , medicine , placebo , dosing , pharmacology , antagonist , receptor , pathology , alternative medicine
plus Caregiver Input (CIBIC+), and the change from baseline in Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-cog) score at Week 24 (intention-to-treat [ITT], mixed model repeated measures [MMRM] analyses). Secondary endpoints included the Repeatable Battery for Assessment of Neuropsychological Status (RBANS), Mini-Mental State Examination (MMSE), Alzheimer’s Disease Cooperative Study Group-Activities of Daily Living Inventory (ADCS-ADL) and Cornell Scale for Depression in Dementia (CSDD). Safety and tolerability were also assessed. Results: Study completion rates were: SB-742457 15 mg/ day, 88%; 35 mg/day, 89%; donepezil, 86%; placebo, 81%. No statistically significant differences from placebo were observed for either dose of SB742457 with CIBIC+ or ADAS-Cog (Table 1). A statistically significant difference from placebo was observed for donepezil at Week 24 for CIBIC+ but not ADAS-Cog (Table 1). No statistically significant differences from placebo were observed for any treatment for ADCS-ADL or CSDD (Table 2). Statistically significant differences from placebo were observed for MMSE at Week 24 for donepezil but not for either dose of SB-742457 (Table 2). The incidence of AEs was similar in the SB-742457 (29% for 15mg and 35mg) and placebo groups (31%) and higher in the donepezil group (43%). Overall, the most common AEs were headache, nasopharyngitis, dizziness and influenza across treatment groups. Conclusions: The study failed to detect any efficacy for SB-742457 as monotherapy. Marginal efficacy was observed for donepezil on global function and MMSE but not on ADAS-Cog, activities of daily living or mood, indicating limited assay sensitivity of the study. Both treatments were generally safe and well tolerated. The limited assay sensitivity of this study warrants consideration in the design of future short-term monotherapy studies.