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[P2–027]: LONG‐TERM OUTCOMES OF A MULTI‐DOMAIN COGNITIVE INTERVENTION AMONG ASIAN PATIENTS WITH MILD DEMENTIA
Author(s) -
Yong Ting Ting,
Yuen Oi Choong TanyaMarie,
Silva Eveline,
Deocariza Guevarra Anne Cristine,
Lim Levinia,
Kandiah Nagaendran
Publication year - 2017
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.2017.06.675
Subject(s) - rehabilitation , dementia , cognition , physical therapy , intervention (counseling) , mini–mental state examination , medicine , affect (linguistics) , cognitive rehabilitation therapy , psychology , cognitive decline , neurology , physical medicine and rehabilitation , clinical psychology , cognitive impairment , psychiatry , disease , communication , pathology
Background: Azeliragon, an oral antagonist of the Receptor for Advanced Glycation Endproducts (RAGE), is being evaluated in a pivotal Phase 3 study for efficacy and safety in patients with mild Alzheimer’s disease. Azeliragon exerts a multimodal mechanism of action including effects on Ab, tau phosphorylation, and inflammation through an initial step of blocking proteins (i.e. Ab, S100b) from binding to RAGE. The present study evaluated the effect of an FDA high fat meal on the pharmacokinetics (PK) of the 5 mg azeliragon Phase 3 capsule formulation. Methods:This was an open-label, randomized, parallel, single-dose study to assess the effect of a high-fat meal on the pharmacokinetics of azeliragon. Subjects were randomized to receive a single dose of azeliragon 5 mg administered either following a 10-h overnight fast or within 30 minutes of the start of ingestion of a high fat meal (150 protein calories, 250 carbohydrate calories and 500-600 fat calories). Serial PK samples were collected for 312 hours following dosing. Safety assessments were performed throughout the 14-day study period. Results:Twenty-eight (14 fasted and 14 fed) subjects (27 males, 1 female), 24 to 55 years old, were randomized, and all completed the study. Fed and fasted groups were similar for age, race, ethnicity, height, weight and BMI. Administration with food resulted in an approximately 16-20% reduction in geometric mean estimates of exposure. AUC(0-last) was 113 ng*h/mL fasted and 90 ng/*h/mL fed (ratio: 0.80, 90% CI: 0.57, 1.12). AUC(0-72h) was 38.3 ng*h/mL fasted and 32.0 ng*h/mL fed (ratio: 0.84, 90% CI: 0.70, 1.00). Cmax was 0.70 ng/mL fasted and 0.58 ng/mL fed (ratio: 0.83, 90% CI: 0.69, 1.00). Azeliragon was well tolerated with only 3 mild treatment-emergent adverse events reported (2 in fasted, 1 in fed) none of which resulted in withdrawal from study. Conclusions: There was an approximately 16-20% reduction in exposure (AUC(0-last), AUC(0-72h), Cmax) following administration of azeliragon 5 mg following a high fat meal. At the Phase 3 dose of 5 mg/day the magnitude of reduction is not anticipated to be clinically meaningful. Consequently, azeliragon may be given without regard to meals.