Tolerability of ORM-12741 and effects on episodic memory in patients with Alzheimer's disease.

INTRODUCTION: ORM-12741 is a novel selective antagonist of alpha-2C adrenoceptors. This trial evaluated the safety and efficacy of ORM-12741 in patients with Alzheimer's disease (AD).

METHODS: A randomized, double-blind, placebo-controlled, exploratory phase 2a trial was conducted in 100 subjects with AD and neuropsychiatric symptoms. Participants were randomized to receive one of two flexible doses of ORM-12741 (30-60 mg or 100-200 mg) or placebo b.i.d. for 12 weeks in addition to standard therapy with cholinesterase inhibitors. Efficacy was assessed primarily with the Cognitive Drug Research (CDR) computerized assessment system and secondarily with the Neuropsychiatric Inventory (NPI).

RESULTS: A statistically significant treatment effect was seen in one of the four primary CDR system end points, Quality of Episodic Memory ( P  = .030; not adjusted for multiple comparisons), favoring ORM-12741 over placebo. NPI caregiver distress scores also favored ORM-12741 ( P  = .034). ORM-12741 was well tolerated.

DISCUSSION: This is the first clinical trial providing evidence on an acceptable safety profile for ORM-12741 in patients with AD and neuropsychiatric symptoms. In addition, the trial provided hints of potential therapeutic benefit, primarily on episodic memory, in this patient population.