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 5.030; not adjusted for multiple comparisons), favoring
ORM-12741 over placebo. NPI caregiver distress scores also favored ORM-12741 (P 5.034). ORM12741
was well tolerated.
Discussion: This is the first clinical trial providing evidence on an acceptable safety profile for ORM12741
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.