Open AccessTolerability of ORM‐12741 and effects on episodic memory in patients with Alzheimer's disease
Author(s) -
Rinne Juha O.,
Wesnes Keith,
Cummings Jeffrey L.,
Hakulinen Pasi,
Hallikainen Merja,
Hänninen Jutta,
Murphy Michael,
Riordan Henry,
Scheinin Mika,
Soininen Hilkka,
Rouru Juha
Publication year - 2017
Publication title -
alzheimer's and dementia: translational research and clinical interventions
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.49
H-Index - 30
ISSN - 2352-8737
DOI - 10.1016/j.trci.2016.11.004
Subject(s) - tolerability , placebo , episodic memory , randomized controlled trial , medicine , clinical trial , population , clinical endpoint , psychology , cognition , adverse effect , psychiatry , alternative medicine , environmental health , pathology
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.