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

Alzheimer's and Dementia: Translational Research and Clinical Interventions - Tập 3 - Trang 1-9 - 2017
Juha O. Rinne1,2, Keith Wesnes3,4,5, Jeffrey L. Cummings6, Pasi Hakulinen7, Merja Hallikainen8, Jutta Hänninen7, Michael Murphy9, Henry Riordan9, Mika Scheinin2,10, Hilkka Soininen8, Juha Rouru7
1Turku PET Centre, Turku, Finland
2Turku University Hospital, Turku, Finland
3Bracket Global, Goring-on-Thames, UK
4Department of Psychology, Northumbria University, Newcastle, UK
5Centre for Human Psychopharmacology, Swinburne University, Melbourne, Australia
6Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, USA.
7Orion Corporation Orion Pharma, R&D, Turku, Finland
8University of Eastern Finland, Kuopio, Finland
9Worldwide Clinical Trials, King of Prussia, PA, USA
10University of Turku, Turku, Finland

Tóm tắt

AbstractIntroductionORM‐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).MethodsA 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).ResultsA 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.DiscussionThis 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.

Tài liệu tham khảo

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Alzheimer's and Dementia: Translational Research and Clinical Interventions

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