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

Juha Rinne; Keith Wesnes; Jeffrey Cummings; Pasi Hakulinen; Merja Hallikainen; Jutta Hänninen; Michael Murphy; Henry Riordan; Mika Scheinin; Hilkka Soininen; Juha Rouru

doi:10.1016/j.trci.2016.11.004

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

Juha Rinne, Keith Wesnes, Jeffrey Cummings, Pasi Hakulinen, Merja Hallikainen, Jutta Hänninen, Michael Murphy, Henry Riordan, Mika Scheinin, Hilkka Soininen, Juha Rouru

Northumbria University

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Abstract

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.

Original language	English
Pages (from-to)	1-9
Journal	Alzheimer's & Dementia: Translational Research & Clinical Interventions
Volume	3
Issue number	1
Early online date	8 Dec 2016
DOIs	https://doi.org/10.1016/j.trci.2016.11.004
Publication status	Published - 1 Jan 2017

Keywords

Alzheimer’s disease
cognition
memory
Alpha-2C adrenoceptor antagonist
ORM-12741
randomized trials
behavioral and psychological symptoms of dementia
neuropsychiatric symptoms

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10.1016/j.trci.2016.11.004Licence: CC BY-NC-ND

1-s2Final published version, 1.31 MBLicence: CC BY-NC-ND

http://nrl.northumbria.ac.uk/29896/

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Rinne, J., Wesnes, K., Cummings, J., Hakulinen, P., Hallikainen, M., Hänninen, J., Murphy, M., Riordan, H., Scheinin, M., Soininen, H., & Rouru, J. (2017). Tolerability of ORM-12741 and effects on episodic memory in patients with Alzheimer's disease. Alzheimer's & Dementia: Translational Research & Clinical Interventions, 3(1), 1-9. https://doi.org/10.1016/j.trci.2016.11.004

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title = "Tolerability of ORM-12741 and effects on episodic memory in patients with Alzheimer's disease",

abstract = "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.",

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author = "Juha Rinne and Keith Wesnes and Jeffrey Cummings and Pasi Hakulinen and Merja Hallikainen and Jutta H{\"a}nninen and Michael Murphy and Henry Riordan and Mika Scheinin and Hilkka Soininen and Juha Rouru",

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Rinne, J, Wesnes, K, Cummings, J, Hakulinen, P, Hallikainen, M, Hänninen, J, Murphy, M, Riordan, H, Scheinin, M, Soininen, H & Rouru, J 2017, 'Tolerability of ORM-12741 and effects on episodic memory in patients with Alzheimer's disease', Alzheimer's & Dementia: Translational Research & Clinical Interventions, vol. 3, no. 1, pp. 1-9. https://doi.org/10.1016/j.trci.2016.11.004

TY - JOUR

T1 - Tolerability of ORM-12741 and effects on episodic memory in patients with Alzheimer's disease

AU - Rinne, Juha

AU - Wesnes, Keith

AU - Cummings, Jeffrey

AU - Hakulinen, Pasi

AU - Hallikainen, Merja

AU - Hänninen, Jutta

AU - Murphy, Michael

AU - Riordan, Henry

AU - Scheinin, Mika

AU - Soininen, Hilkka

AU - Rouru, Juha

PY - 2017/1/1

Y1 - 2017/1/1

N2 - 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.

AB - 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.

KW - Alzheimer’s disease

KW - cognition

KW - memory

KW - Alpha-2C adrenoceptor antagonist

KW - ORM-12741

KW - randomized trials

KW - behavioral and psychological symptoms of dementia

KW - neuropsychiatric symptoms

U2 - 10.1016/j.trci.2016.11.004

DO - 10.1016/j.trci.2016.11.004

M3 - Article

SN - 2352-8737

VL - 3

SP - 1

EP - 9

JO - Alzheimer's & Dementia: Translational Research & Clinical Interventions

JF - Alzheimer's & Dementia: Translational Research & Clinical Interventions

IS - 1

ER -

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

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Keywords

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