Efficacy of ORM-12741 on Agitation/Aggression Symptoms in Alzheimer's Disease

NCT02471196 | Completed Phase 2 DMC

• 1 other identifier: 3098012
• Study Type: interventional
• Target: 308
• Locations: 1 country
• Sites: 1

Brief Summary

This study evaluates the effect of ORM-12741 on agitation/aggression symptoms in Alzheimer's disease. Two thirds of the patients will receive ORM-12741 and one third will receive placebo.

Conditions

Alzheimer's Disease

Outcome Measures

Primary Outcomes (1)

• Efficacy on aggression/agitation symptoms measured by Neuropsychiatric Inventory Clinician Rating scale

  12 weeks

Secondary Outcomes (10)

• Efficacy on aggression/agitation symptoms and overall clinical status measured by Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change

  12 weeks

• Efficacy on cognitive symptoms measured by Cognitive Drug Research computerized test battery

  12 weeks

• Efficacy on daily living measured by Alzheimer's Disease Co-operative Study - Activities of Daily Living inventory

  12 weeks

• Safety measured by assessing adverse events

  12 weeks

• Plasma concentrations of ORM ORM-12741, metabolites and possible other Alzheimer's disease medication

  12 weeks

Study Arms (3)

ORM-12741 low dose

EXPERIMENTAL

ORM-12741 low dose twice a day for 12 weeks.

Drug: ORM-12741

ORM-12741 high dose

EXPERIMENTAL

ORM-12741 high dose twice a day for 12 weeks.

Drug: ORM-12741

Placebo

PLACEBO COMPARATOR

Placebo twice a day for 12 weeks.

Drug: Placebo

Interventions

ORM-12741 DRUG

ORM-12741 low dose twice a day

ORM-12741 low dose

Placebo DRUG

Placebo twice a day

Placebo

Eligibility Criteria

• Age: 55 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent (IC) for participation in the study (co-signed by the subject's next of kin or caregiver, or other legally acceptable representative.
• Written IC obtained from a consistently available caregiver informant who is knowledgeable of the subject's condition and its progression and is willing to accompany the subject to all visits and supervise the administration of the study medication.
• Age of 55-90 years (inclusive).
• Male or female subjects with diagnosis of probable Alzheimer's Disease.
• Brain imaging (computed tomography \[CT\] or magnetic resonance imaging \[MRI\]) consistent with a diagnosis of Alzheimer's Disease (within 18 months or at screening).
• Mini-mental state examination (MMSE) score between 10-24 (inclusive).
• Clinically significant agitation meeting the International Psychogeriatric Association Provisional Criteria for Agitation in Cognitive Impairment. The agitation symptoms need to have been present for at least 4 weeks before the screening visit.
• Neuropsychiatric Inventory agitation/aggression item score at least 4 at screening visit.

You may not qualify if:

• Modified Hachinski Ischemia Score (MHIS) \> 4.
• Changes in AChE inhibitor (donepezil, rivastigmine or galantamine) dosing within 2 months prior to screening.
• Changes in memantine dosing within 2 months prior to the screening.
• Changes in antidepressant dosing or addition of another antidepressant medication within 2 months prior to the screening.
• Use of antipsychotics at any dose within 1 month prior to screening.
• Use of benzodiazepines, other than short-acting sleep medications, for night at a maximum of 3 nights/week, within 2 months prior to screening.
• Use of any anticholinergic medication within 2 months prior to screening.
• Current use (within the 30 days prior to screening) of medications with known relevant alpha-2C AR affinity (e.g. mirtazapine, mianserin, clonidine, guanfacine or tizanidine) or with high noradrenaline transporter affinity (reboxetine, venlafaxine or duloxetine).
• Current use of other psychotropic agents, unless the dosing has been stable during the last 2 months prior to the screening.
• Myocardial infarction or other clinically significant ischemic cardiac disease, heart failure, or arrhythmia tendency within the past 2 years.
• Current or history of malignancy within 5 years before screening.
• Specific findings in MRI or CT that could in the opinion of the investigator affect cognitive function (such as cortical infarct or silent lacuna in a region known to affect cognition).
• Supine heart rate \< 48 bpm or \> 100 bpm.
• Systolic blood pressure (SBP) \> 160 mmHg or diastolic blood pressure (DBP) \> 100 mmHg after a 5-minute rest.
• Symptomatic orthostatic hypotension.

Sponsors & Collaborators

• Orion Corporation, Orion Pharma: lead
• Janssen Pharmaceuticals: collaborator

Study Sites (1)

Clinical Research Services Turku - CRST Oy

Turku, Finland

Location

MeSH Terms

Conditions

Alzheimer Disease

Interventions

ORM-12741

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Officials

• Juha Rinne, Prof

  Clinical Research Services Turku - CRST Oy

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 8, 2015
• First Posted: June 15, 2015
• Study Start: August 14, 2015
• Primary Completion: October 9, 2017
• Study Completion: December 4, 2017
• Last Updated: February 15, 2018

Record last verified: 2018-02

Locations

FI (1)