- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02471196
Efficacy of ORM-12741 on Agitation/Aggression Symptoms in Alzheimer's Disease (Nebula)
February 14, 2018 updated by: Orion Corporation, Orion Pharma
Efficacy of ORM-12741 on Agitation/Aggression Symptoms in Patients With Alzheimer's Disease: A Randomised, Double-blind, Placebo-controlled, Parallel Group, Multicentre Study of 12 Weeks
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
ORM-12741 is a potent and selective alpha-2C adrenoceptor (AR)-antagonist.
Previous results suggest that the compound may have positive effects on both cognitive and neuropsychiatric symptoms of Alzheimer's Disease.
In this study, the effect of ORM-12741 will be evaluated on agitation/aggression symptoms and other neuropsychiatric symptoms.
Furthermore, cognition and psychotic and depressive symptoms will be evaluated.
Study Type
Interventional
Enrollment (Actual)
308
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
-
Turku, Finland
- Clinical Research Services Turku - CRST Oy
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
53 years to 88 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
- Suicidal ideation in the 6 months before screening or current suicide risk based on the Colombia-Suicide Severity Rating Scale (C-SSRS) (items 4 and 5 exclusionary) or current risk of suicide based on the investigator's judgement.
- 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.
- QTc-Fridericia (QTcF) repeatedly > 450 ms in males or > 470 ms in females.
- Clinically significantly abnormal thyroid-stimulating hormone (TSH), vitamin B12 or folate serum levels at screening.
- Resides in a skilled nursing facility.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: ORM-12741 low dose
ORM-12741 low dose twice a day for 12 weeks.
|
ORM-12741 low dose twice a day
ORM-12741 high dose twice a day
|
Experimental: ORM-12741 high dose
ORM-12741 high dose twice a day for 12 weeks.
|
ORM-12741 low dose twice a day
ORM-12741 high dose twice a day
|
Placebo Comparator: Placebo
Placebo twice a day for 12 weeks.
|
Placebo twice a day
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Efficacy on aggression/agitation symptoms measured by Neuropsychiatric Inventory Clinician Rating scale
Time Frame: 12 weeks
|
12 weeks
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Efficacy on aggression/agitation symptoms and overall clinical status measured by Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change
Time Frame: 12 weeks
|
12 weeks
|
Efficacy on cognitive symptoms measured by Cognitive Drug Research computerized test battery
Time Frame: 12 weeks
|
12 weeks
|
Efficacy on daily living measured by Alzheimer's Disease Co-operative Study - Activities of Daily Living inventory
Time Frame: 12 weeks
|
12 weeks
|
Safety measured by assessing adverse events
Time Frame: 12 weeks
|
12 weeks
|
Plasma concentrations of ORM ORM-12741, metabolites and possible other Alzheimer's disease medication
Time Frame: 12 weeks
|
12 weeks
|
Efficacy on aggression/agitation symptoms measured by Cohen Mansfield Agitation Inventory
Time Frame: 12 weeks
|
12 weeks
|
Efficacy on cognitive symptoms measured by Alzheimer's Disease Assessment Scale
Time Frame: 12 weeks
|
12 weeks
|
Safety measured by vital signs
Time Frame: 12 weeks
|
12 weeks
|
Safety measured by electrocardiogram
Time Frame: 12 weeks
|
12 weeks
|
Safety measured by laboratory variables
Time Frame: 12 weeks
|
12 weeks
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: Juha Rinne, Prof, Clinical Research Services Turku - CRST Oy
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
August 14, 2015
Primary Completion (Actual)
October 9, 2017
Study Completion (Actual)
December 4, 2017
Study Registration Dates
First Submitted
June 8, 2015
First Submitted That Met QC Criteria
June 12, 2015
First Posted (Estimate)
June 15, 2015
Study Record Updates
Last Update Posted (Actual)
February 15, 2018
Last Update Submitted That Met QC Criteria
February 14, 2018
Last Verified
February 1, 2018
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 3098012
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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