Safety and Efficacy of ORM-12741 in Patients With Alzheimer's Disease

Study Overview
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Brief Summary
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The purpose of this study is to determine whether ORM-12741 is safe and effective in the treatment of Alzheimer's disease.

Detailed Description
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The purpose of this study is to determine whether ORM-12741 is safe and effective in the treatment of cognitive and behavioral symptoms in patients with Alzheimer's disease.

Official Title
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Safety and Efficacy of ORM-12741 on Cognitive and Behavioral Symptoms in Patients With Alzheimer's Disease

Conditions
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Alzheimer's Disease

Intervention / Treatment
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* Drug: ORM-12741
* Drug: ORM-12741
* Drug: Placebo for ORM-12741


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent obtained from the patient and legally acceptable representative, if required Informed consent obtained from the caregiver Males and and females between 55-90 years Diagnosis of probable Alzheimer's disease, history of progressive cognitive deterioration Brain imaging consistent with Alzheimer's disease Mini-mental state examination score 12-21 Treated with donepezil, rivastigmine or galantamine At least mild level of behavioral symptoms Exclusion Criteria: Other types of dementias Modified Hachinski Ischemia Score > 4 Use of memantine, antipsychotics, anticholinergic medication and benzodiazepines (at a max of 3 nights/week) within 2 months Changes in antidepressant dosing within 2 months Use of other psychotropic agents Myocardial infarction within the past 2 years Malignancy within the past 5 years Suicidal ideation, risk of suicide History of alcoholism or drug abuse within 5 years Clinically significant cardiovascular, pulmonary, gastrointestinal, hepatic, renal, neurological or psychiatric disorder or any other major concurrent illness Specific findings in brain imaging Abnormal findings in heart rate, blood pressure, ECG, laboratory tests, physical examination; orthostatic hypotension Blood donation or participation in a drug study within 60 days Previous AD immunotherapy treatment Patient cannot complete the computerised cognitive training Patients who reside in a skilled nursing facility Patients who are not able to swallow capsules

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low dose of ORM-12741<br> | Drug: ORM-12741<br>* 60mg twice a day<br>|
| Experimental: High dose of ORM-12741<br> | Drug: ORM-12741<br>* 200mg twice a day<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo for ORM-12741<br>* Placebo twice a day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events | Adverse events from start of ORM-12741 treatment until end of study visit. | 3 months | 
| Quality of Episodic Memory | The Cognitive Drug Research (CDR) computerised battery tests is designed to evaluate the effects of novel compounds on the quality of cognitive functioning. Quality of Episodic Memory measures the capability of maintaining information in episodic memory and is assessed as the sum of sensitivity indices from 4 memory tasks on the CDR computerised battery tests. Values are calculated by a computer and higher scores mean better outcome. | 3 months | 
| Quality of Working Memory | The Cognitive Drug Research (CDR) computerised battery tests is designed to evaluate the effects of novel compounds on the quality of cognitive functioning. Quality of Working Memory measures the capability of maintaining information in working memory and is assessed as the sum of sensitivity indices from 2 memory tasks on the CDR computerised battery tests. Values are calculated by a computer and higher scores mean better outcome. | 3 months | 
| Quality of Memory | The Cognitive Drug Research (CDR) computerised battery tests is designed to evaluate the effects of novel compounds on the quality of cognitive functioning. Quality of Memory is a combination of outcome measures Quality of Working Memory & Quality of Episodic Memory. Values are calculated by a computer and higher scores mean better outcome. | 3 months | 
| Speed of Memory | The Cognitive Drug Research (CDR) computerised battery tests is designed to evaluate the effects of novel compounds on the quality of cognitive functioning. Speed of Memory is assessed as the sum of speed measures from 2 memory tasks and 2 recognition tasks on the CDR computerised battery tests. Values are calculated by a computer and higher scores mean better outcome. | 3 months | 
| Power of Attention | The Cognitive Drug Research (CDR) computerised battery tests is designed to evaluate the effects of novel compounds on the quality of cognitive functioning. Power of attention measures speed and attention and is assessed from 3 attentional tasks on the CDR computerised battery tests. Values are calculated by a computer and higher scores mean better outcome. | 3 months | 
| Continuity of Attention | The Cognitive Drug Research (CDR) computerised battery tests is designed to evaluate the effects of novel compounds on the quality of cognitive functioning. Continuity of attention measures speed and accuracy and is calculated from 3 attentional tasks on the CDR computerised battery tests. Values are calculated by a computer and higher scores mean better outcome. | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| NPI Total Score | The total score of Neuropsychiatric Inventory (NPI) was assessed by a caregiver interview. 10 behavioral areas were included: Delusions, Hallucinations, Agitation/Aggression, Depression/Dysphoria, Anxiety, Elation/Euphoria, Apathy/Indifference, Disinhibition, Irritability/Lability, and Aberrant Motor Behaviour. Higher scores mean worse outcome. Minimum value 0, maximum value 120. | 3 months | 
| Caregiver Distress Score | Caregiver distress score generated by adding together the scores of individual NPI distress questions of Neuropsychiatric Inventory NPI. Higher scores mean worse outcome. Minimum value 0, maximum value 120. | 3 months | 
| Pharmacokinetics of ORM-12741 | ORM-12741 plasma trough concentrations at week 12. | 3 months |