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

Phase 2

Completed

Conditions: Alzheimer's Disease

Interventions: Drug: Placebo for ORM-12741
Drug: ORM-12741

Registration Number: NCT01324518

Lead Sponsor: Orion Corporation, Orion Pharma

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

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 100

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo for ORM-12741	-
Low dose of ORM-12741	ORM-12741	-
High dose of ORM-12741	ORM-12741	-

Primary Outcome Measures

Name	Time	Method
Number of Participants With Adverse Events	3 months	Adverse events from start of ORM-12741 treatment until end of study visit.
Quality of Working Memory	3 months	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.
Quality of Memory	3 months	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.
Power of Attention	3 months	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.
Quality of Episodic Memory	3 months	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.
Continuity of Attention	3 months	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.
Speed of Memory	3 months	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.

Secondary Outcome Measures

Name	Time	Method
NPI Total Score	3 months	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.
Pharmacokinetics of ORM-12741	3 months	ORM-12741 plasma trough concentrations at week 12.
Caregiver Distress Score	3 months	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.