An Extension To The B1451006 Protocol To Evaluate The Safety and Efficacy of Dimebon In Subjects With Moderate-to-Severe Alzheimer's Disease

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the long-term safety and tolerability of dimebon in subjects with moderate-to-severe Alzheimer's Disease.

Detailed Description
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This study was terminated on May 7, 2010 due to modification of the dimebon development plan, following the lack of demonstration of efficacy in the completed DIM14 (CONNECTION) Study. The study was not terminated due to any safety findings. Dimebon has been well-tolerated in clinical trials. Demonstration of efficacy for dimebon in Alzheimer's disease is pending completion of the ongoing DIM18 (CONCERT) Study.

Official Title
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An Open-Label Extension To The B1451006 Protocol To Evaluate The Safety And Efficacy Of Dimebon (Latrepirdine, PF-01913539) In Subjects With Moderate-To-Severe Alzheimer's Disease

Conditions
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Alzheimer's Disease

Intervention / Treatment
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* Drug: Dimebon tablet for oral administration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Successful completion of 6 months treatment in the previous B1451006 Phase 3 dimebon study Exclusion Criteria: Any major medical illness or unstable medical condition that may increase the risk associated with study participation or investigational product administration or may interfere with the ability to interpret study safety data

Ages Eligible for Study
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Minimum Age: 50 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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dimebon<br> | Drug: Dimebon tablet for oral administration<br>* 10 mg TID for Week 1, followed by 20 mg TID for remainder of study<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 (AEs) | An adverse event is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. | Baseline up to 4 weeks after last dose of study treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Severe Impairment Battery (SIB) at Week 6, 12 and 26 | SIB developed for evaluation of cognitive function in participants, who demented to a degree that they cannot complete conventional neuropsychological testing. Test items consisted of simple, one-step commands presented with gestural cues and instructions that were repeated if necessary. SIB test consisted of 51-item scale, divided into 9 subscales: social interaction (0-6), memory (0-14), orientation (0-6), language (0-46), attention (0-6), praxis (0-8), visuospatial ability (0-8), construction(0-4), orienting to name(0-2). Total possible score:0-100; lower score=greater cognitive impairment. | Baseline, Week 6, 12, 26 | 
| Change From Baseline in Alzheimer's Disease Cooperative Study-Activities of Daily Living-Severe Version (ADCS-ADLsev) at Week 6, 12 and 26 | ADCS-ADLsev: 19-item scale measures basic and instrumental abilities in participant population and had good metric properties and reliability in detecting change. Individual score range: 0 to 5 for telephone, 0 to 4 for dressing, watch television, get around outside home, 0 to 3 for eating, walking, toilet, bathing, grooming, conversation/small talk, clear dishes, find personal belongings, obtain beverages, dispose of garbage, left on own, 0 to 1 for run water from and turn off faucet to wash hands, turn on and off light. Total score range: 0 to 54 lower scores=greater functional impairment. | Baseline, Week 6, 12, 26 | 
| Change From Baseline in Mini-Mental State Examination (MMSE) at Week 12 and 26 | MMSE measured general cognitive functioning: orientation, memory, attention, concentration, naming, repetition, comprehension, and ability to create a sentence and to copy two intersecting polygons. Total score derived from sub-scores; ranged from 0 to 30, higher score indicates better cognitive state. | Baseline, Week 12, 26 | 
| Change From Baseline in Neuropsychiatric Inventory (NPI) at Week 6, 12 and 26 | NPI:12-domain caregiver assessment of behavioral disturbances occurring in dementia: delusions, hallucinations, agitation/aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/indifference, disinhibition, irritability/lability, motor disturbance, appetite/eating, nighttime behavior. Severity(1=Mild to 3=Severe),frequency(1=occasionally to 4=very frequently) scales recorded for each domain; frequency*severity=each domain score(range 0-12). Total score=sum of each domain score(range 0-144);higher score=greater behavioral disturbances;negative change score from baseline=improvement. | Baseline, Week 6, 12, 26 | 
| Sum of Delusions and Hallucinations Sub-domain Scores of Neuropsychiatric Inventory (NPI) at Week 26 | NPI is a 12-domain caregiver assessment of behavioral disturbances occurring in dementia. Severity (1=Mild to 3=Severe) and frequency (1=occasionally to 4=very frequently) scales were recorded separately for each domain and their product gives individual domain score (range 0-12). Sum of delusions and hallucinations sub-domain scores of NPI was calculated as a measure of Alzheimer's Disease (AD) related psychosis. Total possible score range: 0-24 with higher score indicating greater behavioral disturbances. | Week 26 | 
| Change From Baseline in Resource Utilization in Dementia - Lite Version (RUD-Lite) at Week 12 and 26 | RUD Lite: instrument used to assess amount of both formal and informal resources used by demented participants and primary caregiver. It was completed by caregivers and compiles data on following resources: use of social services, frequency and duration of hospitalizations, all contacts with health care professionals, participant living accommodations, amount of time the caregiver spends giving care and the impact of care giving on the caregiver's job. Overall cost of care was evaluated to quantify the resources utilized. | Baseline, Week 12, 26 | 
| Change From Baseline in European Quality of Life 5 Domain Scale (EQ-5D) at Week 12 and 16 | EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state (confined to bed). Total possible score is sum of individual items, ranged from 5 to 15; lower score indicated a better health state. | Baseline, Week 12, 26 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Delirium, Dementia, Amnestic, Cognitive Disorders, Mental Disorders, Nervous System Diseases, Central Nervous System Diseases