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A Phase 3 Efficacy Study Of Dimebon In Patients With Moderate To Severe Alzheimer's Disease

Primary Purpose

Alzheimer Disease

Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Dimebon 20 mg po TID
Placebo po TID
Sponsored by
Pfizer
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Alzheimer Disease focused on measuring Alzheimer disease moderate-to-severe memantine safety and efficacy

Eligibility Criteria

50 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Are men and women ≥ 50 years of age with a diagnosis of Alzheimers disease.
  • Have a Mini-Mental State Exam between 5 and 14 inclusive.
  • Have been taking the medication memantine (ie., Namenda) for at least six months prior to this study.
  • Must have a caregiver who assists the patient at least five days per week for at least three hours per day, who can accompany patient to study visits, and who has an intimate knowledge of the patient's health states and personal care.

Exclusion Criteria:

  • Have taken medicines for Alzheimers disease other than memantine (e.g., donepezil, rivastigmine, galantamine, tacrine) within 2 months prior to this study.
  • Dementia other than Alzheimers disease.
  • Any medical condition or reason that interferes with the ability of the patient to participate in or complete the trial or places the patient at undue risk, as judged by the study doctor.

Sites / Locations

  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site
  • Pfizer Investigational Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Dimebon

Placebo

Arm Description

Outcomes

Primary Outcome Measures

Change From Baseline in the Severe Impairment Battery (SIB) Score at Week 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.
Change From Baseline in the Alzheimer's Disease Cooperative Study - Activities of Daily Living (Severe) (ADCS-ADLsev) Score at Week 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.

Secondary Outcome Measures

Change From Baseline in the Neuropsychiatric Inventory (NPI) Total Score at Week 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.
Sum of the Delusions and Hallucinations Sub-domain Scores of the NPI
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.
Change From Baseline in the Mini-Mental State Examination (MMSE) Score at Week 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; total ranged from 0 to 30, higher score indicates better cognitive state.
Clinician's Interview-Based Impression of Change Plus Caregiver Input (CIBIC-plus) Scores
Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) version of CIBIC-Plus was used to assess participant's overall disease severity. The corresponding baseline assessment rated participant on 7-point scale: (1) extremely severe AD to (7) no symptoms of AD. Overall impression of change from baseline was rated on a 7-point scale: 1=marked improvement; 2=moderate improvement; 3=minimal improvement; 4=no change; 5=minimal worsening; 6=moderate worsening; 7=marked worsening; all assessments are relative to baseline. Higher score = worsening of global function.
Resource Utilization in Dementia-Lite Version (RUD-Lite)
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 resources utilized.
Euro Quality of Life - 5 Domain (EQ-5D) Assessment
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. Total possible score ranged from 5 to 15; lower score indicated a better health state.
Population Pharmacokinetic (PK) Analysis
Data for this Outcome Measure are not reported here because the analysis population includes participants who were not enrolled in this study. ClinicalTrials.gov is designed for reporting results from only those participants who were enrolled in the study and described in the Participant Flow and Baseline Characteristics modules.
Number of Participants With Adverse Events (AEs)
Any untoward medical occurrence (including clinially important changes in clinical safety laboratory assessments, electrocardiograms and vital signs) in a participant who received study treatment was considered an AE without regard to possibility of causal relationship.

Full Information

First Posted
June 1, 2009
Last Updated
August 30, 2012
Sponsor
Pfizer
Collaborators
Medivation, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT00912288
Brief Title
A Phase 3 Efficacy Study Of Dimebon In Patients With Moderate To Severe Alzheimer's Disease
Official Title
A Phase 3, Multi-Center, Randomized, Double-Blind, Placebo-Controlled 26-Week Trial To Evaluate The Efficacy And Safety Of Dimebon In Patients With Moderate-To-Severe Alzheimer's Disease
Study Type
Interventional

2. Study Status

Record Verification Date
August 2012
Overall Recruitment Status
Terminated
Why Stopped
See termination reason in detailed description.
Study Start Date
September 2009 (undefined)
Primary Completion Date
August 2010 (Actual)
Study Completion Date
August 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer
Collaborators
Medivation, Inc.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
No Dimebon clinical data exist yet in patients with disease that has advanced to the moderate-to-severe stage. Therefore, this study evaluates the safety and efficacy of Dimebon in patients with moderate-to-severe AD who are receiving existing background therapy with memantine.
Detailed Description
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer Disease
Keywords
Alzheimer disease moderate-to-severe memantine safety and efficacy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
86 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Dimebon
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Dimebon 20 mg po TID
Other Intervention Name(s)
PF-01913539, Latrepirdine Dihydrochloride
Intervention Description
Dimebon 10 mg po TID for 1 week followed by Dimebon 20 mg TID for 25 weeks
Intervention Type
Drug
Intervention Name(s)
Placebo po TID
Intervention Description
Placebo (matched to Dimebon) po for 26 weeks
Primary Outcome Measure Information:
Title
Change From Baseline in the Severe Impairment Battery (SIB) Score at Week 26
Description
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.
Time Frame
Baseline, Week 26
Title
Change From Baseline in the Alzheimer's Disease Cooperative Study - Activities of Daily Living (Severe) (ADCS-ADLsev) Score at Week 26
Description
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.
Time Frame
Baseline, Week 26
Secondary Outcome Measure Information:
Title
Change From Baseline in the Neuropsychiatric Inventory (NPI) Total Score at Week 26
Description
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.
Time Frame
Baseline, Week 26
Title
Sum of the Delusions and Hallucinations Sub-domain Scores of the NPI
Description
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.
Time Frame
Week 26
Title
Change From Baseline in the Mini-Mental State Examination (MMSE) Score at Week 26
Description
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; total ranged from 0 to 30, higher score indicates better cognitive state.
Time Frame
Baseline, Week 26
Title
Clinician's Interview-Based Impression of Change Plus Caregiver Input (CIBIC-plus) Scores
Description
Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) version of CIBIC-Plus was used to assess participant's overall disease severity. The corresponding baseline assessment rated participant on 7-point scale: (1) extremely severe AD to (7) no symptoms of AD. Overall impression of change from baseline was rated on a 7-point scale: 1=marked improvement; 2=moderate improvement; 3=minimal improvement; 4=no change; 5=minimal worsening; 6=moderate worsening; 7=marked worsening; all assessments are relative to baseline. Higher score = worsening of global function.
Time Frame
Week 26
Title
Resource Utilization in Dementia-Lite Version (RUD-Lite)
Description
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 resources utilized.
Time Frame
Baseline, Weeks 12, 18, 26
Title
Euro Quality of Life - 5 Domain (EQ-5D) Assessment
Description
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. Total possible score ranged from 5 to 15; lower score indicated a better health state.
Time Frame
Baseline, Weeks 12, 26
Title
Population Pharmacokinetic (PK) Analysis
Description
Data for this Outcome Measure are not reported here because the analysis population includes participants who were not enrolled in this study. ClinicalTrials.gov is designed for reporting results from only those participants who were enrolled in the study and described in the Participant Flow and Baseline Characteristics modules.
Time Frame
Pre-dose, 0.5 to 1.5 hours, 2.5 to 3.5 hours post-dose at Week 12
Title
Number of Participants With Adverse Events (AEs)
Description
Any untoward medical occurrence (including clinially important changes in clinical safety laboratory assessments, electrocardiograms and vital signs) in a participant who received study treatment was considered an AE without regard to possibility of causal relationship.
Time Frame
Baseline up to Week 30 (follow-up)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Are men and women ≥ 50 years of age with a diagnosis of Alzheimers disease. Have a Mini-Mental State Exam between 5 and 14 inclusive. Have been taking the medication memantine (ie., Namenda) for at least six months prior to this study. Must have a caregiver who assists the patient at least five days per week for at least three hours per day, who can accompany patient to study visits, and who has an intimate knowledge of the patient's health states and personal care. Exclusion Criteria: Have taken medicines for Alzheimers disease other than memantine (e.g., donepezil, rivastigmine, galantamine, tacrine) within 2 months prior to this study. Dementia other than Alzheimers disease. Any medical condition or reason that interferes with the ability of the patient to participate in or complete the trial or places the patient at undue risk, as judged by the study doctor.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
Pfizer Investigational Site
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85006
Country
United States
Facility Name
Pfizer Investigational Site
City
Costa Mesa
State/Province
California
ZIP/Postal Code
92626
Country
United States
Facility Name
Pfizer Investigational Site
City
Encino
State/Province
California
ZIP/Postal Code
91316
Country
United States
Facility Name
Pfizer Investigational Site
City
Los Alamitos
State/Province
California
ZIP/Postal Code
90720
Country
United States
Facility Name
Pfizer Investigational Site
City
Newport Beach
State/Province
California
ZIP/Postal Code
92660-2452
Country
United States
Facility Name
Pfizer Investigational Site
City
Newport Beach
State/Province
California
ZIP/Postal Code
92663
Country
United States
Facility Name
Pfizer Investigational Site
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Facility Name
Pfizer Investigational Site
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06510
Country
United States
Facility Name
Pfizer Investigational Site
City
Brooksville
State/Province
Florida
ZIP/Postal Code
34601
Country
United States
Facility Name
Pfizer Investigational Site
City
Delray Beach
State/Province
Florida
ZIP/Postal Code
33445
Country
United States
Facility Name
Pfizer Investigational Site
City
West Palm Beach
State/Province
Florida
ZIP/Postal Code
33407
Country
United States
Facility Name
Pfizer Investigational Site
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46260
Country
United States
Facility Name
Pfizer Investigational Site
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40503
Country
United States
Facility Name
Pfizer Investigational Site
City
Pittsfield
State/Province
Massachusetts
ZIP/Postal Code
01201
Country
United States
Facility Name
Pfizer Investigational Site
City
Princeton
State/Province
New Jersey
ZIP/Postal Code
08540
Country
United States
Facility Name
Pfizer Investigational Site
City
Rochester
State/Province
New York
ZIP/Postal Code
14620
Country
United States
Facility Name
Pfizer Investigational Site
City
Syracuse
State/Province
New York
ZIP/Postal Code
13210
Country
United States
Facility Name
Pfizer Investigational Site
City
Norristown
State/Province
Pennsylvania
ZIP/Postal Code
19401
Country
United States
Facility Name
Pfizer Investigational Site
City
East Providence
State/Province
Rhode Island
ZIP/Postal Code
02914
Country
United States
Facility Name
Pfizer Investigational Site
City
Cordova
State/Province
Tennessee
ZIP/Postal Code
38018
Country
United States
Facility Name
Pfizer Investigational Site
City
Middleton
State/Province
Wisconsin
ZIP/Postal Code
53562
Country
United States
Facility Name
Pfizer Investigational Site
City
Winnipeg
State/Province
Manitoba
ZIP/Postal Code
R3M 0X9
Country
Canada
Facility Name
Pfizer Investigational Site
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H4H-1R3
Country
Canada
Facility Name
Pfizer Investigational Site
City
Quebec
ZIP/Postal Code
G2B 5S1
Country
Canada
Facility Name
Pfizer Investigational Site
City
Berlin
ZIP/Postal Code
13581
Country
Germany
Facility Name
Pfizer Investigational Site
City
Bochum
ZIP/Postal Code
44892
Country
Germany
Facility Name
Pfizer Investigational Site
City
Guenzburg
ZIP/Postal Code
89312
Country
Germany
Facility Name
Pfizer Investigational Site
City
Leipzig
ZIP/Postal Code
04107
Country
Germany
Facility Name
Pfizer Investigational Site
City
Mainz
ZIP/Postal Code
55131
Country
Germany
Facility Name
Pfizer Investigational Site
City
Mittweida
ZIP/Postal Code
09648
Country
Germany
Facility Name
Pfizer Investigational Site
City
Budapest
ZIP/Postal Code
1083
Country
Hungary
Facility Name
Pfizer Investigational Site
City
Gyula
ZIP/Postal Code
5700
Country
Hungary
Facility Name
Pfizer Investigational Site
City
Szekesfehervar
ZIP/Postal Code
8000
Country
Hungary
Facility Name
Pfizer Investigational Site
City
Amadora
ZIP/Postal Code
2700-276
Country
Portugal
Facility Name
Pfizer Investigational Site
City
Coimbra
ZIP/Postal Code
3000-548
Country
Portugal
Facility Name
Pfizer Investigational Site
City
Bratislava
ZIP/Postal Code
82007
Country
Slovakia
Facility Name
Pfizer Investigational Site
City
Michalovce
ZIP/Postal Code
071 01
Country
Slovakia
Facility Name
Pfizer Investigational Site
City
Roznava
ZIP/Postal Code
04801
Country
Slovakia
Facility Name
Pfizer Investigational Site
City
Zilina
ZIP/Postal Code
01001
Country
Slovakia
Facility Name
Pfizer Investigational Site
City
Algorta, Getxo
State/Province
Bilbao
ZIP/Postal Code
48993
Country
Spain
Facility Name
Pfizer Investigational Site
City
Salt
State/Province
Girona
ZIP/Postal Code
17190
Country
Spain
Facility Name
Pfizer Investigational Site
City
Barcelona
ZIP/Postal Code
08014
Country
Spain
Facility Name
Pfizer Investigational Site
City
Barcelona
ZIP/Postal Code
08041
Country
Spain
Facility Name
Pfizer Investigational Site
City
Sevilla
ZIP/Postal Code
41071
Country
Spain
Facility Name
Pfizer Investigational Site
City
Istanbul
ZIP/Postal Code
34390
Country
Turkey
Facility Name
Pfizer Investigational Site
City
Kocaeli
ZIP/Postal Code
41400
Country
Turkey
Facility Name
Pfizer Investigational Site
City
Samsun
ZIP/Postal Code
55139
Country
Turkey

12. IPD Sharing Statement

Links:
URL
https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=B1451006&StudyName=A%20Phase%203%20Efficacy%20Study%20Of%20Dimebon%20In%20Patients%20With%20Moderate%20To%20Severe%20Alzheimer%27s%20Disease
Description
To obtain contact information for a study center near you, click here.

Learn more about this trial

A Phase 3 Efficacy Study Of Dimebon In Patients With Moderate To Severe Alzheimer's Disease

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