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

This study has been terminated.
(See termination reason in detailed description.)
Sponsor:
Collaborator:
Medivation, Inc.
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00912288
First received: June 1, 2009
Last updated: August 30, 2012
Last verified: August 2012
  Purpose

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.


Condition Intervention Phase
Alzheimer Disease
Drug: Dimebon 20 mg po TID
Drug: Placebo po TID
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Change From Baseline in the Severe Impairment Battery (SIB) Score at Week 26 [ Time Frame: Baseline, Week 26 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Week 26 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Week 26 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 26 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Week 26 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 26 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline, Weeks 12, 18, 26 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Weeks 12, 26 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Pre-dose, 0.5 to 1.5 hours, 2.5 to 3.5 hours post-dose at Week 12 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline up to Week 30 (follow-up) ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 86
Study Start Date: September 2009
Study Completion Date: August 2010
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dimebon Drug: Dimebon 20 mg po TID
Dimebon 10 mg po TID for 1 week followed by Dimebon 20 mg TID for 25 weeks
Other Names:
  • PF-01913539
  • Latrepirdine Dihydrochloride
Placebo Comparator: Placebo Drug: Placebo po TID
Placebo (matched to Dimebon) po for 26 weeks

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.

  Eligibility

Ages Eligible for Study:   50 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00912288

  Show 47 Study Locations
Sponsors and Collaborators
Pfizer
Medivation, Inc.
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00912288     History of Changes
Other Study ID Numbers: B1451006
Study First Received: June 1, 2009
Results First Received: July 30, 2012
Last Updated: August 30, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
Alzheimer disease moderate-to-severe memantine safety and efficacy

Additional relevant MeSH terms:
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders

ClinicalTrials.gov processed this record on August 20, 2014