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

Alzheimer Disease Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00912288
• Other study ID #: B1451006
• Status: Terminated
• Phase: Phase 3
• First received: June 1, 2009
• Last updated: August 30, 2012
• Start date: September 2009
• Est. completion date: August 2010

Study information

• Verified date: August 2012
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 86
• Est. completion date: August 2010
• Est. primary completion date: August 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 50 Years and older

Eligibility

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.

Study Design

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

Related Conditions & MeSH terms

• Alzheimer Disease

Intervention

Drug:
• Dimebon 20 mg po TID
Dimebon 10 mg po TID for 1 week followed by Dimebon 20 mg TID for 25 weeks
• Placebo po TID
Placebo (matched to Dimebon) po for 26 weeks

Locations

Country	Name	City	State
Canada	Pfizer Investigational Site	Montreal	Quebec
Canada	Pfizer Investigational Site	Quebec
Canada	Pfizer Investigational Site	Winnipeg	Manitoba
Germany	Pfizer Investigational Site	Berlin
Germany	Pfizer Investigational Site	Bochum
Germany	Pfizer Investigational Site	Guenzburg
Germany	Pfizer Investigational Site	Leipzig
Germany	Pfizer Investigational Site	Mainz
Germany	Pfizer Investigational Site	Mittweida
Hungary	Pfizer Investigational Site	Budapest
Hungary	Pfizer Investigational Site	Gyula
Hungary	Pfizer Investigational Site	Szekesfehervar
Portugal	Pfizer Investigational Site	Amadora
Portugal	Pfizer Investigational Site	Coimbra
Slovakia	Pfizer Investigational Site	Bratislava
Slovakia	Pfizer Investigational Site	Michalovce
Slovakia	Pfizer Investigational Site	Roznava
Slovakia	Pfizer Investigational Site	Zilina
Spain	Pfizer Investigational Site	Algorta, Getxo	Bilbao
Spain	Pfizer Investigational Site	Barcelona
Spain	Pfizer Investigational Site	Barcelona
Spain	Pfizer Investigational Site	Salt	Girona
Spain	Pfizer Investigational Site	Sevilla
Turkey	Pfizer Investigational Site	Istanbul
Turkey	Pfizer Investigational Site	Kocaeli
Turkey	Pfizer Investigational Site	Samsun
United States	Pfizer Investigational Site	Brooksville	Florida
United States	Pfizer Investigational Site	Cordova	Tennessee
United States	Pfizer Investigational Site	Costa Mesa	California
United States	Pfizer Investigational Site	Delray Beach	Florida
United States	Pfizer Investigational Site	Denver	Colorado
United States	Pfizer Investigational Site	East Providence	Rhode Island
United States	Pfizer Investigational Site	Encino	California
United States	Pfizer Investigational Site	Indianapolis	Indiana
United States	Pfizer Investigational Site	Lexington	Kentucky
United States	Pfizer Investigational Site	Los Alamitos	California
United States	Pfizer Investigational Site	Middleton	Wisconsin
United States	Pfizer Investigational Site	New Haven	Connecticut
United States	Pfizer Investigational Site	Newport Beach	California
United States	Pfizer Investigational Site	Newport Beach	California
United States	Pfizer Investigational Site	Norristown	Pennsylvania
United States	Pfizer Investigational Site	Phoenix	Arizona
United States	Pfizer Investigational Site	Pittsfield	Massachusetts
United States	Pfizer Investigational Site	Princeton	New Jersey
United States	Pfizer Investigational Site	Rochester	New York
United States	Pfizer Investigational Site	Syracuse	New York
United States	Pfizer Investigational Site	West Palm Beach	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Pfizer	Medivation, Inc.

Countries where clinical trial is conducted

United States,  Canada,  Germany,  Hungary,  Portugal,  Slovakia,  Spain,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Baseline, Week 26	No
Primary	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.	Baseline, Week 26	No
Secondary	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.	Baseline, Week 26	No
Secondary	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.	Week 26	No
Secondary	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.	Baseline, Week 26	No
Secondary	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.	Week 26	No
Secondary	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.	Baseline, Weeks 12, 18, 26	No
Secondary	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.	Baseline, Weeks 12, 26	No
Secondary	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.	Pre-dose, 0.5 to 1.5 hours, 2.5 to 3.5 hours post-dose at Week 12	No
Secondary	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.	Baseline up to Week 30 (follow-up)	Yes

External Links

•   To obtain contact information for a study center near you, click here.