A Phase 3 Study To Evaluate The Safety And Tolerability Of Dimebon Patients With Mild To Moderate Alzheimer's Disease

A Phase 3, Multi-Center, Randomized, Double-Blind Placebo-Controlled Study To Evaluate The Safety And Tolerability Of Dimebon (PF-01913539) For Up To 26-Weeks In Patients With Mild To Moderate Alzheimer's Disease

This is a multi-center, randomized, double-blind placebo-controlled safety study conducted in 2 study cohorts. In Cohort 1, subjects with Alzheimer's disease (n=250) will receive Dimebon 20 mg or placebo TID for 26 weeks. In Cohort 2 AD subjects (n=500) will be treated with Dimebon 20 mg or placebo TID for 12 weeks After completion of the randomized portion of the study, subjects in both Cohorts will have the opportunity to enroll in a Dimebon open label extension study.

Study Overview

• Status: Completed
• Conditions: Alzheimer's Disease
• Intervention / Treatment: Drug: Dimebon; Drug: Dimebon; Drug: Placebo; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 742
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1J 1Z4
    • Pfizer Investigational Site
  • Quebec, Canada, G2B 5S1
    • Pfizer Investigational Site
  • Alberta
    • Calgary, Alberta, Canada, T3C 3P1
      • Pfizer Investigational Site
    • Medicine Hat, Alberta, Canada, T1B 4E7
      • Pfizer Investigational Site
  • British Columbia
    • Surrey, British Columbia, Canada, V4A 2H9
      • Pfizer Investigational Site
    • Victoria, British Columbia, Canada, V8R 1J8
      • Pfizer Investigational Site
  • New Brunswick
    • Saint John, New Brunswick, Canada, E2L 3L6
      • Pfizer Investigational Site
  • Newfoundland and Labrador
    • Bay Roberts, Newfoundland and Labrador, Canada, A0A 1G0
      • Pfizer Investigational Site
  • Nova Scotia
    • Kentville, Nova Scotia, Canada, B4N 4K9
      • Pfizer Investigational Site
    • Pictou, Nova Scotia, Canada, B0K 1H0
      • Pfizer Investigational Site
  • Ontario
    • Burlington, Ontario, Canada, L7M 4Y1
      • Pfizer Investigational Site
    • Corunna, Ontario, Canada, N0N 1G0
      • Pfizer Investigational Site
    • London, Ontario, Canada, N6A 4V2
      • Pfizer Investigational Site
    • Sarnia, Ontario, Canada, N7T 4X3
      • Pfizer Investigational Site
    • Toronto, Ontario, Canada, M6M 3Z5
      • Pfizer Investigational Site
  • Quebec
    • Greenfield Park, Quebec, Canada, J4V 2J2
      • Pfizer Investigational Site
    • L'Ancienne-Lorette, Quebec, Canada, G2E 2X1
      • Pfizer Investigational Site
    • Sherbrooke, Quebec, Canada, J1H 1Z1
      • Pfizer Investigational Site
    • St-Jean-sur-Richelieu, Quebec, Canada, J2W 1J1
      • Pfizer Investigational Site
    • St. Leonard, Quebec, Canada, H1S 3A9
      • Pfizer Investigational Site
• Puerto Rico
  • Cayey, Puerto Rico, 00736
    • Pfizer Investigational Site
  • Cidra, Puerto Rico, 00739
    • Pfizer Investigational Site
  • Rio Piedras, Puerto Rico, 00924
    • Pfizer Investigational Site
  • San Juan, Puerto Rico, 00907
    • Pfizer Investigational Site
  • San Juan, Puerto Rico, 00918
    • Pfizer Investigational Site
• United States
  • Alabama
    • Mobile, Alabama, United States, 36608
      • Pfizer Investigational Site
    • Northport, Alabama, United States, 35476
      • Pfizer Investigational Site
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Pfizer Investigational Site
  • California
    • Oceanside, California, United States, 92056
      • Pfizer Investigational Site
    • San Diego, California, United States, 92123
      • Pfizer Investigational Site
    • Santa Rosa, California, United States, 95405
      • Pfizer Investigational Site
  • Colorado
    • Pueblo, Colorado, United States, 81001
      • Pfizer Investigational Site
  • Delaware
    • Hockessin, Delaware, United States, 19707
      • Pfizer Investigational Site
  • Florida
    • Bradenton, Florida, United States, 34205
      • Pfizer Investigational Site
    • Brooksville, Florida, United States, 34601
      • Pfizer Investigational Site
    • Clearwater, Florida, United States, 33756
      • Pfizer Investigational Site
    • Daytona Beach, Florida, United States, 32114
      • Pfizer Investigational Site
    • Daytona Beach, Florida, United States, 32117
      • Pfizer Investigational Site
    • Destin, Florida, United States, 32541
      • Pfizer Investigational Site
    • Fort Myers, Florida, United States, 33912
      • Pfizer Investigational Site
    • Fort Walton Beach, Florida, United States, 32547
      • Pfizer Investigational Site
    • Fruitland Park, Florida, United States, 34731
      • Pfizer Investigational Site
    • Melbourne, Florida, United States, 32901
      • Pfizer Investigational Site
    • Naples, Florida, United States, 34102
      • Pfizer Investigational Site
    • Ocala, Florida, United States, 34471
      • Pfizer Investigational Site
    • Ocala, Florida, United States, 34474
      • Pfizer Investigational Site
    • Orlando, Florida, United States, 32806
      • Pfizer Investigational Site
    • Plant City, Florida, United States, 33563
      • Pfizer Investigational Site
    • Port Charlotte, Florida, United States, 33952
      • Pfizer Investigational Site
    • Port Orange, Florida, United States, 32127
      • Pfizer Investigational Site
    • Saint Petersburg, Florida, United States, 33713
      • Pfizer Investigational Site
    • Saint Petersburg, Florida, United States, 33709
      • Pfizer Investigational Site
    • Tampa, Florida, United States, 33606
      • Pfizer Investigational Site
    • Tampa, Florida, United States, 33629
      • Pfizer Investigational Site
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Pfizer Investigational Site
  • Illinois
    • Burr Ridge, Illinois, United States, 60527
      • Pfizer Investigational Site
    • Elk Grove Village, Illinois, United States, 60007
      • Pfizer Investigational Site
  • Indiana
    • Elkhart, Indiana, United States, 46514
      • Pfizer Investigational Site
    • Evansville, Indiana, United States, 47714
      • Pfizer Investigational Site
    • Fort Wayne, Indiana, United States, 46805
      • Pfizer Investigational Site
    • Greenfield, Indiana, United States, 46140-2834
      • Pfizer Investigational Site
  • Kansas
    • Prairie Village, Kansas, United States, 66206
      • Pfizer Investigational Site
    • Wichita, Kansas, United States, 67207
      • Pfizer Investigational Site
  • Louisiana
    • Lake Charles, Louisiana, United States, 70601
      • Pfizer Investigational Site
    • Shreveport, Louisiana, United States, 71105
      • Pfizer Investigational Site
  • Massachusetts
    • West Yarmouth, Massachusetts, United States, 02763
      • Pfizer Investigational Site
  • Mississippi
    • Flowood, Mississippi, United States, 39232
      • Pfizer Investigational Site
    • Olive Branch, Mississippi, United States, 38654
      • Pfizer Investigational Site
  • Missouri
    • Kansas City, Missouri, United States, 64114
      • Pfizer Investigational Site
    • Springfield, Missouri, United States, 65807
      • Pfizer Investigational Site
  • Montana
    • Great Falls, Montana, United States, 59405
      • Pfizer Investigational Site
  • New Jersey
    • Eatontown, New Jersey, United States, 07724
      • Pfizer Investigational Site
    • Oakhurst, New Jersey, United States, 07755
      • Pfizer Investigational Site
    • Toms River, New Jersey, United States, 08755
      • Pfizer Investigational Site
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • Pfizer Investigational Site
  • New York
    • Amherst, New York, United States, 14226
      • Pfizer Investigational Site
    • Buffalo, New York, United States, 14215
      • Pfizer Investigational Site
    • Buffalo, New York, United States, 14211
      • Pfizer Investigational Site
    • Orchard Park, New York, United States, 14127
      • Pfizer Investigational Site
    • Syracuse, New York, United States, 13210
      • Pfizer Investigational Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28211
      • Pfizer Investigational Site
    • Raleigh, North Carolina, United States, 27612
      • Pfizer Investigational Site
    • Raleigh, North Carolina, United States, 27607
      • Pfizer Investigational Site
    • Winston-Salem, North Carolina, United States, 27103
      • Pfizer Investigational Site
  • North Dakota
    • Fargo, North Dakota, United States, 58103
      • Pfizer Investigational Site
    • Fargo, North Dakota, United States, 58104
      • Pfizer Investigational Site
  • Ohio
    • Cincinnati, Ohio, United States, 45227
      • Pfizer Investigational Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Pfizer Investigational Site
  • Oregon
    • Portland, Oregon, United States, 97210
      • Pfizer Investigational Site
  • Pennsylvania
    • Altoona, Pennsylvania, United States, 16602
      • Pfizer Investigational Site
    • Beaver, Pennsylvania, United States, 15009
      • Pfizer Investigational Site
    • Bridgeville, Pennsylvania, United States, 15017
      • Pfizer Investigational Site
    • Grove City, Pennsylvania, United States, 16127
      • Pfizer Investigational Site
    • Indiana, Pennsylvania, United States, 15701
      • Pfizer Investigational Site
    • Norristown, Pennsylvania, United States, 19401
      • Pfizer Investigational Site
    • Pittsburgh, Pennsylvania, United States, 15241
      • Pfizer Investigational Site
    • Scotland, Pennsylvania, United States, 17254
      • Pfizer Investigational Site
    • Upper Saint Clair, Pennsylvania, United States, 15241
      • Pfizer Investigational Site
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Pfizer Investigational Site
    • Greer, South Carolina, United States, 29651
      • Pfizer Investigational Site
    • Murrells Inlet, South Carolina, United States, 29576
      • Pfizer Investigational Site
    • North Charleston, South Carolina, United States, 29406-6076
      • Pfizer Investigational Site
    • Orangeburg, South Carolina, United States, 29118
      • Pfizer Investigational Site
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57105
      • Pfizer Investigational Site
  • Tennessee
    • Franklin, Tennessee, United States, 37067
      • Pfizer Investigational Site
    • Knoxville, Tennessee, United States, 37920
      • Pfizer Investigational Site
    • Nashville, Tennessee, United States, 37203
      • Pfizer Investigational Site
  • Texas
    • Carrollton, Texas, United States, 75007
      • Pfizer Investigational Site
    • Fort Worth, Texas, United States, 76104
      • Pfizer Investigational Site
    • Fort Worth, Texas, United States, 76117
      • Pfizer Investigational Site
    • Grand Prairie, Texas, United States, 75050
      • Pfizer Investigational Site
    • Houston, Texas, United States, 77074
      • Pfizer Investigational Site
    • Lake Jackson, Texas, United States, 77566
      • Pfizer Investigational Site
  • Virginia
    • Williamsburg, Virginia, United States, 23185
      • Pfizer Investigational Site
  • Washington
    • Kirkland, Washington, United States, 98033
      • Pfizer Investigational Site
    • Spokane, Washington, United States, 99216
      • Pfizer Investigational Site
  • West Virginia
    • Charleston, West Virginia, United States, 25304
      • Pfizer Investigational Site
  • Wisconsin
    • La Crosse, Wisconsin, United States, 54650
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of Alzheimer's Disease.
• MMSE 12-26 inclusive.
• If on existing anti-dementia therapy, have been on a stable dose of anti-dementia therapy (cholinesterase inhibitors and/or memantine) for at least 60 days prior to dosing in study.
• If not taking existing anti-dementia therapy, have not received therapy with cholinesterase inhibitors and/or memantine within 60 days prior to dosing in this study.

Exclusion Criteria:

• Have major structural brain disease (e.g., ischemic infarcts, subdural hematoma, hemorrhage, hydrocephalus, brain tumors, multiple subcortical ischemic lesions, or a single lesion in a critical region [e.g., thalamus, hippocampus]).
• Have any major medical illness or unstable medical condition within six months of screening that may interfere with the patient's ability to comply with study procedures and abide by study restrictions.
• Have not been on a stable dose of anti-dementia therapy for at least 60 days prior to dosing or intend to start anti-dementia therapy during the double blind portion of the study.
• Reside in a nursing home or assisted care facility with need for 24-hour care and supervision.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dimebon 20 mg TID (Cohort 1)	Drug: Dimebon; 10 mg TID for week 1 followed by 20 mg TID through Week 26; Drug: Dimebon; 10 mg TID for week 1 followed by 20 mg TID through Week 12
Placebo Comparator: Placebo TID (Cohort 1)	Drug: Placebo; 10 mg TID for week 1 followed by 20 mg TID through Week 26; Drug: Placebo; 20 mg matched Placebo (Cohort 2) 10 mg TID for week 1 followed by 20 mg TID through Week 12
Experimental: Dimebon 20 mg TID (Cohort 2)	Drug: Dimebon; 10 mg TID for week 1 followed by 20 mg TID through Week 26; Drug: Dimebon; 10 mg TID for week 1 followed by 20 mg TID through Week 12
Placebo Comparator: Placebo TID (Cohort 2)	Drug: Placebo; 10 mg TID for week 1 followed by 20 mg TID through Week 26; Drug: Placebo; 20 mg matched Placebo (Cohort 2) 10 mg TID for week 1 followed by 20 mg TID through Week 12

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Abnormal Clinically Significant Vital Signs in Cohort 1	Abnormal clinically significant vital signs included absolute systolic blood pressure (BP) values: less than (<) 90 millimeter of mercury (mmHg), maximum increase or decrease of greater than or equal to (>=) 30 mmHg from baseline; absolute diastolic BP value: <50 mmHg, maximum increase or decrease of >=20 mmHg from baseline; absolute heart rate values: >120 beats per minute (bpm).	Baseline up to Week 30 (follow-up)
Percentage of Participants With Abnormal Clinically Significant Vital Signs in Cohort 2	Abnormal clinically significant vital signs included absolute systolic BP values: <90 mmHg, maximum increase or decrease of >=30 mmHg from baseline; absolute diastolic BP values: <50 mmHg, maximum increase or decrease of >=20 mmHg from baseline; absolute heart rate values: >120 bpm.	Baseline up to Week 16 (follow-up)
Percentage of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings in Cohort 1	Abnormal ECG findings included maximum value of >=300 millisecond (msec), maximum increase of >=25% for baseline value of >200 msec and maximum increase of >=50% for baseline value of <=200 msec for PR interval (int); maximum value of >=200 msec, maximum increase of >=25% for baseline value of >100 msec and maximum increase of >=50% for baseline value of <=100 msec for QRS interval; maximum value of >=500 msec for QT interval; maximum value of 450 to <480, 480 to <500 and >=500 msec, increase of >=30 to <60 and >=60 msec for QT interval corrected using Fridericia's formula (QTcF interval).	Baseline up to Week 30 (follow-up)
Percentage of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings in Cohort 2	Abnormal ECG findings included maximum value of >=300 msec, maximum increase of >=25% for baseline value of >200 msec and maximum increase of >=50% for baseline value of <=200 msec for PR interval; maximum value of >=200 msec, maximum increase of >=25% for baseline value of >100 msec and maximum increase of >=50% for baseline value of <=100 msec for QRS interval; maximum value of >=500 msec for QT interval; maximum value of 450 to <480, 480 to <500 and >=500 msec, increase of >=30 to <60 and >=60 msec for QT interval corrected using Fridericia's formula (QTcF interval).	Baseline up to Week 16 (follow-up)
Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 1	For hematology, liver function, renal function, electrolytes, clinical chemistry, abnormality was reported if the observed value was more than or less than X times the upper limit of normal (ULN) or lower limit of normal (LLN) respectively; X=specified in categories of each parameter in the measured values section. For urinalysis of glucose, ketones, protein, blood, abnormality was reported if result was >=1 in qualitative test of respective parameters, indicating levels in urine were abnormal. Urine pH and specific gravity abnormality reported if pH >8 and specific gravity <1.003 or >1.030.	Baseline up to Week 30 (follow-up)
Percentage of Participants With Abnormal Clinically Significant Laboratory Values in Cohort 2	For hematology, liver function, renal function, electrolytes, clinical chemistry, abnormality was reported if the observed value was more than or less than X times the ULN or LLN respectively; X=specified in categories of each parameter in the measured values section. For urinalysis of glucose, ketones, protein, blood, abnormality was reported if result was >=1 in qualitative test of respective parameters, indicating levels in urine were abnormal. Urine pH and specific gravity abnormality reported if pH >8 and specific gravity <1.003 or >1.030.	Baseline up to Week 16 (follow-up)
Percentage of Participants With Adverse Events (AEs) in Cohort 1	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.	Baseline up to Week 30 (follow-up)
Percentage of Participants With Adverse Events (AEs) in Cohort 2	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.	Baseline up to Week 16 (follow-up)

Collaborators and Investigators

• Sponsor: Pfizer
• Collaborators: Medivation, Inc.

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start: February 1, 2009
• Primary Completion (Actual): January 1, 2010
• Study Completion (Actual): January 1, 2010

Study Registration Dates

• First Submitted: February 5, 2009
• First Submitted That Met QC Criteria: February 5, 2009
• First Posted (Estimate): February 6, 2009

Study Record Updates

• Last Update Posted (Actual): December 6, 2018
• Last Update Submitted That Met QC Criteria: November 6, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: Safety; Alzheimer's Disease; Tolerability; Dimebon
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: B1451027