Efficacy, Safety, & Tolerability of AZD3480 Patients With Mild to Moderate Dementia of the Alzheimer's Type (AD)
Primary Purpose
Alzheimer's Disease
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Donepezil
AZD3480
Sponsored by
About this trial
This is an interventional treatment trial for Alzheimer's Disease focused on measuring Alzheimer's Disease, AD, Dementia
Eligibility Criteria
Inclusion Criteria:
- A clinical diagnosis of AD per NINCDS-ADRDA criteria; mild to moderate severity as defined by Mini-Mental State Examination (MMSE) scores of 12 to 22.
- AD diagnosed at least 12 months prior to Screening, and supported by brain imaging studies within 6 months prior to Screening.
- Absence of vascular dementia both per AIRENS criteria and as defined by modified Hachinski ischemia score (HIS) of </= 4.
- Presence of a caregiver with significant proportion of time in contact with subject and who will oversee administration of study drug during the trial
- Able to complete test assessments and to sign informed consent with the help of a caregiver if needed
Exclusion Criteria:
- Diagnosis or presence of other dementing illnesses
- Use of mood stabilizers, antidepressants, anxiolytics, antipsychotics or hypnotics
- Treatment within 1 month prior to Screening using cognition-affecting agents (e.g. CNS stimulants)
- Tobacco user within 4 months prior to Screening
- Use of smoking cessation therapy within 4 months prior to Screening
- History within past 6 months of alcohol abuse or illicit drug abuse
- Unable, even with caregiver assistance, to comply with study procedures in opinion of investigator
- Myocardial infarction within the 12 months prior to Screening
- Hypothyroidism, vitamin B12 or folic acid deficiency
- Known systemic infection (HBV, HCV, HIV, TB)
- Vascular dementia per NINDS-AIRENS criteria and as defined by a modified Hachinski ischemia score (HIS, Appendix 4) score of > 4 (i.e., vascular dementia is consistent with a modified HIS > 4).
Sites / Locations
- Banner Alzheimer Institute
- Meridien Research
- MD Clinical
- Policlinic
- BRAIN-SOULTHERAPY s.r.o.
- Bialbi.s.r.o. Psychiatrické oddělení
- Psychiatricka Ambulance
- Vojenska Nemocnice Psychiatricke oddeleni
- Clintrial
- PRAGTIS s.r.o.
- Psychosocialni centrum
- Crucea Alba - Dr. Oros si Asociatii - Societate Civila Medicala
- Spitalul de Psihiatrie Sibiu
- Spitalul Clinic Judetean de Urgenta SIBIU
- Spitalul Clinic Judetean de Urgenta, Clinica Psihiatrie
- Spitalul Clinic Judetean de Urgenta, Clinica Neurologie 2
- Neurologicka Ambulancia, s.r.o.
- Univerzitna nemocnica Bratislava, Geronto-psychiatrické oddelenie
- KONZILIUM s.r.o.
- Neurologická ambulancia
- Dnipropetrovsk Regional Clinical Hospital
- Donetsk National Medical University of M. Gorky
- Donetsk Regional Clinical Psychiatric Hospital
- Crimean Republican Institution Psychoneurological Dispensary
- Central Clinical Hospital Ukrzaliznytsi
- Department of Age Physiology and Pathology of Nervous System; Institute of Gerontology NAMS
- Lugansk Regional Clinical Psychoneurological Hospital
- Lviv National Medical University named after Galytskyy
- Lviv Regional Clinical Psychiatric Hospital
- Odessa Regional Psychoneurology Dispensary
- Odessa Regional Psychiatric Hospital # 2
- Ukrainian Medical Stomatological Academy
- Department #3 of the Kherson Regional Psychiatric Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
AZD3480
Donepezil
Arm Description
Donepezil will be administered at 5 mg daily for 4 weeks and escalated to 10 mg daily for the remainder of the study.
Outcomes
Primary Outcome Measures
Change from baseline in the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog)
Change from baseline in the Clinician Interview-Based Impression of Change plus carer interview [CIBIC-(+)]
The CIBIC-(+) is a co-primary endpoint with the ADAS-Cog in the United States.
Change from baseline in the Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL)
The ADCS-ADL is the co-primary endpoint with the ADAS-Cog in Europe.
Secondary Outcome Measures
Change from baseline in the Neuropsychiatric Inventory (NPI)
Change from baseline in the Mini-Mental State Examination (MMSE)
Change from baseline in the Alzheimer's Disease Related Quality of Life (ADRQL)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01466088
Brief Title
Efficacy, Safety, & Tolerability of AZD3480 Patients With Mild to Moderate Dementia of the Alzheimer's Type (AD)
Official Title
Double-Blind, Positive Comparator, Randomized, Parallel Study of Efficacy, Safety, and Tolerability of AZD3480 (TC-1734-226) as Monotherapy in Patients With Mild to Moderate Dementia of the Alzheimer's Type
Study Type
Interventional
2. Study Status
Record Verification Date
July 2014
Overall Recruitment Status
Completed
Study Start Date
October 2011 (undefined)
Primary Completion Date
May 2014 (Actual)
Study Completion Date
May 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Targacept Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
Alzheimer's disease is the most common form of dementia and is the fourth leading cause of death among people 65 years of age and older. The global prevalence of the disease will increase significantly as the population ages, unless preventative treatments can be identified and marketed. The present study seeks to evaluate AZD3480 (TC-1734) compared to an approved medication (donepezil) shown to improve cognition and function in patients with Alzheimer's disease.
Detailed Description
This is a double blind, positive comparator, randomized, multicenter, parallel group study to assess the efficacy, safety, and tolerability of AZD3480 as monotherapy in patients with mild to moderate dementia of the Alzheimer's type (AD). Approximately 300 subjects will be randomized and divided into 2 cohorts. Actual randomization was 293 subjects.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer's Disease
Keywords
Alzheimer's Disease, AD, Dementia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
386 (Actual)
8. Arms, Groups, and Interventions
Arm Title
AZD3480
Arm Type
Experimental
Arm Title
Donepezil
Arm Type
Active Comparator
Arm Description
Donepezil will be administered at 5 mg daily for 4 weeks and escalated to 10 mg daily for the remainder of the study.
Intervention Type
Drug
Intervention Name(s)
Donepezil
Other Intervention Name(s)
Aricept
Intervention Description
Subjects taking donepezil will take 1-2 capsules of 5 mg donepezil and a placebo for AZD3480 (to maintain blind) orally once a day.
Intervention Type
Drug
Intervention Name(s)
AZD3480
Other Intervention Name(s)
TC-1734
Intervention Description
Subjects taking 30 mg AZD3480 will take one capsule of AZD3480 and two capsules of placebo for donepezil (to maintain blind) orally once a day.
Primary Outcome Measure Information:
Title
Change from baseline in the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog)
Time Frame
52 weeks
Title
Change from baseline in the Clinician Interview-Based Impression of Change plus carer interview [CIBIC-(+)]
Description
The CIBIC-(+) is a co-primary endpoint with the ADAS-Cog in the United States.
Time Frame
52 Weeks
Title
Change from baseline in the Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL)
Description
The ADCS-ADL is the co-primary endpoint with the ADAS-Cog in Europe.
Time Frame
52 Weeks
Secondary Outcome Measure Information:
Title
Change from baseline in the Neuropsychiatric Inventory (NPI)
Time Frame
52 Weeks
Title
Change from baseline in the Mini-Mental State Examination (MMSE)
Time Frame
52 Weeks
Title
Change from baseline in the Alzheimer's Disease Related Quality of Life (ADRQL)
Time Frame
52 Weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
60 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
A clinical diagnosis of AD per NINCDS-ADRDA criteria; mild to moderate severity as defined by Mini-Mental State Examination (MMSE) scores of 12 to 22.
AD diagnosed at least 12 months prior to Screening, and supported by brain imaging studies within 6 months prior to Screening.
Absence of vascular dementia both per AIRENS criteria and as defined by modified Hachinski ischemia score (HIS) of </= 4.
Presence of a caregiver with significant proportion of time in contact with subject and who will oversee administration of study drug during the trial
Able to complete test assessments and to sign informed consent with the help of a caregiver if needed
Exclusion Criteria:
Diagnosis or presence of other dementing illnesses
Use of mood stabilizers, antidepressants, anxiolytics, antipsychotics or hypnotics
Treatment within 1 month prior to Screening using cognition-affecting agents (e.g. CNS stimulants)
Tobacco user within 4 months prior to Screening
Use of smoking cessation therapy within 4 months prior to Screening
History within past 6 months of alcohol abuse or illicit drug abuse
Unable, even with caregiver assistance, to comply with study procedures in opinion of investigator
Myocardial infarction within the 12 months prior to Screening
Hypothyroidism, vitamin B12 or folic acid deficiency
Known systemic infection (HBV, HCV, HIV, TB)
Vascular dementia per NINDS-AIRENS criteria and as defined by a modified Hachinski ischemia score (HIS, Appendix 4) score of > 4 (i.e., vascular dementia is consistent with a modified HIS > 4).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pierre Tariot, MD
Organizational Affiliation
Banner Alzheimer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Banner Alzheimer Institute
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85006
Country
United States
Facility Name
Meridien Research
City
Brooksville
State/Province
Florida
ZIP/Postal Code
34601
Country
United States
Facility Name
MD Clinical
City
Hallandale Beach
State/Province
Florida
ZIP/Postal Code
33009
Country
United States
Facility Name
Policlinic
City
Chocen
Country
Czech Republic
Facility Name
BRAIN-SOULTHERAPY s.r.o.
City
Kladno
Country
Czech Republic
Facility Name
Bialbi.s.r.o. Psychiatrické oddělení
City
Litoměřice
Country
Czech Republic
Facility Name
Psychiatricka Ambulance
City
Olomouc
Country
Czech Republic
Facility Name
Vojenska Nemocnice Psychiatricke oddeleni
City
Olomouc
Country
Czech Republic
Facility Name
Clintrial
City
Praha
Country
Czech Republic
Facility Name
PRAGTIS s.r.o.
City
Praha
Country
Czech Republic
Facility Name
Psychosocialni centrum
City
Prerov
Country
Czech Republic
Facility Name
Crucea Alba - Dr. Oros si Asociatii - Societate Civila Medicala
City
Oradea
ZIP/Postal Code
410163
Country
Romania
Facility Name
Spitalul de Psihiatrie Sibiu
City
Sibiu
ZIP/Postal Code
550012
Country
Romania
Facility Name
Spitalul Clinic Judetean de Urgenta SIBIU
City
Sibiu
ZIP/Postal Code
550166
Country
Romania
Facility Name
Spitalul Clinic Judetean de Urgenta, Clinica Psihiatrie
City
Timisoara
ZIP/Postal Code
300128
Country
Romania
Facility Name
Spitalul Clinic Judetean de Urgenta, Clinica Neurologie 2
City
Timisoara
ZIP/Postal Code
300736
Country
Romania
Facility Name
Neurologicka Ambulancia, s.r.o.
City
Banska Bystrica
Country
Slovakia
Facility Name
Univerzitna nemocnica Bratislava, Geronto-psychiatrické oddelenie
City
Bratislava
Country
Slovakia
Facility Name
KONZILIUM s.r.o.
City
Dubnica nad Váhom
Country
Slovakia
Facility Name
Neurologická ambulancia
City
Krompachy
Country
Slovakia
Facility Name
Dnipropetrovsk Regional Clinical Hospital
City
Dnipropetrovsk
ZIP/Postal Code
49005
Country
Ukraine
Facility Name
Donetsk National Medical University of M. Gorky
City
Donetsk
ZIP/Postal Code
83003
Country
Ukraine
Facility Name
Donetsk Regional Clinical Psychiatric Hospital
City
Donetsk
ZIP/Postal Code
83008
Country
Ukraine
Facility Name
Crimean Republican Institution Psychoneurological Dispensary
City
Kerch
ZIP/Postal Code
98310
Country
Ukraine
Facility Name
Central Clinical Hospital Ukrzaliznytsi
City
Kharkiv
ZIP/Postal Code
61103
Country
Ukraine
Facility Name
Department of Age Physiology and Pathology of Nervous System; Institute of Gerontology NAMS
City
Kyiv
ZIP/Postal Code
04114
Country
Ukraine
Facility Name
Lugansk Regional Clinical Psychoneurological Hospital
City
Lugansk
ZIP/Postal Code
91045
Country
Ukraine
Facility Name
Lviv National Medical University named after Galytskyy
City
Lviv
ZIP/Postal Code
79010
Country
Ukraine
Facility Name
Lviv Regional Clinical Psychiatric Hospital
City
Lviv
ZIP/Postal Code
79021
Country
Ukraine
Facility Name
Odessa Regional Psychoneurology Dispensary
City
Odessa
ZIP/Postal Code
65014
Country
Ukraine
Facility Name
Odessa Regional Psychiatric Hospital # 2
City
Oleksandrivka
ZIP/Postal Code
67513
Country
Ukraine
Facility Name
Ukrainian Medical Stomatological Academy
City
Poltava
ZIP/Postal Code
36006
Country
Ukraine
Facility Name
Department #3 of the Kherson Regional Psychiatric Hospital
City
Stepanovka
ZIP/Postal Code
73488
Country
Ukraine
12. IPD Sharing Statement
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Efficacy, Safety, & Tolerability of AZD3480 Patients With Mild to Moderate Dementia of the Alzheimer's Type (AD)
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