Last updated: 11/07/2018 15:51:30
A study of SB-742457, added to donepezil for the treatment of mild-to-moderate Alzheimer’s disease
EudraCT ID
EU CT Number
Not applicable
Trial status
Completed
Completed
Trial overview
Official title: Study AZ3110866, a fixed dose study of SB-742457 versus placebo when added to existing donepezil treatment in subjects with mild-to-moderate Alzheimer’s disease
Trial description: The study is designed to investigate the safety and efficacy of SB-742457 when added to stable donepezil treatment in subjects with mild-to-moderate Alzheimer’s disease.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Allocation:
Randomized
Primary outcomes:
Change from Baseline in Alzheimer’s Disease Assessment Scale – cognitive subscale (ADAS-Cog) total score at Week 24
Timeframe: Baseline(Week 0) and Week 24
Change from Baseline in Clinical Dementia Rating – Sum of Boxes (CDR-SB) score at Week 24
Timeframe: Baseline(Week 0) and Week 24
Secondary outcomes:
Change from Baseline in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) total score at Week 24
Timeframe: Baseline (Week 0) and Week 24
Change from Baseline in ADAS-Cog total score at Week 12, 36 and 48
Timeframe: Baseline (Week 0) and Week 12, 36 and 48
Change from Baseline in CDR-SB score at Week 12, 36 and 48
Timeframe: Baseline (Week 0) and Week 12, 36, 48
Change from Baseline in RBANS score at Week 12, 36 and 48
Timeframe: Baseline (Week 0) and Week 12, 36 and 48
Change from Baseline in Alzheimer’s Disease Co-operative Study Group – Activities of Daily Living Inventory (ADCS- ADL) total score at Weeks 12, 24, 36 and 48
Timeframe: Baseline (Week 0) and Week 12, 24, 36 and 48
Change from Baseline in mini mental state examination (MMSE) total score at Week 24 and 48
Timeframe: Baseline (Week 0) and Week 24 and 48
Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) during treatment phase
Timeframe: Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal)
Number of participants with parameters of clinical concern - Hematology
Timeframe: Up to Week 48
Number of participants with parameters of clinical concern - clinical chemistry
Timeframe: Up to Week 48
Exposure estimates for SB-742457 : area under the concentration time curve over the dosing interval at steady state (AUCτss)
Timeframe: Post-dose at 3, 8 and 24 hours on Week 0, 1, 3, 6, 12, 18, 24, 30, 36, 42 and 48
Exposure estimates for SB-742457 : minimum concentrations at steady state (Cmin-ss)
Timeframe: Post-dose at 3, 8 and 24 hours on Week 0, 1, 3, 6, 12, 18, 24, 30, 36, 42 and 48
Exposure estimates for donepezil (Cavgss)
Timeframe: Post-dose at 12 to 20 hours on Week 0, 1, 3, 6, 12, 18, 24, 30, 36, 42 and 48
Change from Baseline in ADAS-Cog scale in participants with APOE4 gene
Timeframe: Baseline (Week 0) to Week 24 and Week 48
Change from Baseline in CDR-SB scale in participants with APOE4 gene
Timeframe: Baseline (Week 0) to Week 24 and Week 48
Change from Baseline in RBANS scale in participants with APOE4 gene
Timeframe: Baseline (Week 0) to Week 24 and Week 48
Interventions:
Drug: SB-742457 15mg
Drug: SB-742457 35mg
Drug: Placebo
Drug: donepezil 5-10mg
Enrollment:
682
Observational study model:
Not applicable
Primary completion date:
2010-21-05
Time perspective:
Not applicable
Clinical publications:
G Maher-Edwards, C Watson, J Ascher, C Barnett, D Boswell, J Davies, M Fernandez, A Kurz, O Zanetti, B Safirstein, J Schronen, M Zvartau-Hind, M Gold.Two randomized controlled trials of SB742457 in mild-to-moderate Alzheimer's disease.Alzheimers Dement (NY).2015;1(1):23-36
Medical condition
Alzheimer's Disease
Product
SB742457
Collaborators
Not applicable
Study date(s)
July 2008 to November 2010
Type
Interventional
Phase
2
Participation criteria
Sex
Female & Male
Age
50 - 85 years
Accepts healthy volunteers
No
- Subjects and their caregivers must provide informed consent prior to study entry.
- Subjects must have a clinical diagnosis of probable mild-to-moderate Alzheimer's disease with no evidence of disorders that are thought to be the cause of, or contributing to the severity of the subject's dementia and a documented history of at least 6 months of ongoing donepezil therapy with stable dosing for at least the last 2 months.
- Subjects with a diagnosis of possible, probable or definite vascular dementia may not participate.
- Subjects with known hypersensitivity to sunlight or a history of seizures, previous exposure to SB-742457, taking agents for which there is a theoretical risk of interaction with SB-742457, or taking medication for Alzheimer's disease or centrally acting agents which might impact study outcomes may not participate.
Inclusion and exclusion criteria
Inclusion criteria:
- Subjects and their caregivers must provide informed consent prior to study entry.
- Subjects must have a clinical diagnosis of probable mild-to-moderate Alzheimer's disease with no evidence of disorders that are thought to be the cause of, or contributing to the severity of the subject's dementia and a documented history of at least 6 months of ongoing donepezil therapy with stable dosing for at least the last 2 months.
- Subjects must have a regular caregiver who is willing to attend visits, oversee the subject's compliance with the study and report on the subject's status.
- Female subjects of child-bearing potential must agree to abstinence or an approved form of birth control.
- Subjects must have adequate blood pressure and laboratory values.
Exclusion criteria:
- Subjects with a diagnosis of possible, probable or definite vascular dementia may not participate.
- Subjects with known hypersensitivity to sunlight or a history of seizures, previous exposure to SB-742457, taking agents for which there is a theoretical risk of interaction with SB-742457, or taking medication for Alzheimer's disease or centrally acting agents which might impact study outcomes may not participate.
Trial location(s)
Location
GSK Investigational Site
Manchester, New Jersey, United States, 08759
Status
Study Complete
Location
GSK Investigational Site
Woodville, South Australia, Australia, 5011
Status
Study Complete
Location
GSK Investigational Site
Lido di Camaiore (LU), Toscana, Italy, 55043
Status
Study Complete
Location
GSK Investigational Site
Kogarah, New South Wales, Australia, 2217
Status
Study Complete
Location
GSK Investigational Site
Bochum, Nordrhein-Westfalen, Germany, 44869
Status
Study Complete
Location
GSK Investigational Site
Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina, C1022AAO
Status
Study Complete
Location
GSK Investigational Site
San Francisco, California, United States, 94109
Status
Study Complete
Location
GSK Investigational Site
Rancho Mirage, California, United States, 92270
Status
Study Complete
Location
GSK Investigational Site
San Vicente del Raspeig/Alicante, Spain, 03690
Status
Study Complete
Location
GSK Investigational Site
Heidelberg West, Victoria, Australia, 3084
Status
Study Complete
Location
GSK Investigational Site
Peterborough, Ontario, Canada, K9H 2P4
Status
Study Complete
Location
GSK Investigational Site
La Plata, Buenos Aires, Argentina, B1900AVG
Status
Study Complete
Location
GSK Investigational Site
Hallandale Beach, Florida, United States, 33009
Status
Study Complete
Location
GSK Investigational Site
Saint John, New Brunswick, Canada, E2L 3L6
Status
Study Complete
Location
GSK Investigational Site
Castellanza (VA), Lombardia, Italy, 21053
Status
Study Complete
Location
GSK Investigational Site
Tuebingen, Baden-Wuerttemberg, Germany, 72076
Status
Study Complete
Location
GSK Investigational Site
Bennington, Vermont, United States, 05201
Status
Study Complete
Location
GSK Investigational Site
Syracuse, New York, United States, 13210
Status
Study Complete
Location
GSK Investigational Site
Buenos Aires, Buenos Aires, Argentina, 1425
Status
Study Complete
Location
GSK Investigational Site
Ciudad de Buenos Aires, Buenos Aires, Argentina, C1431FWO
Status
Study Complete
Location
GSK Investigational Site
Greenfield Park, Québec, Canada, J4V 2J2
Status
Study Complete
Location
GSK Investigational Site
Ulm, Baden-Wuerttemberg, Germany, 89075
Status
Study Complete
Location
GSK Investigational Site
Memphis, Tennessee, United States, 38119
Status
Study Complete
Location
GSK Investigational Site
Bad Honnef, Nordrhein-Westfalen, Germany, 53604
Status
Study Complete
Location
GSK Investigational Site
Ellwangen, Baden-Wuerttemberg, Germany, 73479
Status
Study Complete
Location
GSK Investigational Site
Fresno, California, United States, 93720
Status
Study Complete
Location
GSK Investigational Site
Nedlands, Western Australia, Australia, 6009
Status
Study Complete
Location
GSK Investigational Site
Santiago, Región Metro De Santiago, Chile, 7510186
Status
Study Complete
Location
GSK Investigational Site
Winston-Salem, North Carolina, United States, 27103
Status
Study Complete
Location
GSK Investigational Site
San Felice a Cancello - Caserta, Campania, Italy, 81027
Status
Study Complete
Location
GSK Investigational Site
Schwerin, Mecklenburg-Vorpommern, Germany, 19055
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Schwerin, Mecklenburg-Vorpommern, Germany, 19053
Status
Study Complete
Location
GSK Investigational Site
Guenzburg, Bayern, Germany, 89312
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Aachen, Nordrhein-Westfalen, Germany, 52062
Status
Study Complete
Location
GSK Investigational Site
Viña del Mar, Valparaíso, Chile, 252-0997
Status
Study Complete
Location
GSK Investigational Site
Kentville, Nova Scotia, Canada, B4N 4K9
Status
Study Complete
Location
GSK Investigational Site
Litchfield Park, Arizona, United States, 85340
Status
Study Complete
Location
GSK Investigational Site
Hialeah, Florida, United States, 33016
Status
Study Complete
Location
GSK Investigational Site
Stuttgart, Baden-Wuerttemberg, Germany, 70176
Status
Study Complete
Study documents
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Completed
Actual primary completion date
2010-21-05
Actual study completion date
2010-16-11
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
Additional information
Not applicable
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