Last updated: 11/07/2018 15:50:52
Study of SB-742457 or donepezil versus placebo in subjects with mild-to-moderate Alzheimer’s disease
EudraCT ID
EU CT Number
Not applicable
Trial status
Completed
Completed
Trial overview
Official title: Study AZ3110865, a study comparing SB-742457 or donepezil versus placebo in subjects with mild-to-moderate Alzheimer’s disease
Trial description: The study is designed to investigate the efficacy, safety and tolerability of SB-742457 versus placebo in subjects with mild-to-moderate Alzheimer’s disease. SB-742457 is an experimental treatment which increases the levels of certain chemicals in the brain that are often decreased in patients with 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
Clinician’s Interview-Based Impression of Change – plus (CIBIC+) score at Week 24
Timeframe: 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
Effect of Baseline severity (including subgroup analyses based on Baseline Mini Mental State Examination [MMSE] scores 16-26) on the change from Baseline in ADAS-Cog total score, the change from Baseline in RBANS total score at Week 24
Timeframe: Baseline (Week 0) and Week 24
Effect of Baseline severity (including subgroup analyses based on Baseline [MMSE scores 10-20) on the change from Baseline in ADAS-Cog total score, the change from Baseline in RBANS total score at Week 24
Timeframe: Baseline (Week 0) and Week 24
Effect of Baseline severity (including subgroup analyses based on Baseline MMSE scores 16-26) on the CIBIC+ score at Week 24
Timeframe: Baseline (Week 0) and Week 24
Effect of Baseline severity (including subgroup analyses based on Baseline MMSE scores 10-20) on the CIBIC+ score at Week 24
Timeframe: Baseline (Week 0) and Week 24
Change from Baseline in ADAS-Cog total score at Week 12
Timeframe: Baseline (Week 0) and Week 12
CIBIC+ score at Week 12
Timeframe: Week 12
Change from Baseline in RBANS total score at Week 12
Timeframe: Baseline (Week 0) and Week 12
Effect of Baseline severity (including subgroup analyses based on Baseline MMSE scores 16-26) on the change from Baseline in ADAS-Cog total score, the change from Baseline in RBANS total score at Week 12
Timeframe: Baseline (Week 0) and Week 12
Effect of Baseline severity (including subgroup analyses based on Baseline MMSE scores 10-20) on the change from Baseline in ADAS-Cog total score, the change from Baseline in RBANS total score at Week 12
Timeframe: Baseline (Week 0) and Week 12
Effect of Baseline severity (including subgroup analyses based on Baseline MMSE scores 16-26) on the CIBIC+ score at Week 12
Timeframe: Week 12
Effect of Baseline severity (including subgroup analyses based on Baseline MMSE scores 10-20) on the CIBIC+ score at Week 12
Timeframe: Week 12
Change from Baseline in Alzheimer’s Disease Cooperative Study – Activities of Daily Living (ADCS-ADL) total score at Weeks 12 and 24
Timeframe: Baseline (Week 0) and Weeks 12 and 24
Change from Baseline in Cornell Scale for Depression in Dementia (CSDD) total score at Week 24
Timeframe: Baseline (Week 0) and Week 24
Change from Baseline in MMSE total score at Week 24
Timeframe: Baseline (Week 0) and Week 24
Change from Baseline in ADCS-ADL-Basic score; ADCS-ADL: Instrumental score and ADCS-ADL: Total independence score at Weeks 12 and 24
Timeframe: Baseline (Week 0) and Weeks 12 and 24
Number of participants with any Adverse Event (serious and non-serious) and serious adverse events (SAEs)
Timeframe: Upto Week 24
Number of participants with vital signs data of potential clinical concern (PCC) any time on treatment (ATOT)
Timeframe: Upto Week 24
Number of participants with hematology data of PCC ATOT
Timeframe: Upto Week 24
Number of participants with chemistry data of PCC ATOT
Timeframe: Upto Week 24
Change from Baseline in clinical chemistry parameters alanine amino transferase, alkaline phosphatase, aspartate amino transferase, creatine kinase, gamma glutamyl transferase and lactate dehydrogenase at Week 24
Timeframe: Baseline (Week 0) and Week 24
Change from Baseline in clinical chemistry parameters albumin and total protein at Week 24
Timeframe: Baseline (Week 0) and Week 24
Change from Baseline in clinical chemistry parameter blood urea nitrogen /creatinine ratio at Week 24
Timeframe: Baseline (Week 0) and Week 24
Change from Baseline in clinical chemistry parameters calcium, CO2 content/bicarbonate, chloride, glucose, HDL cholesterol, LDL cholesterol, magnesium, phosphorus, potassium, sodium, triglycerides, urea/blood urea nitrogen at Week 24
Timeframe: Baseline (Week 0) and Week 24
Change from Baseline in clinical chemistry parameters creatinine, direct bilirubin and total bilirubin at Week 24
Timeframe: Baseline (Week 0) and Week 24
Change from Baseline in hematology parameters basophils, eosinophils, lymphocytes, monocytes, platelet count, segmented neutrophils, total neutrophils, white blood cell count at Week 24
Timeframe: Baseline (Week 0) and Week 24
Change from Baseline in hematology parameter hematocrit
Timeframe: Baseline (Week 0) and Week 24
Change from Baseline in hematology parameters hemoglobin and mean corpuscle hemoglobin concentration at Week 24
Timeframe: Baseline (Week 0) and Week 24
Change from Baseline in hematology parameter mean corpuscle hemoglobin at Week 24
Timeframe: Baseline (Week 0) and Week 24
Change from Baseline in hematology parameter mean corpuscle volume and mean platelet volume at Week 24
Timeframe: Baseline (Week 0) and Week 24
Change from Baseline in hematology parameter red blood cell count at Week 24
Timeframe: Baseline (Week 0) and Week 24
Number of participants with electrocardiogram (ECG) findings as assessed by Investigator and Central Cardiologist
Timeframe: Upto Week 24
Exposure estimates for SB-742457 Area Under Curve over the dosing interval at steady state (AUCτss)
Timeframe: One sample at Day 28±5, 56±5, 84±5, 126±5 and 168±5 post 24 hours of last dose
Exposure estimates for SB-742457 minimum concentration at steady state (Cmin-ss)
Timeframe: One sample at Day 28±5, 56±5, 84±5, 126±5 and 168±5 post 24 hours of last dose
Exposure estimates for donepezil average concentration at steady state (Cavgss)
Timeframe: Weeks 4, 8,12,18 and Week 24
Interventions:
Drug: SB-742457
Drug: Donepezil
Drug: Placebo
Enrollment:
576
Observational study model:
Not applicable
Primary completion date:
2010-09-03
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 March 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 a documented 6-month history of AD symptoms
- Diagnosis of possible, probable or definite vascular dementia.
- History/evidence of any other CNS disorder that could be interpreted as a cause of dementia
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 a documented 6-month history of AD symptoms
- 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 pregnancy testing and approved form of birth control.
Exclusion criteria:
- Diagnosis of possible, probable or definite vascular dementia. -History/evidence of any other CNS disorder that could be interpreted as a cause of dementia
- History of known or suspected seizures, loss of consciousness or significant head trauma
- Subjects with ECG, blood pressure and laboratory values outside of protocol criteria are excluded.
- Subjects with known photosensitivity -Subjects with a history of 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
Santiago, Región Metro De Santiago, Chile, 7510186
Status
Study Complete
Location
GSK Investigational Site
Koeln, Nordrhein-Westfalen, Germany, 50935
Status
Study Complete
Location
GSK Investigational Site
Hannover, Niedersachsen, Germany, 30559
Status
Study Complete
Location
GSK Investigational Site
Bochum, Nordrhein-Westfalen, Germany, 44805
Status
Study Complete
Location
GSK Investigational Site
Duisburg, Nordrhein-Westfalen, Germany, 47051
Status
Study Complete
Location
GSK Investigational Site
Hattingen, Nordrhein-Westfalen, Germany, 45525
Status
Study Complete
Location
GSK Investigational Site
Viña del Mar, Valparaíso, Chile, 252-0997
Status
Study Complete
Location
GSK Investigational Site
Neuburg / Donau, Bayern, Germany, 86633
Status
Study Complete
Location
GSK Investigational Site
Aguascalientes, Ags, Aguascalientes, Mexico, 20127
Status
Study Complete
Location
GSK Investigational Site
Tuebingen, Baden-Wuerttemberg, Germany, 72076
Status
Study Complete
Location
GSK Investigational Site
Bochum, Nordrhein-Westfalen, Germany, 44892
Status
Study Complete
Location
GSK Investigational Site
Siegen, Nordrhein-Westfalen, Germany, 57072
Status
Study Complete
Location
GSK Investigational Site
Dueren, Nordrhein-Westfalen, Germany, 52349
Status
Study Complete
Location
GSK Investigational Site
Tijuana, Baja California Norte, Mexico, 22320
Status
Study Complete
Location
GSK Investigational Site
Stuttgart, Baden-Wuerttemberg, Germany, 70178
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
2010-09-03
Actual study completion date
2010-09-03
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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