Alzheimer's disease
Conditions
Interventions
Product Name: SB-742457
Product Code: SB-742457
Pharmaceutical Form: Capsule, hard
CAS Number: 607742-69-8
Current Sponsor code: SB-742457
Concentration unit: mg milligram(s)
Concentration type: equal
Sponsors
GlaxoSmithKline Research & Development Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: A subject will be eligible for inclusion in the study only if all of the following criteria apply: 1. Male or female subject with a clinical diagnosis of probable Alzheimer's disease in accordance with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria and National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer’s Disease and Related Disorders Association (NINCDS-ADRDA) criteria. 2. Subject has mild to moderate Alzheimer's disease with MMSE score 12-24 inclusive at the screening visit and 12-26 inclusive at the end of the placebo run-in period . 3. Subject has a documented history of symptoms of Alzheimer’s disease for at least 6 months prior to entry into the study. 4. Age = 50 to = 85 years. 5. Female subjects must be post-menopausal (i.e. >24 weeks without menstrual period) or surgically sterile. Female subjects who have been post-menopausal for =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: A subject will not be eligible for inclusion in this study if any of the following criteria apply: Other Causes for Dementia 1. Diagnosis of possible, probable or definite vascular dementia in accordance with National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche l’Enseignement en Neurosciences (NINDS-AIREN) criteria. 2. History and/or evidence (CT or MRI scan performed within the past 12 months or at Screening) of any other central nervous system (CNS) disorder that could be interpreted as a cause of dementia: e.g. cerebrovascular disease, structural or developmental abnormality, epilepsy, infectious, degenerative or inflammatory/demyelinating CNS conditions. 3. Focal findings on the neurological exam (excluding changes attributable to peripheral injury). 4. Untreated abnormal result of any of the following tests: vitamin B12, syphilis serology, thyroid stimulating hormone (TSH), where this is thought to be the cause of, or to contribute to the severity of, the subject’s dementia. Confounding Medical Conditions 5. History of significant psychiatric illness such as schizophrenia or bipolar affective disorder that in the opinion of the Investigator would interfere with participation in the study, or current depression (score on Centre for Epidemiological Studies - Depression Scale (CES-D) >18). 6. History of known or suspected seizures, including febrile seizures, unexplained recent loss of consciousness or history of significant head trauma with loss of consciousness. 7. Known history of photosensitivity or presence of skin conditions (such as porphyria, photo-dermatitis) or treatments (such as medications, UV light) that may predispose the subject to photosensitivity reactions. 8. Any significant medical conditions which, in the opinion of the investigator, may be exacerbated by administration of donepezil (e.g. chronic obstructive pulmonary disease, asthma, peptic ulcer disease). 9. History or presence of significant cardiovascular, gastro-intestinal, endocrine, hepatic, or renal disease or other condition known to interfere with the absorption, distribution, metabolism, or excretion of drugs, or any other clinically relevant abnormality, medical or psychiatric condition, which, in the opinion of the Investigator, makes the subject unsuitable for inclusion in the study. 10. History of alcohol or other substance abuse, according to the DSM-IV criteria. Concomitant Medications 11. Treatment with any concomitant medications as detailed in the protocol. Unacceptable Test/Laboratory Values 12. Systolic blood pressure >165 mmHg or diastolic blood pressure >95 mmHg. 13. Postural hypotension (fall in systolic blood pressure of >30mmHg or fall in diastolic blood pressure of >20mmHg on standing compared to sitting). 14. Abnormal liver/kidney function tests (more than 1.5 times normal). 15. Calculated creatinine clearance < 40ml/min (Cockroft-Gault formula) and/or clinically relevant finding on urinalysis, including microscopy (such as: more than 1+ protein or blood, significant abnormality in albumin/creatinine ratio, etc.) Other 16. Previous participation in study AZ3100603. 17. Known hypersensitivity to donepezil or to piperidine derivatives. 18. Subject is unable (with assistance, if appropriate) to take study medication as prescribed throughout the study, has a history of non-compliance with prescribed medication, or is at risk of non-compliance with study medication or procedures. 19.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate the effects in subjects with mild-to-moderate probable Alzheimer’s disease on cognitive and global functioning of once daily dosing of SB-742457 and donepezil versus placebo after 24 weeks of treatment.;Primary end point(s): 1. Change from baseline to Week 24 in Alzheimer's Disease Assessment Scale (ADAS Cog) total score. 2. Change from baseline to Week 24 in Clinician's Interview-Based Impression of Change – plus (CIBIC+) score. ;Secondary Objective: Secondary objectives are to explore changes in behaviour (NPI), activities of daily living (DAD), paired associate learning (PAL) and other psychometric tests, digit vigilance test (DVT), trail making tests, any correlations with ApoE and other pharmacogenetic markers, relationship between exposure and cognitive function, and to investigate the safety and tolerability of SB-742457 and donepezil in this population. See Protocol for full details. | — |
Countries
Austria, Estonia, Germany, Hungary, United Kingdom
Outcome results
None listed