Alzheimer's disease MedDRA version: 9.1 Level: LLT Classification code 10001896 Term: Alzheimer's disease
Conditions
Interventions
Product Code: SB-742457
Pharmaceutical Form: Tablet
Current Sponsor code: SB-742457
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 15-
Pharmaceutical form of the p
Sponsors
GlaxoSmithKline Research & Development Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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 a documented history of symptoms of AD for at least 6 months prior to entry into the study 3. Subject has MMSE score 12-24 inclusive at Screening and a baseline MMSE score 10-26 inclusive. The MMSE score at baseline must be within ± 3 points of the Screening value 4. Hachinski Ischaemia score = 4 at Screening 5. Age = 50 to = 85 years 6. A female subject must be: a. Of non-childbearing potential (i.e., any female who is post-menopausal [ > 1 year without menstrual period in the absence of hormone replacement therapy1] or surgically sterile; or, b. If pre-menopausal or menopausal for 1 year or less, must have a negative pregnancy test and must not be lactating at the Screening and Baseline Visits and agrees to satisfy one of the requirements listed in Appendix 4 7. Subject has the ability to comply with procedures for cognitive and other testing in the opinion of the investigator 8. Subject lives with (or has substantial periods of contact with) a regular caregiver who is willing to attend all visits, oversee the subject's compliance with protocol specified procedures and study medication, and report on subject's status Note: A non-cohabiting caregiver must spend sufficient time with the subject so that in the opinion of the Investigator, the caregiver can reliably assess cognitive function, activities and behaviour, and report on the subject’s compliance and health. GSK should be consulted if adequacy of a caregiver situation is in doubt. However, as guidance, the ability for a caregiver to meet his/her expected responsibilities for this study would normally be possible when the caregiver spends no less than 10 hours per week with the subject, divided over multiple days 9. Subject has provided full written informed consent prior to the performance of any protocol-specified procedure; or if unable to provide informed consent due to cognitive status, subject has provided assent and full written informed consent on behalf of the subject has been provided by a legally acceptable representative 10. Caregiver has provided full written informed consent on his/her own behalf prior to the performance of any protocol-specified procedure Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 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 (in the opinion of the investigator): e.g. cerebrovascular disease (stroke, haemorrhage), structural or developmental abnormality, epilepsy, infectious, degenerative or inflammatory/demyelinating CNS conditions, Parkinson’s disease2 3.Focal findings on the neurological exam (excluding changes attributable to AD or peripheral injury) 4.Evidence of the following disorders: current vitamin B12 deficiency, positive syphilis serology (unless neurosyphilis was ruled out) or active thyroid dysfunction (particularly suggestive of hypothyroidism), including abnormally high or low serum levels of thyroid stimulating hormone (TSH), where this is thought to be the cause of, or to contribute to the severity of, the subject’s dementia (Note: testing is required for each parameter only when no result is available from previous 12 months) 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, major depressive disorder (according to DSM-IV) in the past year, or current active depression requiring initiation of treatment Note: If not currently treated, but active depression is suspected, the Cornell Scale for Depression in Dementia (CSDD) may be used by the Investigator as a guide for deciding whether a prospective subject requires treatment. If the subject has a CSDD score >7, the Investigator should decide if the subject has depression in need of prescribed medication, and a CSDD score > 12 is considered a strong indicator that treatment is needed. Subjects will be allowed to re-screen after their depression has been adequately managed for > 3 months 6.History of known or suspected seizures, including febrile seizures (except a clearly documented single brief febrile convulsion in infancy), 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, or recent or remote history of the same if that could be a contributing factor to the dementia 11.Participation in another investigational drug or device study in AD during the 60 days prior to the Screening visit (Visit 1), or
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): 1. Change from baseline in ADAS-Cog total score at Week 24 2. CIBIC+ score at Week 24;Main Objective: 1. To assess the effects of once daily dosing of SB-742457 and donepezil versus placebo after 24 weeks of treatment on cognitive function 2. To assess the effects of once daily dosing of SB-742457 and donepezil versus placebo after 24 weeks of treatment on global function;Secondary Objective: 1. To investigate how baseline severity affects efficacy outcome measures (cognitive and global function) after 24 weeks of treatment 2. To investigate effects on cognitive and global function of SB-742457 and donepezil versus placebo after 12 weeks of treatment 3. To investigate how baseline severity affects efficacy outcome measures (cognitive and global function) after 12 weeks of treatment 4. To investigate effects on activities of daily living of SB-742457 and donepezil versus placebo after 12 and 24 weeks of treatment 5. To investigate effects on depressive symptoms of SB-742457 and donepezil versus placebo after 24 weeks of treatment 6. To verify the SB-742457 plasma concentrations and donepezil plasma concentrations in subjects 7. To estimate the individual exposures of SB-742457 so they can be related to efficacy or safety endpoints when appropriate 8. To assess the safety and tolerability of SB-742457 and donepezil versus placebo | — |
Countries
Bulgaria, Czech Republic, Estonia, Germany, Greece
Outcome results
None listed