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
CAS Number: 607742-69-8
Current Sponsor code: SB-742457
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 15-
Phar
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 (Section 11.12 Appendix 12) and National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer’s Disease and Related Disorders Association (NINCDS-ADRDA) criteria (Section 11.13 Appendix 13). 2. Subject has a documented history of at least 6 months of ongoing donepezil therapy for Alzheimer’s disease, with stable dosing of 5-10mg/day for at least the last 2 months (and with no intent to change for the duration of the study). 3. Subject has MMSE (Section 11.10 Appendix 10) 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 (Section 11.14 Appendix 14) = 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 therapy]1 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 Section 11.4 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: 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 (Section 11.15 Appendix 15). 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 disease1. 3. Focal findings on the neurological exam (excluding changes attributable to 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). 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, major depressive disorder (according to DSM-IV ;Section 11.16 Appendix 16) 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 ;Section 11.9 Appendix 9) 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. History or presence of significant cardiovascular, gastro-intestinal, endocrine, hepatic or renal disease or other conditions 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. 9. History of alcohol or other substance abuse, according to the DSM-IV criteria (Section 11.17 Appendix 17), or recent or remote history of the same if that could be a contributing factor to the dementia. Concomitant Medications 10. Participation in another investigational drug or device study in AD during the 60 days prior to the Screening visit (Visit 1), or within
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To assess the effects of once daily dosing of SB-742457 versus placebo as an adjunct therapy to stable donepezil treatment after 24 weeks of treatment on cognitive function. • To assess the effects of once daily dosing of SB-742457 versus placebo as an adjunct therapy to stable donepezil treatment after 24 weeks of treatment on global function.;Secondary Objective: 1.Investigate how baseline severity affects efficacy outcome measures(cognitive and global function)after 24wks of treatment 2.To investigate effects on cognitive and global function of SB-742457 vs placebo as an adjunct therapy to stable donepezil treatment after 12,36,48wks of treatment. 3.To investigate how baseline severity affects efficacy outcome measures (cognitive and global function) after 12,36,48wks of treatment 4.To investigate effects on activities of daily living of SB-742457 vs placebo as an adjunct therapy to stable donepezil treatment after 12,24,36,48wks of treatment. 5.To verify the SB-742457 plasma concentrations and donepezil plasma concentrations in the subjects 6.To estimate the individual exposures of SB-742457 so they can be related to efficacy or safety endpoints as appropriate 7.To confirm the lack of PK interaction between SB-742457 and donepezil 8.To assess the safety and tolerability of SB-742457 as an adjunct therapy to stable donepezil treatment;Primary end point(s): • Change from baseline in ADAS-Cog total score at Week 24 • Change from baseline in CDR-SB score at Week 24 | — |
Countries
Czech Republic, Germany, Italy, Spain
Outcome results
None listed