Alzheimer’s disease
Conditions
Interventions
Product Name: SB-742457
Product Code: SB-742457
Pharmaceutical Form: Capsule, hard
Current Sponsor code: SB-742457
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5
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 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. Fifty to 85 years of age inclusive. 4. 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. History or presence of significant cardiovascular, gastro-intestinal, 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. 9. History of alcohol or other substance abuse, according to the DSM-IV criteria. Concomitant Medications 10. Treatment with cholinesterase inhibitors (including tacrine), memantine or selegiline is not permitted: • within the past 3 months • at any point in the past if the treatment was discontinued for lack of efficacy or significant adverse events, which are also likely to occur with SB-742457. 11. Current use or use of any of the following within 30 days or 5 half-lives prior to screening (whichever is longer) is not permitted: • Any other treatments approved in the countries for treatment of cognitive symptoms of AD • Butyrophenones, phenothiazines or atypical antipsychotics • Barbiturates • MAO inhibitors • Any investigational drug • PRN use of benzodiazepines or other sedatives/hypnotics (used for hypnotic or anxiolytic effects) with half-life greater than or equal to 6 hours • Chronic short or long term use of benzodiazepines • Potent Pgp inhibitors (itraconazole, ketoconazole, cyclosporin, loperamide, diltiazem, verapamil, spironolactone, quinidine, bepridil, quinine, carvedilol) 12. Use of the following is not permitted unless prescribed at a stable dose for at least 2 months prior to screening (changes to dose during the study must be discussed with the medical monitor): • Antidepressants (other than monoamine oxidase
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To investigate the effects on cognitive function of once daily dosing for 24 weeks with SB-742457 versus placebo. • To investigate the effects on global functioning of once daily dosing for 24 weeks with SB-742457 versus placebo. ;Secondary Objective: • To investigate the effects on cognitive function of SB-742457 or placebo after 8 and 12 weeks of treatment • To investigate the effects on global functioning of SB-742457 or placebo after 8 and 12 weeks of treatment • To investigate the effects on behaviour of SB-742457 or placebo after 8, 12 and 24 weeks of treatment • To investigate the effects on activities of daily living of SB-742457 or placebo after 8, 12 and 24 weeks of treatment • To seek post-hoc correlation of any effects of SB-742457 with apolipoprotein E (ApoE) genotype and possibly other pharmacogenetic markers. • To investigate the safety and tolerability of SB-742457 or placebo in subjects with mild to moderate AD. • To evaluate the PK of SB-742457 in subjects with mild to moderate AD. • To evaluate the relationship, if any, between SB-742457 exposure and cognitive function and global functioning. • To evaluate patient and caregiver perception of benefit of treatment with SB-742457 for 24 weeks. ;Primary end point(s): The co-primary endpoints to assess cognition and global functioning are: 1. Change from baseline to Week 24 in Alzheimer's Disease Assessment Scale cognitive (ADAS-cog) score (Appendix 5 of Protocol). 2. Change from baseline to Week 24 in Clinician's Interview-Based Impression of Change – plus (CIBIC+) score (Appendix 6 of Protocol). | — |
Countries
Austria, Czech Republic, Slovakia, Spain
Outcome results
None listed