Study AZ3110866, a fixed dose study of SB-742457 versus placebo when added to existing donepezil treatment in subjects with mild-to-moderate Alzheimer's disease

• Conditions: Alzheimer's disease; MedDRA version: 9.1Level: LLTClassification code 10001896Term: Alzheimer's disease

• Registration Number: EUCTR2008-000827-25-CZ
• Lead Sponsor: GlaxoSmithKline Research & Development Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-05-07
• Last Update Posted: 3 September 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 672

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

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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified