| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10001896 |
| E.1.2 | Term | Alzheimer's disease |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
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 |
|
| E.2.2 | Secondary objectives of the trial |
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 |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal 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 |
|
| E.4 | Principal 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 intitiation of treatment.
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)
Please refer to protocol AZ3110865 (dated 2009-01-20) section 4.3 for further criteria. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
1. Change from baseline in ADAS-Cog total score at Week 24
2. CIBIC+ score at Week 24 |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 21 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 43 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 8 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 8 |
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