| 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 |
• 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. |
|
| E.2.2 | Secondary objectives of the trial |
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 |
|
| 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 (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. |
|
| E.4 | Principal 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 5half-lives of use of the investigational drug prior to the Screening visit,whichever is longer.In exceptional circumstances, for subjects participating in another investigational drug study evaulating symptomatic treatment of AD,a shorter period may be permitted folloving consultation with the Medical Monitor. In addition,subjects who were previously screened for another study in AD but failed the entry criteria for that study may be screened for AZ3110866 with no time delay prior to the Screening visit, provided that, in the opinion of the Investigator, there is a realistic possibility that the subject would be eligible for AZ3110866.
11. Treatment with any concomitant medications detailed in Table 1: |
|
| E.5 End points |
| E.5.1 | 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 |
|
| 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 | Yes |
| 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
| Information not present in EudraCT |
| 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 | 8 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 47 |
| 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 | Yes |
| 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 | 2 |
| E.8.9.1 | In the Member State concerned months | 1 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 1 |
Print
