Bridging Study With GSK239512 In Patients With Mild To Moderate Alzheimer's Disease
Bridging Study With GSK239512 In Patients With Mild To Moderate Alzheimer's Disease
This is a safety and tolerability study to investigate the effect of GSK239512 on mild to
 moderate Alzheimers disease patients. The dose of GSK239512 will be titrated to reach the
 most well tolerated dose in the patients.
Inclusion Criteria:

 -  Male or female subjects with a clinical diagnosis of probable Alzheimer's disease

 -  The subject has an MMSE score at screening of 12 to 26 for Part A and 16-26 for Part
 B.

 -  Age ≥ 50 and above.

 -  If female, the subject must be post-menopausal (i.e. 12 months without menstrual
 period) or surgically sterile.

 -  Male subjects must be willing to abstain from sexual intercourse with pregnant or
 lactating women; or be willing to use a condom/spermicide in addition to having their
 female partner use another form of contraception if the woman could become pregnant,
 from the time of the first dose of GSK239512 until 84 days following completion of the
 study.

 -  The subject has the ability to comply with the study procedures.

 -  The subject has a permanent caregiver and is willing to attend all study visits for
 Parts A and B.

 -  The subject has provided full written informed consent prior to the performance of any
 protocol specific procedure, or if unable to provide informed consent due to cognitive
 status, full written informed consent on behalf of the subject has been provided by a
 legally acceptable representative.

 -  The caregiver has provided his / her written consent prior to the performance of any
 protocol specific procedure.

 Exclusion Criteria:

 -  In the opinion of the investigator, following review of CT/MRI scans in the past 12
 months and completion of neurological review there could be other probable causes of
 dementia

 -  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 (a score of ≥8 on the Cornell Scale for Depression in
 Dementia), or subjects with other psychiatric features in their AD which would in the
 opinion of the investigator, would increase risk to safety.

 -  History of significant sleep disturbance, for example, when it is associated with
 nocturnal wandering, nocturnal confusion / disorientation / agitation, which in the
 opinion of the investigator, may increase safety risk.

 -  History or presence of known or suspected seizures, unexplained significant loss of
 consciousness within last 6 months. Subjects who had febrile seizures in childhood may
 be included if these ceased by age 10 and they have had no other type of seizure in
 their medical history and have not been on anti-epileptic medications.

 -  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.

 -  History of alcohol or other substance abuse, according to the Diagnostic and
 Statistical Manual of Mental Disorders - Substance related disorders (DSM-IV)
 criteria.

 -  Clinically significant abnormalities in laboratory tests, including subjects with
 active liver disease or uncontrolled thyroid disease.

 -  Uncontrolled hypertension with systolic BP ≥160 and/or diastolic ≥95 mmHg. Subjects
 with controlled hypertension with systolic BP < 160 mmHg and diastolic <95 mmHg for at
 least 4 weeks are acceptable.

 -  Systolic BP <100 mmHg and/or diastolic <60 mmHg.

 -  Subjects with ECG criteria outside ranges specified in the protocol

 -  History of hypersensitivity to GSK239512 or its excipients.

 -  Treatment with cholinesterase inhibitors, (including Tacrine), memantine or selegiline
 within the previous month. No patients with AD who are already on these medications at
 the time of screening will be recruited, as it would be unethical to withdraw these
 medications for study participation. Only AD subjects who are not yet on these
 medications, or who have withdrawn from these medications for other reasons
 previously, may be enrolled into this study.

 -  Subjects who are currently taking or who have taken in the last month anti-psychotic
 drugs (typical or atypical dopaminergic antagonists or modulators) or mood
 stabilization drugs (including SSRI, DNRI, SNRI, MAO inhibitors, tricyclic
 antidepressants, lithium, valproate, carbamazepine).

 -  Subjects who are currently taking Pgp inhibitors or any CYP3A4 inhibitors.

 -  Subjects on chronic sedative medications (≥ 4 days per week for the past 4 weeks).

 -  Subject or caregiver is an immediate family member or employee of the participating
 Investigator, any of the participating site staff or GSK staff.

 -  Has received any other investigational treatment in the previous 3 months.