Rosiglitazone (Extended Release Tablets) As Adjunctive Therapy For Subjects With Mild To Moderate Alzheimer's Disease

Inclusion criteria:

• A subject will be eligible for inclusion in this study only if all of the followingcriteria apply:

• Male or female subject with a clinical diagnosis of probable Alzheimer's disease inaccordance with NINCDS-ADRDA criteria.

(Note: National Institute of Neurological and Communicative Disorders and Stroke (NINCDS)and Alzheimer's Disease and Related Disorders Association (ADRDA).)

• Subject has mild to moderate Alzheimer's disease as defined by a MMSE score 10 to 26inclusive at Screening.

• Hachinski Ischemia Score ≤ 4 at Screening.

• Age ≥50 and ≤90 years.

• At least 6 months of ongoing donepezil therapy for Alzheimer's disease, with stabledosing for at least the last 2 months (and with no intent to change for the durationof the study).

• Current use of medication is in accordance with the criteria listed in Table 2 (Permitted Medications,).

• Female subjects must be post-menopausal (i.e. >1 year without menstrual period),surgically sterile, or agree to use adequate method of contraception for the durationof the study. Female subjects who are pre-menopausal or who have been post-menopausalfor <1 year must undertake pregnancy testing (urine test) at Visit 1, which must benegative.

• Brain CT or MRI scan performed within the past 12 months or at Screening, showing noevidence of any other potential cause of dementia other than Alzheimer's disease.

(Note: Questionable CT or MRI scans should be discussed with the medical monitor, usingcentral imaging guidelines.)

• Neurological exam without focal changes (excluding changes attributable to AD orperipheral trauma).

• Subject has the ability to comply with procedures for cognitive and other testing.

• Subject lives with (or has substantial periods of contact with) a regular caregiverwho is willing to attend all visits, oversee the subject's compliance withprotocol-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, inthe opinion of the Investigator, the caregiver can reliably assess cognitive function,activities and behavior, and report on the subject's compliance and health. As caregivertime spent with a potential subject is anticipated to be highly variable across countriesand cultures, GSK will consider a variety of different measures by which this stipulationmay be met, and 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 responsibilitiesfor this study would normally be possible when the caregiver spends no less than 10 hoursper week with the subject, divided over multiple days.)

• Subject has provided full written informed consent prior to the performance of anyprotocol-specified procedure; or if unable to provide informed consent due tocognitive status, full written informed consent on behalf of the subject has beenprovided by a legally acceptable representative.

(Note: Consent by legally acceptable representative is allowed where this is in accordancewith local laws, regulations and ethics committee policy.)

• Caregiver has provided full written informed consent on his/her own behalf prior tothe performance of any protocol-specified procedure.

• Subjects considered for enrolment must have a QTc (either QTc B (Bazett's correction)or QTc F (Fridericia's correction)) <450msec at Visit 1, with the exception ofsubjects with bundle branch block (for whom either QTc B or QTc F must be <480msec).

• (Note: For the purposes of these criteria, QTc B is defined as (QT interval [msec]) / (square root of RR interval [seconds]); and QTc F is defined as (QT interval [msec]) / (cube root of RR interval [seconds]).)

Exclusion criteria:

• A subject will not be eligible for inclusion in this study if any of the followingcriteria apply:

• Diagnosis of possible, probable, or definite vascular dementia in accordance withNINDS-AIREN criteria.

(Note: National Institute of Neurological Disorders and Stroke (NINDS) and AssociationInternationale pour la Recherche et l'Enseignement en Neurosciences (AIREN).)

• History or evidence of any other CNS disorder that could be interpreted as a cause ofdementia: e.g. cerebrovascular disease (stroke, hemorrhage), structural abnormality,epilepsy, infectious or inflammatory/demyelinating CNS conditions, Parkinson'sdisease.

• Evidence of the following disorders: current vitamin B12 deficiency, positive syphilisserology, or active thyroid dysfunction (particularly that suggestive ofhypothyroidism), including abnormally high or low serum levels of thyroid stimulatinghormone (TSH) that are clinically significant in the opinion of the investigator.

(Note: Testing is required for each parameter only when no result is available fromprevious 12 months.)

• History of Type 1 diabetes mellitus or secondary diabetes mellitus.

• Type 2 diabetes mellitus where the subject is being treated with insulin, a PPARγagonist, or an insulin secretagogue (e.g. a sulfonylurea or glitinide).

• Any patient with an HbA1c ≥8.5%. (See Section 6.3.7.4 for Safety Measures for EnrolledSubjects with Type 2 Diabetes Mellitus.)

• History or clinical/investigational evidence of congestive heart failure defined bythe New York Heart Association criteria (Class I to IV cardiac status;).

• History of cardiovascular event within the last 6 months (i.e. intervention,percutaneous coronary intervention, vascular surgery, acute coronary syndrome [nonQ-wave myocardial infarction, Q-wave myocardial infarction, unstable angina] orsignificant arrhythmia; or major intervention (e.g. cardiac surgery or angiographyplus stenting) scheduled).

• History of significant psychiatric illness such as schizophrenia or bipolar affectivedisorder that in the opinion of the Investigator would interfere with participation inthe study, major depressive disorder (according to DSM-IV) in the past year, orcurrent active depression requiring initiation of treatment.

(Note: If not currently treated, but active depression is suspected, the Cornell Scale forDepression in Dementia (CSDD) can be used by the Investigator as a guide for decidingwhether a prospective subject requires treatment. If the subject has a CSDD score >7, theInvestigator should decide if the subject has depression in need of prescribed medication,and a CSDD >12 is considered a strong indicator that treatment is needed. Subjects will beallowed to re-screen after their depression has been adequately managed for >3 months.)

• History or presence of gastro-intestinal, hepatic, or renal disease or other conditionknown to interfere with the absorption, distribution, metabolism, or excretion ofdrugs, or any other clinically relevant abnormality, medical or psychiatric condition,which, in the opinion of the Investigator, makes the subject unsuitable for inclusionin the study.

• Clinically significant peripheral edema at the time of screening.

• Current or recent drug or alcohol abuse or dependence (defined by DSM-IV criteria forsubstance-related disorders), or recent or remote history of the same if that could bea contributing factor to the dementia.

• Systolic blood pressure >165 or <90 mmHg or diastolic blood pressure >95 or <60 mmHgat the time of screening.

• Clinically significant anemia (i.e. hemoglobin <11 g/dL for males or <10 g/dL forfemales) or presence of hemoglobinopathies which would prevent accurate assessment ofHbA1c.

• Abnormal kidney function tests (>1.5 the upper limit of normal (ULN)).

• ALT, AST, or alkaline phosphatase values >2.5 times the ULN, total bilirubin values >1.5 times the ULN, or history of severe hepatobiliary disease (e.g. hepatitis B or C,or cirrhosis, Child-Pugh Class B/C).

(Note: For subjects with a diagnosis of Gilberts Syndrome and an isolated increase in totalbilirubin >1.5 ULN, fractionation should be performed. If all of the following conditionsare met, the patient may enter or remain in the study, even if total bilirubin >1.5 ULN:

• an elevated unconjugated (indirect) bilirubin;

• the percentage of direct bilirubin <35%;

• ALT, AST, and alkaline phosphatase <2.5 ULN if subject is in screening (<2.0 ULN forCanadian subjects only), or ≤3 ULN if subject is already randomized into the study)

• History of a bone marrow transplant.

• Subject is unable (with assistance, if appropriate) to take study medication asprescribed throughout the study or is at risk of non-compliance with study medicationor procedures.

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

• In France, a subject is neither affiliated with nor a beneficiary of a social securitycategory.

• The French subject has participated in any study using an investigational drug duringthe previous 30 days or 5 half-lives (whichever is longer).

• Cognitive tasks prescribed for cognitive rehabilitation and performed under medicalsupervision are prohibited for 6 months prior to Screening, as well as for theduration of the study.