Rosiglitazone (Extended Release Tablets) As Adjunctive Therapy In 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 following criteria apply:

• Male or female subject with a clinical diagnosis of probable Alzheimer's disease in accordance with NINCDS-ADRDA criteria (Appendix 2).

(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 26 inclusive at Screening.
• Hachinski Ischemia Score ≤ 4 at Screening (See Appendix 3).
• Age ≥50 and ≤90 years.
• At least 6 months of ongoing acetylcholinesterase inhibitor therapy for Alzheimer's disease, with stable dosing for at least the last 2 months (and with no intent to change for the duration of the study).
• Current use of medication is in accordance with the criteria listed in Table 2 (Permitted Medications, Section 8.1).
• Female subjects must be post-menopausal (i.e. >1 year without menstrual period), surgically sterile, or agree to use adequate method of contraception (Appendix 4) for the duration of the study. Female subjects who are pre-menopausal or who have been post-menopausal for 7, the Investigator 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 be allowed 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 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.
• Clinically significant peripheral edema at the time of screening.
• Current or recent drug or alcohol abuse or dependence (defined by DSM-IV criteria for substance-related disorders), or recent or remote history of the same if that could be a contributing factor to the dementia.
• Systolic blood pressure >165 or 95 or 1.5 times 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 total bilirubin >1.5 ULN, fractionation should be performed. If all of the following conditions are 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 for Canadian 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 as prescribed throughout the study or is at risk of non-compliance with study medication or 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 security category.
• The French subject has participated in any study using an investigational drug during the previous 30 days or 5 half-lives (whichever is longer).
• Cognitive tasks prescribed for cognitive rehabilitation and performed under medical supervision are prohibited for 6 months prior to Screening, as well as for the duration of the study.