Open-Label Extension Study Of Rosiglitazone XR As Adjunctive Therapy In Subjects With Mild-to-Moderate Alzheimers

An AE is defined as any untoward medical occurrence in a patient or clinical investigation participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. The severity of the AE'S was categorized as mild, moderate and severe. Number of participants reporting AEs during the on treatment phase of the study.

Time frame: Up to 76 Weeks

Population: All Subjects (Full population), comprised of all participants who took at least one dose of open-label study medication.

The 11-item ADAS-Cog assessed a range of cognitive abilities including memory, comprehension, orientation in time and place and spontaneous speech. Most items were evaluated by tests, but some were dependent on clinician ratings on a five point scale. Scores ranged from 0 to 70 with higher scores indicating greater dysfunction. Baseline for the open-label study was the latest assessment from Week 48 of parent studies to the first dose of open-label medication (Week 0). Change from Baseline was calculated as the Baseline value minus the value at the specified time point.

Time frame: Baseline (Week 0) and Week 24, 52

Population: All subject (Full population). Only those participants available at the specified time points were analyzed. The analysis was done on the full population and was repeated for APOE subgroups (negative, positive, homozygotes, heterozygotes).

The CDR-SB is a validated clinical assessment of global function in par. with Alzheimer's disease (AD). Impairment was scored in each of 6 cognitive categories on a scale in which none = 0, questionable = 0.5, mild = 1, moderate = 2, and severe = 3. The 6 individual category ratings, or box scores, were added together to give the CDR-Sum of Boxes which ranged from 0 to 18 (severe impairment). Baseline for the open-label study was the latest assessment from Week 48 of parent studies to the first dose of open-label medication (Week 0). Change from Baseline was calculated as the Baseline value minus the value at the specified time point.

Time frame: Baseline (Week 0) and Week 24, 52

Population: All subject population. Only those participants available at the specified time points were analyzed. The analysis was done on the full population and was repeated for APOE subgroups (negatives, positives, homozygotes, heterozygotes).

DAD, assessed the ability of a participant to execute basic and instrumental activities of daily living (ADL) and leisure activities. The scale consists of 40 questions assessing basic and instrumental ADLs. This scale assesses a participant's ability to initiate, plan, and perform activities related to hygiene, dressing, continence, eating, meal preparation, telephoning, going on an outing, finance and correspondence, medications, leisure, and housework. Each item was scored as yes: 1, no: 0 and N/A: not applicable. Higher scores indicate less disability with a score of 100 indicating no disability and 0 indicating no functional ability. The percentage score was calculated as (DAD total score/total number of applicable items) \* 100. Baseline for the open-label study was the latest assessment from Week 48 of parent studies to the first dose of open-label medication (Week 0). Change from Baseline was calculated as the Baseline value minus the value at the specified time point.

Time frame: Baseline (Week 0) and Week 24, 52

Population: All subject (Full population). Only those participants available at the specified time points were analyzed.The analysis was done on the full population and was repeated for APOE subgroups (negatives, positives, homozygotes, heterozygotes).

The MMSE consisted of 11 tests of orientation, memory (recent and immediate), concentration, language and praxis. Scores ranged from 0 to 30, with lower scores indicating greater cognitive impairment. Baseline for the open-label study was the latest assessment from Week 48 of parent studies to the first dose of open-label medication (Week 0). Change from Baseline was calculated as the Baseline value minus the value at the specified time point.

Time frame: Baseline (Week 0) and Week 24, 52

Population: All subject (Full population). Only those participants available at the specified time points were analyzed. The analysis was done on the full population and was repeated for APOE subgroups (negatives, positives, homozygotes, heterozygotes).

12-domain caregiver assessment of behavioral disturbances occurring in dementia: delusions, hallucinations, agitation, depression, anxiety, euphoria, apathy, disinhibition, irritability, motor disturbance, appetite, nighttime behavior. A screening question is asked about each sub-domain. If the responses to these questions=participant has problems with a particular sub-domain of behavior, the caregiver asked all the questions about that domain, rating the frequency (1=occasionally to 4=very frequently) on a 4-point scale, their severity (1=Mild to 3=Severe) on a 3-point scale, and the distress on a 5-point scale. Total score=sum of each domain score(range 0-144);higher score=greater behavioral disturbances. Baseline for the open-label study was the latest assessment from Week 48 of parent studies to the first dose of open-label medication (Week 0). Change from Baseline was calculated as the Baseline value minus the value at the specified time point.

Time frame: Baseline (Week 0) and Week 24, 52

Population: All subject (Full population). Only those participants available at the specified time points were analyzed.The analysis was done on the full population and was repeated for APOE subgroups (negatives, positives, homozygotes, heterozygotes).

The clinical chemistry data included non-fasting measures of lipid metabolism (TC,HDL,LDL,triglycerides). Baseline for the open-label study was the latest assessment from Week 48 of parent studies to the first dose of open-label medication. Change from Baseline was measured as the lipids (TC,HDL,LDL,triglycerides) value recorded at specified visit minus the Baseline value.

Time frame: Up to 82 Weeks (including follow up)

Population: All subject (Full population). Only those participants available at the specified time points were analyzed.

BW was measured at all visits, without shoes and wearing light clothing. Baseline for the open-label study was the latest assessment from Week 48 of parent studies to the first dose of open-label medication. Change from Baseline was measured as the body weight at specified visit minus the Baseline value.

Time frame: Up to 70 Weeks (including follow up)

Population: All subject (Full population). Only those participants available at the specified time points were analyzed.

Vital sign HR was measured at each visit. HR was measured once, after the participant sat quietly for at least 5 minutes. Baseline for the open-label study was the latest assessment from Week 48 of parent studies to the first dose of open-label medication. Change from Baseline was measured as the HR at specified visit minus the Baseline value.

Time frame: Up to 70 Weeks (including follow up)

Population: All subject (Full population). Only those participants available at the specified time points were analyzed.

Vital signs SBP and DBP were measured at each visit. All measurements were made on the participant non-dominant arm supported at heart level, using the same cuff size and same equipment. Blood pressure was measured once, after the participant sat quietly for at least 5 minutes. DBP was measured at the disappearance of Korotkoff sounds (Phase V). If the participant was a smoker or used tobacco products, a period of 30 minutes without tobacco was allowed before taking these measurements. Baseline for the open-label study was the latest assessment from Week 48 of parent studies to the first dose of open-label medication. Change from Baseline was measured as the blood pressure value recorded at specified visit minus the Baseline value.

Time frame: Up to 70 Weeks (including follow up)

Population: All subject (Full population). Only those participants available at the specified time points were analyzed.

Oedema was considered as adverse event of special interest (AESI). The process for AESI selection was based on RSG's pharmacologic class and relevant AEs potentially associated with RSG. The number of participants and their percentage for the adverse event of the various types of oedema were reported.

Time frame: Up to 76 Weeks

Population: All subject (Full population)

The frequency of participant vital sign weight was obtained to check if the values have CFB of PCC IFB \>=7 percent. With the exception of Week 4, when participants were first titrated to the 8mg RSG XR dose, at every time point in the study where weight was measured the percentage of participants experienced an increase in BW of PCC was approximately 2 times greater than the percentage of participants experiencing an decrease in BW of PCC DFB \>=7 percent. The number of participants with values of PCC including follow up were reported.

Time frame: Up to 70 Weeks (including follow up)

Population: All subject (Full population). Only those participants available at the specified time points were analyzed.

The clinical chemistry data included alanine amino transferase (ALT), albumin, aldolase, asparatate amino transferase (AST), BUN/creatinine ratio, carbon dioxide(CO2) content, chloride, cholesterol, creatinine kinase (CK), creatinine, direct bilirubin (DB), gamma glutamyl transferase (GGT), glucose, glycosylated Hemoglobin (HbA1C), HDL, LDL, lactate dehydrogenase (LD), magnesium, potassium, sodium, total bilirubin (TB), triglycerides, troponin I, urea. The number of participants with values of PCC (defined as high and low) ATOT were reported.

Time frame: Up to Week 82 (including follow up)

Population: All subject population (Full population). Only those participants available at the specified time points were analyzed.

The hematology data included eosinophils, haematocrit, haemoglobin, lymphocytes, mean corpuscular haemoglobin (MCH), mean corpuscular volume (MCV), monocytes, platelet count, red cell distribution width (RDW), red blood cell (RBC) count, segmented neutrophils (SN), total neutrophils (TN), white blood cell (WBC) count. The number of participants with values of PCC (defined as high and low) ATOT were reported.

Time frame: Up to Week 82 (including follow up)

Population: All subject (Full population). Only those participants available at the specified time points were analyzed.

HR was measured once, after the participant sat quietly for at least 5 minutes. The frequency of participant vital sign heart rate was obtained to check if the values lie outside of a pre-determined reference range (RR) 50-100 bpm or have a change from Baseline of PCC IFB \>=30 and DFB \>=30. The number of participants with values of PCC including follow up were reported.

Time frame: Up to 70 Weeks (including follow up)

Population: All subject (Full population). Only those participants available at the specified time points were analyzed.

The frequency of participant vital sign sitting blood pressure was obtained to check if the values lie outside of a pre-determined reference range (RR) for SBP 90-140 mmHg, DBP 50-90 mmHg or have a change from Baseline of PCC for SBP increase from Baseline (IFB) \>=40, decrease from Baseline (DFB) \>= 30 for and for DBP (IFB) \>= 30 ,DFB \>= 20. The number of participants with values of PCC at any time on treatment (ATOT) and follow up were reported.

Time frame: Up to 70 Weeks (including follow up)

Population: All subject (Full population). Only those participants available at the specified time points were analyzed.

A SAE is defined as any untoward medical occurrence that, at any dose results in death, is a life-threatening condition, requires hospitalization or prolongation of existing hospitalization, results in disability or incapacity, or a congenital anomaly or birth defect. Number of participants with SAEs and deaths were reported for treatment duration of the study.

Time frame: Up to 76 Weeks

Population: All subject (Full population)