Study Of Rosiglitazone XR In Subjects With Mild-to-Moderate Alzheimers

A serious adverse event is defined as any untoward medical occurrence that, at any dose results in death, life-threatening condition, requires hospitalization or prolongation of existing hospitalization, results in disability or incapacity, or a congenital anomaly or birth defect. The SAEs and deaths are reported from Visit 1 (W0) till end of the follow-up period (W110)

Edema 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. Percentage of participants reported with edema as AESI were reported.

SBP and DBP of participant were recorded in sitting posture as vital sign at each visit. The blood pressure (BP) values were identified as of potential clinical concern if the vales were out of the reference range (for SBP, 90 to 140 mmHg and DBP, 50 to 90 mmHg) or meet a change from Baseline criterion. The change from Baseline criterion for SBP, was increase from Baseline (high) if increased by more than or equal to (>=) 40 mmHg from Baseline; decrease from Baseline (low) if decreased by >= 30 mmHg from Baseline. For DBP, increase form Baseline (high) if increased by >= 30 mmHg from Baseline; decrease from Baseline (low) if decreased by >= 20 mmHg from Baseline. The Baseline assessments were referred to assessments at Visit 1 (W 0). Change from Baseline was measured as the blood pressure value recorded at specified visit minus the Baseline value.

HR of participants was recorded as vital sign at each visit. The HR values were identified as of potential clinical concern if the vales were out of the reference range 50 to 100 beats per minute (BPM) or meet a change from Baseline criterion. The change from Baseline criterion was as, increase in HR (high) from Baseline if HR was increased by >= 30 bpm or decrease in HR (Low) from Baseline if HR was decreased by >= 30 bpm from Baseline. The Baseline assessments were referred to assessments at Visit 1 (W 0). Change from Baseline was measured as the HR at specified visit minus the Baseline value.

SBP and DBP of participant were recorded in sitting posture as vital sign at each visit. The blood pressure (BP) values were identified as of potential clinical concern if the vales were out of the reference range (for SBP, 90 to 140 mmHg and DBP, 50 to 90 mmHg) or meet a change from Baseline criterion. The change from Baseline criterion for SBP, was increase from Baseline (high) if increased by more than or equal to (>=) 40 mmHg from Baseline; decrease from Baseline (low) if decreased by >= 30 mmHg from Baseline. For DBP, increase form Baseline (high) if increased by >= 30 mmHg from Baseline; decrease from Baseline (low) if decreased by >= 20 mmHg from Baseline. The Baseline assessments were referred to assessments at Visit 1 (W 0). Change from Baseline was measured as the blood pressure value recorded at specified visit minus the Baseline value.

HR of participants was recorded as vital sign at each visit. The HR values were identified as of potential clinical concern if the vales were out of the reference range 50 to 100 beats per minute (BPM) or meet a change from Baseline criterion. The change from Baseline criterion was as, increase in HR (high) from Baseline if HR was increased by >= 30 bpm or decrease in HR (Low) from Baseline if HR was decreased by >= 30 bpm from Baseline. The Baseline assessments were referred to assessments at Visit 1 (W 0). Change from Baseline was measured as the HR at specified visit minus the Baseline value. Number of participants with abnormal HR at any time during treatment period were reported.

BW of participants were recorded as vital sign at each visit. The BW were identified as of potential clinical concern if the vales were increased or decreased from Baseline by >=7%. The Baseline assessments were referred to assessments at Visit 1 (W0). Change from Baseline was measured as the BW at specified visit minus the Baseline value.

BW of participants were recorded as vital sign at each visit. The BW were identified as of potential clinical concern if the vales were increased or decreased from Baseline by >=7%. The Baseline assessments were referred to assessments at Visit 1 (W0). Change from Baseline in BW was measured as the BW value at specified visit minus the Baseline BW value. Number of participants with abnormal BW at any time during treatment period were reported.

Non-fasting measures of lipid metabolism including cholesterol (TC), high density lipoprotein (HDL), low density lipoprotein (LDL), triglycerides (TG) were measured at Baseline (W0), W4, W16, W36, W52, Year 2 W24 and Follow-up. The Baseline assessments were referred to assessments at Visit 1 (W0). Change from Baseline was calculated as the value at the indicated visit minus the Baseline value.

The hematological parameters including eosinophils, lymphocytes, monocytes, platelet count, Segmented Neutrophils, total neutrophils, white blood cell (WBC), red blood cell (RBC) counts, hemoglobin, hematocrit count, mean corpuscle hemoglobin (MCH) and mean corpuscle volume (MCV) were analyzed as safety parameters. The number of participants with values outside the reference range (potential clinical concern ) at any time on treatment (ATOT) and follow-up period were reported. The treatment period was till W104 followed by 6 weeks of follow-up period till W110 of study.

The clinical chemistry parameters including alanine amino transferase (ALT), aldolase, aspartate amino transferase (AST), blood urea nitrogen /creatinine (BUN/Creat) ratio, cholesterol (Chol), creatine kinase, creatinine, direct bilirubin, gamma glutamyl transferase (GGT), glucose, high density lipid (HDL), low density lipid (LDL), potassium, troponin 1, and urea were assessed as safety parameters. The number of participants with values outside the reference range (potential clinical concern ) at any time on treatment (ATOT) and follow-up period were reported. The treatment period was till W104 followed by 6 weeks of follow-up period till W110 of study.

The 11-item ADAS-cog was used to 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 was referred to Visit 1 (W0)assessments. Change from Baseline was calculated as value at scheduled time point minus Baseline value.

The CIBIC+ score used for global functioning assessment. The CIBIC+ assessment comprised of a 7-point rating of severity. It was rated on a scale of 1 to 7 as 1: markedly improved, 2.: moderately improved, 3: minimally improved, 4: no change, 5: minimally worse, 6: moderately worse and 7: markedly worse; The lower score indicated betterment in functioning and higher score means greater dysfunction. The scale was based on interviews with the participant and the caregiver and was completed by an independent rater.

The MMSE consisted of 11 tests of orientation, memory (recent and immediate), concentration, language and praxis. Scores range from 0 to 30, with lower scores indicating greater cognitive impairment. The scale was completed by the investigator, based on the performance of the participant, and took approximately 5 to 10 minutes to administer. Change from parent Baseline in MMSE was analyzed using a mixed model for repeated measures (MMRM). Baseline was referred to Visit 1 (W0)assessments. Change from Baseline was calculated as value at scheduled time point minus Baseline value.

The 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) multiplied by 100. The DAD was conducted as an interview with the caregiver and took approximately 20 minutes. Baseline was referred to Visit 1 (W0) assessments. Change from Baseline was calculated as value at scheduled time point minus Baseline value.

The NPI assessed behavioural disturbances comprises 10 dimensions: delusions, hallucinations, dysphoria, apathy, euphoria, disinhibition, aggressiveness and agitation, irritability, anxiety and aberrant motor activity. The participant caregiver asked about behaviour in the participant. If "Yes", the informant then rates both the severity on a 3-point scale, 1: mild to 3: severe (total range: 0-36) and the frequency using a 4-point scale, 1: occasionally to 4: very frequently. The total domain score was frequency × severity. The distress was scored on 5-point scale, 0: no distress to 5 - very severe or extreme. A total NPI score was calculated by adding all domain scores together: NPI total score (from 0-144) and NPI distress score (from 0-60), with higher scores indicating more severe behavioral disturbance. Baseline was referred to Visit 1 (W0) assessments. Change from Baseline was calculated as value at scheduled time point minus Baseline value.

HbA1c was evaluated as safety parameter in this study. The values of change from Baseline was presented. The Baseline assessments were referred to assessments at Visit 1 (W0). Change from Baseline was measured as the BW at specified visit minus the Baseline value.