rosiglitazone

The 11-item ADAS-Cog assessed a range of cognitive abilities including memory, comprehension, orientation in time and place and spontaneous speech. Items were evaluated by tests and clinician ratings on a 5-point scale. Scores ranged from 0-70 with higher scores indicates more dysfunction. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline is defined as value at W0. Estimated value was calculated by Active treatment minus Placebo. The adjusted means were presented. A hierarchical testing procedure was used to control for the two rosiglitazone dose groups and the three genetic subgroups. There was no adjustment for the donepezil versus placebo comparisons, which were included to assess the sensitivity of the trial to detect a treatment effect.

The 11-item ADAS-Cog assessed a range of cognitive abilities including memory, comprehension, orientation in time and place and spontaneous speech. Items were evaluated by tests and clinician ratings on a 5-point scale. Scores ranged from 0-70 with higher scores indicates more dysfunction. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline is defined as value at W0. Estimated value was calculated by Active treatment minus Placebo. A hierarchical testing procedure was used to control for the two rosiglitazone dose groups and the three genetic subgroups. There was no adjustment for the donepezil versus placebo comparisons, which were included to assess the sensitivity of the trial to detect a treatment effect.

The 11-item ADAS-Cog assessed a range of cognitive abilities including memory, comprehension, orientation in time and place and spontaneous speech. Items were evaluated by tests and clinician ratings on a 5-point scale. Scores ranged from 0-70 with higher scores indicates more dysfunction. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline is defined as value at W0. Estimated value was calculated by Active treatment minus Placebo. A hierarchical testing procedure was used to control for the two rosiglitazone dose groups and the three genetic subgroups. There was no adjustment for the donepezil versus placebo comparisons, which were included to assess the sensitivity of the trial to detect a treatment effect.

The CIBIC+ assessment comprised of a 7-point rating of severity (at baseline) and change (at indicated time points). 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; higher score means greater dysfunction. It was based on interviews with the par. and caregiver by an independent rater. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at W0. Endpoint treatment differences which were adjusted to take account of missing data are derived. Estimated value was calculated by Active treatment minus Placebo. A hierarchical testing procedure was used to control for the two rosiglitazone dose groups and the three genetic subgroups. There was no adjustment for the donepezil versus placebo comparisons, which were included to assess the sensitivity of the trial to detect a treatment effect.

The CIBIC+ assessment comprised of a 7-point rating of severity (at baseline) and change (at indicated time points). 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; higher score means greater dysfunction. It was based on interviews with the par. and caregiver by an independent rater. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at W0. Endpoint treatment differences which were adjusted to take account of missing data are derived. Estimated value was calculated by Active treatment minus Placebo. A hierarchical testing procedure was used to control for the two rosiglitazone dose groups and the three genetic subgroups. There was no adjustment for the donepezil versus placebo comparisons, which were included to assess the sensitivity of the trial to detect a treatment effect.

The CIBIC+ assessment comprised of a 7-point rating of severity (at baseline) and change (at indicated time points). 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; higher score means greater dysfunction. It was based on interviews with the par. and caregiver by an independent rater. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at W0. Endpoint treatment differences which were adjusted to take account of missing data are derived. Estimated value was calculated by Active treatment minus Placebo. A hierarchical testing procedure was used to control for the two rosiglitazone dose groups and the three genetic subgroups. There was no adjustment for the donepezil versus placebo comparisons, which were included to assess the sensitivity of the trial to detect a treatment effect.

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 range from 0 to 70 with higher scores indicating greater dysfunction. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at Week 0. Estimated value was calculated by Active treatment minus Placebo. The adjusted means were presented. A hierarchical testing procedure was used to control for statistical tests in the two RSG dose groups and the genetic subgroups.

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 range from 0 to 70 with higher scores indicating greater dysfunction. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value a t Week 0. Estimated value was calculated by Active treatment minus Placebo. The adjusted means were presented. A hierarchical testing procedure was used to control for statistical tests in the two RSG dose groups and the genetic subgroups.

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 range from 0 to 70 with higher scores indicating greater dysfunction. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value a t Week 0. Estimated value was calculated by Active treatment minus Placebo. The adjusted means were presented. A hierarchical testing procedure was used to control for statistical tests in the two RSG dose groups and the genetic subgroups.

The CDR-SB was a validated clinical assessment of global function in patients with 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", can be added together to give the CDR-Sum of Boxes which ranges from 0 to 18 (severe impairment). Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value a t Week 0. Estimated value was calculated by Active treatment minus Placebo. The adjusted means were presented. Primary inference will be based on the week 48 treatment differences obtained from the MMRM model. A hierarchical testing procedure was used to control for statistical tests in the two RSG dose groups and the genetic subgroups.

The CDR-SB was a validated clinical assessment of global function in patients with 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", can be added together to give the CDR-Sum of Boxes which ranges from 0 to 18 (severe impairment). Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value a t Week 0. Estimated value was calculated by Active treatment minus Placebo. The adjusted means were presented. Primary inference will be based on the week 48 treatment differences obtained from the MMRM model. A hierarchical testing procedure was used to control for statistical tests in the two RSG dose groups and the genetic subgroups.

The CDR-SB was a validated clinical assessment of global function in patients with 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", can be added together to give the CDR-Sum of Boxes which ranges from 0 to 18 (severe impairment). Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value a t Week 0. Estimated value was calculated by Active treatment minus Placebo. The adjusted means were presented. Primary inference will be based on the week 48 treatment differences obtained from the MMRM model. A hierarchical testing procedure was used to control for statistical tests in the two RSG dose groups and the genetic subgroups.

Baseline value was value on Day 0. Change from Baseline was defined as value at Week 16 minus Baseline value. The full analysis set used which was defined as remaining after participant who infringed on the following events were excluded from the randomized participants, who did not take the investigational drug during or after the treatment period (amount of investigational drug taken was zero tablets) and who were not measured for HbA1c even once as the observation period Baseline value or in the treatment period (after the investigational drug was prescribed), or for whom the above were unavailable (including cases that the above were considered missing measurements due to a defective sample).

The primary efficacy endpoint was change in PAV (defined as total atheroma volume divided by total vessel volume x 100) within a 40 mm segment in non-intervened coronary arteries from Baseline to Month 18, based upon Intravascular Ultrasound (IVUS) assessment.

Model Adjusted Change (MAC) = Baseline + Region + Sex + Treatment + Cardiac Procedure + Prior Oral Anti-Hyperglycemic Diabetic Medications(s) (OAD).

The number of participants with cardiovascular death events (death due to cardiovascular causes or deaths with insufficient information to rule out a cardiovascular cause) and cardiovascular hospitalisation events (hospitalisation for a cardiovascular event, excluding planned admissions not associated with a worsening of the disease/condition of the participant) was recorded.

All deaths identified during the original record study and discovered after the re-adjudication efforts began were included.

IR was based on original RECORD endpoint definitions. CV death= no unequivocal non-CV cause (sudden death, death from acute vascular events, heart failure, acute MI, other CV causes, and deaths adjudicated as unknown cause). MI event=hospitalization + elevation of specific cardiac biomarkers above the upper limit of normal + cardiac ischemia symptoms/new pathological electrocardiogram findings. Stroke event=hospitalization + rapidly developed clinical signs of focal/global disturbance of cerebral function for more than 24 hours, with no apparent cause other than a vascular origin.

Independent re-adjudication was based on the Standard Data Collection for Cardiovascular Trials Initiative (draft October 2011) endpoint definitions. CV death included death resulting from an acute MI; sudden cardiac death and death due to heart failure, stroke, and to other CV causes. Deaths of unknown cause were counted as CV deaths. MI was defined as evidence of myocardial necrosis in a clinical setting consistent with myocardial ischemia. Stroke was defined as an acute episode of neurological dysfunction caused by focal or global brain, spinal cord, or retinal vascular injury.

The number of participants with a CV death (or unknown) as determined by independent re-adjudication using the original RECORD endpoint definitions was recorded. CV death was defined as any death for which an unequivocal non-CV cause could not be established. CV death included death following heart failure, death following acute myocardial infarction (MI), sudden death, death due to acute vascular events, and other CV causes. Deaths due to unknown causes were classified as "unknown deaths," but were counted as CV deaths for the analysis of this endpoint.

The number of participants with a CV (or unknown) death as determined by independent re-adjudication using the Standard Data Collection for Cardiovascular Trials Initiative (draft October 2011) endpoint definitions was recorded. CV death included death resulting from an acute myocardial infarction (MI), sudden cardiac death, death due to heart failure, death due to stroke, and death due to other CV causes. Deaths of unknown cause were counted as CV deaths.

The number of participants with an MI (fatal or non-fatal) event as determined by independent re-adjudication using the original RECORD endpoint definitions was recorded. An event of MI was defined as hospitalization plus elevation of cardiac biomarkers troponin (TN) I and/or TNT above the upper limit of normal (ULN) or creatinine kinase (CK) MB (M=muscle type; B=brain type) isoenzyme \>= 2x the ULN or CK \> 2x the ULN plus typical symptoms of cardiac ischemia or new pathological electrocardiogram findings, or cause of death adjudicated as MI.

The number of participants with an MI (fatal or non-fatal) event as determined by independent re-adjudication using the Standard Data Collection for Cardiovascular Trials Initiative (draft October 2011) endpoint definitions was recorded. An event of MI was defined as evidence of myocardial necrosis in a clinical setting consistent with myocardial ischemia.

Par. with a stroke (fatal or non-fatal) event as determined by independent re-adjudication using the original RECORD endpoint definitions was recorded. A stroke event=hospitalization plus rapidly developed clinical signs of focal (or global) disturbance of cerebral function lasting more than 24 hours (unless interrupted by thrombolysis, surgery, or death), with no apparent cause other than a vascular origin, including par. presenting clinical signs/symptoms suggestive of subarachnoid haemorrhage/intracerebral haemorrhage/cerebral ischemic necrosis or cause of death adjudicated as stroke.

The number of participants with a stroke (fatal or non-fatal) event as determined by independent re-adjudication using the Standard Data Collection for Cardiovascular Trials Initiative (draft October 2011) endpoint definitions was recorded. An event of stroke was defined as an acute episode of neurological dysfunction caused by focal or global brain, spinal cord, or retinal vascular injury.

An AE was defined as any untoward medical occurrence or clinical investigation in a participant, temporally associated with the use of a medicinal product, whether or not, considered related to the medicinal product. For marketed medicinal products, this also included failure to produce expected benefits (i.e. lack of efficacy), abuse or misuse. The number of participants with all AEs, drug related AEs, serious adverse events (SAEs), AE leading to permanent (prm) discontinuation (disc) of study drug or withdrawal were reported.

Global CMRGlu index was related to grey matter of brain. Regional CMRGlu index was related to assessment of different regions of brain namely posterior cingulate gyrus, frontal lobe, parietal lobe, posterior temporal lobe, cerebellum, and medial temporal lobe. Evaluation of medial temporal lobe CMRGlu included assessment of medial anterior temporal lobe, paraHippocampal Ambiens gyrus, amygdala, and hippocampus. The regional CMRGlu index is directly proportional to the true metabolic rate of glucose. Baseline was defined as Day 1 of the 12 months treatment period. Change from Baseline is the value at indicated time point minus the Baseline value. Data has been presented for arithmetic mean; however, statistical analysis has been presented for adjusted or least square (LS) mean.

Mayo score decrease \>=2 points adjusted for age and smoking status.

The area under the plot of plasma concentration of drug against time after drug administration is defined as the area under the curve (AUC). The AUC 0-t is calculated from time 0 (prior to administration of medication) to time t (the time of the last quantifiable concentration). The AUC is of particular use in estimating the bioavailability of drugs, by measuring the extent of absorption. ng, nanograms; ml, milliliter.

Cmax is defined as the maximum or "peak" concentration of a drug observed after its administration. Cmax is one of the parameters of particular use in estimating the bioavailability of drugs, by measuring the total amount of drug absorbed.

The area under the plot of plasma concentration of drug against time after drug administration is defined as the area under the curve (AUC). The AUC0-infinity is calculated from time 0 (prior to administration of medication) to infinity (the time of complete elimination of the drug). The AUC is of particular use in estimating the bioavailability of drugs, by measuring the extent of absorption.

The area under the plot of plasma concentration of drug against time after drug administration is defined as the area under the curve (AUC). The AUC0-t is calculated from time 0 (prior to administration of medication) to time t (the time of the last quantifiable concentration). The AUC is of particular use in estimating the bioavailability of drugs, by measuring the extent of absorption. ng, nanograms; ml, milliliter.

The area under the plot of plasma concentration of drug against time after drug administration is defined as the area under the curve (AUC). The AUC0-infinity is calculated from time 0 (prior to administration of medication) to infinity (the time of complete elimination of the drug). The AUC is of particular use in estimating the bioavailability of drugs, by measuring the extent of absorption.

Cmax is defined as the maximum or "peak" concentration of a drug observed after its administration. Cmax is one of the parameters of particular use in estimating the bioavailability of drugs, by measuring the total amount of drug absorbed.

Plasma AUC (0-inf) of probe and metabolite (where applicable) when administered alone, in combination with other probes/inhibitors