Trial Outcomes & Findings for Brain Imaging Study Of Rosiglitazone Efficacy And Safety In Alzheimer's Disease (NCT NCT00265148)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

80 participants

Primary outcome timeframe

Baseline (Day 1) and Month 12

Results posted on

2020-11-18

Participant Flow

This study was conducted from 18 May 2004 to 10 July 2008 at centers across Canada, the United States (US), and the United Kingdom (UK). A total of 80 participants with mild to moderate Alzheimer's disease were planned to be enrolled.

A total of 135 participants were screened of which 80 participants were randomized, during which they received oral Rosiglitazone-extended (RSG-XR) release 4 milligrams (mg) once daily. Intent- to-treat (ITT) population included 78 participants who had more than or equal to 1 efficacy, pharmacokinetic, pharmacodynamics, or genetic assessment.

Participant milestones

Participant milestones
Measure	Placebo Eligible participants received unit oral dose of visually matching Placebo 4 milligrams (mg) for one month. Participants received escalated dose of 8 mg matching placebo for next 12 months and were followed-up to 30 days.	Rosiglitazone Eligibale participants received unit oral Rosiglitazone extended release (RSG XR) 4 mg for one month with or without food. Participants received escalated dose of rosiglitazone-XR for next 12 months and were followed-up to 30 days.
Overall Study STARTED	40	40
Overall Study COMPLETED	31	31
Overall Study NOT COMPLETED	9	9

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Eligible participants received unit oral dose of visually matching Placebo 4 milligrams (mg) for one month. Participants received escalated dose of 8 mg matching placebo for next 12 months and were followed-up to 30 days.	Rosiglitazone Eligibale participants received unit oral Rosiglitazone extended release (RSG XR) 4 mg for one month with or without food. Participants received escalated dose of rosiglitazone-XR for next 12 months and were followed-up to 30 days.
Overall Study Adverse Event	2	2
Overall Study Lack of Efficacy	0	2
Overall Study Protocol Violation	3	2
Overall Study Lost to Follow-up	0	1
Overall Study Withdrawal by Subject	2	1
Overall Study Physician Decision	1	0
Overall Study Increasing frailty	0	1
Overall Study Subject chose to change of the dose	1	0

Baseline Characteristics

Brain Imaging Study Of Rosiglitazone Efficacy And Safety In Alzheimer's Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=39 Participants Eligible participants received unit oral dose of visually matching Placebo 4 milligrams (mg) for one month. Participants received escalated dose of 8 mg matching placebo for next 12 months and were followed-up to 30 days.	Rosiglitazone n=39 Participants Eligible participants received unit oral rosiglitazone extended release (RSG XR) 4 mg for one month with or without food. Participants received escalated dose of rosiglitazone-XR for next 12 months and were followed-up to 30 days.	Total n=78 Participants Total of all reporting groups
Age, Continuous	70.2 Years STANDARD_DEVIATION 9.28 • n=5 Participants	72.5 Years STANDARD_DEVIATION 9.60 • n=7 Participants	71.4 Years STANDARD_DEVIATION 9.45 • n=5 Participants
Sex: Female, Male Female	19 Participants n=5 Participants	17 Participants n=7 Participants	36 Participants n=5 Participants
Sex: Female, Male Male	20 Participants n=5 Participants	22 Participants n=7 Participants	42 Participants n=5 Participants
Race/Ethnicity, Customized American hispanic	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Black	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized White/Caucasian	37 Participants n=5 Participants	37 Participants n=7 Participants	74 Participants n=5 Participants
Race/Ethnicity, Customized Other Caucasiann/ Japanese	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1) and Month 12

Population: Intent-to-treat (ITT) population included all participants from all subjects population who had at least one or more than one post-baseline pharmacodynamic (PD) or biomarker, efficacy, or pharmacogenetic (PGx) assessment. Only those participants available at the time of assessment were analyzed.

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.

Outcome measures

Outcome measures
Measure	Placebo n=39 Participants Eligible participants received unit oral dose of visually matching Placebo 4 mg for one month. Participants received escalated dose of 8 mg matching placebo for next 12 months and were followed-up to 30 days.	Rosiglitazone n=39 Participants Eligible participants received unit oral rosiglitazone extended release (RSG XR) 4 mg for one month with or without food. Participants received escalated dose of rosiglitazone-XR for next 12 months and were followed-up to 30 days.
Change From Baseline (Day 1) in Global and Regional Indices of Cerebral Metabolic Rate of Glucose (CMRglu) at Month 12 Cerebellum	-0.2523 Milligrams per cubic centimeter(mg/cm^3) Standard Deviation 0.46730	-0.0248 Milligrams per cubic centimeter(mg/cm^3) Standard Deviation 0.38874
Change From Baseline (Day 1) in Global and Regional Indices of Cerebral Metabolic Rate of Glucose (CMRglu) at Month 12 Medial temporal lobe	-0.1950 Milligrams per cubic centimeter(mg/cm^3) Standard Deviation 0.33360	-0.0349 Milligrams per cubic centimeter(mg/cm^3) Standard Deviation 0.32429
Change From Baseline (Day 1) in Global and Regional Indices of Cerebral Metabolic Rate of Glucose (CMRglu) at Month 12 Grey matter	-0.2793 Milligrams per cubic centimeter(mg/cm^3) Standard Deviation 0.48541	-0.0887 Milligrams per cubic centimeter(mg/cm^3) Standard Deviation 0.34985
Change From Baseline (Day 1) in Global and Regional Indices of Cerebral Metabolic Rate of Glucose (CMRglu) at Month 12 Posterior cingulate gyrus	-0.3143 Milligrams per cubic centimeter(mg/cm^3) Standard Deviation 0.57567	-0.0786 Milligrams per cubic centimeter(mg/cm^3) Standard Deviation 0.36019
Change From Baseline (Day 1) in Global and Regional Indices of Cerebral Metabolic Rate of Glucose (CMRglu) at Month 12 Frontal lobe	-0.3087 Milligrams per cubic centimeter(mg/cm^3) Standard Deviation 0.55631	-0.1131 Milligrams per cubic centimeter(mg/cm^3) Standard Deviation 0.36876
Change From Baseline (Day 1) in Global and Regional Indices of Cerebral Metabolic Rate of Glucose (CMRglu) at Month 12 Parietal lobe	-0.3081 Milligrams per cubic centimeter(mg/cm^3) Standard Deviation 0.50596	-0.1175 Milligrams per cubic centimeter(mg/cm^3) Standard Deviation 0.33335
Change From Baseline (Day 1) in Global and Regional Indices of Cerebral Metabolic Rate of Glucose (CMRglu) at Month 12 Posterior temporal lobe	-0.2771 Milligrams per cubic centimeter(mg/cm^3) Standard Deviation 0.40458	-0.1122 Milligrams per cubic centimeter(mg/cm^3) Standard Deviation 0.32346

SECONDARY outcome

Timeframe: Baseline (Day 1), Months 1, and 6

Population: ITT population. Only those participants available at the time of assessment were analyzed

Global CMRGlu index was related to grey matter of brain. Baseline measurement was performed on Day 1. Change from Baseline is the value at indicated time point minus the Baseline value.

Outcome measures

Outcome measures
Measure	Placebo n=39 Participants Eligible participants received unit oral dose of visually matching Placebo 4 mg for one month. Participants received escalated dose of 8 mg matching placebo for next 12 months and were followed-up to 30 days.	Rosiglitazone n=39 Participants Eligible participants received unit oral rosiglitazone extended release (RSG XR) 4 mg for one month with or without food. Participants received escalated dose of rosiglitazone-XR for next 12 months and were followed-up to 30 days.
Change From Baseline (Day 1) in CMRGlu Indices at Months 1 and 6 Month 1	-0.1049 mg/cm^3 Standard Deviation 0.39301	0.0475 mg/cm^3 Standard Deviation 0.46904
Change From Baseline (Day 1) in CMRGlu Indices at Months 1 and 6 Month 6	-0.1556 mg/cm^3 Standard Deviation 0.36397	-0.0269 mg/cm^3 Standard Deviation 0.35311

SECONDARY outcome

Timeframe: Baseline (Day 1), and Months 1, 6, and 12

Population: ITT population. Only the participants available at the time of assessment were analyzed.

The BSR test included evaluating short-term memory of a participant to remember a list of unrelated words, to learn the words over 8 trials and to remember these words over 8 trials, and to remember these words during a 20 minute delay. The number of words recalled in delayed free recalls were analyzed. Other parameters analyzed included number recalled Trial 1 immediate, number recalled Trial 8 immediate, total number for all 8 immediate trials, and total number of uncued words recalled. Higher number of words recalled indicated better short term memory and positive treatment differences in these number of words recalled were indicative of superiority of drug over placebo. Baseline measurement was performed on Day 1. Change from Baseline is the value at indicated time point minus the Baseline value. Statistical analysis is presented for difference of means.

Outcome measures

SECONDARY outcome

Timeframe: Baseline (Day 1), Months1, 6, and 12

Population: ITT population. Only the participants available at the time of assessment were analyzed.

It is a measure of change from Baseline (Day 1) in clinical scale of AD status. A 3-card version test includes all card containing 50 items each. Participants were asked to complete all items and time in seconds was recorded. Participants first read color words printed in black, then named the printed color of the colored patches, and finally named the printed color of the colored words. The word condition was used to verify that participants were able to read colored words and time to perform color condition was considered as ' control'. The dependent variable was the time to complete the interference condition and the test could have presented in pencil and paper or on screen, both the ways. Change from Baseline is the value at indicated time point minus the Baseline value. Statistical analysis is presented for difference of means.

Outcome measures

Outcome measures
Measure	Placebo n=39 Participants Eligible participants received unit oral dose of visually matching Placebo 4 mg for one month. Participants received escalated dose of 8 mg matching placebo for next 12 months and were followed-up to 30 days.	Rosiglitazone n=39 Participants Eligible participants received unit oral rosiglitazone extended release (RSG XR) 4 mg for one month with or without food. Participants received escalated dose of rosiglitazone-XR for next 12 months and were followed-up to 30 days.
Change From Baseline (Day 1) in Delayed Free Recall Items Over Period by Stroop Colour Word Interference (SCWI) at Months 1, 6 and 12 Month 12	0.5 Milliseconds Standard Deviation 1.09	-0.3 Milliseconds Standard Deviation 1.78
Change From Baseline (Day 1) in Delayed Free Recall Items Over Period by Stroop Colour Word Interference (SCWI) at Months 1, 6 and 12 Month 1	-0.0 Milliseconds Standard Deviation 0.88	-0.4 Milliseconds Standard Deviation 1.33
Change From Baseline (Day 1) in Delayed Free Recall Items Over Period by Stroop Colour Word Interference (SCWI) at Months 1, 6 and 12 Month 6	0.1 Milliseconds Standard Deviation 0.97	-0.2 Milliseconds Standard Deviation 1.06

SECONDARY outcome

Timeframe: Baseline (Day 1), Months 1, 6, and 12

Population: ITT population. Only those participants available at the time of assessment were analyzed.

Change from Baseline = value at the indicated time point minus the Baseline(Day1) value. SSPAL is a cognitive test that involves object-location memory and learning. It is used to examine cognitive deficits in AD. Participants were asked to sit 50 cm away from screen and different pictures (target and distracter) were shown on a monitor. Responses were acquired from response box. Participants were informed by visual feedback whether the response was correct or incorrect and the accuracy was collected automatically. SSPAL responses were captured as new accuracy and global accuracy. New accuracy was defined as proportion of accurate responses per participant for recall of any new item (picture). Global accuracy was defined as proportion of accurate responses per participant for recall of all new items and their displayed locations (i.e. right or left position on the screen). The possible range for new and global accuracy is 0(worst) to 1(best). Higher values indicate better performance.

Outcome measures

Outcome measures
Measure	Placebo n=39 Participants Eligible participants received unit oral dose of visually matching Placebo 4 mg for one month. Participants received escalated dose of 8 mg matching placebo for next 12 months and were followed-up to 30 days.	Rosiglitazone n=39 Participants Eligible participants received unit oral rosiglitazone extended release (RSG XR) 4 mg for one month with or without food. Participants received escalated dose of rosiglitazone-XR for next 12 months and were followed-up to 30 days.
Change From Baseline (Day 1) in Simplified Spatial Paired Associate Learning (SSPAL) Response Over Period Global accuracy, Month 1	-0.0 Proportion of accurate responses Standard Deviation 0.16	0.0 Proportion of accurate responses Standard Deviation 0.06
Change From Baseline (Day 1) in Simplified Spatial Paired Associate Learning (SSPAL) Response Over Period Global accuracy, Month 6	-0.0 Proportion of accurate responses Standard Deviation 0.14	-0.0 Proportion of accurate responses Standard Deviation 0.12
Change From Baseline (Day 1) in Simplified Spatial Paired Associate Learning (SSPAL) Response Over Period Global accuracy, Month 12	-0.0 Proportion of accurate responses Standard Deviation 0.15	0.0 Proportion of accurate responses Standard Deviation 0.12
Change From Baseline (Day 1) in Simplified Spatial Paired Associate Learning (SSPAL) Response Over Period New accuracy, Month 1	0.1 Proportion of accurate responses Standard Deviation 0.22	0.0 Proportion of accurate responses Standard Deviation 0.17
Change From Baseline (Day 1) in Simplified Spatial Paired Associate Learning (SSPAL) Response Over Period New accuracy, Month 6	0.0 Proportion of accurate responses Standard Deviation 0.19	-0.0 Proportion of accurate responses Standard Deviation 0.29
Change From Baseline (Day 1) in Simplified Spatial Paired Associate Learning (SSPAL) Response Over Period New accuracy, Month 12	-0.0 Proportion of accurate responses Standard Deviation 0.22	-0.1 Proportion of accurate responses Standard Deviation 0.22

SECONDARY outcome

Timeframe: Baseline (Day 1) and up to 12 months

Population: ITT population. Only those participants available at the time of assessment were analyzed.

A motor reaction task was presented 4 runs of 50 trials each. In each trial, presentation of a central crosshair for 200 milliseconds (ms) was followed by display of a grey square for 800 ms. The square appeared in two of five possible positions relative to the crosshair (leftmost or rightmost). When the grey square became white, the participant was trained to press the a button. In each trial of the Simple Reaction Time Task, presentation of a central crosshair for 200 ms was followed by display of one square for 800 ms. For both simple and choice versions of the task, trial duration was 4000 ms maximum. The participant was immediately informed (by color changes of the white square) whether the response to each trial was correct or incorrect, and accuracy and reaction time (RT) are automatically calculated. Change from Baseline is the value at indicated time point minus the Baseline value.

Outcome measures

Outcome measures
Measure	Placebo n=39 Participants Eligible participants received unit oral dose of visually matching Placebo 4 mg for one month. Participants received escalated dose of 8 mg matching placebo for next 12 months and were followed-up to 30 days.	Rosiglitazone n=39 Participants Eligible participants received unit oral rosiglitazone extended release (RSG XR) 4 mg for one month with or without food. Participants received escalated dose of rosiglitazone-XR for next 12 months and were followed-up to 30 days.
Change From Baseline (Day 1) in Accuracy by Choice Reaction Time (CRT) Test Over Period Accuracy, Left, Month 6	-0.1 Percent accuracy Standard Deviation 0.16	0.0 Percent accuracy Standard Deviation 0.14
Change From Baseline (Day 1) in Accuracy by Choice Reaction Time (CRT) Test Over Period Accuracy, Right, Month 1	0.0 Percent accuracy Standard Deviation 0.02	0.0 Percent accuracy Standard Deviation 0.15
Change From Baseline (Day 1) in Accuracy by Choice Reaction Time (CRT) Test Over Period Accuracy, Left, Month 1	-0.0 Percent accuracy Standard Deviation 0.04	0.0 Percent accuracy Standard Deviation 0.15
Change From Baseline (Day 1) in Accuracy by Choice Reaction Time (CRT) Test Over Period Accuracy, Left, Month 12	-0.1 Percent accuracy Standard Deviation 0.14	0.0 Percent accuracy Standard Deviation 0.12
Change From Baseline (Day 1) in Accuracy by Choice Reaction Time (CRT) Test Over Period Accuracy, Right, Month 6	-0.0 Percent accuracy Standard Deviation 0.02	0.0 Percent accuracy Standard Deviation 0.15
Change From Baseline (Day 1) in Accuracy by Choice Reaction Time (CRT) Test Over Period Accuracy, Right, Month 12	-0.0 Percent accuracy Standard Deviation 0.13	0.0 Percent accuracy Standard Deviation 0.14

SECONDARY outcome

Timeframe: Baseline (Day 1) and up to 12 months

Population: ITT population. Only those participants available at the time of assessment were analyzed.

A motor reaction task was presented 4 runs of 50 trials each. In each trial, presentation of a central crosshair for 200 milliseconds (ms) was followed by display of a grey square for 800 ms. The square appeared in two of five possible positions relative to the crosshair (leftmost or rightmost). When the grey square became white, the participant was trained to press the a button. In each trial of the Simple Reaction Time Task, presentation of a central crosshair for 200 ms was followed by display of one square for 800 ms. For both simple and choice versions of the task, trial duration was 4000 ms maximum. The participant was immediately informed (by color changes of the white square) whether the response to each trial was correct or incorrect, and accuracy and reaction time (RT) are automatically calculated. Baseline measurement was performed on Day 1. Change from Baseline is the value at indicated time point minus the Baseline value.

Outcome measures

Outcome measures
Measure	Placebo n=39 Participants Eligible participants received unit oral dose of visually matching Placebo 4 mg for one month. Participants received escalated dose of 8 mg matching placebo for next 12 months and were followed-up to 30 days.	Rosiglitazone n=39 Participants Eligible participants received unit oral rosiglitazone extended release (RSG XR) 4 mg for one month with or without food. Participants received escalated dose of rosiglitazone-XR for next 12 months and were followed-up to 30 days.
Change From Baseline in Cognitive Test by Simple Reaction Time (SRT) Method Over Period Month 6	37.8 Milliseconds Standard Deviation 170.67	59.3 Milliseconds Standard Deviation 158.32
Change From Baseline in Cognitive Test by Simple Reaction Time (SRT) Method Over Period Month 12	177.7 Milliseconds Standard Deviation 359.91	76.4 Milliseconds Standard Deviation 179.78
Change From Baseline in Cognitive Test by Simple Reaction Time (SRT) Method Over Period Month 1	-17.1 Milliseconds Standard Deviation 161.70	36.5 Milliseconds Standard Deviation 162.72

SECONDARY outcome

Timeframe: Baseline (Day 1), and Months 1, 6, and 12

Population: ITT population. Only the participants available at the time of assessment were analyzed.

Change from Baseline is the value at indicated time point minus the Baseline value. ADAS-COG is a 13 item, 11 questionnaire assessment of range of cognitive abilities including memory, comprehension, orientation in time and place, and spontaneous speech. The scale ranges from 0 to 70, with negative changes from Baseline indicating the improvement and positive changes indicating worsening of condition. Arithmetic means are presented as raw data; however, statistical analysis is based on LS means.

Outcome measures

Outcome measures
Measure	Placebo n=39 Participants Eligible participants received unit oral dose of visually matching Placebo 4 mg for one month. Participants received escalated dose of 8 mg matching placebo for next 12 months and were followed-up to 30 days.	Rosiglitazone n=39 Participants Eligible participants received unit oral rosiglitazone extended release (RSG XR) 4 mg for one month with or without food. Participants received escalated dose of rosiglitazone-XR for next 12 months and were followed-up to 30 days.
Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Scale (ADAS-COG) Total Score Over Period Month 6	1.7 Scores on a scale Standard Deviation 6.73	3.2 Scores on a scale Standard Deviation 5.58
Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Scale (ADAS-COG) Total Score Over Period Month 12	5.7 Scores on a scale Standard Deviation 7.52	6.6 Scores on a scale Standard Deviation 7.80
Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Scale (ADAS-COG) Total Score Over Period Month 1	-0. Scores on a scale Standard Deviation 5.38	-0.5 Scores on a scale Standard Deviation 4.84

SECONDARY outcome

Timeframe: Baseline (Day 1) and Months 1, 6, and 12

Population: ITT population. Only the participants available at the time of assessment were analyzed.

The CBIC+ assessment for global functioning consists of a 7 point rating scale of severity and change with 1 indicating marked improvement and 7 indicating marked worsening. This scale was used to analyze clinically relevant effect. This was supposed to be performed by an independent investigator who is not a part of the ongoing study. Change from Baseline is the value at indicated time point minus the Baseline value. This scale was used to decide clinical status of AD. Arithmetic means are presented as raw data; however, statistical analysis has been presented for LS means.

Outcome measures

Outcome measures
Measure	Placebo n=39 Participants Eligible participants received unit oral dose of visually matching Placebo 4 mg for one month. Participants received escalated dose of 8 mg matching placebo for next 12 months and were followed-up to 30 days.	Rosiglitazone n=39 Participants Eligible participants received unit oral rosiglitazone extended release (RSG XR) 4 mg for one month with or without food. Participants received escalated dose of rosiglitazone-XR for next 12 months and were followed-up to 30 days.
Change From Baseline in Clinician Based Impression of Change-plus (CBIC +) Score Over Period Month 1	3.9 Scores on a scale Standard Deviation 1.08	3.9 Scores on a scale Standard Deviation 0.95
Change From Baseline in Clinician Based Impression of Change-plus (CBIC +) Score Over Period Month 12	4.9 Scores on a scale Standard Deviation 1.03	4.8 Scores on a scale Standard Deviation 1.38
Change From Baseline in Clinician Based Impression of Change-plus (CBIC +) Score Over Period Month 6	4.7 Scores on a scale Standard Deviation 0.93	4.5 Scores on a scale Standard Deviation 1.22

SECONDARY outcome

Timeframe: Baseline (Day 1), Months 1, 6 and 12

Population: ITT population. Only the participants available at the time of assessment were analyzed.

The NPI assesses the frequency and severity of behavioral disturbances in dementia across 10 domains. The total NPI score was calculated by adding all individual domains cores. The scale ranges from 0 to 120 , 0 indicating no / least burden and 120 indicating maximum burden. A negative change from Baseline indicated improvement. Baseline measurement was performed on Day 1. Change from Baseline is the value at indicated time point minus the Baseline value.

Outcome measures

Outcome measures
Measure	Placebo n=39 Participants Eligible participants received unit oral dose of visually matching Placebo 4 mg for one month. Participants received escalated dose of 8 mg matching placebo for next 12 months and were followed-up to 30 days.	Rosiglitazone n=39 Participants Eligible participants received unit oral rosiglitazone extended release (RSG XR) 4 mg for one month with or without food. Participants received escalated dose of rosiglitazone-XR for next 12 months and were followed-up to 30 days.
Change From Baseline in Neuropsychiatric Inventory Score Over Period Month 12	0.9 Scores on a scale Standard Deviation 8.39	1.8 Scores on a scale Standard Deviation 13.84
Change From Baseline in Neuropsychiatric Inventory Score Over Period Month 1	-1.6 Scores on a scale Standard Deviation 6.30	-2.6 Scores on a scale Standard Deviation 6.82
Change From Baseline in Neuropsychiatric Inventory Score Over Period Month 6	2.1 Scores on a scale Standard Deviation 8.63	-0.8 Scores on a scale Standard Deviation 11.59

SECONDARY outcome

Timeframe: Baseline (Day 1), and up to Month 12

Population: ITT population. Only those participants available at the time of assessment were analyzed.

The MMSE consists of 11 categories of orientation, memory (recent and immediate), concentration, language, and praxis. The scale ranges from 0 to 30 with lower scores indicating greater cognitive impairment. Negative changes from Baseline indicate improvement and positive changes indicate increasing symptoms. Change from Baseline is the value at indicated time point minus the Baseline value.

Outcome measures

Outcome measures
Measure	Placebo n=30 Participants Eligible participants received unit oral dose of visually matching Placebo 4 mg for one month. Participants received escalated dose of 8 mg matching placebo for next 12 months and were followed-up to 30 days.	Rosiglitazone n=30 Participants Eligible participants received unit oral rosiglitazone extended release (RSG XR) 4 mg for one month with or without food. Participants received escalated dose of rosiglitazone-XR for next 12 months and were followed-up to 30 days.
Change From Baseline in Mini-mental State Examination (MMSE) Score Over Period	-3.3 Scores on a scale Standard Deviation 4.09	-2.6 Scores on a scale Standard Deviation 3.27

SECONDARY outcome

Timeframe: Baseline (Day 1), Month 6 and Month 12

Population: ITT population. Only those participants available at the time of assessment were analyzed.

Normalized brain volume is a function of global changes in brain structure. Reduction in brain volume is indicative of reduction in Grey matter and thus the AD stage. The method used was structural magnetic resonance imaging (MRI). Change from Baseline is the value at indicated time point minus the Baseline value. Arithmetic means have been presented; however, statistical analysis is based upon the least square (LS) means.

Outcome measures

Outcome measures
Measure	Placebo n=39 Participants Eligible participants received unit oral dose of visually matching Placebo 4 mg for one month. Participants received escalated dose of 8 mg matching placebo for next 12 months and were followed-up to 30 days.	Rosiglitazone n=39 Participants Eligible participants received unit oral rosiglitazone extended release (RSG XR) 4 mg for one month with or without food. Participants received escalated dose of rosiglitazone-XR for next 12 months and were followed-up to 30 days.
Change From Baseline in Normalized Brain Volume Over Period Month 6	-4553.1 Cubic millimeter Standard Deviation 43069.12	-15995.6 Cubic millimeter Standard Deviation 41075.95
Change From Baseline in Normalized Brain Volume Over Period Month 12	-16599.9 Cubic millimeter Standard Deviation 47173.85	-13929.6 Cubic millimeter Standard Deviation 31031.06

SECONDARY outcome

Timeframe: Baseline (Day 1), Month 6, and Month 12

Population: ITT population. Only those participants available at the time of assessment were analyzed.

Percent volume change of brain is a function of global changes in brain structure. Reduction in brain volume is indicative of reduction in Grey matter and thus the AD stage. The method used was structural magnetic resonance imaging (MRI). Baseline value was recorded on Day 1. Change from Baseline is the value at indicated time point minus the Baseline value. Arithmetic means have been presented; however, statistical analysis is based upon the LS means.

Outcome measures

Outcome measures
Measure	Placebo n=39 Participants Eligible participants received unit oral dose of visually matching Placebo 4 mg for one month. Participants received escalated dose of 8 mg matching placebo for next 12 months and were followed-up to 30 days.	Rosiglitazone n=39 Participants Eligible participants received unit oral rosiglitazone extended release (RSG XR) 4 mg for one month with or without food. Participants received escalated dose of rosiglitazone-XR for next 12 months and were followed-up to 30 days.
Percent Change From Baseline in Brain Volume Over Period Month 6	-0.9 Percent change Standard Deviation 0.62	-1.4 Percent change Standard Deviation 0.94
Percent Change From Baseline in Brain Volume Over Period Month 12	-2.4 Percent change Standard Deviation 1.40	-2.6 Percent change Standard Deviation 1.48

SECONDARY outcome

Timeframe: Baseline (Day 1) and Month 12

Population: ITT population. Only the participants available at the time of assessment were analyzed.

Fasting plasma glucose are indicative of Glucose metabolism. Baseline measurement was performed on Day 1. Change from Baseline is the value at indicated time point minus the Baseline value.

Outcome measures

Outcome measures
Measure	Placebo n=27 Participants Eligible participants received unit oral dose of visually matching Placebo 4 mg for one month. Participants received escalated dose of 8 mg matching placebo for next 12 months and were followed-up to 30 days.	Rosiglitazone n=28 Participants Eligible participants received unit oral rosiglitazone extended release (RSG XR) 4 mg for one month with or without food. Participants received escalated dose of rosiglitazone-XR for next 12 months and were followed-up to 30 days.
Change From Baseline in Fasting Plasma Glucose at Month 12	0.2556 Millimoles per Liter Standard Deviation 0.99974	-0.1750 Millimoles per Liter Standard Deviation 0.48810

SECONDARY outcome

Timeframe: Baseline (Day 1) and Month 12

Population: ITT population. Only those participants available at the time of assessment were analyzed.

HbA1c levels are measure of glucose metabolism in body. Baseline value measurement was performed on Day 1. Change from Baseline is the value at indicated time point minus the Baseline value.

Outcome measures

Outcome measures
Measure	Placebo n=32 Participants Eligible participants received unit oral dose of visually matching Placebo 4 mg for one month. Participants received escalated dose of 8 mg matching placebo for next 12 months and were followed-up to 30 days.	Rosiglitazone n=31 Participants Eligible participants received unit oral rosiglitazone extended release (RSG XR) 4 mg for one month with or without food. Participants received escalated dose of rosiglitazone-XR for next 12 months and were followed-up to 30 days.
Change From Baseline in Glycosylated Hemoglobin [HbA1C] at Month 12	0.0625 Percentage of HbA1c Standard Deviation 0.43533	0.3871 Percentage of HbA1c Standard Deviation 0.49514

SECONDARY outcome

Timeframe: Baseline (Day 1) and Month 12

Population: ITT population. Only those participants available at the time of assessment were analyzed.

Lipid (cholesterol) and apo-lipoprotein (A and B) are biomarkers of glucose metabolism in blood. The method used for analyzes was positron emission tomography (PET) using radiolabelled \[18F\] -fluoro-deoxy-glucose (FDG). Baseline measurement was performed on Day 1. Change from baseline is the value at indicated time point minus the Baseline value.

Outcome measures

Outcome measures
Measure	Placebo n=39 Participants Eligible participants received unit oral dose of visually matching Placebo 4 mg for one month. Participants received escalated dose of 8 mg matching placebo for next 12 months and were followed-up to 30 days.	Rosiglitazone n=39 Participants Eligible participants received unit oral rosiglitazone extended release (RSG XR) 4 mg for one month with or without food. Participants received escalated dose of rosiglitazone-XR for next 12 months and were followed-up to 30 days.
Change From Baseline in Lipid (Cholesterol) and Apo-lipoprotein Levels at Month 12 Apolipoprotein A	-0.0478 Grams per Liter Standard Deviation 0.29284	-0.2058 Grams per Liter Standard Deviation 0.27424
Change From Baseline in Lipid (Cholesterol) and Apo-lipoprotein Levels at Month 12 Apolipoprotein B	-0.0191 Grams per Liter Standard Deviation 0.18714	-0.0006 Grams per Liter Standard Deviation 0.25070
Change From Baseline in Lipid (Cholesterol) and Apo-lipoprotein Levels at Month 12 Cholesterol	-0.2556 Grams per Liter Standard Deviation 0.69756	0.1340 Grams per Liter Standard Deviation 1.09229

SECONDARY outcome

Timeframe: Baseline (Day 1) and Month 12

Population: ITT population. Only those participants available at the time of assessment were analyzed.

The inflammatory biomarkers namely CD40, C-reactive protein (CRP) , interleukin (IL)-6, and tumor necrosing factor (TNF)-alpha) were analyzed. Baseline measurement was performed on Day 1. Change from Baseline is the value at indicated time point minus the Baseline value.

Outcome measures

Outcome measures
Measure	Placebo n=39 Participants Eligible participants received unit oral dose of visually matching Placebo 4 mg for one month. Participants received escalated dose of 8 mg matching placebo for next 12 months and were followed-up to 30 days.	Rosiglitazone n=39 Participants Eligible participants received unit oral rosiglitazone extended release (RSG XR) 4 mg for one month with or without food. Participants received escalated dose of rosiglitazone-XR for next 12 months and were followed-up to 30 days.
Change From Baseline in Inflammatory Biomarkers (CD40, C-reactive Protein [CRP] , Interleukin [ IL ]-6, and Tumor Necrosing Factor [TNF]-Alpha) CD40	-236.79 Nanograms per Liter Standard Deviation 2500.30	130.543 Nanograms per Liter Standard Deviation 2580.16
Change From Baseline in Inflammatory Biomarkers (CD40, C-reactive Protein [CRP] , Interleukin [ IL ]-6, and Tumor Necrosing Factor [TNF]-Alpha) CRP	0.8161 Nanograms per Liter Standard Deviation 5.94099	-1.4800 Nanograms per Liter Standard Deviation 4.63565
Change From Baseline in Inflammatory Biomarkers (CD40, C-reactive Protein [CRP] , Interleukin [ IL ]-6, and Tumor Necrosing Factor [TNF]-Alpha) IL-6	6.3390 Nanograms per Liter Standard Deviation 22.5103	2.6370 Nanograms per Liter Standard Deviation 11.1159
Change From Baseline in Inflammatory Biomarkers (CD40, C-reactive Protein [CRP] , Interleukin [ IL ]-6, and Tumor Necrosing Factor [TNF]-Alpha) TNF-alpha	16.7893 Nanograms per Liter Standard Deviation 53.0817	3.8407 Nanograms per Liter Standard Deviation 15.9970

SECONDARY outcome

Timeframe: Baseline (Day 1) and Month 12

Population: ITT population. Only those participants available at the time of assessment were analyzed.

This is a measure of assessing insulin sensitivity. HOMA IR was calculated by multiplying fasting insulin by fasting plasma glucose and dividing the multiplied digit by 22.5. All samples were collected under fasting condition. Baseline measurement was performed on Day 1. Change from Baseline is the value at indicated time point minus the Baseline value.

Outcome measures

Outcome measures
Measure	Placebo n=31 Participants Eligible participants received unit oral dose of visually matching Placebo 4 mg for one month. Participants received escalated dose of 8 mg matching placebo for next 12 months and were followed-up to 30 days.	Rosiglitazone n=31 Participants Eligible participants received unit oral rosiglitazone extended release (RSG XR) 4 mg for one month with or without food. Participants received escalated dose of rosiglitazone-XR for next 12 months and were followed-up to 30 days.
Change From Baseline in Insulin Sensitivity Measured by Homeostasis Model Assessment of Insulin Resistance (HOMA IR)	-0.2703 HOMA IR score Standard Deviation 12.6037	-5.9910 HOMA IR score Standard Deviation 9.79511

SECONDARY outcome

Timeframe: Up to 12 months

Population: PGx population included all ITT participants with evaluable PGx data (had consented to genotyping, provided and identified blood sample for genotyping and were successfully genotyped for at least one of the genetic markers under study). Only those participants available at time of assessment were analyzed.

Participants were categorized into two major types namely those with APOE4 genotype and without APOE4 genotype. Further, 6 subtypes/ alleles of APOE4 gene (as mentioned in the categories below) were analyzed. Participants were also classified as having 0 or 1 or 2 copies of this gene.

Outcome measures

Outcome measures
Measure	Placebo n=30 Participants Eligible participants received unit oral dose of visually matching Placebo 4 mg for one month. Participants received escalated dose of 8 mg matching placebo for next 12 months and were followed-up to 30 days.	Rosiglitazone n=29 Participants Eligible participants received unit oral rosiglitazone extended release (RSG XR) 4 mg for one month with or without food. Participants received escalated dose of rosiglitazone-XR for next 12 months and were followed-up to 30 days.
Number of Participants by Apo-lipoprotein -e (APOE Epsilon)-4 Allele Subtype 0 copies of APOE4 gene	6 Participants	14 Participants
Number of Participants by Apo-lipoprotein -e (APOE Epsilon)-4 Allele Subtype With APOE4 gene	24 Participants	15 Participants
Number of Participants by Apo-lipoprotein -e (APOE Epsilon)-4 Allele Subtype Without APOE4 gene	6 Participants	14 Participants
Number of Participants by Apo-lipoprotein -e (APOE Epsilon)-4 Allele Subtype With E4E4 allele	7 Participants	6 Participants
Number of Participants by Apo-lipoprotein -e (APOE Epsilon)-4 Allele Subtype With E3E4 allele	17 Participants	8 Participants
Number of Participants by Apo-lipoprotein -e (APOE Epsilon)-4 Allele Subtype With E2E4 allele	0 Participants	1 Participants
Number of Participants by Apo-lipoprotein -e (APOE Epsilon)-4 Allele Subtype With E3E3 allele	5 Participants	12 Participants
Number of Participants by Apo-lipoprotein -e (APOE Epsilon)-4 Allele Subtype With E2E3 allele	1 Participants	1 Participants
Number of Participants by Apo-lipoprotein -e (APOE Epsilon)-4 Allele Subtype With E2E2 allele	0 Participants	1 Participants
Number of Participants by Apo-lipoprotein -e (APOE Epsilon)-4 Allele Subtype 2 copies of APOE4 gene	7 Participants	6 Participants
Number of Participants by Apo-lipoprotein -e (APOE Epsilon)-4 Allele Subtype 1 copies of APOE4 gene	17 Participants	9 Participants

SECONDARY outcome

Timeframe: Up to 12 months

Population: All subjects population included all randomized subjects who receive at least one dose of study drug.

Adverse event (AE) is an unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain time period after the study has ended. This change may or may not be caused by the intervention being studied. Serious adverse event (SAE) is an adverse event that results in death, is life-threatening, requires inpatient hospitalization or extends a current hospital stay, results in an ongoing or significant incapacity or interferes substantially with normal life functions, or causes a congenital anomaly or birth defect. Medical events that do not result in death, are not life-threatening, or do not require hospitalization may be considered serious adverse events if they put the participant in danger or require medical or surgical intervention to prevent one of the results listed above.

Outcome measures

Outcome measures
Measure	Placebo n=40 Participants Eligible participants received unit oral dose of visually matching Placebo 4 mg for one month. Participants received escalated dose of 8 mg matching placebo for next 12 months and were followed-up to 30 days.	Rosiglitazone n=40 Participants Eligible participants received unit oral rosiglitazone extended release (RSG XR) 4 mg for one month with or without food. Participants received escalated dose of rosiglitazone-XR for next 12 months and were followed-up to 30 days.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Any SAE	6 Participants	4 Participants
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Any AE	32 Participants	33 Participants

SECONDARY outcome

Timeframe: At Month 12

Population: All subjects population. Only the participants available at the time of assessment were analyzed.

Number of participants with SBP or DBP outside the defined range of clinical concern were collectively presented for any time on-treatment period. SBP of \<90 millimeters of mercury (mmHg) and \>140 mmHg was considered as of clinical concern. DBP of \<50 and \>90 mmHg was considered as of clinical concern. Increase in SBP from Baseline of \>=40 mmHg and Decrease of \>=30 mmHg was also recorded. Increase in DBP from Baseline of \>=30 mmHg and Decrease of \>=20 mmHg was also recorded.

Outcome measures

Outcome measures
Measure	Placebo n=39 Participants Eligible participants received unit oral dose of visually matching Placebo 4 mg for one month. Participants received escalated dose of 8 mg matching placebo for next 12 months and were followed-up to 30 days.	Rosiglitazone n=40 Participants Eligible participants received unit oral rosiglitazone extended release (RSG XR) 4 mg for one month with or without food. Participants received escalated dose of rosiglitazone-XR for next 12 months and were followed-up to 30 days.
Number of Participants With Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Outside the Concern Range at Month 12 DBP, Decrease from Baseline>=20	3 Participants	7 Participants
Number of Participants With Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Outside the Concern Range at Month 12 SBP, >140 or <90	20 Participants	23 Participants
Number of Participants With Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Outside the Concern Range at Month 12 SBP, Increase from Baseline>=40	1 Participants	3 Participants
Number of Participants With Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Outside the Concern Range at Month 12 SBP, Decrease from Baseline>=30	12 Participants	13 Participants
Number of Participants With Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Outside the Concern Range at Month 12 DBP, >90 or <50	5 Participants	2 Participants
Number of Participants With Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Outside the Concern Range at Month 12 DBP, Increase from Baseline>=30	1 Participants	1 Participants

SECONDARY outcome

Timeframe: At Month 12

Population: All subjects population. Only those participants available at the time of assessment were analyzed.

Heart rate was measured in supine position. Number of participants with any time on-treatment values of heart rate values outside the clinical concern were presented. Heart rate values of \>100 or \<50 were considered as of clinical concern. Increase in heart rate from Baseline of \>=30 beats per minute (bpm) and decrease in heart rate from Baseline of \>=30 bpm was also recorded and presented.

Outcome measures

Outcome measures
Measure	Placebo n=39 Participants Eligible participants received unit oral dose of visually matching Placebo 4 mg for one month. Participants received escalated dose of 8 mg matching placebo for next 12 months and were followed-up to 30 days.	Rosiglitazone n=40 Participants Eligible participants received unit oral rosiglitazone extended release (RSG XR) 4 mg for one month with or without food. Participants received escalated dose of rosiglitazone-XR for next 12 months and were followed-up to 30 days.
Number of Participants With Heart Rate/ Pulse Rate Outside the Concern Range at Month 12 Heart rate >100 or <50	4 Participants	3 Participants
Number of Participants With Heart Rate/ Pulse Rate Outside the Concern Range at Month 12 Increase in heart rate from Baseline of >=30	2 Participants	4 Participants
Number of Participants With Heart Rate/ Pulse Rate Outside the Concern Range at Month 12 Dncrease in heart rate from Baseline of >=30	0 Participants	0 Participants

SECONDARY outcome

Timeframe: At screening (within 1 month of Day 1) and follow-up period (within 2 weeks of final dose [12 months])

Population: All subjects population.

Two screening visits were arranged within 30 days of Day 1 of screening period and within 7 to 10 days of Day 1 of screening period. Follow-up period was arranged within 14 days of the last dose (post 12 months) of the study drug. Data for only the participants with abnormal ECG values has been presented.

Outcome measures

Outcome measures
Measure	Placebo n=40 Participants Eligible participants received unit oral dose of visually matching Placebo 4 mg for one month. Participants received escalated dose of 8 mg matching placebo for next 12 months and were followed-up to 30 days.	Rosiglitazone n=40 Participants Eligible participants received unit oral rosiglitazone extended release (RSG XR) 4 mg for one month with or without food. Participants received escalated dose of rosiglitazone-XR for next 12 months and were followed-up to 30 days.
Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Parameters at Screening and Follow-up At screening	18 Participants	18 Participants
Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Parameters at Screening and Follow-up At follow-up	5 Participants	10 Participants

SECONDARY outcome

Timeframe: At Month 12

Population: All subjects population. Only those participants available at the time of assessment were analyzed.

Body weight and height are the parameters of physical examination. Body weight is also a measure of fluid retention. Body weight increase or decrease of \>= 7 % was considered as of clinical concern. Since there would be no or negligible (insignificant) change in height of a participant, no data has been presented for change from Baseline in height of participants after exposure to the study drug.

Outcome measures

Outcome measures
Measure	Placebo n=33 Participants Eligible participants received unit oral dose of visually matching Placebo 4 mg for one month. Participants received escalated dose of 8 mg matching placebo for next 12 months and were followed-up to 30 days.	Rosiglitazone n=31 Participants Eligible participants received unit oral rosiglitazone extended release (RSG XR) 4 mg for one month with or without food. Participants received escalated dose of rosiglitazone-XR for next 12 months and were followed-up to 30 days.
Number of Participants With Body Weight and Height Outside the Clinical Concern at Month 12 Increase from Baseline >=7%	2 Participants	5 Participants
Number of Participants With Body Weight and Height Outside the Clinical Concern at Month 12 Decrease from Baseline >=7%	2 Participants	2 Participants

SECONDARY outcome

Timeframe: At Month 12

Population: PGx ITT population included all participants in ITT population who had evaluable PGx data (who consented to genotyping, provided an identified blood sample for genotyping and were successfully genotyped for at least one of the genetic markers under study. Only the participants available at the time of assessment were analyzed.

The CMRglu was analyzed based on the APOE Epsilon-4 gene allele, whether it was present (positive) or was missing (negative) among the participants. The data has been presented for Month 12. Data has been presented for arithmetic mean; however, statistical analysis presented is based on LS means.

Outcome measures

Outcome measures
Measure	Placebo n=40 Participants Eligible participants received unit oral dose of visually matching Placebo 4 mg for one month. Participants received escalated dose of 8 mg matching placebo for next 12 months and were followed-up to 30 days.	Rosiglitazone n=40 Participants Eligible participants received unit oral rosiglitazone extended release (RSG XR) 4 mg for one month with or without food. Participants received escalated dose of rosiglitazone-XR for next 12 months and were followed-up to 30 days.
Global and Regional CMRglu Index by APOE Epsilon-4 Allele Subtype at 12 Month Grey matter, APOE positive	-0.2649 milligrams per cubic centimeter Standard Deviation 0.58442	-0.0903 milligrams per cubic centimeter Standard Deviation 0.44270
Global and Regional CMRglu Index by APOE Epsilon-4 Allele Subtype at 12 Month Cerebellum, APOE positive	-0.2280 milligrams per cubic centimeter Standard Deviation 0.54477	-0.0375 milligrams per cubic centimeter Standard Deviation 0.49150
Global and Regional CMRglu Index by APOE Epsilon-4 Allele Subtype at 12 Month Medial temporal lobe, APOE positive	-0.1647 milligrams per cubic centimeter Standard Deviation 0.39800	-0.0004 milligrams per cubic centimeter Standard Deviation 0.43929
Global and Regional CMRglu Index by APOE Epsilon-4 Allele Subtype at 12 Month Grey matter, APOE negative	-0.1577 milligrams per cubic centimeter Standard Deviation 0.06551	-0.0107 milligrams per cubic centimeter Standard Deviation 0.16654
Global and Regional CMRglu Index by APOE Epsilon-4 Allele Subtype at 12 Month Posterior cingulate gyrus, APOE negative	-0.2655 milligrams per cubic centimeter Standard Deviation 0.11854	0.0141 milligrams per cubic centimeter Standard Deviation 0.17927
Global and Regional CMRglu Index by APOE Epsilon-4 Allele Subtype at 12 Month Frontal lobe, APOE negative	-0.1967 milligrams per cubic centimeter Standard Deviation 0.09081	-0.0323 milligrams per cubic centimeter Standard Deviation 0.17438
Global and Regional CMRglu Index by APOE Epsilon-4 Allele Subtype at 12 Month Posterior cingulate gyrus, APOE positive	-0.2728 milligrams per cubic centimeter Standard Deviation 0.69449	-0.0987 milligrams per cubic centimeter Standard Deviation 0.43553
Global and Regional CMRglu Index by APOE Epsilon-4 Allele Subtype at 12 Month Frontal lobe, APOE positive	-0.2939 milligrams per cubic centimeter Standard Deviation 0.66878	-0.1046 milligrams per cubic centimeter Standard Deviation 0.45385
Global and Regional CMRglu Index by APOE Epsilon-4 Allele Subtype at 12 Month Parietal lobe, APOE positive	-0.2919 milligrams per cubic centimeter Standard Deviation 0.60832	-0.1404 milligrams per cubic centimeter Standard Deviation 0.42635
Global and Regional CMRglu Index by APOE Epsilon-4 Allele Subtype at 12 Month Posterior temporal lobe, APOE positive	-0.2722 milligrams per cubic centimeter Standard Deviation 0.48425	-0.1175 milligrams per cubic centimeter Standard Deviation 0.42617
Global and Regional CMRglu Index by APOE Epsilon-4 Allele Subtype at 12 Month Parietal lobe, APOE negative	-0.1549 milligrams per cubic centimeter Standard Deviation 0.08056	-0.0362 milligrams per cubic centimeter Standard Deviation 0.17425
Global and Regional CMRglu Index by APOE Epsilon-4 Allele Subtype at 12 Month Posterior temporal lobe, APOE negative	-0.1391 milligrams per cubic centimeter Standard Deviation 0.11660	-0.0443 milligrams per cubic centimeter Standard Deviation 0.16786
Global and Regional CMRglu Index by APOE Epsilon-4 Allele Subtype at 12 Month Cerebellum, APOE negative	-0.1732 milligrams per cubic centimeter Standard Deviation 0.05698	0.0742 milligrams per cubic centimeter Standard Deviation 0.15230
Global and Regional CMRglu Index by APOE Epsilon-4 Allele Subtype at 12 Month Medial temporal lobe, APOE negative	-0.1134 milligrams per cubic centimeter Standard Deviation 0.06707	0.0026 milligrams per cubic centimeter Standard Deviation 0.14382

SECONDARY outcome

Timeframe: At Month 12

Population: All subjects population. Only the participants available at the time of assessment were analyzed.

Participants were analyzed for any abnormality in basophils, eosinophils, hemoglobin, lymphocytes, monocytes, neutrophils, segmented neutrophils, platelets, red blood cells, and white blood cells with data outside the respective reference ranges. The values higher (H) or lower (L) than the reference range were analyzed at each month. The parameter has not been presented for participants who did not have any abnormality.

Outcome measures

Outcome measures
Measure	Placebo n=40 Participants Eligible participants received unit oral dose of visually matching Placebo 4 mg for one month. Participants received escalated dose of 8 mg matching placebo for next 12 months and were followed-up to 30 days.	Rosiglitazone n=40 Participants Eligible participants received unit oral rosiglitazone extended release (RSG XR) 4 mg for one month with or without food. Participants received escalated dose of rosiglitazone-XR for next 12 months and were followed-up to 30 days.
Number of Participants With Hematological Data of Potential Clinical Concern (PCC) at End of Treatment (Month 12) Neutrophils, Month 12, L	0 Participants	1 Participants
Number of Participants With Hematological Data of Potential Clinical Concern (PCC) at End of Treatment (Month 12) Platelets, Month 12, L	0 Participants	1 Participants
Number of Participants With Hematological Data of Potential Clinical Concern (PCC) at End of Treatment (Month 12) Hemoglobin, Month 12, L	0 Participants	1 Participants
Number of Participants With Hematological Data of Potential Clinical Concern (PCC) at End of Treatment (Month 12) White cells, Month 12, L	1 Participants	1 Participants
Number of Participants With Hematological Data of Potential Clinical Concern (PCC) at End of Treatment (Month 12) Lymphoctes percentage, Month 12, L	1 Participants	0 Participants

SECONDARY outcome

Timeframe: At Month 12

Population: All subjects population. Only the participants available at the time of assessment were analyzed.

Participants were analyzed for any abnormality in albumin, alanine aminotransferases, alkaline phosphatase, apolipoprotein A, apolipoprotein B, aspartate aminotransferases, Vitamin B12, direct bilirubin, indirect bilirubin, total bilirubin, cholesterol, creatinine, C-reactive protein, serum glucose, and non-fasting glucose, with data of PCC range. The values higher (H) or lower (L) than the reference range were analyzed at each month. The parameter has not been presented for participants who did not have any abnormality.

Outcome measures

Outcome measures
Measure	Placebo n=40 Participants Eligible participants received unit oral dose of visually matching Placebo 4 mg for one month. Participants received escalated dose of 8 mg matching placebo for next 12 months and were followed-up to 30 days.	Rosiglitazone n=40 Participants Eligible participants received unit oral rosiglitazone extended release (RSG XR) 4 mg for one month with or without food. Participants received escalated dose of rosiglitazone-XR for next 12 months and were followed-up to 30 days.
Number of Participants With Clinical Chemistry Data of PCC at End of the Treatment (Month 12) Direct bilirubin, H	1 Participants	0 Participants
Number of Participants With Clinical Chemistry Data of PCC at End of the Treatment (Month 12) Cholesterol, H	1 Participants	0 Participants
Number of Participants With Clinical Chemistry Data of PCC at End of the Treatment (Month 12) Glucose, H	1 Participants	0 Participants
Number of Participants With Clinical Chemistry Data of PCC at End of the Treatment (Month 12) Low density lipoprotein cholesterol, H	2 Participants	5 Participants

Adverse Events

Placebo

Serious events: 6 serious events

Other events: 32 other events

Deaths: 0 deaths

Rosiglitazone

Serious events: 4 serious events

Other events: 33 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=40 participants at risk Eligible participants received unit oral dose of visually matching Placebo 4 mg for one month. Participants received escalated dose of 8 mg matching placebo for next 12 months and were followed-up to 30 days.	Rosiglitazone n=40 participants at risk Eligible participants received unit oral rosiglitazone extended release (RSG XR) 4 mg for one month with or without food. Participants received escalated dose of rosiglitazone-XR for next 12 months and were followed-up to 30 days.
Infections and infestations LABYRINTHITIS	2.5% 1/40 • Up to 13 months All subjects population was used to report AEs and SAEs.	0.00% 0/40 • Up to 13 months All subjects population was used to report AEs and SAEs.
Infections and infestations PNEUMONIA	2.5% 1/40 • Up to 13 months All subjects population was used to report AEs and SAEs.	0.00% 0/40 • Up to 13 months All subjects population was used to report AEs and SAEs.
Infections and infestations UROSEPSIS	2.5% 1/40 • Up to 13 months All subjects population was used to report AEs and SAEs.	0.00% 0/40 • Up to 13 months All subjects population was used to report AEs and SAEs.
Gastrointestinal disorders ABDOMINAL PAIN	2.5% 1/40 • Up to 13 months All subjects population was used to report AEs and SAEs.	0.00% 0/40 • Up to 13 months All subjects population was used to report AEs and SAEs.
Gastrointestinal disorders FAECALOMA	0.00% 0/40 • Up to 13 months All subjects population was used to report AEs and SAEs.	2.5% 1/40 • Up to 13 months All subjects population was used to report AEs and SAEs.
Injury, poisoning and procedural complications COMPRESSION FRACTURE	2.5% 1/40 • Up to 13 months All subjects population was used to report AEs and SAEs.	0.00% 0/40 • Up to 13 months All subjects population was used to report AEs and SAEs.
Injury, poisoning and procedural complications PELVIC FRACTURE	0.00% 0/40 • Up to 13 months All subjects population was used to report AEs and SAEs.	2.5% 1/40 • Up to 13 months All subjects population was used to report AEs and SAEs.
Respiratory, thoracic and mediastinal disorders INTERSTITIAL LUNG DISEASE	2.5% 1/40 • Up to 13 months All subjects population was used to report AEs and SAEs.	0.00% 0/40 • Up to 13 months All subjects population was used to report AEs and SAEs.
Respiratory, thoracic and mediastinal disorders PULMONARY EMBOLISM	0.00% 0/40 • Up to 13 months All subjects population was used to report AEs and SAEs.	2.5% 1/40 • Up to 13 months All subjects population was used to report AEs and SAEs.
Cardiac disorders MYOCARDIAL INFARCTION	2.5% 1/40 • Up to 13 months All subjects population was used to report AEs and SAEs.	0.00% 0/40 • Up to 13 months All subjects population was used to report AEs and SAEs.
Metabolism and nutrition disorders HYPONATRAEMIA	2.5% 1/40 • Up to 13 months All subjects population was used to report AEs and SAEs.	0.00% 0/40 • Up to 13 months All subjects population was used to report AEs and SAEs.
Psychiatric disorders ABNORMAL BEHAVIOUR	0.00% 0/40 • Up to 13 months All subjects population was used to report AEs and SAEs.	2.5% 1/40 • Up to 13 months All subjects population was used to report AEs and SAEs.

Other adverse events

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo n=39 Participants Eligible participants received unit oral dose of visually matching Placebo 4 mg for one month. Participants received escalated dose of 8 mg matching placebo for next 12 months and were followed-up to 30 days.	Rosiglitazone n=39 Participants Eligible participants received unit oral rosiglitazone extended release (RSG XR) 4 mg for one month with or without food. Participants received escalated dose of rosiglitazone-XR for next 12 months and were followed-up to 30 days.
Change From Baseline (Day 1) in Delayed Free Recall Words at Months 1, 6, and 12 by Buschke Selective Reminding (BSR) Test Delayed free recall, Month 1	0.1 Number of words recalled Standard Deviation 1.72	0.2 Number of words recalled Standard Deviation 1.23
Change From Baseline (Day 1) in Delayed Free Recall Words at Months 1, 6, and 12 by Buschke Selective Reminding (BSR) Test Delayed free recall, Month 12	-0.4 Number of words recalled Standard Deviation 1.32	-0.4 Number of words recalled Standard Deviation 1.53
Change From Baseline (Day 1) in Delayed Free Recall Words at Months 1, 6, and 12 by Buschke Selective Reminding (BSR) Test Trial 1 immediate, Month 12	-0.6 Number of words recalled Standard Deviation 1.32	-0.5 Number of words recalled Standard Deviation 1.27
Change From Baseline (Day 1) in Delayed Free Recall Words at Months 1, 6, and 12 by Buschke Selective Reminding (BSR) Test Trial 8 immediate, Month 1	-0.2 Number of words recalled Standard Deviation 1.82	0.0 Number of words recalled Standard Deviation 1.45
Change From Baseline (Day 1) in Delayed Free Recall Words at Months 1, 6, and 12 by Buschke Selective Reminding (BSR) Test Delayed free recall, Month 6	-0.1 Number of words recalled Standard Deviation 1.56	0.0 Number of words recalled Standard Deviation 1.21
Change From Baseline (Day 1) in Delayed Free Recall Words at Months 1, 6, and 12 by Buschke Selective Reminding (BSR) Test Trial 1 immediate, Month 1	0.2 Number of words recalled Standard Deviation 1.30	-0.1 Number of words recalled Standard Deviation 1.13
Change From Baseline (Day 1) in Delayed Free Recall Words at Months 1, 6, and 12 by Buschke Selective Reminding (BSR) Test Trial 1 immediate, Month 6	-0.2 Number of words recalled Standard Deviation 1.69	-0.1 Number of words recalled Standard Deviation 1.42
Change From Baseline (Day 1) in Delayed Free Recall Words at Months 1, 6, and 12 by Buschke Selective Reminding (BSR) Test Trial 8 immediate, Month 6	-0.3 Number of words recalled Standard Deviation 1.29	-0.2 Number of words recalled Standard Deviation 1.21
Change From Baseline (Day 1) in Delayed Free Recall Words at Months 1, 6, and 12 by Buschke Selective Reminding (BSR) Test Trial 8 immediate, Month 12	-0.9 Number of words recalled Standard Deviation 1.32	-0.2 Number of words recalled Standard Deviation 1.03
Change From Baseline (Day 1) in Delayed Free Recall Words at Months 1, 6, and 12 by Buschke Selective Reminding (BSR) Test For all 8 immediate trial, Month 1	-1.4 Number of words recalled Standard Deviation 7.27	0.9 Number of words recalled Standard Deviation 5.51
Change From Baseline (Day 1) in Delayed Free Recall Words at Months 1, 6, and 12 by Buschke Selective Reminding (BSR) Test For all 8 immediate trial, Month 6	-3.0 Number of words recalled Standard Deviation 7.31	0.4 Number of words recalled Standard Deviation 5.85
Change From Baseline (Day 1) in Delayed Free Recall Words at Months 1, 6, and 12 by Buschke Selective Reminding (BSR) Test For all 8 immediate trial, Month 12	-5.8 Number of words recalled Standard Deviation 7.95	-0.9 Number of words recalled Standard Deviation 5.27
Change From Baseline (Day 1) in Delayed Free Recall Words at Months 1, 6, and 12 by Buschke Selective Reminding (BSR) Test Uncued words recalled, Month 1	-1.7 Number of words recalled Standard Deviation 8.56	0.9 Number of words recalled Standard Deviation 5.43
Change From Baseline (Day 1) in Delayed Free Recall Words at Months 1, 6, and 12 by Buschke Selective Reminding (BSR) Test Uncued words recalled, Month 6	-3.2 Number of words recalled Standard Deviation 7.92	0.9 Number of words recalled Standard Deviation 7.55
Change From Baseline (Day 1) in Delayed Free Recall Words at Months 1, 6, and 12 by Buschke Selective Reminding (BSR) Test Uncued words recalled, Month 12	-7.0 Number of words recalled Standard Deviation 9.91	-2.0 Number of words recalled Standard Deviation 8.59

Measure	Placebo n=40 participants at risk Eligible participants received unit oral dose of visually matching Placebo 4 mg for one month. Participants received escalated dose of 8 mg matching placebo for next 12 months and were followed-up to 30 days.	Rosiglitazone n=40 participants at risk Eligible participants received unit oral rosiglitazone extended release (RSG XR) 4 mg for one month with or without food. Participants received escalated dose of rosiglitazone-XR for next 12 months and were followed-up to 30 days.
Infections and infestations Upper respiratory tract infection	7.5% 3/40 • Up to 13 months All subjects population was used to report AEs and SAEs.	10.0% 4/40 • Up to 13 months All subjects population was used to report AEs and SAEs.
Nervous system disorders Dizziness	7.5% 3/40 • Up to 13 months All subjects population was used to report AEs and SAEs.	7.5% 3/40 • Up to 13 months All subjects population was used to report AEs and SAEs.
General disorders Edema peripheral	0.00% 0/40 • Up to 13 months All subjects population was used to report AEs and SAEs.	7.5% 3/40 • Up to 13 months All subjects population was used to report AEs and SAEs.
Infections and infestations Herpes zoster	2.5% 1/40 • Up to 13 months All subjects population was used to report AEs and SAEs.	7.5% 3/40 • Up to 13 months All subjects population was used to report AEs and SAEs.
Infections and infestations Urinary tract infection	5.0% 2/40 • Up to 13 months All subjects population was used to report AEs and SAEs.	7.5% 3/40 • Up to 13 months All subjects population was used to report AEs and SAEs.
Musculoskeletal and connective tissue disorders Back pain	2.5% 1/40 • Up to 13 months All subjects population was used to report AEs and SAEs.	5.0% 2/40 • Up to 13 months All subjects population was used to report AEs and SAEs.
Nervous system disorders Dementia Alzheimer's type	0.00% 0/40 • Up to 13 months All subjects population was used to report AEs and SAEs.	5.0% 2/40 • Up to 13 months All subjects population was used to report AEs and SAEs.
Psychiatric disorders Depression	2.5% 1/40 • Up to 13 months All subjects population was used to report AEs and SAEs.	5.0% 2/40 • Up to 13 months All subjects population was used to report AEs and SAEs.
Injury, poisoning and procedural complications Fall	12.5% 5/40 • Up to 13 months All subjects population was used to report AEs and SAEs.	5.0% 2/40 • Up to 13 months All subjects population was used to report AEs and SAEs.
General disorders Fatigue	2.5% 1/40 • Up to 13 months All subjects population was used to report AEs and SAEs.	5.0% 2/40 • Up to 13 months All subjects population was used to report AEs and SAEs.
General disorders Gait disturbance	0.00% 0/40 • Up to 13 months All subjects population was used to report AEs and SAEs.	5.0% 2/40 • Up to 13 months All subjects population was used to report AEs and SAEs.
Nervous system disorders Headache	0.00% 0/40 • Up to 13 months All subjects population was used to report AEs and SAEs.	5.0% 2/40 • Up to 13 months All subjects population was used to report AEs and SAEs.
Injury, poisoning and procedural complications Joint sprain	0.00% 0/40 • Up to 13 months All subjects population was used to report AEs and SAEs.	5.0% 2/40 • Up to 13 months All subjects population was used to report AEs and SAEs.
Injury, poisoning and procedural complications Procedural pain	0.00% 0/40 • Up to 13 months All subjects population was used to report AEs and SAEs.	5.0% 2/40 • Up to 13 months All subjects population was used to report AEs and SAEs.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	7.5% 3/40 • Up to 13 months All subjects population was used to report AEs and SAEs.	2.5% 1/40 • Up to 13 months All subjects population was used to report AEs and SAEs.
Gastrointestinal disorders Diarrhea	7.5% 3/40 • Up to 13 months All subjects population was used to report AEs and SAEs.	2.5% 1/40 • Up to 13 months All subjects population was used to report AEs and SAEs.
Musculoskeletal and connective tissue disorders Muscle Spasms	5.0% 2/40 • Up to 13 months All subjects population was used to report AEs and SAEs.	2.5% 1/40 • Up to 13 months All subjects population was used to report AEs and SAEs.
Infections and infestations Pneumonia	5.0% 2/40 • Up to 13 months All subjects population was used to report AEs and SAEs.	2.5% 1/40 • Up to 13 months All subjects population was used to report AEs and SAEs.
Gastrointestinal disorders Nausea	7.5% 3/40 • Up to 13 months All subjects population was used to report AEs and SAEs.	2.5% 1/40 • Up to 13 months All subjects population was used to report AEs and SAEs.
Respiratory, thoracic and mediastinal disorders Cough	7.5% 3/40 • Up to 13 months All subjects population was used to report AEs and SAEs.	2.5% 1/40 • Up to 13 months All subjects population was used to report AEs and SAEs.
Skin and subcutaneous tissue disorders Rash	7.5% 3/40 • Up to 13 months All subjects population was used to report AEs and SAEs.	0.00% 0/40 • Up to 13 months All subjects population was used to report AEs and SAEs.
Gastrointestinal disorders Vomiting	7.5% 3/40 • Up to 13 months All subjects population was used to report AEs and SAEs.	0.00% 0/40 • Up to 13 months All subjects population was used to report AEs and SAEs.
Psychiatric disorders Agitation	5.0% 2/40 • Up to 13 months All subjects population was used to report AEs and SAEs.	0.00% 0/40 • Up to 13 months All subjects population was used to report AEs and SAEs.
Investigations Blood pressure increased	5.0% 2/40 • Up to 13 months All subjects population was used to report AEs and SAEs.	0.00% 0/40 • Up to 13 months All subjects population was used to report AEs and SAEs.
Injury, poisoning and procedural complications Excoriation	5.0% 2/40 • Up to 13 months All subjects population was used to report AEs and SAEs.	0.00% 0/40 • Up to 13 months All subjects population was used to report AEs and SAEs.
Gastrointestinal disorders Frequent bowel movements	5.0% 2/40 • Up to 13 months All subjects population was used to report AEs and SAEs.	0.00% 0/40 • Up to 13 months All subjects population was used to report AEs and SAEs.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	5.0% 2/40 • Up to 13 months All subjects population was used to report AEs and SAEs.	0.00% 0/40 • Up to 13 months All subjects population was used to report AEs and SAEs.