Trial Outcomes & Findings for Rosiglitazone (Extended Release Tablets) As Adjunctive Therapy For Subjects With Mild To Moderate Alzheimer's Disease (NCT NCT00348309)

Last Updated: 2017-11-28

Results Overview

ADAS is a performance-based test that measures specific cognitive and behavioral dysfunctions in participants with Alzheimer's Disease. The cognitive subscale of the ADAS (ADAS-Cog) comprises 11 items that are summed to a total score ranging from 0 to 70, with lower scores indicating less severe impairment. Change from baseline is calculated as Week 48 value minus the baseline value. APOE4 negative, All except E4/E4's: comprised of APOE4 negative and E4 heterozygote and full population was analyzed for this outcome measure. A hierarchical testing procedure was used to control for the two rosiglitazone dose groups and the genetic subgroups. Least square mean is entered for adjusted mean.

Recruitment status

COMPLETED

Study phase

Target enrollment

1496 participants

Primary outcome timeframe

Baseline (Week 0) and Week 48

Results posted on

2017-11-28

Participant Flow

The study was conducted on participants with mild to moderate Alzheimer's disease(AD), who received donepezil for at least 6 months and who received a stable dose of donepezil for at least 2 months immediately before study entry from 06 July 2006 to 28 January 2009 across 228 centers of 19 countries.

A total of 1496 participants were randomized for the study, out of which seventeen participants did not receive study medication. A total of 1479 were included in the Safety population.

Participant milestones

Participant milestones
Measure	Placebo Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.	2mg Rosiglitazone Extended Release Participants received rosiglitazone extended release 2 milligram (mg) tablet orally, once daily until Week 48 followed by placebo tablet orally once daily until Week 54.	8mg Rosiglitazone Extended Release Participants received rosiglitazone extended release 4 mg tablet orally, once daily until Week 4 followed by 8 mg tablet orally once daily from Week 4 until Week 48 followed by placebo tablet orally once daily until Week 54.
Overall Study STARTED	496	494	489
Overall Study COMPLETED	362	396	346
Overall Study NOT COMPLETED	134	98	143

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.	2mg Rosiglitazone Extended Release Participants received rosiglitazone extended release 2 milligram (mg) tablet orally, once daily until Week 48 followed by placebo tablet orally once daily until Week 54.	8mg Rosiglitazone Extended Release Participants received rosiglitazone extended release 4 mg tablet orally, once daily until Week 4 followed by 8 mg tablet orally once daily from Week 4 until Week 48 followed by placebo tablet orally once daily until Week 54.
Overall Study Adverse Event	56	28	63
Overall Study Lost to Follow-up	6	7	4
Overall Study Protocol Violation	7	12	7
Overall Study Withdrawal by Subject	33	37	40
Overall Study Non-compliance	8	6	8
Overall Study Death of caregiver	1	0	1
Overall Study Lack of insight, dementia	1	0	0
Overall Study Wrong bottle allocated	1	0	0
Overall Study Caregiver sick	1	0	0
Overall Study Use of prohibited medication	5	2	2
Overall Study Caregiver withdrawal	3	0	7
Overall Study Unable to complete ET visit	1	0	0
Overall Study PI closing medical practice	1	0	0
Overall Study Principal investigator's decision	1	0	0
Overall Study No disponibility of medication	1	0	0
Overall Study Worsened neurodegenerative disease	1	0	0
Overall Study Cognitive and behaviour worsening	2	0	0
Overall Study Worsening of alzheimer	1	0	1
Overall Study Did not appear in time for Visit 3	1	0	0
Overall Study Participant died	2	1	1
Overall Study Decision of sponsor	1	0	0
Overall Study Ineffectiveness of treatment	0	1	0
Overall Study A foul of exclusion criteria	0	1	0
Overall Study Participant was hospitalized	0	1	0
Overall Study Sponsor refuseal	0	1	1
Overall Study Forgot often medication	0	1	0
Overall Study Medical Monitor decision	0	0	1
Overall Study Increased dose of Aricept	0	0	1
Overall Study Site closure	0	0	1
Overall Study Adverse event not attended	0	0	1
Overall Study ECG abnormal	0	0	2
Overall Study Cardiologist recommendations	0	0	1
Overall Study HCV career	0	0	1

Baseline Characteristics

Rosiglitazone (Extended Release Tablets) As Adjunctive Therapy For Subjects With Mild To Moderate Alzheimer's Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=496 Participants Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.	2mg Rosiglitazone Extended Release n=494 Participants Participants received rosiglitazone extended release 2 milligram (mg) tablet orally, once daily until Week 48 followed by placebo tablet orally once daily until Week 54.	8mg Rosiglitazone Extended Release n=489 Participants Participants received rosiglitazone extended release 4 mg tablet orally, once daily until Week 4 followed by 8 mg tablet orally once daily from Week 4 until Week 48 followed by placebo tablet orally once daily until Week 54.	Total n=1479 Participants Total of all reporting groups
Age, Continuous	74.2 Years STANDARD_DEVIATION 7.95 • n=5 Participants	74.5 Years STANDARD_DEVIATION 8.06 • n=7 Participants	74.4 Years STANDARD_DEVIATION 7.83 • n=5 Participants	74.4 Years STANDARD_DEVIATION 7.94 • n=4 Participants
Sex: Female, Male Female	304 Participants n=5 Participants	286 Participants n=7 Participants	305 Participants n=5 Participants	895 Participants n=4 Participants
Sex: Female, Male Male	192 Participants n=5 Participants	208 Participants n=7 Participants	184 Participants n=5 Participants	584 Participants n=4 Participants
Race/Ethnicity, Customized Hispanic or Latino	97 Participants n=5 Participants	86 Participants n=7 Participants	82 Participants n=5 Participants	265 Participants n=4 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	399 Participants n=5 Participants	408 Participants n=7 Participants	407 Participants n=5 Participants	1214 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline (Week 0) and Week 48

Population: ITT population included all the participants who were randomized to treatment, who had received at least one dose of study medication and who had at least one post baseline efficacy assessment. Only those participants available at the specified time points were analyzed.

Outcome measures

Outcome measures
Measure	Placebo n=461 Participants Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.	2mg Rosiglitazone Extended Release n=473 Participants Participants received rosiglitazone extended release 2 milligram (mg) tablet orally, once daily until Week 48 followed by placebo tablet orally once daily until Week 54.	8mg Rosiglitazone Extended Release n=459 Participants Participants received rosiglitazone extended release 4 mg tablet orally, once daily until Week 4 followed by 8 mg tablet orally once daily from Week 4 until Week 48 followed by placebo tablet orally once daily until Week 54.
Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) Total Score at Week 48 APOE4 negatives	2.9 Score on a scale Standard Error 0.54	1.6 Score on a scale Standard Error 0.42	2.7 Score on a scale Standard Error 0.56
Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) Total Score at Week 48 All except E4/E4s	3.1 Score on a scale Standard Error 0.36	2.1 Score on a scale Standard Error 0.29	3.1 Score on a scale Standard Error 0.37
Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) Total Score at Week 48 Full populations	3.4 Score on a scale Standard Error 0.35	2.4 Score on a scale Standard Error 0.30	3.2 Score on a scale Standard Error 0.35

PRIMARY outcome

Timeframe: Baseline (Week 0) and Week 48

Population: ITT population. Only those participants available at the specified time points were analyzed.

CDR-SB is a semi-structured interview of participants and their caregivers. Participant's cognitive status is rated across 6 domains of functioning, including memory, orientation, judgment/problem solving, community affairs, home/hobbies, and personal care. Severity score assigned for each of 6 domains; Total score (SB) ranges from 0 to 18. Higher scores indicate greater disease severity. Change from baseline is calculated as Week 48 value minus the baseline value. APOE4 negative, All except E4/E4's: comprised of APOE4 negative and E4 heterozygote and full population was analyzed for this outcome measure. A hierarchical testing procedure was used to control for the two rosiglitazone dose groups and the genetic subgroups.

Outcome measures

Outcome measures
Measure	Placebo n=461 Participants Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.	2mg Rosiglitazone Extended Release n=473 Participants Participants received rosiglitazone extended release 2 milligram (mg) tablet orally, once daily until Week 48 followed by placebo tablet orally once daily until Week 54.	8mg Rosiglitazone Extended Release n=459 Participants Participants received rosiglitazone extended release 4 mg tablet orally, once daily until Week 4 followed by 8 mg tablet orally once daily from Week 4 until Week 48 followed by placebo tablet orally once daily until Week 54.
Change From Baseline in Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) at Week 48 for APOE E4 Full population	1.6 Score on a scale Standard Error 0.14	1.0 Score on a scale Standard Error 0.12	1.7 Score on a scale Standard Error 0.13
Change From Baseline in Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) at Week 48 for APOE E4 APOE4 negatives	1.3 Score on a scale Standard Error 0.21	0.8 Score on a scale Standard Error 0.16	1.5 Score on a scale Standard Error 0.20
Change From Baseline in Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) at Week 48 for APOE E4 All except E4/E4s	1.5 Score on a scale Standard Error 0.14	1.0 Score on a scale Standard Error 0.12	1.7 Score on a scale Standard Error 0.14

SECONDARY outcome

Timeframe: Baseline (Week 0), Week 8, 16, 24 and 48

Population: ITT population. Only those participants available at the specified time points were analyzed.

The DAD measures instrumental and basic activities of daily living in participants with Alzheimer's Disease (AD). This scale assesses a participants' 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. The scale includes 23 items relating to instrumental activities of daily living and 17 items relating to basic self-care. Each item can be scored as 1 = yes, 0 = no, non applicable = NA. Total score was obtained by adding the rating for each question and converting this total score out of 100. The total score ranged from 0 to 100, where higher score indicated better function and lower score indicated greater severity of symptoms; a positive change from baseline indicated an improvement. Change from baseline is calculated as endpoint value minus the baseline value.

Outcome measures

Outcome measures
Measure	Placebo n=436 Participants Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.	2mg Rosiglitazone Extended Release n=458 Participants Participants received rosiglitazone extended release 2 milligram (mg) tablet orally, once daily until Week 48 followed by placebo tablet orally once daily until Week 54.	8mg Rosiglitazone Extended Release n=441 Participants Participants received rosiglitazone extended release 4 mg tablet orally, once daily until Week 4 followed by 8 mg tablet orally once daily from Week 4 until Week 48 followed by placebo tablet orally once daily until Week 54.
Change From Baseline in Disability Assessment for Dementia Scale (DAD) Total Score At Week 8	0.1 Scores on a scale Standard Error 0.56	-0.5 Scores on a scale Standard Error 0.48	-1.1 Scores on a scale Standard Error 0.47
Change From Baseline in Disability Assessment for Dementia Scale (DAD) Total Score At Week 16	-1.6 Scores on a scale Standard Error 0.62	-1.6 Scores on a scale Standard Error 0.59	-2.1 Scores on a scale Standard Error 0.56
Change From Baseline in Disability Assessment for Dementia Scale (DAD) Total Score At Week 24	-3.5 Scores on a scale Standard Error 0.69	-2.2 Scores on a scale Standard Error 0.64	-3.3 Scores on a scale Standard Error 0.69
Change From Baseline in Disability Assessment for Dementia Scale (DAD) Total Score At Week 48	-7.8 Scores on a scale Standard Error 0.82	-5.7 Scores on a scale Standard Error 0.78	-8.4 Scores on a scale Standard Error 0.84

SECONDARY outcome

Timeframe: Baseline (Week 0), Week 8, 16, 24 and 48

Population: ITT population. Only those participants available at the specified time points were analyzed.

The NPI is a questionnaire that quantifies behavioral changes in dementia. For each of 12 behavioral domains there are 4 scores: Frequency (scale:1=occasionally to 4=very frequently), Severity (scale:1=Mild to 3=Severe), Total (frequency x severity), Caregiver distress (scale: 0=not at all distressing to 5=extremely distressing).The NPI Psychosis Subscale consists of the two domains of Delusions and Hallucinations, calculated by adding the Individual Item Scores, to yield a possible total score of 0 to 24. Lower score=less severity. Change from baseline is calculated as endpoint value minus the baseline value.

Outcome measures

Outcome measures
Measure	Placebo n=461 Participants Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.	2mg Rosiglitazone Extended Release n=473 Participants Participants received rosiglitazone extended release 2 milligram (mg) tablet orally, once daily until Week 48 followed by placebo tablet orally once daily until Week 54.	8mg Rosiglitazone Extended Release n=459 Participants Participants received rosiglitazone extended release 4 mg tablet orally, once daily until Week 4 followed by 8 mg tablet orally once daily from Week 4 until Week 48 followed by placebo tablet orally once daily until Week 54.
Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score At Week 8	-0.3 Score on a scale Standard Error 0.39	-0.7 Score on a scale Standard Error 0.32	-0.3 Score on a scale Standard Error 0.39
Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score At Week 16	-0.3 Score on a scale Standard Error 0.43	-0.6 Score on a scale Standard Error 0.36	0.1 Score on a scale Standard Error 0.43
Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score At Week 24	0.4 Score on a scale Standard Error 0.47	-0.2 Score on a scale Standard Error 0.39	0.2 Score on a scale Standard Error 0.48
Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score At Week 48	1.6 Score on a scale Standard Error 0.61	0.1 Score on a scale Standard Error 0.44	1.8 Score on a scale Standard Error 0.55

SECONDARY outcome

Timeframe: Screening (Week -4) and Week 48

Population: ITT population. Only those participants available at the specified time points were analyzed.

The MMSE consists of 11 tests of orientation, memory (recent and immediate), concentration, language and praxis. The scale was completed by the investigator, based on the performance of the participant, and took approximately 5 to 10 minutes to administer. The scores from 11 tests were combined to obtain the total score. The total scores range from 0 to 30, with lower scores indicating greater cognitive impairment and higher score indicating better outcome; a positive change from screening indicated an improvement. The total MMSE score for participants at screening was between 10 and 26, inclusive, in order to be eligible to participate in the trial. Change from screening is calculated as endpoint value minus the screening value.

Outcome measures

Outcome measures
Measure	Placebo n=348 Participants Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.	2mg Rosiglitazone Extended Release n=388 Participants Participants received rosiglitazone extended release 2 milligram (mg) tablet orally, once daily until Week 48 followed by placebo tablet orally once daily until Week 54.	8mg Rosiglitazone Extended Release n=335 Participants Participants received rosiglitazone extended release 4 mg tablet orally, once daily until Week 4 followed by 8 mg tablet orally once daily from Week 4 until Week 48 followed by placebo tablet orally once daily until Week 54.
Change From Screening in Mini Mental State Examination (MMSE) Total Score	-1.6 Score on a scale Standard Error 0.21	-1.6 Score on a scale Standard Error 0.20	-1.7 Score on a scale Standard Error 0.21

SECONDARY outcome

Timeframe: Baseline (Week 0), Week 12, 24, 36 and 48

Population: ITT population. Only those participants available at the specified time points were analyzed.

The RUD instrument was developed as a comprehensive tool to assess the amount of resource use among demented patients. RUD assessd both formal and informal resource use of the patient and the primary caregiver, making it possible to calculate costs from a societal perspective. Q1 corresponds to the number of hours during the last month the caregiver spent assisting the patient with toilet visits, eating, dressing, grooming, walking and bathing and Q2 corresponds to the number of hours during the last month the caregiver spent assisting the patient with shopping, food preparation, housekeeping, laundry, transportation, taking medication and managing financial matters. 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.

Outcome measures

Outcome measures
Measure	Placebo n=461 Participants Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.	2mg Rosiglitazone Extended Release n=473 Participants Participants received rosiglitazone extended release 2 milligram (mg) tablet orally, once daily until Week 48 followed by placebo tablet orally once daily until Week 54.	8mg Rosiglitazone Extended Release n=459 Participants Participants received rosiglitazone extended release 4 mg tablet orally, once daily until Week 4 followed by 8 mg tablet orally once daily from Week 4 until Week 48 followed by placebo tablet orally once daily until Week 54.
Change From Baseline in the Domains of the Resource Utilization in Dementia Scale (RUD) Q1: Week 12	1.6 hours Standard Error 2.25	2.4 hours Standard Error 2.50	-0.1 hours Standard Error 3.18
Change From Baseline in the Domains of the Resource Utilization in Dementia Scale (RUD) Q1: Week 24	10.7 hours Standard Error 3.52	3.4 hours Standard Error 1.84	7.0 hours Standard Error 4.06
Change From Baseline in the Domains of the Resource Utilization in Dementia Scale (RUD) Q1: Week 36	16.3 hours Standard Error 3.60	10.0 hours Standard Error 3.43	15.2 hours Standard Error 4.95
Change From Baseline in the Domains of the Resource Utilization in Dementia Scale (RUD) Q1: Week 48	21.7 hours Standard Error 4.16	17.0 hours Standard Error 4.17	18.1 hours Standard Error 4.72
Change From Baseline in the Domains of the Resource Utilization in Dementia Scale (RUD) Q2: Week 12	-6.4 hours Standard Error 4.64	2.4 hours Standard Error 4.16	1.5 hours Standard Error 4.50
Change From Baseline in the Domains of the Resource Utilization in Dementia Scale (RUD) Q2: Week 24	0.3 hours Standard Error 4.89	1.6 hours Standard Error 4.17	6.5 hours Standard Error 4.88
Change From Baseline in the Domains of the Resource Utilization in Dementia Scale (RUD) Q2: Week 36	5.0 hours Standard Error 5.34	4.6 hours Standard Error 4.44	13.3 hours Standard Error 5.35
Change From Baseline in the Domains of the Resource Utilization in Dementia Scale (RUD) Q2: Week 48	10.8 hours Standard Error 5.51	8.4 hours Standard Error 4.88	27.0 hours Standard Error 6.24

SECONDARY outcome

Timeframe: Baseline (Week 0), Week 12, 36 and 48

Population: ITT population. Only those participants available at the specified time points were analyzed.

The EQ-5D Proxy is a two part scale that evaluated the participant's health status via Thermometer and Utility scores. The Thermometer score was the caregiver's rating of the participant's overall health status on a VAS (0 \["worst possible status"\] to 100 \["best imaginable status"\]). The Utility score was a caregiver rating of health status on dimensions of mobility, self-care, usual activities, pain/discomfort, and anxiety/depression\] where '1' indicated better health state (no problems); '3' indicated worst health state ("confined to bed"). Total possible score was the sum of individual items, ranged from 5 to 15; lower score indicated a better health state and higher score indicated greater severity of symptoms. A positive change from baseline indicated improvement in the Thermometer score and a negative change from baseline indicated improvement in the Utility score. Change from baseline is calculated as endpoint value minus the baseline value.

Outcome measures

Outcome measures
Measure	Placebo n=461 Participants Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.	2mg Rosiglitazone Extended Release n=473 Participants Participants received rosiglitazone extended release 2 milligram (mg) tablet orally, once daily until Week 48 followed by placebo tablet orally once daily until Week 54.	8mg Rosiglitazone Extended Release n=459 Participants Participants received rosiglitazone extended release 4 mg tablet orally, once daily until Week 4 followed by 8 mg tablet orally once daily from Week 4 until Week 48 followed by placebo tablet orally once daily until Week 54.
Change From Baseline in European Quality of Life-5 Dimensions Proxy Version (EQ-5D Proxy) Scale Total Score Assessed by Thermometer (Visual Analog Scale [VAS]) and Utility Thermometer: Week 12	0.5 Score on a scale Standard Error 0.84	0.3 Score on a scale Standard Error 0.82	-0.5 Score on a scale Standard Error 0.94
Change From Baseline in European Quality of Life-5 Dimensions Proxy Version (EQ-5D Proxy) Scale Total Score Assessed by Thermometer (Visual Analog Scale [VAS]) and Utility Thermometer: Week 36	0.8 Score on a scale Standard Error 0.95	-1.6 Score on a scale Standard Error 0.97	-2.1 Score on a scale Standard Error 1.03
Change From Baseline in European Quality of Life-5 Dimensions Proxy Version (EQ-5D Proxy) Scale Total Score Assessed by Thermometer (Visual Analog Scale [VAS]) and Utility Thermometer: Week 48	-1.5 Score on a scale Standard Error 1.05	-0.3 Score on a scale Standard Error 0.96	-2.4 Score on a scale Standard Error 1.08
Change From Baseline in European Quality of Life-5 Dimensions Proxy Version (EQ-5D Proxy) Scale Total Score Assessed by Thermometer (Visual Analog Scale [VAS]) and Utility Utility: Week 12	0.01 Score on a scale Standard Error 0.009	0.02 Score on a scale Standard Error 0.009	-0.01 Score on a scale Standard Error 0.010
Change From Baseline in European Quality of Life-5 Dimensions Proxy Version (EQ-5D Proxy) Scale Total Score Assessed by Thermometer (Visual Analog Scale [VAS]) and Utility Utility: Week 36	-0.02 Score on a scale Standard Error 0.011	-0.01 Score on a scale Standard Error 0.010	-0.04 Score on a scale Standard Error 0.012
Change From Baseline in European Quality of Life-5 Dimensions Proxy Version (EQ-5D Proxy) Scale Total Score Assessed by Thermometer (Visual Analog Scale [VAS]) and Utility Utility: Week 48	-0.04 Score on a scale Standard Error 0.012	-0.02 Score on a scale Standard Error 0.011	-0.05 Score on a scale Standard Error 0.013

SECONDARY outcome

Timeframe: Baseline (Week 0), Week 8, 16, 24, 36 and 48

Population: ITT population. Only those participants available at the specified time points were analyzed.

ADAS is a performance-based test that measures specific cognitive and behavioral dysfunctions in patients with Alzheimer's Disease. The cognitive subscale of the ADAS (ADAS-Cog) comprises 11 items that are summed to a total score ranging from 0 to 70, with lower scores indicating less severe impairment. Change from baseline is calculated as endpoint value minus the baseline value.

Outcome measures

Outcome measures
Measure	Placebo n=461 Participants Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.	2mg Rosiglitazone Extended Release n=473 Participants Participants received rosiglitazone extended release 2 milligram (mg) tablet orally, once daily until Week 48 followed by placebo tablet orally once daily until Week 54.	8mg Rosiglitazone Extended Release n=459 Participants Participants received rosiglitazone extended release 4 mg tablet orally, once daily until Week 4 followed by 8 mg tablet orally once daily from Week 4 until Week 48 followed by placebo tablet orally once daily until Week 54.
Change From Baseline in ADAS-Cog Total Score for Observed Cases at Weeks 8, 16, 24, 36 and 48 Week 8	-0.2 Score on a scale Standard Deviation 4.21	-0.6 Score on a scale Standard Deviation 4.57	-0.2 Score on a scale Standard Deviation 4.44
Change From Baseline in ADAS-Cog Total Score for Observed Cases at Weeks 8, 16, 24, 36 and 48 Week 16	-0.1 Score on a scale Standard Deviation 5.09	-0.5 Score on a scale Standard Deviation 4.76	0.1 Score on a scale Standard Deviation 5.13
Change From Baseline in ADAS-Cog Total Score for Observed Cases at Weeks 8, 16, 24, 36 and 48 Week 24	1.0 Score on a scale Standard Deviation 5.86	-0.2 Score on a scale Standard Deviation 5.17	0.8 Score on a scale Standard Deviation 5.66
Change From Baseline in ADAS-Cog Total Score for Observed Cases at Weeks 8, 16, 24, 36 and 48 Week 36	1.8 Score on a scale Standard Deviation 6.08	1.3 Score on a scale Standard Deviation 5.79	2.2 Score on a scale Standard Deviation 6.40
Change From Baseline in ADAS-Cog Total Score for Observed Cases at Weeks 8, 16, 24, 36 and 48 Week 48	2.9 Score on a scale Standard Deviation 6.85	2.1 Score on a scale Standard Deviation 6.25	2.6 Score on a scale Standard Deviation 6.76

SECONDARY outcome

Timeframe: Baseline (Week 0), Week 12, 24, 36 and 48

Population: ITT population. Only those participants available at the specified time points were analyzed.

Outcome measures

Outcome measures
Measure	Placebo n=461 Participants Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.	2mg Rosiglitazone Extended Release n=473 Participants Participants received rosiglitazone extended release 2 milligram (mg) tablet orally, once daily until Week 48 followed by placebo tablet orally once daily until Week 54.	8mg Rosiglitazone Extended Release n=459 Participants Participants received rosiglitazone extended release 4 mg tablet orally, once daily until Week 4 followed by 8 mg tablet orally once daily from Week 4 until Week 48 followed by placebo tablet orally once daily until Week 54.
Change From Baseline in CDR-SB Score for Observed Cases at Weeks 12, 24, 36 and 48 Week 12	0.4 Score on a scale Standard Deviation 1.55	0.3 Score on a scale Standard Deviation 1.36	0.3 Score on a scale Standard Deviation 1.40
Change From Baseline in CDR-SB Score for Observed Cases at Weeks 12, 24, 36 and 48 Week 24	0.7 Score on a scale Standard Deviation 2.01	0.5 Score on a scale Standard Deviation 1.67	0.8 Score on a scale Standard Deviation 1.83
Change From Baseline in CDR-SB Score for Observed Cases at Weeks 12, 24, 36 and 48 Week 36	1.0 Score on a scale Standard Deviation 2.26	0.7 Score on a scale Standard Deviation 2.06	1.2 Score on a scale Standard Deviation 2.30
Change From Baseline in CDR-SB Score for Observed Cases at Weeks 12, 24, 36 and 48 Week 48	1.5 Score on a scale Standard Deviation 2.68	1.0 Score on a scale Standard Deviation 2.28	1.6 Score on a scale Standard Deviation 2.56

SECONDARY outcome

Timeframe: Week 48 and 54

Population: ITT population. Only those participants available at the specified time points were analyzed.

ADAS is a performance-based test that measures specific cognitive and behavioral dysfunctions in patients with Alzheimer's Disease. The cognitive subscale of the ADAS (ADAS-Cog) comprises 11 items that are summed to a total score ranging from 0 to 70, with lower scores indicating less severe impairment. Change was calculated as endpoint value (Week 54) minus Week 48 value.

Outcome measures

Outcome measures
Measure	Placebo n=332 Participants Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.	2mg Rosiglitazone Extended Release n=366 Participants Participants received rosiglitazone extended release 2 milligram (mg) tablet orally, once daily until Week 48 followed by placebo tablet orally once daily until Week 54.	8mg Rosiglitazone Extended Release n=305 Participants Participants received rosiglitazone extended release 4 mg tablet orally, once daily until Week 4 followed by 8 mg tablet orally once daily from Week 4 until Week 48 followed by placebo tablet orally once daily until Week 54.
Change in ADAS-Cog Total Score for Observed Cases at Week 54 Compared to Week 48	0.7 Score on a scale Standard Error 0.28	1.1 Score on a scale Standard Error 0.27	1.1 Score on a scale Standard Error 0.29

SECONDARY outcome

Timeframe: Week 48 and 54

Population: ITT population. Only those participants available at the specified time points were analyzed.

Outcome measures

Outcome measures
Measure	Placebo n=328 Participants Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.	2mg Rosiglitazone Extended Release n=364 Participants Participants received rosiglitazone extended release 2 milligram (mg) tablet orally, once daily until Week 48 followed by placebo tablet orally once daily until Week 54.	8mg Rosiglitazone Extended Release n=302 Participants Participants received rosiglitazone extended release 4 mg tablet orally, once daily until Week 4 followed by 8 mg tablet orally once daily from Week 4 until Week 48 followed by placebo tablet orally once daily until Week 54.
Change in CDR-SB Total Score at Week 54 Compared to Week 48	0.2 Score on a scale Standard Error 0.07	0.2 Score on a scale Standard Error 0.07	0.1 Score on a scale Standard Error 0.07

SECONDARY outcome

Timeframe: Baseline (Week 0) and Week 48

Population: ITT population. Only those participants available at the specified time points were analyzed.

Blood samples of participants were collected for HbA1c assessment. HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over a 2- to 3-month period. Change from Baseline in HbA1c was calculated as the value at Week 48 minus the value at Baseline.

Outcome measures

Outcome measures
Measure	Placebo n=321 Participants Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.	2mg Rosiglitazone Extended Release n=352 Participants Participants received rosiglitazone extended release 2 milligram (mg) tablet orally, once daily until Week 48 followed by placebo tablet orally once daily until Week 54.	8mg Rosiglitazone Extended Release n=313 Participants Participants received rosiglitazone extended release 4 mg tablet orally, once daily until Week 4 followed by 8 mg tablet orally once daily from Week 4 until Week 48 followed by placebo tablet orally once daily until Week 54.
Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 48	0.14 Percentage of total hemoglobin Standard Error 0.020	0.21 Percentage of total hemoglobin Standard Error 0.020	0.18 Percentage of total hemoglobin Standard Error 0.020

SECONDARY outcome

Timeframe: Up to Week 54

Population: The safety population included all participants randomized to treatment and received at least one dose of study medication.

An adverse event (AE) was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started. An adverse event was therefore any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose results in death, are life threatening, requires hospitalization or prolongation of hospitalization or results in disability/incapacity, and congenital anomaly/birth defect. The data was reported for prospective period.

Outcome measures

Outcome measures
Measure	Placebo n=496 Participants Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.	2mg Rosiglitazone Extended Release n=494 Participants Participants received rosiglitazone extended release 2 milligram (mg) tablet orally, once daily until Week 48 followed by placebo tablet orally once daily until Week 54.	8mg Rosiglitazone Extended Release n=489 Participants Participants received rosiglitazone extended release 4 mg tablet orally, once daily until Week 4 followed by 8 mg tablet orally once daily from Week 4 until Week 48 followed by placebo tablet orally once daily until Week 54.
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) Any TEAEs	304 Participants	273 Participants	327 Participants
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) Any SAEs	62 Participants	45 Participants	50 Participants

SECONDARY outcome

Timeframe: Baseline (Week 0), Week 4, 8, 12, 16, 24, 36, 48 and 56

Population: Safety population. Only those participants available at the specified time points were analyzed. Data for Site 040449 was not included in analysis due to audit finding.

The plethysmographic method was used to measure BP throughout the study. Change in Systolic and Diastolic BP was calculated as endpoint value minus the baseline value.

Outcome measures

SECONDARY outcome

Timeframe: Baseline (Week 0), Week 4, 8, 12, 16, 24, 36, 48 and 56

Population: Safety population. Only those participants available at the specified time points were analyzed. Data for Site 040449 was not included in analysis due to audit finding.

Mean Change From Baseline in heart rate was calculated as endpoint value minus the baseline value.

Outcome measures

Outcome measures
Measure	Placebo n=477 Participants Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.	2mg Rosiglitazone Extended Release n=481 Participants Participants received rosiglitazone extended release 2 milligram (mg) tablet orally, once daily until Week 48 followed by placebo tablet orally once daily until Week 54.	8mg Rosiglitazone Extended Release n=470 Participants Participants received rosiglitazone extended release 4 mg tablet orally, once daily until Week 4 followed by 8 mg tablet orally once daily from Week 4 until Week 48 followed by placebo tablet orally once daily until Week 54.
Mean Change From Baseline in Heart Rate Week 4	0.8 beats per min (bpm) Standard Deviation 8.42	1.1 beats per min (bpm) Standard Deviation 7.95	0.6 beats per min (bpm) Standard Deviation 8.36
Mean Change From Baseline in Heart Rate Week 8	1.5 beats per min (bpm) Standard Deviation 8.98	1.3 beats per min (bpm) Standard Deviation 9.19	1.0 beats per min (bpm) Standard Deviation 8.91
Mean Change From Baseline in Heart Rate Week 12	1.6 beats per min (bpm) Standard Deviation 9.06	1.8 beats per min (bpm) Standard Deviation 9.04	0.7 beats per min (bpm) Standard Deviation 9.68
Mean Change From Baseline in Heart Rate Week 16	1.0 beats per min (bpm) Standard Deviation 9.23	1.3 beats per min (bpm) Standard Deviation 9.18	0.8 beats per min (bpm) Standard Deviation 9.52
Mean Change From Baseline in Heart Rate Week 24	0.9 beats per min (bpm) Standard Deviation 9.41	1.3 beats per min (bpm) Standard Deviation 8.70	0.8 beats per min (bpm) Standard Deviation 10.19
Mean Change From Baseline in Heart Rate Week 36	0.9 beats per min (bpm) Standard Deviation 9.30	1.8 beats per min (bpm) Standard Deviation 9.42	1.1 beats per min (bpm) Standard Deviation 9.58
Mean Change From Baseline in Heart Rate Week 48	1.2 beats per min (bpm) Standard Deviation 9.10	1.4 beats per min (bpm) Standard Deviation 8.92	0.7 beats per min (bpm) Standard Deviation 9.43
Mean Change From Baseline in Heart Rate Week 54	0.5 beats per min (bpm) Standard Deviation 10.10	1.4 beats per min (bpm) Standard Deviation 9.55	0.0 beats per min (bpm) Standard Deviation 11.05

SECONDARY outcome

Timeframe: Baseline (Week 0), Week 4, 8, 12, 16, 24, 36, 48 and 56

Population: Safety population. Here, n=number of participants with observed data contributing to the analysis. Data for Site 040449 was not included in analysis due to audit finding.

Body weight was measured at all visits, without shoes and wearing light clothing. Mean Change From Baseline in Weight was calculated as endpoint value minus the baseline value.

Outcome measures

Outcome measures
Measure	Placebo n=477 Participants Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.	2mg Rosiglitazone Extended Release n=481 Participants Participants received rosiglitazone extended release 2 milligram (mg) tablet orally, once daily until Week 48 followed by placebo tablet orally once daily until Week 54.	8mg Rosiglitazone Extended Release n=470 Participants Participants received rosiglitazone extended release 4 mg tablet orally, once daily until Week 4 followed by 8 mg tablet orally once daily from Week 4 until Week 48 followed by placebo tablet orally once daily until Week 54.
Mean Change From Baseline in Weight Week 4	0.1 kilogram (kg) Standard Deviation 2.04	0.2 kilogram (kg) Standard Deviation 1.66	0.3 kilogram (kg) Standard Deviation 1.88
Mean Change From Baseline in Weight Week 8	0.2 kilogram (kg) Standard Deviation 2.35	0.3 kilogram (kg) Standard Deviation 1.95	0.7 kilogram (kg) Standard Deviation 2.37
Mean Change From Baseline in Weight Week 12	0.2 kilogram (kg) Standard Deviation 2.50	0.3 kilogram (kg) Standard Deviation 2.09	0.9 kilogram (kg) Standard Deviation 2.33
Mean Change From Baseline in Weight Week 16	0.1 kilogram (kg) Standard Deviation 2.88	0.3 kilogram (kg) Standard Deviation 2.44	1.0 kilogram (kg) Standard Deviation 2.56
Mean Change From Baseline in Weight Week 24	0.1 kilogram (kg) Standard Deviation 2.88	0.6 kilogram (kg) Standard Deviation 2.77	0.9 kilogram (kg) Standard Deviation 3.26
Mean Change From Baseline in Weight Week 36	0.0 kilogram (kg) Standard Deviation 3.37	0.7 kilogram (kg) Standard Deviation 3.00	1.3 kilogram (kg) Standard Deviation 3.92
Mean Change From Baseline in Weight Week 48	0.4 kilogram (kg) Standard Deviation 3.54	0.8 kilogram (kg) Standard Deviation 3.47	1.3 kilogram (kg) Standard Deviation 4.13
Mean Change From Baseline in Weight Week 54	0.3 kilogram (kg) Standard Deviation 3.74	0.7 kilogram (kg) Standard Deviation 3.69	0.8 kilogram (kg) Standard Deviation 4.53

SECONDARY outcome

Timeframe: Baseline (Week 0), Week 4, 16, 36 and 48

Population: Safety population. Only those participants available at the specified time points were analyzed.

Blood samples of participants were collected for Hemoglobin. Change from baseline in Hemoglobin was calculated as endpoint value minus the baseline value.

Outcome measures

Outcome measures
Measure	Placebo n=496 Participants Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.	2mg Rosiglitazone Extended Release n=494 Participants Participants received rosiglitazone extended release 2 milligram (mg) tablet orally, once daily until Week 48 followed by placebo tablet orally once daily until Week 54.	8mg Rosiglitazone Extended Release n=489 Participants Participants received rosiglitazone extended release 4 mg tablet orally, once daily until Week 4 followed by 8 mg tablet orally once daily from Week 4 until Week 48 followed by placebo tablet orally once daily until Week 54.
Change From Baseline in Hemoglobin Values Week 4	-0.4 grams per litre (g/L) Standard Deviation 6.45	-2.5 grams per litre (g/L) Standard Deviation 6.92	-3.7 grams per litre (g/L) Standard Deviation 6.19
Change From Baseline in Hemoglobin Values Week 16	-0.6 grams per litre (g/L) Standard Deviation 7.01	-6.2 grams per litre (g/L) Standard Deviation 7.76	-11.9 grams per litre (g/L) Standard Deviation 8.65
Change From Baseline in Hemoglobin Values Week 36	-2.0 grams per litre (g/L) Standard Deviation 7.25	-6.4 grams per litre (g/L) Standard Deviation 8.04	-12.5 grams per litre (g/L) Standard Deviation 9.38
Change From Baseline in Hemoglobin Values Week 48	-1.9 grams per litre (g/L) Standard Deviation 7.86	-6.5 grams per litre (g/L) Standard Deviation 8.45	-12.2 grams per litre (g/L) Standard Deviation 10.62

SECONDARY outcome

Timeframe: Baseline (Week 0), Week 4, 8, 12, 16, 36 and 48

Population: Safety population. Only those participants available at the specified time points were analyzed.

Blood samples of participants were collected for Hematocrit . Change from baseline in Hematocrit was calculated as endpoint value minus the baseline value.

Outcome measures

Outcome measures
Measure	Placebo n=496 Participants Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.	2mg Rosiglitazone Extended Release n=494 Participants Participants received rosiglitazone extended release 2 milligram (mg) tablet orally, once daily until Week 48 followed by placebo tablet orally once daily until Week 54.	8mg Rosiglitazone Extended Release n=489 Participants Participants received rosiglitazone extended release 4 mg tablet orally, once daily until Week 4 followed by 8 mg tablet orally once daily from Week 4 until Week 48 followed by placebo tablet orally once daily until Week 54.
Change From Baseline in Hematocrit Values Week 4	-0.0007 litre Standard Deviation 0.02133	-0.0068 litre Standard Deviation 0.02189	-0.0115 litre Standard Deviation 0.01994
Change From Baseline in Hematocrit Values Week 16	-0.0003 litre Standard Deviation 0.02318	-0.0174 litre Standard Deviation 0.02460	-0.0339 litre Standard Deviation 0.02697
Change From Baseline in Hematocrit Values Week 36	-0.0037 litre Standard Deviation 0.02246	-0.0167 litre Standard Deviation 0.02471	-0.0352 litre Standard Deviation 0.02834
Change From Baseline in Hematocrit Values Week 48	-0.0029 litre Standard Deviation 0.02447	-0.0177 litre Standard Deviation 0.02658	-0.0346 litre Standard Deviation 0.03177

SECONDARY outcome

Timeframe: Baseline (Week 0), Week 8, 16, 24, 36, 48 and 56

Population: ITT population. Only those participants available at the specified time points were analyzed.

Short term memory assessment score was based on ADAS-Cog questionnaire (Question 1 and 7). ADAS is a performance-based test that measures specific cognitive and behavioral dysfunctions in participants with AD. Question 1 (Word Recall) and Question 7 (Word Recognition) of the ADAS-Cog questionnaire were summed to get a short term memory assessment score. Word recall task consist of the participants score was the mean number of words not recalled on three trials (maximum score 10) and word recognition task, to score this item the number of incorrect responses was counted (maximum error score was 12). The total score ranged from 0 to 22 with 0 indicating absence of symptoms and higher scores indicating greater dysfunction; a negative change from baseline indicated improvement. Change from Baseline in short term memory assessment was calculated as endpoint value minus the baseline value.

Outcome measures

Outcome measures
Measure	Placebo n=461 Participants Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.	2mg Rosiglitazone Extended Release n=473 Participants Participants received rosiglitazone extended release 2 milligram (mg) tablet orally, once daily until Week 48 followed by placebo tablet orally once daily until Week 54.	8mg Rosiglitazone Extended Release n=459 Participants Participants received rosiglitazone extended release 4 mg tablet orally, once daily until Week 4 followed by 8 mg tablet orally once daily from Week 4 until Week 48 followed by placebo tablet orally once daily until Week 54.
Mean Change From Baseline in Short Term Memory Assessment Score Week 8	-0.3 Score on a scale Standard Deviation 2.71	-0.4 Score on a scale Standard Deviation 3.03	-0.3 Score on a scale Standard Deviation 2.76
Mean Change From Baseline in Short Term Memory Assessment Score Week 16	-0.4 Score on a scale Standard Deviation 2.93	-0.7 Score on a scale Standard Deviation 2.92	-0.4 Score on a scale Standard Deviation 3.07
Mean Change From Baseline in Short Term Memory Assessment Score Week 24	0.1 Score on a scale Standard Deviation 2.96	-0.4 Score on a scale Standard Deviation 3.03	-0.1 Score on a scale Standard Deviation 3.06
Mean Change From Baseline in Short Term Memory Assessment Score Week 36	0.4 Score on a scale Standard Deviation 2.79	0.3 Score on a scale Standard Deviation 3.18	0.7 Score on a scale Standard Deviation 3.04
Mean Change From Baseline in Short Term Memory Assessment Score Week 48	0.6 Score on a scale Standard Deviation 3.01	0.3 Score on a scale Standard Deviation 3.07	0.4 Score on a scale Standard Deviation 3.06
Mean Change From Baseline in Short Term Memory Assessment Score Week 54	1.1 Score on a scale Standard Deviation 2.96	0.8 Score on a scale Standard Deviation 3.10	0.9 Score on a scale Standard Deviation 3.17

SECONDARY outcome

Timeframe: Baseline (Week 0) and Week 12, 24 and 36

Population: Safety population. Week 12, Week 24 and Week 36 assessments of HbA1c were only needed in participants whose HbA1c was \>= 6.5% at screening or who had known Type 2 diabetes. Only those participants available at the specified time points were analyzed.

Outcome measures

Outcome measures
Measure	Placebo n=145 Participants Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.	2mg Rosiglitazone Extended Release n=150 Participants Participants received rosiglitazone extended release 2 milligram (mg) tablet orally, once daily until Week 48 followed by placebo tablet orally once daily until Week 54.	8mg Rosiglitazone Extended Release n=127 Participants Participants received rosiglitazone extended release 4 mg tablet orally, once daily until Week 4 followed by 8 mg tablet orally once daily from Week 4 until Week 48 followed by placebo tablet orally once daily until Week 54.
Change From Baseline in HbA1c at Week 12, Week 24 and Week 36 Week 36	0.20 Percent of total hemoglobin Standard Deviation 0.400	0.19 Percent of total hemoglobin Standard Deviation 0.430	0.15 Percent of total hemoglobin Standard Deviation 0.526
Change From Baseline in HbA1c at Week 12, Week 24 and Week 36 Week 12	0.01 Percent of total hemoglobin Standard Deviation 0.336	0.14 Percent of total hemoglobin Standard Deviation 0.634	0.16 Percent of total hemoglobin Standard Deviation 0.407
Change From Baseline in HbA1c at Week 12, Week 24 and Week 36 Week 24	0.07 Percent of total hemoglobin Standard Deviation 0.401	0.12 Percent of total hemoglobin Standard Deviation 0.422	0.06 Percent of total hemoglobin Standard Deviation 0.551

SECONDARY outcome

Timeframe: Baseline (Week 0), Week 4, 8, 12, 16, 24, 36, 48 and 56

Population: Safety population. Only those participants available at the specified time points were analyzed.

Only those parameters for which at least one value of clinical concern (CC) was reported are summarized. Pre-defined limits of potential clinical concern (CC Low \[relative to the lower limit of normal\], CC High \[relative to the upper limit of normal\]) are: Hematocrit 0.8, 1.2; hemoglobin 10-11, 16.5-18; Red blood corpuscles(RBC) 0.8, 1.2; mean corpuscular volume (MCV) 0.8, 1.2; mean corpuscular hemoglobin (MCH) 0.8, 1.2; White blood corpuscles (WBC) 3- absolute value, 15-absolute value, Red Cell Distribution Width (RDW) 0.8, 1.2; Lymphocytes 0.75, 1.5; Monocytes NA, 2; Eosinophil NA, 2; platelet count 100-absolute, 500-absoulte; segmented neutrophil (SN) 0.75, 1.5 and Total Neutrophil (TN) 0.75, 1.5.

Outcome measures

Outcome measures
Measure	Placebo n=496 Participants Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.	2mg Rosiglitazone Extended Release n=494 Participants Participants received rosiglitazone extended release 2 milligram (mg) tablet orally, once daily until Week 48 followed by placebo tablet orally once daily until Week 54.	8mg Rosiglitazone Extended Release n=489 Participants Participants received rosiglitazone extended release 4 mg tablet orally, once daily until Week 4 followed by 8 mg tablet orally once daily from Week 4 until Week 48 followed by placebo tablet orally once daily until Week 54.
Number of Participants With Laboratory Potential Clinical Concern (PCC) Values Eosinophils high	0 participants	3 participants	0 participants
Number of Participants With Laboratory Potential Clinical Concern (PCC) Values Hematocrit low	2 participants	2 participants	5 participants
Number of Participants With Laboratory Potential Clinical Concern (PCC) Values Hemoglobin high	2 participants	0 participants	0 participants
Number of Participants With Laboratory Potential Clinical Concern (PCC) Values Hemoglobin low	8 participants	11 participants	31 participants
Number of Participants With Laboratory Potential Clinical Concern (PCC) Values Lymphocytes high	0 participants	1 participants	2 participants
Number of Participants With Laboratory Potential Clinical Concern (PCC) Values Lymphocytes low	8 participants	10 participants	13 participants
Number of Participants With Laboratory Potential Clinical Concern (PCC) Values Mean CH high	0 participants	0 participants	1 participants
Number of Participants With Laboratory Potential Clinical Concern (PCC) Values Mean CH low	2 participants	2 participants	0 participants
Number of Participants With Laboratory Potential Clinical Concern (PCC) Values Mean CV high	0 participants	0 participants	1 participants
Number of Participants With Laboratory Potential Clinical Concern (PCC) Values Mean CV low	2 participants	1 participants	0 participants
Number of Participants With Laboratory Potential Clinical Concern (PCC) Values Monocytes low	81 participants	55 participants	65 participants
Number of Participants With Laboratory Potential Clinical Concern (PCC) Values Platelet count high	4 participants	2 participants	7 participants
Number of Participants With Laboratory Potential Clinical Concern (PCC) Values Platelet count low	1 participants	2 participants	4 participants
Number of Participants With Laboratory Potential Clinical Concern (PCC) Values RDW high	18 participants	31 participants	86 participants
Number of Participants With Laboratory Potential Clinical Concern (PCC) Values RBC high	0 participants	1 participants	0 participants
Number of Participants With Laboratory Potential Clinical Concern (PCC) Values RBC low	0 participants	1 participants	8 participants
Number of Participants With Laboratory Potential Clinical Concern (PCC) Values SN high	8 participants	2 participants	4 participants
Number of Participants With Laboratory Potential Clinical Concern (PCC) Values SN low	2 participants	6 participants	13 participants
Number of Participants With Laboratory Potential Clinical Concern (PCC) Values TN high	4 participants	1 participants	2 participants
Number of Participants With Laboratory Potential Clinical Concern (PCC) Values TN low	2 participants	6 participants	13 participants
Number of Participants With Laboratory Potential Clinical Concern (PCC) Values WBC high	4 participants	1 participants	3 participants
Number of Participants With Laboratory Potential Clinical Concern (PCC) Values WBC low	1 participants	5 participants	12 participants

SECONDARY outcome

Timeframe: Baseline (Week 0), Week 12, 36 and 48

Population: ITT population. Only those participants available at the specified time points were analyzed.

The ACQLI was an assessment of caregiver quality of life. This instrument consists of 30 questions exploring various aspects of carer's quality of life. Each of the questions had a two point response and the 30 questions were summed to provide a total score. Items are assumed to be unidimensional (i.e., represent a single variable) and are scored 0/1 (false/true) before summation into a total score with a 0-30 range. The total score ranged from 0 to 30, where 0 indicated absence of symptoms and higher score indicated worse outcomes; a negative change from baseline indicated improvement. Change from baseline was calculated as endpoint value minus the baseline value.

Outcome measures

Outcome measures
Measure	Placebo n=461 Participants Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.	2mg Rosiglitazone Extended Release n=473 Participants Participants received rosiglitazone extended release 2 milligram (mg) tablet orally, once daily until Week 48 followed by placebo tablet orally once daily until Week 54.	8mg Rosiglitazone Extended Release n=459 Participants Participants received rosiglitazone extended release 4 mg tablet orally, once daily until Week 4 followed by 8 mg tablet orally once daily from Week 4 until Week 48 followed by placebo tablet orally once daily until Week 54.
Change From Baseline in Alzheimer's Carer Quality of Life Instrument (ACQLI) Total Score Week 12	0.5 Score on a scale Standard Error 0.23	-0.2 Score on a scale Standard Error 0.23	-0.0 Score on a scale Standard Error 0.22
Change From Baseline in Alzheimer's Carer Quality of Life Instrument (ACQLI) Total Score Week 36	1.0 Score on a scale Standard Error 0.28	0.6 Score on a scale Standard Error 0.27	0.6 Score on a scale Standard Error 0.26
Change From Baseline in Alzheimer's Carer Quality of Life Instrument (ACQLI) Total Score Week 48	1.2 Score on a scale Standard Error 0.30	0.3 Score on a scale Standard Error 0.28	1.1 Score on a scale Standard Error 0.31

Adverse Events

Placebo

Serious events: 62 serious events

Other events: 11 other events

Deaths: 12 deaths

2mg Rosiglitazone Extended Release

Serious events: 45 serious events

Other events: 29 other events

Deaths: 6 deaths

8mg Rosiglitazone Extended Release

Serious events: 50 serious events

Other events: 69 other events

Deaths: 8 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo n=496 participants at risk Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.	2mg Rosiglitazone Extended Release n=494 participants at risk Participants received rosiglitazone extended release 2 mg tablet orally, once daily until Week 48 followed by placebo tablet orally once daily until Week 54.	8mg Rosiglitazone Extended Release n=489 participants at risk Participants received rosiglitazone extended release 4 mg tablet orally, once daily until Week 4 followed by 8 mg tablet orally once daily from Week 4 until Week 48 followed by placebo tablet orally once daily until Week 54.
General disorders Oedema peripheral	2.2% 11/496 • Up to Week 48 An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.	5.9% 29/494 • Up to Week 48 An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.	14.1% 69/489 • Up to Week 48 An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.

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=477 Participants Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.	2mg Rosiglitazone Extended Release n=481 Participants Participants received rosiglitazone extended release 2 milligram (mg) tablet orally, once daily until Week 48 followed by placebo tablet orally once daily until Week 54.	8mg Rosiglitazone Extended Release n=470 Participants Participants received rosiglitazone extended release 4 mg tablet orally, once daily until Week 4 followed by 8 mg tablet orally once daily from Week 4 until Week 48 followed by placebo tablet orally once daily until Week 54.
Mean Change From Baseline in Systolic and Diastolic Blood Pressure (BP) Systolic BP Week 4	-0.7 Millimeter of mercury (mmHg) Standard Deviation 15.21	-1.0 Millimeter of mercury (mmHg) Standard Deviation 13.21	-2.3 Millimeter of mercury (mmHg) Standard Deviation 13.43
Mean Change From Baseline in Systolic and Diastolic Blood Pressure (BP) Systolic BP Week 8	-0.3 Millimeter of mercury (mmHg) Standard Deviation 15.49	-0.7 Millimeter of mercury (mmHg) Standard Deviation 14.55	-2.9 Millimeter of mercury (mmHg) Standard Deviation 14.49
Mean Change From Baseline in Systolic and Diastolic Blood Pressure (BP) Systolic BP Week 12	-0.5 Millimeter of mercury (mmHg) Standard Deviation 16.48	-2.5 Millimeter of mercury (mmHg) Standard Deviation 14.49	-4.2 Millimeter of mercury (mmHg) Standard Deviation 15.25
Mean Change From Baseline in Systolic and Diastolic Blood Pressure (BP) Systolic BP Week 16	-0.8 Millimeter of mercury (mmHg) Standard Deviation 15.80	-1.7 Millimeter of mercury (mmHg) Standard Deviation 14.80	-3.7 Millimeter of mercury (mmHg) Standard Deviation 15.75
Mean Change From Baseline in Systolic and Diastolic Blood Pressure (BP) Systolic BP Week 24	-1.2 Millimeter of mercury (mmHg) Standard Deviation 15.95	-1.0 Millimeter of mercury (mmHg) Standard Deviation 15.22	-3.5 Millimeter of mercury (mmHg) Standard Deviation 14.74
Mean Change From Baseline in Systolic and Diastolic Blood Pressure (BP) Systolic BP Week 36	-1.6 Millimeter of mercury (mmHg) Standard Deviation 16.65	-0.3 Millimeter of mercury (mmHg) Standard Deviation 15.79	-2.7 Millimeter of mercury (mmHg) Standard Deviation 15.97
Mean Change From Baseline in Systolic and Diastolic Blood Pressure (BP) Systolic BP Week 48	-1.0 Millimeter of mercury (mmHg) Standard Deviation 17.08	-0.6 Millimeter of mercury (mmHg) Standard Deviation 15.05	-2.5 Millimeter of mercury (mmHg) Standard Deviation 16.55
Mean Change From Baseline in Systolic and Diastolic Blood Pressure (BP) Systolic BP Week 54	0.0 Millimeter of mercury (mmHg) Standard Deviation 17.24	-1.1 Millimeter of mercury (mmHg) Standard Deviation 14.95	-2.3 Millimeter of mercury (mmHg) Standard Deviation 15.56
Mean Change From Baseline in Systolic and Diastolic Blood Pressure (BP) Diastolic BP Week 4	-0.4 Millimeter of mercury (mmHg) Standard Deviation 9.54	-0.7 Millimeter of mercury (mmHg) Standard Deviation 9.21	-1.2 Millimeter of mercury (mmHg) Standard Deviation 8.51
Mean Change From Baseline in Systolic and Diastolic Blood Pressure (BP) Diastolic BP Week 8	-0.0 Millimeter of mercury (mmHg) Standard Deviation 9.55	-0.9 Millimeter of mercury (mmHg) Standard Deviation 9.20	-2.1 Millimeter of mercury (mmHg) Standard Deviation 9.21
Mean Change From Baseline in Systolic and Diastolic Blood Pressure (BP) Diastolic BP Week 12	0.0 Millimeter of mercury (mmHg) Standard Deviation 9.63	-1.3 Millimeter of mercury (mmHg) Standard Deviation 9.25	-2.5 Millimeter of mercury (mmHg) Standard Deviation 9.49
Mean Change From Baseline in Systolic and Diastolic Blood Pressure (BP) Diastolic BP Week 16	-0.7 Millimeter of mercury (mmHg) Standard Deviation 9.78	-1.3 Millimeter of mercury (mmHg) Standard Deviation 9.16	-3.0 Millimeter of mercury (mmHg) Standard Deviation 9.62
Mean Change From Baseline in Systolic and Diastolic Blood Pressure (BP) Diastolic BP Week 24	-1.1 Millimeter of mercury (mmHg) Standard Deviation 9.87	-1.2 Millimeter of mercury (mmHg) Standard Deviation 9.55	-2.6 Millimeter of mercury (mmHg) Standard Deviation 9.48
Mean Change From Baseline in Systolic and Diastolic Blood Pressure (BP) Diastolic BP Week 36	-1.2 Millimeter of mercury (mmHg) Standard Deviation 10.27	-0.6 Millimeter of mercury (mmHg) Standard Deviation 9.94	-3.3 Millimeter of mercury (mmHg) Standard Deviation 10.68
Mean Change From Baseline in Systolic and Diastolic Blood Pressure (BP) Diastolic BP Week 48	-0.8 Millimeter of mercury (mmHg) Standard Deviation 10.85	-0.5 Millimeter of mercury (mmHg) Standard Deviation 10.02	-1.9 Millimeter of mercury (mmHg) Standard Deviation 11.07
Mean Change From Baseline in Systolic and Diastolic Blood Pressure (BP) Diastolic BP Week 54	-0.9 Millimeter of mercury (mmHg) Standard Deviation 10.35	-0.4 Millimeter of mercury (mmHg) Standard Deviation 9.62	-1.8 Millimeter of mercury (mmHg) Standard Deviation 10.04