REFLECT-2: Rosiglitazone (Extended Release Tablets) As Adjunctive Therapy For Subjects With Mild To Moderate Alzheimer's Disease

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00348309
• Collaborator: (none)
• Enrollment: 1,496
• Locations: 249
• Arms: 3
• Duration (Months): 30.8
• Patients Per Site: 6
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

Rosiglitazone (RSG) has been tested in clinical studies and is approved by the FDA as a treatment for type II diabetes mellitus, a disease that occurs when the body is unable to effectively use glucose. RSG XR, the investigational drug used in this study, is an extended-release form of RSG.

This study tests whether RSG XR safely provides clinical benefit to people with mild to moderate Alzheimer's disease (AD) when combined with the currently approved AD medication, Aricept (donepezil). RSG XR is a new approach to AD therapy and this study tests a new way to treat AD by testing whether one's genetic makeup affects their response to the study drug. Clinical data suggesting that RSG may benefit AD patients was first seen in a small study performed at the University of Washington and then from a larger GSK study conducted in Europe and New Zealand. In the first study, subjects receiving RSG once daily for 6 months scored significantly better on 3 tests of memory and thought than those who did not receive RSG. In the GSK study, those that appeared to benefit most from treatment with RSG XR had a specific genetic pattern. They did not have the gene that caused them to produce the protein apolipoprotein E e4 (APOE e4). Subjects who have the APOE e4 gene may have two copies, one from each parent, or they may have only one APOE e4 gene meaning that they inherited either the APOE e2 or APOE e3 version of the gene, instead of APOE e4, from one of their parents. Subjects with one copy of the APOE e4 gene remained at their same level of thinking ability while those with two copies of the APOE e4 gene, continued to worsen during the 6-month treatment. The current study will more directly test the effectiveness or RSG XR on people who either have or lack the APOE e4 gene.

Condition or Disease	Intervention/Treatment	Phase
Alzheimer's Disease	Drug: Rosiglitazone Extended Release 2mg; Drug: Rosiglitazone Extended Release 8mg; Other: Placebo; Other: Donepezil	N/A

Detailed Description

A 54-week, double-blind, randomized, placebo-controlled, parallel-group study to investigate the effects of rosiglitazone (extended release tablets) as adjunctive therapy to donepezil on cognition and overall clinical response in APOE e4-stratified subjects with mild to moderate Alzheimer's disease (REFLECT-2)

Study Design

• Study Type: Interventional
• Actual Enrollment: 1496 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A 54-week, Double-blind, Randomized, Placebo-controlled, Parallel-group Study to Investigate the Effects of Rosiglitazone (Extended Release Tablets) as Adjunctive Therapy to Donepezil on Cognition and Overall Clinical Response in APOE ε4-stratified Subjects With Mild to Moderate Alzheimer's Disease.
• Study Start Date: Jul 6, 2006
• Actual Primary Completion Date: Jan 1, 2009
• Actual Study Completion Date: Jan 28, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm 1 Rosiglitazone Extended Release 2mg OD	Drug: Rosiglitazone Extended Release 2mg; Rosiglitazone Extended Release 2mg OD; Other: Donepezil; Donepezil (At least 6 months of ongoing donepezil therapy for Alzheimer's disease, with stable dosing for at least the last 2 months (and with no intent to change for the duration of the study).; Other Names: Aricept
Experimental: Arm 2 Rosiglitazone Extended Release 8mg OD	Drug: Rosiglitazone Extended Release 8mg; Rosiglitazone Extended Release 8mg OD; Other: Donepezil; Donepezil (At least 6 months of ongoing donepezil therapy for Alzheimer's disease, with stable dosing for at least the last 2 months (and with no intent to change for the duration of the study).; Other Names: Aricept
Placebo Comparator: Arm 3 Placebo	Other: Placebo; Placebo; Other: Donepezil; Donepezil (At least 6 months of ongoing donepezil therapy for Alzheimer's disease, with stable dosing for at least the last 2 months (and with no intent to change for the duration of the study).; Other Names: Aricept

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) Total Score at Week 48 [Baseline (Week 0) and Week 48]

   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.

2. Change From Baseline in Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) at Week 48 for APOE E4 [Baseline (Week 0) and Week 48]

   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.

Secondary Outcome Measures

1. Change From Baseline in Disability Assessment for Dementia Scale (DAD) Total Score [Baseline (Week 0), Week 8, 16, 24 and 48]

   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.

2. Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score [Baseline (Week 0), Week 8, 16, 24 and 48]

   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.

3. Change From Screening in Mini Mental State Examination (MMSE) Total Score [Screening (Week -4) and Week 48]

   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.

4. Change From Baseline in the Domains of the Resource Utilization in Dementia Scale (RUD) [Baseline (Week 0), Week 12, 24, 36 and 48]

   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.

5. 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 [Baseline (Week 0), Week 12, 36 and 48]

   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.

6. Change From Baseline in ADAS-Cog Total Score for Observed Cases at Weeks 8, 16, 24, 36 and 48 [Baseline (Week 0), Week 8, 16, 24, 36 and 48]

   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.

7. Change From Baseline in CDR-SB Score for Observed Cases at Weeks 12, 24, 36 and 48 [Baseline (Week 0), Week 12, 24, 36 and 48]

   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 endpoint value minus the baseline value.

8. Change in ADAS-Cog Total Score for Observed Cases at Week 54 Compared to Week 48 [Week 48 and 54]

   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.

9. Change in CDR-SB Total Score at Week 54 Compared to Week 48 [Week 48 and 54]

   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 was calculated as endpoint value (Week 54) minus Week 48 value.

10. Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 48 [Baseline (Week 0) and Week 48]

    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.

11. Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [Up to Week 54]

    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.

12. Mean Change From Baseline in Systolic and Diastolic Blood Pressure (BP) [Baseline (Week 0), Week 4, 8, 12, 16, 24, 36, 48 and 56]

    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.

13. Mean Change From Baseline in Heart Rate [Baseline (Week 0), Week 4, 8, 12, 16, 24, 36, 48 and 56]

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

14. Mean Change From Baseline in Weight [Baseline (Week 0), Week 4, 8, 12, 16, 24, 36, 48 and 56]

    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.

15. Change From Baseline in Hemoglobin Values [Baseline (Week 0), Week 4, 16, 36 and 48]

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

16. Change From Baseline in Hematocrit Values [Baseline (Week 0), Week 4, 8, 12, 16, 36 and 48]

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

17. Mean Change From Baseline in Short Term Memory Assessment Score [Baseline (Week 0), Week 8, 16, 24, 36, 48 and 56]

    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.

18. Change From Baseline in HbA1c at Week 12, Week 24 and Week 36 [Baseline (Week 0) and Week 12, 24 and 36]

    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 time point minus the value at Baseline.

19. Number of Participants With Laboratory Potential Clinical Concern (PCC) Values [Baseline (Week 0), Week 4, 8, 12, 16, 24, 36, 48 and 56]

    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.

20. Change From Baseline in Alzheimer's Carer Quality of Life Instrument (ACQLI) Total Score [Baseline (Week 0), Week 12, 36 and 48]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years to 90 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria:

• A subject will be eligible for inclusion in this study only if all of the following criteria apply:

• Male or female subject with a clinical diagnosis of probable Alzheimer's disease in accordance with NINCDS-ADRDA criteria.

(Note: National Institute of Neurological and Communicative Disorders and Stroke (NINCDS) and Alzheimer's Disease and Related Disorders Association (ADRDA).)

• Subject has mild to moderate Alzheimer's disease as defined by a MMSE score 10 to 26 inclusive at Screening.

• Hachinski Ischemia Score ≤ 4 at Screening.

• Age ≥50 and ≤90 years.

• At least 6 months of ongoing donepezil therapy for Alzheimer's disease, with stable dosing for at least the last 2 months (and with no intent to change for the duration of the study).

• Current use of medication is in accordance with the criteria listed in Table 2 (Permitted Medications,).

• Female subjects must be post-menopausal (i.e. >1 year without menstrual period), surgically sterile, or agree to use adequate method of contraception for the duration of the study. Female subjects who are pre-menopausal or who have been post-menopausal for <1 year must undertake pregnancy testing (urine test) at Visit 1, which must be negative.

• Brain CT or MRI scan performed within the past 12 months or at Screening, showing no evidence of any other potential cause of dementia other than Alzheimer's disease.

(Note: Questionable CT or MRI scans should be discussed with the medical monitor, using central imaging guidelines.)

• Neurological exam without focal changes (excluding changes attributable to AD or peripheral trauma).

• Subject has the ability to comply with procedures for cognitive and other testing.

• Subject lives with (or has substantial periods of contact with) a regular caregiver who is willing to attend all visits, oversee the subject's compliance with protocol-specified procedures and study medication, and report on subject's status.

Note: A non-cohabiting caregiver must spend sufficient time with the subject so that, in the opinion of the Investigator, the caregiver can reliably assess cognitive function, activities and behavior, and report on the subject's compliance and health. As caregiver time spent with a potential subject is anticipated to be highly variable across countries and cultures, GSK will consider a variety of different measures by which this stipulation may be met, and GSK should be consulted if adequacy of a caregiver situation is in doubt. However, as guidance, the ability for a caregiver to meet his/her expected responsibilities for this study would normally be possible when the caregiver spends no less than 10 hours per week with the subject, divided over multiple days.)

• Subject has provided full written informed consent prior to the performance of any protocol-specified procedure; or if unable to provide informed consent due to cognitive status, full written informed consent on behalf of the subject has been provided by a legally acceptable representative.

(Note: Consent by legally acceptable representative is allowed where this is in accordance with local laws, regulations and ethics committee policy.)

• Caregiver has provided full written informed consent on his/her own behalf prior to the performance of any protocol-specified procedure.

• Subjects considered for enrolment must have a QTc (either QTc B (Bazett's correction) or QTc F (Fridericia's correction)) <450msec at Visit 1, with the exception of subjects with bundle branch block (for whom either QTc B or QTc F must be <480msec).

• (Note: For the purposes of these criteria, QTc B is defined as (QT interval [msec]) / (square root of RR interval [seconds]); and QTc F is defined as (QT interval [msec]) / (cube root of RR interval [seconds]).)

Exclusion criteria:

• A subject will not be eligible for inclusion in this study if any of the following criteria apply:

• Diagnosis of possible, probable, or definite vascular dementia in accordance with NINDS-AIREN criteria.

(Note: National Institute of Neurological Disorders and Stroke (NINDS) and Association Internationale pour la Recherche et l'Enseignement en Neurosciences (AIREN).)

• History or evidence of any other CNS disorder that could be interpreted as a cause of dementia: e.g. cerebrovascular disease (stroke, hemorrhage), structural abnormality, epilepsy, infectious or inflammatory/demyelinating CNS conditions, Parkinson's disease.

• Evidence of the following disorders: current vitamin B12 deficiency, positive syphilis serology, or active thyroid dysfunction (particularly that suggestive of hypothyroidism), including abnormally high or low serum levels of thyroid stimulating hormone (TSH) that are clinically significant in the opinion of the investigator.

(Note: Testing is required for each parameter only when no result is available from previous 12 months.)

• History of Type 1 diabetes mellitus or secondary diabetes mellitus.

• Type 2 diabetes mellitus where the subject is being treated with insulin, a PPARγ agonist, or an insulin secretagogue (e.g. a sulfonylurea or glitinide).

• Any patient with an HbA1c ≥8.5%. (See Section 6.3.7.4 for Safety Measures for Enrolled Subjects with Type 2 Diabetes Mellitus.)

• History or clinical/investigational evidence of congestive heart failure defined by the New York Heart Association criteria (Class I to IV cardiac status;).

• History of cardiovascular event within the last 6 months (i.e. intervention, percutaneous coronary intervention, vascular surgery, acute coronary syndrome [non Q-wave myocardial infarction, Q-wave myocardial infarction, unstable angina] or significant arrhythmia; or major intervention (e.g. cardiac surgery or angiography plus stenting) scheduled).

• History of significant psychiatric illness such as schizophrenia or bipolar affective disorder that in the opinion of the Investigator would interfere with participation in the study, major depressive disorder (according to DSM-IV) in the past year, or current active depression requiring initiation of treatment.

(Note: If not currently treated, but active depression is suspected, the Cornell Scale for Depression in Dementia (CSDD) can be used by the Investigator as a guide for deciding whether a prospective subject requires treatment. If the subject has a CSDD score >7, the Investigator should decide if the subject has depression in need of prescribed medication, and a CSDD >12 is considered a strong indicator that treatment is needed. Subjects will be allowed to re-screen after their depression has been adequately managed for >3 months.)

• History or presence of gastro-intestinal, hepatic, or renal disease or other condition known to interfere with the absorption, distribution, metabolism, or excretion of drugs, or any other clinically relevant abnormality, medical or psychiatric condition, which, in the opinion of the Investigator, makes the subject unsuitable for inclusion in the study.

• Clinically significant peripheral edema at the time of screening.

• Current or recent drug or alcohol abuse or dependence (defined by DSM-IV criteria for substance-related disorders), or recent or remote history of the same if that could be a contributing factor to the dementia.

• Systolic blood pressure >165 or <90 mmHg or diastolic blood pressure >95 or <60 mmHg at the time of screening.

• Clinically significant anemia (i.e. hemoglobin <11 g/dL for males or <10 g/dL for females) or presence of hemoglobinopathies which would prevent accurate assessment of HbA1c.

• Abnormal kidney function tests (>1.5 the upper limit of normal (ULN)).

• ALT, AST, or alkaline phosphatase values >2.5 times the ULN, total bilirubin values

1.5 times the ULN, or history of severe hepatobiliary disease (e.g. hepatitis B or C, or cirrhosis, Child-Pugh Class B/C).

(Note: For subjects with a diagnosis of Gilberts Syndrome and an isolated increase in total bilirubin >1.5 ULN, fractionation should be performed. If all of the following conditions are met, the patient may enter or remain in the study, even if total bilirubin >1.5 ULN:

• an elevated unconjugated (indirect) bilirubin;

• the percentage of direct bilirubin <35%;

• ALT, AST, and alkaline phosphatase <2.5 ULN if subject is in screening (<2.0 ULN for Canadian subjects only), or ≤3 ULN if subject is already randomized into the study)

• History of a bone marrow transplant.

• Subject is unable (with assistance, if appropriate) to take study medication as prescribed throughout the study or is at risk of non-compliance with study medication or procedures.

• Subject is an immediate family member or employee of the participating Investigator, of any of the participating site staff, or of GSK.

• In France, a subject is neither affiliated with nor a beneficiary of a social security category.

• The French subject has participated in any study using an investigational drug during the previous 30 days or 5 half-lives (whichever is longer).

• Cognitive tasks prescribed for cognitive rehabilitation and performed under medical supervision are prohibited for 6 months prior to Screening, as well as for the duration of the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Litchfield Park	Arizona	United States	85340
2	GSK Investigational Site	Phoenix	Arizona	United States	85004
3	GSK Investigational Site	Phoenix	Arizona	United States	85006
4	GSK Investigational Site	Phoenix	Arizona	United States	85050
5	GSK Investigational Site	Little Rock	Arkansas	United States	72205
6	GSK Investigational Site	Fresno	California	United States	93720
7	GSK Investigational Site	Rancho Mirage	California	United States	92270
8	GSK Investigational Site	Sacramento	California	United States	95816
9	GSK Investigational Site	Sherman Oaks	California	United States	91403
10	GSK Investigational Site	Denver	Colorado	United States	80212
11	GSK Investigational Site	New Haven	Connecticut	United States	06510
12	GSK Investigational Site	Delray Beach	Florida	United States	33445
13	GSK Investigational Site	Hallandale Beach	Florida	United States	33009
14	GSK Investigational Site	Miami	Florida	United States	33143
15	GSK Investigational Site	Saint Petersburg	Florida	United States	33701
16	GSK Investigational Site	Sarasota	Florida	United States	34233
17	GSK Investigational Site	West Palm Beach	Florida	United States	33407
18	GSK Investigational Site	Hoffman Estates	Illinois	United States	60194
19	GSK Investigational Site	Fort Wayne	Indiana	United States	46805
20	GSK Investigational Site	Indianapolis	Indiana	United States	46202
21	GSK Investigational Site	Baltimore	Maryland	United States	21224
22	GSK Investigational Site	Glen Burnie	Maryland	United States	21061
23	GSK Investigational Site	Rockville	Maryland	United States	20852
24	GSK Investigational Site	Saint Paul	Minnesota	United States	55101
25	GSK Investigational Site	Lebanon	New Hampshire	United States	03756
26	GSK Investigational Site	Morristown	New Jersey	United States	07960
27	GSK Investigational Site	Nutley	New Jersey	United States	07110
28	GSK Investigational Site	Princeton	New Jersey	United States	08540
29	GSK Investigational Site	Stratford	New Jersey	United States	08084
30	GSK Investigational Site	Albany	New York	United States	12205
31	GSK Investigational Site	Brooklyn	New York	United States	11235
32	GSK Investigational Site	New York	New York	United States	10021
33	GSK Investigational Site	Durham	North Carolina	United States	27705
34	GSK Investigational Site	Raleigh	North Carolina	United States	27607
35	GSK Investigational Site	Portland	Oregon	United States	97239
36	GSK Investigational Site	Providence	Rhode Island	United States	02906
37	GSK Investigational Site	Nashville	Tennessee	United States	37203
38	GSK Investigational Site	Austin	Texas	United States	78757
39	GSK Investigational Site	Houston	Texas	United States	77030
40	GSK Investigational Site	South Ogden	Utah	United States	84403
41	GSK Investigational Site	Bennington	Vermont	United States	05201
42	GSK Investigational Site	Ciudad Autónoma de Buenos Aires	Buenos Aires	Argentina	C1192AAW
43	GSK Investigational Site	Ciudad Autónoma de Buenos Aires	Buenos Aires	Argentina	C1419HDN
44	GSK Investigational Site	Ciudad de Buenos Aires	Buenos Aires	Argentina	C1431FWO
45	GSK Investigational Site	Cordoba	Córdova	Argentina	5000
46	GSK Investigational Site	Córdoba	Córdova	Argentina	X5004AOA
47	GSK Investigational Site	Córdoba	Córdova	Argentina	x5009bin
48	GSK Investigational Site	Godoy Cruz	Mendoza	Argentina	M5504FMI
49	GSK Investigational Site	Ciudad Autonoma de Buenos Aires		Argentina	C1425CDC
50	GSK Investigational Site	Mendoza		Argentina	CPM5500HIF
51	GSK Investigational Site	Hall in Tirol		Austria	A-6060
52	GSK Investigational Site	Innsbruck		Austria	A-6020
53	GSK Investigational Site	Vienna		Austria	1010
54	GSK Investigational Site	Vienna		Austria	1030
55	GSK Investigational Site	Vienna		Austria	A-1130
56	GSK Investigational Site	Vienna		Austria	A-1220
57	GSK Investigational Site	Belo Horizonte		Brazil	30130-110
58	GSK Investigational Site	Ribeirão Preto		Brazil	14048-900
59	GSK Investigational Site	São Paulo		Brazil	040023-900
60	GSK Investigational Site	Calgary	Alberta	Canada	T2N 4N1
61	GSK Investigational Site	Medicine Hat	Alberta	Canada	T1A 4C2
62	GSK Investigational Site	Victoria	British Columbia	Canada	V8T 5G1
63	GSK Investigational Site	Moncton	New Brunswick	Canada	E1C 4B7
64	GSK Investigational Site	Barrie	Ontario	Canada	L4M 4S5
65	GSK Investigational Site	Kingston	Ontario	Canada	K7L 4X3
66	GSK Investigational Site	Peterborough	Ontario	Canada	K9H 2P4
67	GSK Investigational Site	Toronto	Ontario	Canada	M5T 2S8
68	GSK Investigational Site	Toronto	Ontario	Canada	M6M 3Z5
69	GSK Investigational Site	Whitby	Ontario	Canada	L1N 5S9
70	GSK Investigational Site	Charlottetown	Prince Edward Island	Canada	C1A 5Y8
71	GSK Investigational Site	Greenfield Park	Quebec	Canada	J4V 2J2
72	GSK Investigational Site	Montreal	Quebec	Canada	H1T 2M4
73	GSK Investigational Site	Montreal	Quebec	Canada	H4H 1R3
74	GSK Investigational Site	Sherbrooke	Quebec	Canada	J1H 1Z1
75	GSK Investigational Site	Regina	Saskatchewan	Canada	S4T 1A5
76	GSK Investigational Site	Québec		Canada	G1R 3X5
77	GSK Investigational Site	Providencia / Santiago	Región Metro De Santiago	Chile	7500710
78	GSK Investigational Site	Puente Alto - Santiago	Región Metro De Santiago	Chile	8207257
79	GSK Investigational Site	Santiago	Región Metro De Santiago	Chile	7560356
80	GSK Investigational Site	Viña del Mar	Valparaíso	Chile	252-0997
81	GSK Investigational Site	Ostrava		Czechia	702 00
82	GSK Investigational Site	Praha 10		Czechia	10000
83	GSK Investigational Site	Praha 2		Czechia	120 00
84	GSK Investigational Site	Praha 5		Czechia	150 18
85	GSK Investigational Site	Praha 7		Czechia	170 00
86	GSK Investigational Site	Angoulême		France	16000
87	GSK Investigational Site	Arcachon		France	33120
88	GSK Investigational Site	Avignon		France	84000
89	GSK Investigational Site	Bourg en Bresse		France	01012
90	GSK Investigational Site	Caen		France	14033
91	GSK Investigational Site	Dijon		France	21000
92	GSK Investigational Site	Issy Les Moulineaux		France	92130
93	GSK Investigational Site	Ivry		France	94206
94	GSK Investigational Site	Luynes		France	37230
95	GSK Investigational Site	Lyon		France	69006
96	GSK Investigational Site	Marseille		France	13008
97	GSK Investigational Site	Marseille		France	13009
98	GSK Investigational Site	Metz		France	57038
99	GSK Investigational Site	Montpellier		France	34080
100	GSK Investigational Site	Nantes		France	44000
101	GSK Investigational Site	Nantes		France	44093
102	GSK Investigational Site	Nantes		France	44200
103	GSK Investigational Site	Nice		France	06002
104	GSK Investigational Site	Paris		France	75012
105	GSK Investigational Site	Paris		France	75013
106	GSK Investigational Site	Paris		France	75018
107	GSK Investigational Site	Pau		France	64000
108	GSK Investigational Site	Pessac		France	33604
109	GSK Investigational Site	Reims		France	51100
110	GSK Investigational Site	Rennes		France	35000
111	GSK Investigational Site	Rodez		France	12000
112	GSK Investigational Site	Saint Jean de Luz		France	64500
113	GSK Investigational Site	Saint Ouen la Rouerie		France	35460
114	GSK Investigational Site	Saint-Etienne		France	42100
115	GSK Investigational Site	Saint-Nicolas de Port		France	54210
116	GSK Investigational Site	Tinteniac		France	35190
117	GSK Investigational Site	Tours		France	37100
118	GSK Investigational Site	Verny		France	57420
119	GSK Investigational Site	Vichy		France	03200
120	GSK Investigational Site	Boeblingen	Baden-Wuerttemberg	Germany	71034
121	GSK Investigational Site	Ostfildern	Baden-Wuerttemberg	Germany	73760
122	GSK Investigational Site	Stuttgart	Baden-Wuerttemberg	Germany	70178
123	GSK Investigational Site	Ulm	Baden-Wuerttemberg	Germany	89073
124	GSK Investigational Site	Muenchen	Bayern	Germany	80331
125	GSK Investigational Site	Muenchen	Bayern	Germany	80333
126	GSK Investigational Site	Muenchen	Bayern	Germany	80336
127	GSK Investigational Site	Muenchen	Bayern	Germany	81377
128	GSK Investigational Site	Muenchen	Bayern	Germany	81667
129	GSK Investigational Site	Neuburg / Donau	Bayern	Germany	86633
130	GSK Investigational Site	Nuernberg	Bayern	Germany	90402
131	GSK Investigational Site	Nuernberg	Bayern	Germany	90403
132	GSK Investigational Site	Regensburg	Bayern	Germany	93053
133	GSK Investigational Site	Wuerzburg	Bayern	Germany	97070
134	GSK Investigational Site	Huettenberg	Hessen	Germany	35625
135	GSK Investigational Site	Schwerin	Mecklenburg-Vorpommern	Germany	19053
136	GSK Investigational Site	Schwerin	Mecklenburg-Vorpommern	Germany	19055
137	GSK Investigational Site	Achim	Niedersachsen	Germany	28832
138	GSK Investigational Site	Bockhorn	Niedersachsen	Germany	26345
139	GSK Investigational Site	Ganderkesee	Niedersachsen	Germany	27777
140	GSK Investigational Site	Goettingen	Niedersachsen	Germany	37075
141	GSK Investigational Site	Hannover	Niedersachsen	Germany	30559
142	GSK Investigational Site	Hildesheim	Niedersachsen	Germany	31134
143	GSK Investigational Site	Lueneburg	Niedersachsen	Germany	21335
144	GSK Investigational Site	Westerstede	Niedersachsen	Germany	26655
145	GSK Investigational Site	Bad Honnef	Nordrhein-Westfalen	Germany	53604
146	GSK Investigational Site	Baesweiler	Nordrhein-Westfalen	Germany	52499
147	GSK Investigational Site	Bergisch Gladbach	Nordrhein-Westfalen	Germany	51465
148	GSK Investigational Site	Bochum	Nordrhein-Westfalen	Germany	44791
149	GSK Investigational Site	Bochum	Nordrhein-Westfalen	Germany	44805
150	GSK Investigational Site	Bochum	Nordrhein-Westfalen	Germany	44809
151	GSK Investigational Site	Bochum	Nordrhein-Westfalen	Germany	44869
152	GSK Investigational Site	Bochum	Nordrhein-Westfalen	Germany	44892
153	GSK Investigational Site	Dueren	Nordrhein-Westfalen	Germany	52349
154	GSK Investigational Site	Duisburg	Nordrhein-Westfalen	Germany	47051
155	GSK Investigational Site	Essen	Nordrhein-Westfalen	Germany	45138
156	GSK Investigational Site	Hattingen	Nordrhein-Westfalen	Germany	45525
157	GSK Investigational Site	Juelich	Nordrhein-Westfalen	Germany	52428
158	GSK Investigational Site	Koeln	Nordrhein-Westfalen	Germany	50767
159	GSK Investigational Site	Koeln	Nordrhein-Westfalen	Germany	51069
160	GSK Investigational Site	Krefeld	Nordrhein-Westfalen	Germany	47800
161	GSK Investigational Site	Remscheid	Nordrhein-Westfalen	Germany	42853
162	GSK Investigational Site	Siegen	Nordrhein-Westfalen	Germany	57072
163	GSK Investigational Site	Hamburg		Germany	20249
164	GSK Investigational Site	Hamburg		Germany	21149
165	GSK Investigational Site	Hamburg		Germany	22083
166	GSK Investigational Site	Hamburg		Germany	22143
167	GSK Investigational Site	Athens		Greece	115 21
168	GSK Investigational Site	Athens		Greece	151 23
169	GSK Investigational Site	Melissia		Greece	151 27
170	GSK Investigational Site	Thessaloniki		Greece	57010
171	GSK Investigational Site	Debrecen		Hungary	4043
172	GSK Investigational Site	Győr		Hungary	9024
173	GSK Investigational Site	Szeged		Hungary	6725
174	GSK Investigational Site	Bangalore		India	560 054
175	GSK Investigational Site	Bangalore		India	560034
176	GSK Investigational Site	Hyderabad		India	500 034
177	GSK Investigational Site	Mumbai		India	400010
178	GSK Investigational Site	Nagpur		India	440010
179	GSK Investigational Site	New Delhi		India	110002
180	GSK Investigational Site	Pune		India	411004
181	GSK Investigational Site	Varanasi		India	221005
182	GSK Investigational Site	Chieti Scalo	Abruzzo	Italy	66013
183	GSK Investigational Site	Napoli	Campania	Italy	80131
184	GSK Investigational Site	San Felice a Cancello Caserta	Campania	Italy	81027
185	GSK Investigational Site	Bologna	Emilia-Romagna	Italy	40138
186	GSK Investigational Site	Roma	Lazio	Italy	00148
187	GSK Investigational Site	Roma	Lazio	Italy	00163
188	GSK Investigational Site	Roma	Lazio	Italy	00186
189	GSK Investigational Site	Brescia	Lombardia	Italy	25123
190	GSK Investigational Site	Brescia	Lombardia	Italy	25125
191	GSK Investigational Site	Milano	Lombardia	Italy	20122
192	GSK Investigational Site	Milano	Lombardia	Italy	20127
193	GSK Investigational Site	Pavia	Lombardia	Italy	27100
194	GSK Investigational Site	Rho	Lombardia	Italy	20017
195	GSK Investigational Site	Ancona	Marche	Italy	60020
196	GSK Investigational Site	Bari	Puglia	Italy	70124
197	GSK Investigational Site	Arezzo	Toscana	Italy	52100
198	GSK Investigational Site	Firenze	Toscana	Italy	50134
199	GSK Investigational Site	Pisa	Toscana	Italy	56126
200	GSK Investigational Site	Verona	Veneto	Italy	37100
201	GSK Investigational Site	Aichi		Japan	451-0052
202	GSK Investigational Site	Aichi		Japan	455-8530
203	GSK Investigational Site	Fukuoka		Japan	813-8588
204	GSK Investigational Site	Fukuoka		Japan	819-0165
205	GSK Investigational Site	Gunma		Japan	375-0017
206	GSK Investigational Site	Hiroshima		Japan	733-0864
207	GSK Investigational Site	Hokkaido		Japan	005-0853
208	GSK Investigational Site	Hokkaido		Japan	080-2470
209	GSK Investigational Site	Hyogo		Japan	672-8043
210	GSK Investigational Site	Ibaraki		Japan	300-0053
211	GSK Investigational Site	Kagawa		Japan	761-8024
212	GSK Investigational Site	Kanagawa		Japan	231-0023
213	GSK Investigational Site	Kanagawa		Japan	238-0042
214	GSK Investigational Site	Kochi		Japan	780-0842
215	GSK Investigational Site	Kumamoto		Japan	861-8002
216	GSK Investigational Site	Kyoto		Japan	607-8062
217	GSK Investigational Site	Nagano		Japan	399-8695
218	GSK Investigational Site	Osaka		Japan	567-0011
219	GSK Investigational Site	Osaka		Japan	569-1041
220	GSK Investigational Site	Tokyo		Japan	193-0998
221	GSK Investigational Site	Saltillo	Coahuila	Mexico	25000
222	GSK Investigational Site	Monterrey	Nuevo León	Mexico	64660
223	GSK Investigational Site	Monterrey	Nuevo León	Mexico	64710
224	GSK Investigational Site	Mexico		Mexico	14000
225	GSK Investigational Site	Bydgoszcz		Poland	85-096
226	GSK Investigational Site	Katowice		Poland	40-752
227	GSK Investigational Site	Lodz		Poland	91-348
228	GSK Investigational Site	Mosina		Poland	62-050
229	GSK Investigational Site	Poznan		Poland	61-298
230	GSK Investigational Site	Sopot		Poland	81-824
231	GSK Investigational Site	Warszawa		Poland	02-507
232	GSK Investigational Site	Coimbra		Portugal	3000-548
233	GSK Investigational Site	Lisboa		Portugal	1649-035
234	GSK Investigational Site	Burgos		Spain	09006
235	GSK Investigational Site	Castellón		Spain	12004
236	GSK Investigational Site	Elche (Alicante)		Spain	03202
237	GSK Investigational Site	Galdakano		Spain	48960
238	GSK Investigational Site	Gerona		Spain	17190
239	GSK Investigational Site	Granada		Spain	18013
240	GSK Investigational Site	La Coruña		Spain	15006
241	GSK Investigational Site	Madrid		Spain	28006
242	GSK Investigational Site	Madrid		Spain	28040
243	GSK Investigational Site	Madrid		Spain	28046
244	GSK Investigational Site	Murcia		Spain	30120
245	GSK Investigational Site	Málaga		Spain	29071
246	GSK Investigational Site	Pamplona		Spain	31008
247	GSK Investigational Site	San Sebastián		Spain	20014
248	GSK Investigational Site	Valencia		Spain	46010
249	GSK Investigational Site	Zuerich		Switzerland	8032

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Publications

• Harrington C, Sawchak S, Chiang C, Davies J, Donovan C, Saunders AM, Irizarry M, Jeter B, Zvartau-Hind M, van Dyck CH, Gold M. Rosiglitazone does not improve cognition or global function when used as adjunctive therapy to AChE inhibitors in mild-to-moderate Alzheimer's disease: two phase 3 studies. Curr Alzheimer Res. 2011 Aug;8(5):592-606.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT00348309
• Other Study ID Numbers: AVA102672
• First Posted: Jul 4, 2006
• Last Update Posted: Nov 28, 2017
• Last Verified: Sep 1, 2017

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by GlaxoSmithKline: apolipoprotein E; Alzheimer's disease; cognition; rosiglitazone; adjunctive therapy
• Additional relevant MeSH terms: Alzheimer Disease; Rosiglitazone; Donepezil

Study Results

Participant Flow

Recruitment Details	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.
Pre-assignment Detail	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.

Arm/Group Title	Placebo	2mg Rosiglitazone Extended Release	8mg Rosiglitazone Extended Release
Arm/Group Description	Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.	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.	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.
Period Title: Overall Study
STARTED	496	494	489
COMPLETED	362	396	346
NOT COMPLETED	134	98	143

Baseline Characteristics

Arm/Group Title	Placebo	2mg Rosiglitazone Extended Release	8mg Rosiglitazone Extended Release	Total
Arm/Group Description	Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.	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.	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 of all reporting groups
Overall Participants	496	494	489	1479
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	74.2 (7.95)	74.5 (8.06)	74.4 (7.83)	74.4 (7.94)
Sex: Female, Male (Count of Participants)
Female	304 61.3%	286 57.9%	305 62.4%	895 60.5%
Male	192 38.7%	208 42.1%	184 37.6%	584 39.5%
Race/Ethnicity, Customized (Number) [Number]
Hispanic or Latino	97 19.6%	86 17.4%	82 16.8%	265 17.9%
Not Hispanic or Latino	399 80.4%	408 82.6%	407 83.2%	1214 82.1%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) Total Score at Week 48
Description	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.
Time Frame	Baseline (Week 0) and Week 48

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	2mg Rosiglitazone Extended Release	8mg Rosiglitazone Extended Release
Arm/Group Description	Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.	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.	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.
Measure Participants	461	473	459
APOE4 negatives	2.9 (0.54)	1.6 (0.42)	2.7 (0.56)
All except E4/E4s	3.1 (0.36)	2.1 (0.29)	3.1 (0.37)
Full populations	3.4 (0.35)	2.4 (0.30)	3.2 (0.35)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 2mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.049
	Comments	APOE4 negatives
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.3
	Confidence Interval	(2-Sided) 95%; -2.7 to -0.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 8mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.808
	Comments	APOE4 negatives
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -1.7 to 1.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, 2mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.035
	Comments	All except E4/E4s
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.0
	Confidence Interval	(2-Sided) 95%; -1.9 to -0.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, 8mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.999
	Comments	All except E4/E4s
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -1.0 to 1.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, 2mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.020
	Comments	Full population
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.0
	Confidence Interval	(2-Sided) 95%; -1.9 to -0.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, 8mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.661
	Comments	Full population
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -1.2 to 0.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Change From Baseline in Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) at Week 48 for APOE E4
Description	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.
Time Frame	Baseline (Week 0) and Week 48

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	2mg Rosiglitazone Extended Release	8mg Rosiglitazone Extended Release
Arm/Group Description	Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.	Participants received rosiglitazone extended release 2 mg tablet orally, once daily until Week 48 followed by placebo tablet orally once daily until Week 54.	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.
Measure Participants	461	473	459
APOE4 negatives	1.3 (0.21)	0.8 (0.16)	1.5 (0.20)
All except E4/E4s	1.5 (0.14)	1.0 (0.12)	1.7 (0.14)
Full population	1.6 (0.14)	1.0 (0.12)	1.7 (0.13)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 2mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	=0.056
	Comments	APOE4 negatives
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.5
	Confidence Interval	(2-Sided) 95%; -1.0 to 0.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 8mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	=0.587
	Comments	APOE4 negatives
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.2
	Confidence Interval	(2-Sided) 95%; -0.4 to 0.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, 2mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	=0.004
	Comments	All except E4/E4s
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.5
	Confidence Interval	(2-Sided) 95%; -0.9 to -0.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, 8mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	=0.402
	Comments	All except E4/E4s
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.2
	Confidence Interval	(2-Sided) 95%; -0.2 to 0.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, 2mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	=0.002
	Comments	Full population
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.5
	Confidence Interval	(2-Sided) 95%; -0.9 to -0.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, 8mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	=0.478
	Comments	Full population
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.1
	Confidence Interval	(2-Sided) 95%; -0.2 to 0.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline in Disability Assessment for Dementia Scale (DAD) Total Score
Description	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.
Time Frame	Baseline (Week 0), Week 8, 16, 24 and 48

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	2mg Rosiglitazone Extended Release	8mg Rosiglitazone Extended Release
Arm/Group Description	Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.	Participants received rosiglitazone extended release 2 mg tablet orally, once daily until Week 48 followed by placebo tablet orally once daily until Week 54.	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.
Measure Participants	436	458	441
At Week 8	0.1 (0.56)	-0.5 (0.48)	-1.1 (0.47)
At Week 16	-1.6 (0.62)	-1.6 (0.59)	-2.1 (0.56)
At Week 24	-3.5 (0.69)	-2.2 (0.64)	-3.3 (0.69)
At Week 48	-7.8 (0.82)	-5.7 (0.78)	-8.4 (0.84)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 2mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	=0.340
	Comments	Week 8
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.6
	Confidence Interval	(2-Sided) 95%; -2.0 to 0.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 8mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	=0.079
	Comments	Week 8
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.2
	Confidence Interval	(2-Sided) 95%; -2.5 to 0.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, 2mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	=0.910
	Comments	Week 16
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95%; -1.7 to 1.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, 8mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.521
	Comments	Week 16
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.5
	Confidence Interval	(2-Sided) 95%; -2.1 to 1.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, 2mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	=0.154
	Comments	Week 24
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.3
	Confidence Interval	(2-Sided) 95%; -0.5 to 3.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, 8mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	=0.836
	Comments	Week 24
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.2
	Confidence Interval	(2-Sided) 95%; -1.6 to 2.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, 2mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.061
	Comments	Week 48
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	2.1
	Confidence Interval	(2-Sided) 95%; -0.1 to 4.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, 8mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	=0.566
	Comments	Week 48
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.7
	Confidence Interval	(2-Sided) 95%; -2.9 to 1.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score
Description	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.
Time Frame	Baseline (Week 0), Week 8, 16, 24 and 48

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	2mg Rosiglitazone Extended Release	8mg Rosiglitazone Extended Release
Arm/Group Description	Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.	Participants received rosiglitazone extended release 2 mg tablet orally, once daily until Week 48 followed by placebo tablet orally once daily until Week 54.	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.
Measure Participants	461	473	459
At Week 8	-0.3 (0.39)	-0.7 (0.32)	-0.3 (0.39)
At Week 16	-0.3 (0.43)	-0.6 (0.36)	0.1 (0.43)
At Week 24	0.4 (0.47)	-0.2 (0.39)	0.2 (0.48)
At Week 48	1.6 (0.61)	0.1 (0.44)	1.8 (0.55)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 2mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	=0.414
	Comments	Week 8
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.4
	Confidence Interval	(2-Sided) 95%; -1.3 to 0.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 8mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.931
	Comments	Week 8
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -1.0 to 1.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, 2mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.485
	Comments	Week 16
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.4
	Confidence Interval	(2-Sided) 95%; -1.4 to 0.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, 8mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.550
	Comments	Week 16
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.3
	Confidence Interval	(2-Sided) 95%; -0.8 to 1.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, 2mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.264
	Comments	Week 24
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.6
	Confidence Interval	(2-Sided) 95%; -1.8 to 0.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, 8mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.732
	Comments	Week 24
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -1.5 to 1.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, 2mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.043
	Comments	Week 48
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.5
	Confidence Interval	(2-Sided) 95%; -2.9 to -0.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, 8mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.814
	Comments	Week 48
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.2
	Confidence Interval	(2-Sided) 95%; -1.4 to 1.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Change From Screening in Mini Mental State Examination (MMSE) Total Score
Description	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.
Time Frame	Screening (Week -4) and Week 48

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	2mg Rosiglitazone Extended Release	8mg Rosiglitazone Extended Release
Arm/Group Description	Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.	Participants received rosiglitazone extended release 2 mg tablet orally, once daily until Week 48 followed by placebo tablet orally once daily until Week 54.	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.
Measure Participants	348	388	335
Least Squares Mean (Standard Error) [Score on a scale]	-1.6 (0.21)	-1.6 (0.20)	-1.7 (0.21)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 2mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.870
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -0.5 to 0.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 8mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.617
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95%; -0.7 to 0.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Change From Baseline in the Domains of the Resource Utilization in Dementia Scale (RUD)
Description	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.
Time Frame	Baseline (Week 0), Week 12, 24, 36 and 48

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	2mg Rosiglitazone Extended Release	8mg Rosiglitazone Extended Release
Arm/Group Description	Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.	Participants received rosiglitazone extended release 2 mg tablet orally, once daily until Week 48 followed by placebo tablet orally once daily until Week 54.	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.
Measure Participants	461	473	459
Q1: Week 12	1.6 (2.25)	2.4 (2.50)	-0.1 (3.18)
Q1: Week 24	10.7 (3.52)	3.4 (1.84)	7.0 (4.06)
Q1: Week 36	16.3 (3.60)	10.0 (3.43)	15.2 (4.95)
Q1: Week 48	21.7 (4.16)	17.0 (4.17)	18.1 (4.72)
Q2: Week 12	-6.4 (4.64)	2.4 (4.16)	1.5 (4.50)
Q2: Week 24	0.3 (4.89)	1.6 (4.17)	6.5 (4.88)
Q2: Week 36	5.0 (5.34)	4.6 (4.44)	13.3 (5.35)
Q2: Week 48	10.8 (5.51)	8.4 (4.88)	27.0 (6.24)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 2mg Rosiglitazone Extended Release
	Comments	Week 12 Q1
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.789
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.8
	Confidence Interval	(2-Sided) 95%; -5.2 to 6.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 8mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.643
	Comments	Week 12Q1
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.7
	Confidence Interval	(2-Sided) 95%; -9.0 to 5.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, 2mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.052
	Comments	Week 24 Q1
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-7.3
	Confidence Interval	(2-Sided) 95%; -14.7 to 0.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, 8mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.481
	Comments	Week 24 Q1
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.7
	Confidence Interval	(2-Sided) 95%; -14.0 to 6.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, 2mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.195
	Comments	Week 36 Q1
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-6.2
	Confidence Interval	(2-Sided) 95%; -15.6 to 3.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, 8mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.857
	Comments	Week 36 Q1
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.1
	Confidence Interval	(2-Sided) 95%; -12.9 to 10.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, 2mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.422
	Comments	Week 48 Q1
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-4.6
	Confidence Interval	(2-Sided) 95%; -15.9 to 6.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, 8mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.562
	Comments	Week 48 Q1
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.6
	Confidence Interval	(2-Sided) 95%; -15.7 to 8.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, 2mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.129
	Comments	Week 12 Q2
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	8.8
	Confidence Interval	(2-Sided) 95%; -2.6 to 20.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Placebo, 8mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.194
	Comments	Week 12 Q2
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	7.9
	Confidence Interval	(2-Sided) 95%; -4.0 to 19.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Placebo, 2mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.832
	Comments	Week 24 Q2
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.3
	Confidence Interval	(2-Sided) 95%; -10.5 to 13.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Placebo, 8mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.351
	Comments	Week 24 Q2
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	6.1
	Confidence Interval	(2-Sided) 95%; -6.8 to 19.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Placebo, 2mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.949
	Comments	Week 36 Q2
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.4
	Confidence Interval	(2-Sided) 95%; -13.3 to 12.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Placebo, 8mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.253
	Comments	Week 36 Q2
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	8.3
	Confidence Interval	(2-Sided) 95%; -6.0 to 22.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Placebo, 2mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.735
	Comments	Week 48 Q2
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.4
	Confidence Interval	(2-Sided) 95%; -16.2 to 11.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Placebo, 8mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.046
	Comments	Week 48 Q2
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	16.2
	Confidence Interval	(2-Sided) 95%; 0.3 to 32.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	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
Description	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.
Time Frame	Baseline (Week 0), Week 12, 36 and 48

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	2mg Rosiglitazone Extended Release	8mg Rosiglitazone Extended Release
Arm/Group Description	Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.	Participants received rosiglitazone extended release 2 mg tablet orally, once daily until Week 48 followed by placebo tablet orally once daily until Week 54.	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.
Measure Participants	461	473	459
Thermometer: Week 12	0.5 (0.84)	0.3 (0.82)	-0.5 (0.94)
Thermometer: Week 36	0.8 (0.95)	-1.6 (0.97)	-2.1 (1.03)
Thermometer: Week 48	-1.5 (1.05)	-0.3 (0.96)	-2.4 (1.08)
Utility: Week 12	0.01 (0.009)	0.02 (0.009)	-0.01 (0.010)
Utility: Week 36	-0.02 (0.011)	-0.01 (0.010)	-0.04 (0.012)
Utility: Week 48	-0.04 (0.012)	-0.02 (0.011)	-0.05 (0.013)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 2mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.914
	Comments	Week 12 Thermometer
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95%; -2.3 to 2.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 8mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.415
	Comments	Week 12 Thermometer
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.0
	Confidence Interval	(2-Sided) 95%; -3.3 to 1.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, 2mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.063
	Comments	Week 36 Thermometer
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.4
	Confidence Interval	(2-Sided) 95%; -4.9 to 0.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, 8mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.030
	Comments	Week 36 Thermometer
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.9
	Confidence Interval	(2-Sided) 95%; -5.6 to -0.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, 2mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.392
	Comments	Week 48 Thermometer
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.2
	Confidence Interval	(2-Sided) 95%; -1.5 to 3.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, 8mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.557
	Comments	Week 48 Thermometer
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.9
	Confidence Interval	(2-Sided) 95%; -3.7 to 2.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, 2mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.320
	Comments	Week 12 Utility
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.01
	Confidence Interval	(2-Sided) 95%; -0.01 to 0.03
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, 8mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.180
	Comments	Week 12 Utility
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.02
	Confidence Interval	(2-Sided) 95%; -0.04 to 0.01
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, 2mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.498
	Comments	Week 36 Utility
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.01
	Confidence Interval	(2-Sided) 95%; -0.02 to 0.04
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Placebo, 8mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.081
	Comments	Week 36 Utility
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.03
	Confidence Interval	(2-Sided) 95%; -0.06 to 0.00
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Placebo, 2mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.077
	Comments	Week 48 Utility
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.03
	Confidence Interval	(2-Sided) 95%; -0.00 to 0.06
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Placebo, 8mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.640
	Comments	Week 48 Utility
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.01
	Confidence Interval	(2-Sided) 95%; -0.04 to 0.03
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Change From Baseline in ADAS-Cog Total Score for Observed Cases at Weeks 8, 16, 24, 36 and 48
Description	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.
Time Frame	Baseline (Week 0), Week 8, 16, 24, 36 and 48

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	2mg Rosiglitazone Extended Release	8mg Rosiglitazone Extended Release
Arm/Group Description	Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.	Participants received rosiglitazone extended release 2 mg tablet orally, once daily until Week 48 followed by placebo tablet orally once daily until Week 54.	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.
Measure Participants	461	473	459
Week 8	-0.2 (4.21)	-0.6 (4.57)	-0.2 (4.44)
Week 16	-0.1 (5.09)	-0.5 (4.76)	0.1 (5.13)
Week 24	1.0 (5.86)	-0.2 (5.17)	0.8 (5.66)
Week 36	1.8 (6.08)	1.3 (5.79)	2.2 (6.40)
Week 48	2.9 (6.85)	2.1 (6.25)	2.6 (6.76)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 2mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.105
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.7
	Confidence Interval	(2-Sided) 95%; -1.6 to 0.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 8mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.483
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -1.3 to 0.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Change From Baseline in CDR-SB Score for Observed Cases at Weeks 12, 24, 36 and 48
Description	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 endpoint value minus the baseline value.
Time Frame	Baseline (Week 0), Week 12, 24, 36 and 48

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	2mg Rosiglitazone Extended Release	8mg Rosiglitazone Extended Release
Arm/Group Description	Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.	Participants received rosiglitazone extended release 2 mg tablet orally, once daily until Week 48 followed by placebo tablet orally once daily until Week 54.	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.
Measure Participants	461	473	459
Week 12	0.4 (1.55)	0.3 (1.36)	0.3 (1.40)
Week 24	0.7 (2.01)	0.5 (1.67)	0.8 (1.83)
Week 36	1.0 (2.26)	0.7 (2.06)	1.2 (2.30)
Week 48	1.5 (2.68)	1.0 (2.28)	1.6 (2.56)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 2mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.004
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.5
	Confidence Interval	(2-Sided) 95%; -0.9 to -0.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 8mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.554
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.1
	Confidence Interval	(2-Sided) 95%; -0.3 to 0.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Change in ADAS-Cog Total Score for Observed Cases at Week 54 Compared to Week 48
Description	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.
Time Frame	Week 48 and 54

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	2mg Rosiglitazone Extended Release	8mg Rosiglitazone Extended Release
Arm/Group Description	Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.	Participants received rosiglitazone extended release 2 mg tablet orally, once daily until Week 48 followed by placebo tablet orally once daily until Week 54.	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.
Measure Participants	332	366	305
Least Squares Mean (Standard Error) [Score on a scale]	0.7 (0.28)	1.1 (0.27)	1.1 (0.29)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 2mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.292
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.4
	Confidence Interval	(2-Sided) 95%; -0.3 to 1.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 8mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.297
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.4
	Confidence Interval	(2-Sided) 95%; -0.3 to 1.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

Title	Change in CDR-SB Total Score at Week 54 Compared to Week 48
Description	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 was calculated as endpoint value (Week 54) minus Week 48 value.
Time Frame	Week 48 and 54

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	2mg Rosiglitazone Extended Release	8mg Rosiglitazone Extended Release
Arm/Group Description	Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.	Participants received rosiglitazone extended release 2 mg tablet orally, once daily until Week 48 followed by placebo tablet orally once daily until Week 54.	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.
Measure Participants	328	364	302
Least Squares Mean (Standard Error) [Score on a scale]	0.2 (0.07)	0.2 (0.07)	0.1 (0.07)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 2mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.598
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -0.2 to 0.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 8mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.073
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -0.4 to 0.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Secondary Outcome

Title	Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 48
Description	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.
Time Frame	Baseline (Week 0) and Week 48

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	2mg Rosiglitazone Extended Release	8mg Rosiglitazone Extended Release
Arm/Group Description	Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.	Participants received rosiglitazone extended release 2 mg tablet orally, once daily until Week 48 followed by placebo tablet orally once daily until Week 54.	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.
Measure Participants	321	352	313
Least Squares Mean (Standard Error) [Percentage of total hemoglobin]	0.14 (0.020)	0.21 (0.020)	0.18 (0.020)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 2mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.006
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.07
	Confidence Interval	(2-Sided) 95%; 0.02 to 0.12
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 8mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.140
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.04
	Confidence Interval	(2-Sided) 95%; -0.01 to 0.09
	Parameter Dispersion	Type: Value:
	Estimation Comments

13. Secondary Outcome

Title	Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description	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.
Time Frame	Up to Week 54

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	2mg Rosiglitazone Extended Release	8mg Rosiglitazone Extended Release
Arm/Group Description	Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.	Participants received rosiglitazone extended release 2 mg tablet orally, once daily until Week 48 followed by placebo tablet orally once daily until Week 54.	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.
Measure Participants	496	494	489
Any TEAEs	304 61.3%	273 55.3%	327 66.9%
Any SAEs	62 12.5%	45 9.1%	50 10.2%

14. Secondary Outcome

Title	Mean Change From Baseline in Systolic and Diastolic Blood Pressure (BP)
Description	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.
Time Frame	Baseline (Week 0), Week 4, 8, 12, 16, 24, 36, 48 and 56

Outcome Measure Data

Analysis Population Description

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.

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

15. Secondary Outcome

Title	Mean Change From Baseline in Heart Rate
Description	Mean Change From Baseline in heart rate was calculated as endpoint value minus the baseline value.
Time Frame	Baseline (Week 0), Week 4, 8, 12, 16, 24, 36, 48 and 56

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	2mg Rosiglitazone Extended Release	8mg Rosiglitazone Extended Release
Arm/Group Description	Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.	Participants received rosiglitazone extended release 2 mg tablet orally, once daily until Week 48 followed by placebo tablet orally once daily until Week 54.	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.
Measure Participants	477	481	470
Week 4	0.8 (8.42)	1.1 (7.95)	0.6 (8.36)
Week 8	1.5 (8.98)	1.3 (9.19)	1.0 (8.91)
Week 12	1.6 (9.06)	1.8 (9.04)	0.7 (9.68)
Week 16	1.0 (9.23)	1.3 (9.18)	0.8 (9.52)
Week 24	0.9 (9.41)	1.3 (8.70)	0.8 (10.19)
Week 36	0.9 (9.30)	1.8 (9.42)	1.1 (9.58)
Week 48	1.2 (9.10)	1.4 (8.92)	0.7 (9.43)
Week 54	0.5 (10.10)	1.4 (9.55)	0.0 (11.05)

16. Secondary Outcome

Title	Mean Change From Baseline in Weight
Description	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.
Time Frame	Baseline (Week 0), Week 4, 8, 12, 16, 24, 36, 48 and 56

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	2mg Rosiglitazone Extended Release	8mg Rosiglitazone Extended Release
Arm/Group Description	Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.	Participants received rosiglitazone extended release 2 mg tablet orally, once daily until Week 48 followed by placebo tablet orally once daily until Week 54.	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.
Measure Participants	477	481	470
Week 4	0.1 (2.04)	0.2 (1.66)	0.3 (1.88)
Week 8	0.2 (2.35)	0.3 (1.95)	0.7 (2.37)
Week 12	0.2 (2.50)	0.3 (2.09)	0.9 (2.33)
Week 16	0.1 (2.88)	0.3 (2.44)	1.0 (2.56)
Week 24	0.1 (2.88)	0.6 (2.77)	0.9 (3.26)
Week 36	0.0 (3.37)	0.7 (3.00)	1.3 (3.92)
Week 48	0.4 (3.54)	0.8 (3.47)	1.3 (4.13)
Week 54	0.3 (3.74)	0.7 (3.69)	0.8 (4.53)

17. Secondary Outcome

Title	Change From Baseline in Hemoglobin Values
Description	Blood samples of participants were collected for Hemoglobin. Change from baseline in Hemoglobin was calculated as endpoint value minus the baseline value.
Time Frame	Baseline (Week 0), Week 4, 16, 36 and 48

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	2mg Rosiglitazone Extended Release	8mg Rosiglitazone Extended Release
Arm/Group Description	Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.	Participants received rosiglitazone extended release 2 mg tablet orally, once daily until Week 48 followed by placebo tablet orally once daily until Week 54.	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.
Measure Participants	496	494	489
Week 4	-0.4 (6.45)	-2.5 (6.92)	-3.7 (6.19)
Week 16	-0.6 (7.01)	-6.2 (7.76)	-11.9 (8.65)
Week 36	-2.0 (7.25)	-6.4 (8.04)	-12.5 (9.38)
Week 48	-1.9 (7.86)	-6.5 (8.45)	-12.2 (10.62)

18. Secondary Outcome

Title	Change From Baseline in Hematocrit Values
Description	Blood samples of participants were collected for Hematocrit . Change from baseline in Hematocrit was calculated as endpoint value minus the baseline value.
Time Frame	Baseline (Week 0), Week 4, 8, 12, 16, 36 and 48

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	2mg Rosiglitazone Extended Release	8mg Rosiglitazone Extended Release
Arm/Group Description	Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.	Participants received rosiglitazone extended release 2 mg tablet orally, once daily until Week 48 followed by placebo tablet orally once daily until Week 54.	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.
Measure Participants	496	494	489
Week 4	-0.0007 (0.02133)	-0.0068 (0.02189)	-0.0115 (0.01994)
Week 16	-0.0003 (0.02318)	-0.0174 (0.02460)	-0.0339 (0.02697)
Week 36	-0.0037 (0.02246)	-0.0167 (0.02471)	-0.0352 (0.02834)
Week 48	-0.0029 (0.02447)	-0.0177 (0.02658)	-0.0346 (0.03177)

19. Secondary Outcome

Title	Mean Change From Baseline in Short Term Memory Assessment Score
Description	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.
Time Frame	Baseline (Week 0), Week 8, 16, 24, 36, 48 and 56

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	2mg Rosiglitazone Extended Release	8mg Rosiglitazone Extended Release
Arm/Group Description	Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.	Participants received rosiglitazone extended release 2 mg tablet orally, once daily until Week 48 followed by placebo tablet orally once daily until Week 54.	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.
Measure Participants	461	473	459
Week 8	-0.3 (2.71)	-0.4 (3.03)	-0.3 (2.76)
Week 16	-0.4 (2.93)	-0.7 (2.92)	-0.4 (3.07)
Week 24	0.1 (2.96)	-0.4 (3.03)	-0.1 (3.06)
Week 36	0.4 (2.79)	0.3 (3.18)	0.7 (3.04)
Week 48	0.6 (3.01)	0.3 (3.07)	0.4 (3.06)
Week 54	1.1 (2.96)	0.8 (3.10)	0.9 (3.17)

20. Secondary Outcome

Title	Change From Baseline in HbA1c at Week 12, Week 24 and Week 36
Description	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 time point minus the value at Baseline.
Time Frame	Baseline (Week 0) and Week 12, 24 and 36

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	2mg Rosiglitazone Extended Release	8mg Rosiglitazone Extended Release
Arm/Group Description	Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.	Participants received rosiglitazone extended release 2 mg tablet orally, once daily until Week 48 followed by placebo tablet orally once daily until Week 54.	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.
Measure Participants	145	150	127
Week 12	0.01 (0.336)	0.14 (0.634)	0.16 (0.407)
Week 24	0.07 (0.401)	0.12 (0.422)	0.06 (0.551)
Week 36	0.20 (0.400)	0.19 (0.430)	0.15 (0.526)

21. Secondary Outcome

Title	Number of Participants With Laboratory Potential Clinical Concern (PCC) Values
Description	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.
Time Frame	Baseline (Week 0), Week 4, 8, 12, 16, 24, 36, 48 and 56

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	2mg Rosiglitazone Extended Release	8mg Rosiglitazone Extended Release
Arm/Group Description	Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.	Participants received rosiglitazone extended release 2 mg tablet orally, once daily until Week 48 followed by placebo tablet orally once daily until Week 54.	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.
Measure Participants	496	494	489
Eosinophils high	0 0%	3 0.6%	0 0%
Hematocrit low	2 0.4%	2 0.4%	5 1%
Hemoglobin high	2 0.4%	0 0%	0 0%
Hemoglobin low	8 1.6%	11 2.2%	31 6.3%
Lymphocytes high	0 0%	1 0.2%	2 0.4%
Lymphocytes low	8 1.6%	10 2%	13 2.7%
Mean CH high	0 0%	0 0%	1 0.2%
Mean CH low	2 0.4%	2 0.4%	0 0%
Mean CV high	0 0%	0 0%	1 0.2%
Mean CV low	2 0.4%	1 0.2%	0 0%
Monocytes low	81 16.3%	55 11.1%	65 13.3%
Platelet count high	4 0.8%	2 0.4%	7 1.4%
Platelet count low	1 0.2%	2 0.4%	4 0.8%
RDW high	18 3.6%	31 6.3%	86 17.6%
RBC high	0 0%	1 0.2%	0 0%
RBC low	0 0%	1 0.2%	8 1.6%
SN high	8 1.6%	2 0.4%	4 0.8%
SN low	2 0.4%	6 1.2%	13 2.7%
TN high	4 0.8%	1 0.2%	2 0.4%
TN low	2 0.4%	6 1.2%	13 2.7%
WBC high	4 0.8%	1 0.2%	3 0.6%
WBC low	1 0.2%	5 1%	12 2.5%

22. Secondary Outcome

Title	Change From Baseline in Alzheimer's Carer Quality of Life Instrument (ACQLI) Total Score
Description	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.
Time Frame	Baseline (Week 0), Week 12, 36 and 48

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	2mg Rosiglitazone Extended Release	8mg Rosiglitazone Extended Release
Arm/Group Description	Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.	Participants received rosiglitazone extended release 2 mg tablet orally, once daily until Week 48 followed by placebo tablet orally once daily until Week 54.	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.
Measure Participants	461	473	459
Week 12	0.5 (0.23)	-0.2 (0.23)	-0.0 (0.22)
Week 36	1.0 (0.28)	0.6 (0.27)	0.6 (0.26)
Week 48	1.2 (0.30)	0.3 (0.28)	1.1 (0.31)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 2mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.027
	Comments	Week 12
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.7
	Confidence Interval	(2-Sided) 95%; -1.2 to -0.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 8mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.091
	Comments	Week 12
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.5
	Confidence Interval	(2-Sided) 95%; -1.1 to 0.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, 2mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.268
	Comments	Week 36
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.4
	Confidence Interval	(2-Sided) 95%; -1.1 to 0.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, 8mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.318
	Comments	Week 36
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.4
	Confidence Interval	(2-Sided) 95%; -1.1 to 0.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, 2mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.030
	Comments	Week 48
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.9
	Confidence Interval	(2-Sided) 95%; -1.6 to -0.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, 8mg Rosiglitazone Extended Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.797
	Comments	Week 48
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95%; -0.9 to 0.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Up to Week 48
Adverse Event Reporting Description	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.
Arm/Group Title	Placebo		2mg Rosiglitazone Extended Release		8mg Rosiglitazone Extended Release
Arm/Group Description	Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.		Participants received rosiglitazone extended release 2 mg tablet orally, once daily until Week 48 followed by placebo tablet orally once daily until Week 54.		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.
All Cause Mortality
	Placebo		2mg Rosiglitazone Extended Release		8mg Rosiglitazone Extended Release
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/496 (2.4%)		6/494 (1.2%)		8/489 (1.6%)
Serious Adverse Events
	Placebo		2mg Rosiglitazone Extended Release		8mg Rosiglitazone Extended Release
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	62/496 (12.5%)		45/494 (9.1%)		50/489 (10.2%)
Blood and lymphatic system disorders
Iron deficiency anaemia	1/496 (0.2%)		1/494 (0.2%)		0/489 (0%)
Anaemia	0/496 (0%)		0/494 (0%)		1/489 (0.2%)
Normochromic normocytic anaemia	0/496 (0%)		0/494 (0%)		1/489 (0.2%)
Cardiac disorders
Myocardial infarction	5/496 (1%)		1/494 (0.2%)		0/489 (0%)
Cardiac arrest	2/496 (0.4%)		2/494 (0.4%)		1/489 (0.2%)
Angina pectoris	1/496 (0.2%)		1/494 (0.2%)		0/489 (0%)
Atrial fibrillation	0/496 (0%)		0/494 (0%)		2/489 (0.4%)
Bradycardia	0/496 (0%)		1/494 (0.2%)		1/489 (0.2%)
Cardiac failure congestive	1/496 (0.2%)		1/494 (0.2%)		0/489 (0%)
Coronary artery stenosis	0/496 (0%)		1/494 (0.2%)		1/489 (0.2%)
Myocardial ischaemia	0/496 (0%)		0/494 (0%)		2/489 (0.4%)
Acute myocardial infarction	1/496 (0.2%)		0/494 (0%)		0/489 (0%)
Cardiac failure	0/496 (0%)		0/494 (0%)		1/489 (0.2%)
Cardio-respiratory arrest	1/496 (0.2%)		0/494 (0%)		0/489 (0%)
Coronary artery disease	0/496 (0%)		1/494 (0.2%)		0/489 (0%)
Sick sinus syndrome	0/496 (0%)		0/494 (0%)		1/489 (0.2%)
Tachyarrhythmia	0/496 (0%)		1/494 (0.2%)		0/489 (0%)
Ear and labyrinth disorders
Vertigo	0/496 (0%)		1/494 (0.2%)		0/489 (0%)
Eye disorders
Angle closure glaucoma	0/496 (0%)		1/494 (0.2%)		0/489 (0%)
Cataract	1/496 (0.2%)		0/494 (0%)		0/489 (0%)
Gastrointestinal disorders
Inguinal hernia	0/496 (0%)		2/494 (0.4%)		0/489 (0%)
Colonic polyp	1/496 (0.2%)		0/494 (0%)		0/489 (0%)
Diarrhoea	0/496 (0%)		0/494 (0%)		1/489 (0.2%)
Diverticulum intestinal	0/496 (0%)		0/494 (0%)		1/489 (0.2%)
Duodenal ulcer haemorrhage	0/496 (0%)		0/494 (0%)		1/489 (0.2%)
Haemorrhoids	1/496 (0.2%)		0/494 (0%)		0/489 (0%)
Large intestine perforation	1/496 (0.2%)		0/494 (0%)		0/489 (0%)
Peptic ulcer perforation	0/496 (0%)		0/494 (0%)		1/489 (0.2%)
Rectal haemorrhage	1/496 (0.2%)		0/494 (0%)		0/489 (0%)
Rectal polyp	0/496 (0%)		0/494 (0%)		1/489 (0.2%)
General disorders
Malaise	1/496 (0.2%)		0/494 (0%)		1/489 (0.2%)
Death	0/496 (0%)		0/494 (0%)		1/489 (0.2%)
Oedema peripheral	0/496 (0%)		0/494 (0%)		1/489 (0.2%)
Hepatobiliary disorders
Bile duct stone	0/496 (0%)		1/494 (0.2%)		0/489 (0%)
Cholecystitis	0/496 (0%)		1/494 (0.2%)		0/489 (0%)
Cholelithiasis	1/496 (0.2%)		0/494 (0%)		0/489 (0%)
Hepatitis toxic	1/496 (0.2%)		0/494 (0%)		0/489 (0%)
Jaundice	1/496 (0.2%)		0/494 (0%)		0/489 (0%)
Infections and infestations
Pneumonia	5/496 (1%)		1/494 (0.2%)		6/489 (1.2%)
Urinary tract infection	1/496 (0.2%)		0/494 (0%)		2/489 (0.4%)
Appendicitis	0/496 (0%)		2/494 (0.4%)		0/489 (0%)
Bronchitis	1/496 (0.2%)		0/494 (0%)		1/489 (0.2%)
Bronchopneumonia	1/496 (0.2%)		1/494 (0.2%)		0/489 (0%)
Diverticulitis	0/496 (0%)		0/494 (0%)		1/489 (0.2%)
Gastroenteritis	1/496 (0.2%)		0/494 (0%)		0/489 (0%)
Gastroenteritis norovirus	0/496 (0%)		1/494 (0.2%)		0/489 (0%)
Gastroenteritis rotavirus	0/496 (0%)		1/494 (0.2%)		0/489 (0%)
Gastrointestinal infection	0/496 (0%)		0/494 (0%)		1/489 (0.2%)
Herpes zoster	1/496 (0.2%)		0/494 (0%)		0/489 (0%)
Lung infection	0/496 (0%)		0/494 (0%)		1/489 (0.2%)
Pneumonia primary atypical	0/496 (0%)		0/494 (0%)		1/489 (0.2%)
Pyelonephritis	0/496 (0%)		0/494 (0%)		1/489 (0.2%)
Sinusitis	0/496 (0%)		1/494 (0.2%)		0/489 (0%)
Viral infection	0/496 (0%)		1/494 (0.2%)		0/489 (0%)
Injury, poisoning and procedural complications
Hip fracture	3/496 (0.6%)		4/494 (0.8%)		1/489 (0.2%)
Femoral neck fracture	0/496 (0%)		1/494 (0.2%)		3/489 (0.6%)
Fall	1/496 (0.2%)		1/494 (0.2%)		1/489 (0.2%)
Humerus fracture	1/496 (0.2%)		1/494 (0.2%)		1/489 (0.2%)
Femur fracture	2/496 (0.4%)		0/494 (0%)		0/489 (0%)
Concussion	0/496 (0%)		0/494 (0%)		1/489 (0.2%)
Contusion	1/496 (0.2%)		0/494 (0%)		0/489 (0%)
Dislocation of joint	0/496 (0%)		1/494 (0.2%)		0/489 (0%)
Face injury	1/496 (0.2%)		0/494 (0%)		0/489 (0%)
Injury	0/496 (0%)		0/494 (0%)		1/489 (0.2%)
Ligament rupture	0/496 (0%)		1/494 (0.2%)		0/489 (0%)
Lower limb fracture	0/496 (0%)		1/494 (0.2%)		0/489 (0%)
Meniscus lesion	0/496 (0%)		1/494 (0.2%)		0/489 (0%)
Overdose	1/496 (0.2%)		0/494 (0%)		0/489 (0%)
Pelvic fracture	1/496 (0.2%)		0/494 (0%)		0/489 (0%)
Radius fracture	0/496 (0%)		0/494 (0%)		1/489 (0.2%)
Rib fracture	0/496 (0%)		1/494 (0.2%)		0/489 (0%)
Spinal compression fracture	0/496 (0%)		1/494 (0.2%)		0/489 (0%)
Tibia fracture	0/496 (0%)		1/494 (0.2%)		0/489 (0%)
Investigations
Platelet count decreased	0/496 (0%)		1/494 (0.2%)		0/489 (0%)
Weight decreased	1/496 (0.2%)		0/494 (0%)		0/489 (0%)
Metabolism and nutrition disorders
Dehydration	1/496 (0.2%)		2/494 (0.4%)		0/489 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/496 (0.2%)		1/494 (0.2%)		0/489 (0%)
Arthropathy	0/496 (0%)		1/494 (0.2%)		0/489 (0%)
Lateral patellar compression syndrome	1/496 (0.2%)		0/494 (0%)		0/489 (0%)
Muscle spasms	0/496 (0%)		1/494 (0.2%)		0/489 (0%)
Pain in extremity	0/496 (0%)		0/494 (0%)		1/489 (0.2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lymphoma	0/496 (0%)		0/494 (0%)		2/489 (0.4%)
Basal cell carcinoma	1/496 (0.2%)		0/494 (0%)		0/489 (0%)
Bile duct cancer	0/496 (0%)		0/494 (0%)		1/489 (0.2%)
Bile duct cancer recurrent	1/496 (0.2%)		0/494 (0%)		0/489 (0%)
Breast cancer	0/496 (0%)		1/494 (0.2%)		0/489 (0%)
Hepatic neoplasm malignant	1/496 (0.2%)		0/494 (0%)		0/489 (0%)
Intraductal papilloma of breast	1/496 (0.2%)		0/494 (0%)		0/489 (0%)
Prostate cancer	1/496 (0.2%)		0/494 (0%)		0/489 (0%)
Sarcoma	1/496 (0.2%)		0/494 (0%)		0/489 (0%)
Uterine neoplasm	0/496 (0%)		0/494 (0%)		1/489 (0.2%)
Nervous system disorders
Syncope	1/496 (0.2%)		3/494 (0.6%)		2/489 (0.4%)
Cerebrovascular accident	0/496 (0%)		1/494 (0.2%)		1/489 (0.2%)
Cerebral haemorrhage	1/496 (0.2%)		0/494 (0%)		0/489 (0%)
Convulsion	0/496 (0%)		0/494 (0%)		1/489 (0.2%)
Dementia Alzheimer's type	0/496 (0%)		0/494 (0%)		1/489 (0.2%)
Dizziness	0/496 (0%)		0/494 (0%)		1/489 (0.2%)
Epilepsy	0/496 (0%)		0/494 (0%)		1/489 (0.2%)
Haemorrhagic stroke	1/496 (0.2%)		0/494 (0%)		0/489 (0%)
Loss of consciousness	1/496 (0.2%)		0/494 (0%)		0/489 (0%)
Transient ischaemic attack	1/496 (0.2%)		0/494 (0%)		0/489 (0%)
Vertebrobasilar insufficiency	0/496 (0%)		0/494 (0%)		1/489 (0.2%)
Psychiatric disorders
Confusional state	2/496 (0.4%)		0/494 (0%)		1/489 (0.2%)
Aggression	1/496 (0.2%)		1/494 (0.2%)		0/489 (0%)
Agitation	1/496 (0.2%)		0/494 (0%)		1/489 (0.2%)
Anxiety	0/496 (0%)		0/494 (0%)		1/489 (0.2%)
Delirium	1/496 (0.2%)		0/494 (0%)		0/489 (0%)
Delusion	1/496 (0.2%)		0/494 (0%)		0/489 (0%)
Depression	0/496 (0%)		0/494 (0%)		1/489 (0.2%)
Hallucination	0/496 (0%)		0/494 (0%)		1/489 (0.2%)
Panic attack	0/496 (0%)		0/494 (0%)		1/489 (0.2%)
Psychotic disorder due to a general medical condition	0/496 (0%)		1/494 (0.2%)		0/489 (0%)
Suicidal ideation	0/496 (0%)		0/494 (0%)		1/489 (0.2%)
Suicide attempt	1/496 (0.2%)		0/494 (0%)		0/489 (0%)
Renal and urinary disorders
Renal failure acute	1/496 (0.2%)		0/494 (0%)		0/489 (0%)
Reproductive system and breast disorders
Benign prostatic hyperplasia	2/496 (0.4%)		0/494 (0%)		0/489 (0%)
Metrorrhagia	1/496 (0.2%)		0/494 (0%)		0/489 (0%)
Respiratory, thoracic and mediastinal disorders
Lung disorder	2/496 (0.4%)		0/494 (0%)		1/489 (0.2%)
Pulmonary embolism	1/496 (0.2%)		0/494 (0%)		1/489 (0.2%)
Bronchospasm	0/496 (0%)		0/494 (0%)		1/489 (0.2%)
Interstitial lung disease	0/496 (0%)		0/494 (0%)	0	1/489 (0.2%)	0
Skin and subcutaneous tissue disorders
Skin fissures	1/496 (0.2%)		0/494 (0%)		0/489 (0%)
Skin ulcer	1/496 (0.2%)		0/494 (0%)		0/489 (0%)
Vascular disorders
Aortic aneurysm	1/496 (0.2%)		1/494 (0.2%)		1/489 (0.2%)
Aortic dissection	1/496 (0.2%)		0/494 (0%)		0/489 (0%)
Deep vein thrombosis	1/496 (0.2%)		0/494 (0%)		0/489 (0%)
Haematoma	0/496 (0%)		0/494 (0%)		1/489 (0.2%)
Hypertensive crisis	1/496 (0.2%)		0/494 (0%)		0/489 (0%)
Venous thrombosis	0/496 (0%)		0/494 (0%)		1/489 (0.2%)
Other (Not Including Serious) Adverse Events
	Placebo		2mg Rosiglitazone Extended Release		8mg Rosiglitazone Extended Release
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/496 (2.2%)		29/494 (5.9%)		69/489 (14.1%)
General disorders
Oedema peripheral	11/496 (2.2%)		29/494 (5.9%)		69/489 (14.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.