Rosiglitazone (Extended Release Tablets) As Adjunctive Th... | NCT00348309

Label	Type	Description	Intervention Names
Arm 1	Experimental	Rosiglitazone Extended Release 2mg OD	Drug: Rosiglitazone Extended Release 2mg Other: Donepezil
Arm 2	Experimental	Rosiglitazone Extended Release 8mg OD	Drug: Rosiglitazone Extended Release 8mg Other: Donepezil
Arm 3	Placebo Comparator	Placebo	Other: Placebo Other: Donepezil

Name	Type	Description	Arm Group Labels	Other Names
Rosiglitazone Extended Release 2mg	Drug	Rosiglitazone Extended Release 2mg OD	Arm 1

Measure	Description	Time Frame
Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) Total Score at 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.	Baseline (Week 0) and Week 48
Change From Baseline in Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) at Week 48 for APOE E4	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.	Baseline (Week 0) and Week 48

Measure	Description	Time Frame
Change From Baseline in Disability Assessment for Dementia Scale (DAD) Total Score	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.

Eligibility Module

Eligibility Criteria

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.

Name	Affiliation	Role
GSK Clinical Trials	GlaxoSmithKline	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
GSK Investigational Site		Litchfield Park	Arizona	85340	United States
GSK Investigational Site

PubMed Identifier	Type	Citation	Retractions
21592048	Background	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. doi: 10.2174/156720511796391935.

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

ID	Type	URL	Comment
AVA102672	Clinical Study Report	View IPD

ID	Title	Description
FG000	Placebo	Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.
FG001	2mg Rosiglitazone Extended Release	Participants received rosiglitazone extended release 2 milligram (mg) tablet orally, once daily until Week 48 followed by placebo tablet orally once daily until Week 54.

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) Total Score at 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.

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.

Posted

Least Squares Mean

Standard Error

Score on a scale

Baseline (Week 0) and Week 48

ID	Title	Description
OG000	Placebo	Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.
OG001	2mg Rosiglitazone Extended Release	Participants received rosiglitazone extended release 2 milligram (mg) tablet orally, once daily until Week 48 followed by placebo tablet orally once daily until Week 54.
OG002	8mg Rosiglitazone Extended Release	Participants received rosiglitazone extended release 4 mg tablet orally, once daily until Week 4 followed by 8 mg tablet orally once daily from Week 4 until Week 48 followed by placebo tablet orally once daily until Week 54.

Units	Counts
Participants	OG000461 OG001473 OG002459

Title

Denominators

Categories

APOE4 negatives

- ParticipantsOG000153
- ParticipantsOG001172
- ParticipantsOG002141

Title	Measurements

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Mixed Models Analysis		0.049	APOE4 negatives	Mean Difference (Final Values)	-1.3			2-Sided	95	-2.7	-0.0					Superiority or Other
OG000 OG002		Mixed Models Analysis

Primary

Change From Baseline in Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) at Week 48 for APOE E4

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.

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

Posted

Least Squares Mean

Standard Error

Score on a scale

Baseline (Week 0) and Week 48

ID	Title	Description
OG000	Placebo	Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.
OG001	2mg Rosiglitazone Extended Release	Participants received rosiglitazone extended release 2 mg tablet orally, once daily until Week 48 followed by placebo tablet orally once daily until Week 54.

Secondary

Change From Baseline in Disability Assessment for Dementia Scale (DAD) Total Score

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.

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

Posted

Least Squares Mean

Standard Error

Scores on a scale

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

ID	Title	Description
OG000	Placebo	Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.
OG001	2mg Rosiglitazone Extended Release	Participants received rosiglitazone extended release 2 mg tablet orally, once daily until Week 48 followed by placebo tablet orally once daily until Week 54.

Secondary

Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score

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.

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

Posted

Least Squares Mean

Standard Error

Score on a scale

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

ID	Title	Description
OG000	Placebo	Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.
OG001	2mg Rosiglitazone Extended Release	Participants received rosiglitazone extended release 2 mg tablet orally, once daily until Week 48 followed by placebo tablet orally once daily until Week 54.
OG002	8mg Rosiglitazone Extended Release

Secondary

Change From Screening in Mini Mental State Examination (MMSE) Total Score

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.

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

Posted

Least Squares Mean

Standard Error

Score on a scale

Screening (Week -4) and Week 48

ID	Title	Description
OG000	Placebo	Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.
OG001	2mg Rosiglitazone Extended Release	Participants received rosiglitazone extended release 2 mg tablet orally, once daily until Week 48 followed by placebo tablet orally once daily until Week 54.
OG002

Secondary

Change From Baseline in the Domains of the Resource Utilization in Dementia Scale (RUD)

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.

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

Posted

Least Squares Mean

Standard Error

hours

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

ID	Title	Description
OG000	Placebo	Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.
OG001	2mg Rosiglitazone Extended Release	Participants received rosiglitazone extended release 2 mg tablet orally, once daily until Week 48 followed by placebo tablet orally once daily until Week 54.

Secondary

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

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.

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

Posted

Least Squares Mean

Standard Error

Score on a scale

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

ID	Title	Description
OG000	Placebo	Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.
OG001	2mg Rosiglitazone Extended Release

Secondary

Change From Baseline in ADAS-Cog Total Score for Observed Cases at Weeks 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.

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

Posted

Mean

Standard Deviation

Score on a scale

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

ID	Title	Description
OG000	Placebo	Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.
OG001	2mg Rosiglitazone Extended Release	Participants received rosiglitazone extended release 2 mg tablet orally, once daily until Week 48 followed by placebo tablet orally once daily until Week 54.
OG002	8mg Rosiglitazone Extended Release	Participants received rosiglitazone extended release 4 mg tablet orally, once daily until Week 4 followed by 8 mg tablet orally once daily from Week 4 until Week 48 followed by placebo tablet orally once daily until Week 54.

Secondary

Change From Baseline in CDR-SB Score for Observed Cases at Weeks 12, 24, 36 and 48

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

Posted

Mean

Standard Deviation

Score on a scale

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

ID	Title	Description
OG000	Placebo	Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.
OG001	2mg Rosiglitazone Extended Release	Participants received rosiglitazone extended release 2 mg tablet orally, once daily until Week 48 followed by placebo tablet orally once daily until Week 54.
OG002	8mg Rosiglitazone Extended Release	Participants received rosiglitazone extended release 4 mg tablet orally, once daily until Week 4 followed by 8 mg tablet orally once daily from Week 4 until Week 48 followed by placebo tablet orally once daily until Week 54.

Secondary

Change in ADAS-Cog Total Score for Observed Cases at Week 54 Compared to Week 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 was calculated as endpoint value (Week 54) minus Week 48 value.

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

Posted

Least Squares Mean

Standard Error

Score on a scale

Week 48 and 54

ID	Title	Description
OG000	Placebo	Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.
OG001	2mg Rosiglitazone Extended Release	Participants received rosiglitazone extended release 2 mg tablet orally, once daily until Week 48 followed by placebo tablet orally once daily until Week 54.
OG002	8mg Rosiglitazone Extended Release	Participants received rosiglitazone extended release 4 mg tablet orally, once daily until Week 4 followed by 8 mg tablet orally once daily from Week 4 until Week 48 followed by placebo tablet orally once daily until Week 54.

Secondary

Change in CDR-SB Total Score at Week 54 Compared to Week 48

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

Posted

Least Squares Mean

Standard Error

Score on a scale

Week 48 and 54

ID	Title	Description
OG000	Placebo	Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.
OG001	2mg Rosiglitazone Extended Release	Participants received rosiglitazone extended release 2 mg tablet orally, once daily until Week 48 followed by placebo tablet orally once daily until Week 54.
OG002	8mg Rosiglitazone Extended Release	Participants received rosiglitazone extended release 4 mg tablet orally, once daily until Week 4 followed by 8 mg tablet orally once daily from Week 4 until Week 48 followed by placebo tablet orally once daily until Week 54.

Secondary

Change From Baseline in Glycosylated Hemoglobin (HbA1c) at 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.

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

Posted

Least Squares Mean

Standard Error

Percentage of total hemoglobin

Baseline (Week 0) and Week 48

ID	Title	Description
OG000	Placebo	Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.
OG001	2mg Rosiglitazone Extended Release	Participants received rosiglitazone extended release 2 mg tablet orally, once daily until Week 48 followed by placebo tablet orally once daily until Week 54.
OG002	8mg Rosiglitazone Extended Release	Participants received rosiglitazone extended release 4 mg tablet orally, once daily until Week 4 followed by 8 mg tablet orally once daily from Week 4 until Week 48 followed by placebo tablet orally once daily until Week 54.

Secondary

Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

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.

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

Posted

Number

Participants

Up to Week 54

ID	Title	Description
OG000	Placebo	Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.
OG001	2mg Rosiglitazone Extended Release	Participants received rosiglitazone extended release 2 mg tablet orally, once daily until Week 48 followed by placebo tablet orally once daily until Week 54.
OG002	8mg Rosiglitazone Extended Release

Secondary

Mean Change From Baseline in Systolic and Diastolic Blood Pressure (BP)

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.

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.

Posted

Mean

Standard Deviation

Millimeter of mercury (mmHg)

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

ID	Title	Description
OG000	Placebo	Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.
OG001	2mg Rosiglitazone Extended Release	Participants received rosiglitazone extended release 2 mg tablet orally, once daily until Week 48 followed by placebo tablet orally once daily until Week 54.
OG002	8mg Rosiglitazone Extended Release	Participants received rosiglitazone extended release 4 mg tablet orally, once daily until Week 4 followed by 8 mg tablet orally once daily from Week 4 until Week 48 followed by placebo tablet orally once daily until Week 54.

Secondary

Mean Change From Baseline in Heart Rate

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

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.

Posted

Mean

Standard Deviation

beats per min (bpm)

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

ID	Title	Description
OG000	Placebo	Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.
OG001	2mg Rosiglitazone Extended Release	Participants received rosiglitazone extended release 2 mg tablet orally, once daily until Week 48 followed by placebo tablet orally once daily until Week 54.
OG002	8mg Rosiglitazone Extended Release	Participants received rosiglitazone extended release 4 mg tablet orally, once daily until Week 4 followed by 8 mg tablet orally once daily from Week 4 until Week 48 followed by placebo tablet orally once daily until Week 54.

Secondary

Mean Change From Baseline in Weight

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.

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.

Posted

Mean

Standard Deviation

kilogram (kg)

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

ID	Title	Description
OG000	Placebo	Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.
OG001	2mg Rosiglitazone Extended Release	Participants received rosiglitazone extended release 2 mg tablet orally, once daily until Week 48 followed by placebo tablet orally once daily until Week 54.
OG002	8mg Rosiglitazone Extended Release	Participants received rosiglitazone extended release 4 mg tablet orally, once daily until Week 4 followed by 8 mg tablet orally once daily from Week 4 until Week 48 followed by placebo tablet orally once daily until Week 54.

Secondary

Change From Baseline in Hemoglobin Values

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

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

Posted

Mean

Standard Deviation

grams per litre (g/L)

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

ID	Title	Description
OG000	Placebo	Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.
OG001	2mg Rosiglitazone Extended Release	Participants received rosiglitazone extended release 2 mg tablet orally, once daily until Week 48 followed by placebo tablet orally once daily until Week 54.
OG002	8mg Rosiglitazone Extended Release	Participants received rosiglitazone extended release 4 mg tablet orally, once daily until Week 4 followed by 8 mg tablet orally once daily from Week 4 until Week 48 followed by placebo tablet orally once daily until Week 54.

Secondary

Change From Baseline in Hematocrit Values

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

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

Posted

Mean

Standard Deviation

litre

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

ID	Title	Description
OG000	Placebo	Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.
OG001	2mg Rosiglitazone Extended Release	Participants received rosiglitazone extended release 2 mg tablet orally, once daily until Week 48 followed by placebo tablet orally once daily until Week 54.
OG002	8mg Rosiglitazone Extended Release	Participants received rosiglitazone extended release 4 mg tablet orally, once daily until Week 4 followed by 8 mg tablet orally once daily from Week 4 until Week 48 followed by placebo tablet orally once daily until Week 54.

Secondary

Mean Change From Baseline in Short Term Memory Assessment Score

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.

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

Posted

Mean

Standard Deviation

Score on a scale

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

ID	Title	Description
OG000	Placebo	Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.
OG001	2mg Rosiglitazone Extended Release	Participants received rosiglitazone extended release 2 mg tablet orally, once daily until Week 48 followed by placebo tablet orally once daily until Week 54.

Secondary

Change From Baseline in HbA1c at Week 12, Week 24 and Week 36

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.

Posted

Mean

Standard Deviation

Percent of total hemoglobin

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

ID	Title	Description
OG000	Placebo	Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.
OG001	2mg Rosiglitazone Extended Release	Participants received rosiglitazone extended release 2 mg tablet orally, once daily until Week 48 followed by placebo tablet orally once daily until Week 54.
OG002	8mg Rosiglitazone Extended Release	Participants received rosiglitazone extended release 4 mg tablet orally, once daily until Week 4 followed by 8 mg tablet orally once daily from Week 4 until Week 48 followed by placebo tablet orally once daily until Week 54.

Secondary

Number of Participants With Laboratory Potential Clinical Concern (PCC) Values

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.

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

Posted

Number

participants

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

ID	Title	Description
OG000	Placebo	Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.
OG001	2mg Rosiglitazone Extended Release	Participants received rosiglitazone extended release 2 mg tablet orally, once daily until Week 48 followed by placebo tablet orally once daily until Week 54.
OG002

Secondary

Change From Baseline in Alzheimer's Carer Quality of Life Instrument (ACQLI) Total Score

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.

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

Posted

Least Squares Mean

Standard Error

Score on a scale

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

ID	Title	Description
OG000	Placebo	Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.
OG001	2mg Rosiglitazone Extended Release	Participants received rosiglitazone extended release 2 mg tablet orally, once daily until Week 48 followed by placebo tablet orally once daily until Week 54.
OG002

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Hip fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0003 affected496 at risk EG0014 affected494 at risk EG0021 affected489 at risk
Femoral neck fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected496 at risk EG0011 affected494 at risk EG0023 affected489 at risk
Fall	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected496 at risk EG0011 affected494 at risk EG0021 affected489 at risk
Humerus fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected496 at risk EG0011 affected494 at risk EG0021 affected489 at risk
Femur fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0002 affected496 at risk EG0010 affected494 at risk EG0020 affected489 at risk
Concussion	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected496 at risk EG0010 affected494 at risk EG0021 affected489 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected496 at risk EG0010 affected494 at risk EG0020 affected489 at risk
Dislocation of joint	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected496 at risk EG0011 affected494 at risk EG0020 affected489 at risk
Face injury	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected496 at risk EG0010 affected494 at risk EG0020 affected489 at risk
Injury	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected496 at risk EG0010 affected494 at risk EG0021 affected489 at risk
Ligament rupture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected496 at risk EG0011 affected494 at risk EG0020 affected489 at risk
Lower limb fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected496 at risk EG0011 affected494 at risk EG0020 affected489 at risk
Meniscus lesion	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected496 at risk EG0011 affected494 at risk EG0020 affected489 at risk
Overdose	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected496 at risk EG0010 affected494 at risk EG0020 affected489 at risk
Pelvic fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected496 at risk EG0010 affected494 at risk EG0020 affected489 at risk
Radius fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected496 at risk EG0010 affected494 at risk EG0021 affected489 at risk
Rib fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected496 at risk EG0011 affected494 at risk EG0020 affected489 at risk
Spinal compression fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected496 at risk EG0011 affected494 at risk EG0020 affected489 at risk
Tibia fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected496 at risk EG0011 affected494 at risk EG0020 affected489 at risk
Pneumonia	Infections and infestations	MedDRA	Systematic Assessment	EG0005 affected496 at risk EG0011 affected494 at risk EG0026 affected489 at risk
Urinary tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected496 at risk EG0010 affected494 at risk EG0022 affected489 at risk
Appendicitis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected496 at risk EG0012 affected494 at risk EG0020 affected489 at risk
Bronchitis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected496 at risk EG0010 affected494 at risk EG0021 affected489 at risk
Bronchopneumonia	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected496 at risk EG0011 affected494 at risk EG0020 affected489 at risk
Diverticulitis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected496 at risk EG0010 affected494 at risk EG0021 affected489 at risk
Gastroenteritis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected496 at risk EG0010 affected494 at risk EG0020 affected489 at risk
Gastroenteritis norovirus	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected496 at risk EG0011 affected494 at risk EG0020 affected489 at risk
Gastroenteritis rotavirus	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected496 at risk EG0011 affected494 at risk EG0020 affected489 at risk
Gastrointestinal infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected496 at risk EG0010 affected494 at risk EG0021 affected489 at risk
Herpes zoster	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected496 at risk EG0010 affected494 at risk EG0020 affected489 at risk
Lung infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected496 at risk EG0010 affected494 at risk EG0021 affected489 at risk
Pneumonia primary atypical	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected496 at risk EG0010 affected494 at risk EG0021 affected489 at risk
Pyelonephritis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected496 at risk EG0010 affected494 at risk EG0021 affected489 at risk
Sinusitis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected496 at risk EG0011 affected494 at risk EG0020 affected489 at risk
Viral infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected496 at risk EG0011 affected494 at risk EG0020 affected489 at risk
Myocardial infarction	Cardiac disorders	MedDRA	Systematic Assessment	EG0005 affected496 at risk EG0011 affected494 at risk EG0020 affected489 at risk
Cardiac arrest	Cardiac disorders	MedDRA	Systematic Assessment	EG0002 affected496 at risk EG0012 affected494 at risk EG0021 affected489 at risk
Angina pectoris	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected496 at risk EG0011 affected494 at risk EG0020 affected489 at risk
Atrial fibrillation	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected496 at risk EG0010 affected494 at risk EG0022 affected489 at risk
Bradycardia	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected496 at risk EG0011 affected494 at risk EG0021 affected489 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected496 at risk EG0011 affected494 at risk EG0020 affected489 at risk
Coronary artery stenosis	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected496 at risk EG0011 affected494 at risk EG0021 affected489 at risk
Myocardial ischaemia	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected496 at risk EG0010 affected494 at risk EG0022 affected489 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected496 at risk EG0010 affected494 at risk EG0020 affected489 at risk
Cardiac failure	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected496 at risk EG0010 affected494 at risk EG0021 affected489 at risk
Cardio-respiratory arrest	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected496 at risk EG0010 affected494 at risk EG0020 affected489 at risk
Coronary artery disease	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected496 at risk EG0011 affected494 at risk EG0020 affected489 at risk
Sick sinus syndrome	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected496 at risk EG0010 affected494 at risk EG0021 affected489 at risk
Tachyarrhythmia	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected496 at risk EG0011 affected494 at risk EG0020 affected489 at risk
Syncope	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected496 at risk EG0013 affected494 at risk EG0022 affected489 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected496 at risk EG0011 affected494 at risk EG0021 affected489 at risk
Cerebral haemorrhage	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected496 at risk EG0010 affected494 at risk EG0020 affected489 at risk
Convulsion	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected496 at risk EG0010 affected494 at risk EG0021 affected489 at risk
Dementia Alzheimer's type	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected496 at risk EG0010 affected494 at risk EG0021 affected489 at risk
Dizziness	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected496 at risk EG0010 affected494 at risk EG0021 affected489 at risk
Epilepsy	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected496 at risk EG0010 affected494 at risk EG0021 affected489 at risk
Haemorrhagic stroke	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected496 at risk EG0010 affected494 at risk EG0020 affected489 at risk
Loss of consciousness	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected496 at risk EG0010 affected494 at risk EG0020 affected489 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected496 at risk EG0010 affected494 at risk EG0020 affected489 at risk
Vertebrobasilar insufficiency	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected496 at risk EG0010 affected494 at risk EG0021 affected489 at risk
Confusional state	Psychiatric disorders	MedDRA	Systematic Assessment	EG0002 affected496 at risk EG0010 affected494 at risk EG0021 affected489 at risk
Aggression	Psychiatric disorders	MedDRA	Systematic Assessment	EG0001 affected496 at risk EG0011 affected494 at risk EG0020 affected489 at risk
Agitation	Psychiatric disorders	MedDRA	Systematic Assessment	EG0001 affected496 at risk EG0010 affected494 at risk EG0021 affected489 at risk
Anxiety	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected496 at risk EG0010 affected494 at risk EG0021 affected489 at risk
Delirium	Psychiatric disorders	MedDRA	Systematic Assessment	EG0001 affected496 at risk EG0010 affected494 at risk EG0020 affected489 at risk
Delusion	Psychiatric disorders	MedDRA	Systematic Assessment	EG0001 affected496 at risk EG0010 affected494 at risk EG0020 affected489 at risk
Depression	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected496 at risk EG0010 affected494 at risk EG0021 affected489 at risk
Hallucination	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected496 at risk EG0010 affected494 at risk EG0021 affected489 at risk
Panic attack	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected496 at risk EG0010 affected494 at risk EG0021 affected489 at risk
Psychotic disorder due to a general medical condition	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected496 at risk EG0011 affected494 at risk EG0020 affected489 at risk
Suicidal ideation	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected496 at risk EG0010 affected494 at risk EG0021 affected489 at risk
Suicide attempt	Psychiatric disorders	MedDRA	Systematic Assessment	EG0001 affected496 at risk EG0010 affected494 at risk EG0020 affected489 at risk
Inguinal hernia	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected496 at risk EG0012 affected494 at risk EG0020 affected489 at risk
Colonic polyp	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected496 at risk EG0010 affected494 at risk EG0020 affected489 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected496 at risk EG0010 affected494 at risk EG0021 affected489 at risk
Diverticulum intestinal	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected496 at risk EG0010 affected494 at risk EG0021 affected489 at risk
Duodenal ulcer haemorrhage	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected496 at risk EG0010 affected494 at risk EG0021 affected489 at risk
Haemorrhoids	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected496 at risk EG0010 affected494 at risk EG0020 affected489 at risk
Large intestine perforation	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected496 at risk EG0010 affected494 at risk EG0020 affected489 at risk
Peptic ulcer perforation	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected496 at risk EG0010 affected494 at risk EG0021 affected489 at risk
Rectal haemorrhage	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected496 at risk EG0010 affected494 at risk EG0020 affected489 at risk
Rectal polyp	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected496 at risk EG0010 affected494 at risk EG0021 affected489 at risk
Lymphoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected496 at risk EG0010 affected494 at risk EG0022 affected489 at risk
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected496 at risk EG0010 affected494 at risk EG0020 affected489 at risk
Bile duct cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected496 at risk EG0010 affected494 at risk EG0021 affected489 at risk
Bile duct cancer recurrent	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected496 at risk EG0010 affected494 at risk EG0020 affected489 at risk
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected496 at risk EG0011 affected494 at risk EG0020 affected489 at risk
Hepatic neoplasm malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected496 at risk EG0010 affected494 at risk EG0020 affected489 at risk
Intraductal papilloma of breast	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected496 at risk EG0010 affected494 at risk EG0020 affected489 at risk
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected496 at risk EG0010 affected494 at risk EG0020 affected489 at risk
Sarcoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected496 at risk EG0010 affected494 at risk EG0020 affected489 at risk
Uterine neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected496 at risk EG0010 affected494 at risk EG0021 affected489 at risk
Aortic aneurysm	Vascular disorders	MedDRA	Systematic Assessment	EG0001 affected496 at risk EG0011 affected494 at risk EG0021 affected489 at risk
Aortic dissection	Vascular disorders	MedDRA	Systematic Assessment	EG0001 affected496 at risk EG0010 affected494 at risk EG0020 affected489 at risk
Deep vein thrombosis	Vascular disorders	MedDRA	Systematic Assessment	EG0001 affected496 at risk EG0010 affected494 at risk EG0020 affected489 at risk
Haematoma	Vascular disorders	MedDRA	Systematic Assessment	EG0000 affected496 at risk EG0010 affected494 at risk EG0021 affected489 at risk
Hypertensive crisis	Vascular disorders	MedDRA	Systematic Assessment	EG0001 affected496 at risk EG0010 affected494 at risk EG0020 affected489 at risk
Venous thrombosis	Vascular disorders	MedDRA	Systematic Assessment	EG0000 affected496 at risk EG0010 affected494 at risk EG0021 affected489 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected496 at risk EG0011 affected494 at risk EG0020 affected489 at risk
Arthropathy	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected496 at risk EG0011 affected494 at risk EG0020 affected489 at risk
Lateral patellar compression syndrome	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected496 at risk EG0010 affected494 at risk EG0020 affected489 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected496 at risk EG0011 affected494 at risk EG0020 affected489 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected496 at risk EG0010 affected494 at risk EG0021 affected489 at risk
Lung disorder	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0002 affected496 at risk EG0010 affected494 at risk EG0021 affected489 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected496 at risk EG0010 affected494 at risk EG0021 affected489 at risk
Bronchospasm	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected496 at risk EG0010 affected494 at risk EG0021 affected489 at risk
Interstitial lung disease	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected496 at risk EG0010 events0 affected494 at risk EG0021 affected489 at risk
Bile duct stone	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0000 affected496 at risk EG0011 affected494 at risk EG0020 affected489 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0000 affected496 at risk EG0011 affected494 at risk EG0020 affected489 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0001 affected496 at risk EG0010 affected494 at risk EG0020 affected489 at risk
Hepatitis toxic	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0001 affected496 at risk EG0010 affected494 at risk EG0020 affected489 at risk
Jaundice	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0001 affected496 at risk EG0010 affected494 at risk EG0020 affected489 at risk
Iron deficiency anaemia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0001 affected496 at risk EG0011 affected494 at risk EG0020 affected489 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0000 affected496 at risk EG0010 affected494 at risk EG0021 affected489 at risk
Normochromic normocytic anaemia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0000 affected496 at risk EG0010 affected494 at risk EG0021 affected489 at risk
Malaise	General disorders	MedDRA	Systematic Assessment	EG0001 affected496 at risk EG0010 affected494 at risk EG0021 affected489 at risk
Death	General disorders	MedDRA	Systematic Assessment	EG0000 affected496 at risk EG0010 affected494 at risk EG0021 affected489 at risk
Oedema peripheral	General disorders	MedDRA	Systematic Assessment	EG0000 affected496 at risk EG0010 affected494 at risk EG0021 affected489 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 affected496 at risk EG0012 affected494 at risk EG0020 affected489 at risk
Benign prostatic hyperplasia	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0002 affected496 at risk EG0010 affected494 at risk EG0020 affected489 at risk
Metrorrhagia	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0001 affected496 at risk EG0010 affected494 at risk EG0020 affected489 at risk
Angle closure glaucoma	Eye disorders	MedDRA	Systematic Assessment	EG0000 affected496 at risk EG0011 affected494 at risk EG0020 affected489 at risk
Cataract	Eye disorders	MedDRA	Systematic Assessment	EG0001 affected496 at risk EG0010 affected494 at risk EG0020 affected489 at risk
Platelet count decreased	Investigations	MedDRA	Systematic Assessment	EG0000 affected496 at risk EG0011 affected494 at risk EG0020 affected489 at risk
Weight decreased	Investigations	MedDRA	Systematic Assessment	EG0001 affected496 at risk EG0010 affected494 at risk EG0020 affected489 at risk
Skin fissures	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0001 affected496 at risk EG0010 affected494 at risk EG0020 affected489 at risk
Skin ulcer	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0001 affected496 at risk EG0010 affected494 at risk EG0020 affected489 at risk
Vertigo	Ear and labyrinth disorders	MedDRA	Systematic Assessment	EG0000 affected496 at risk EG0011 affected494 at risk EG0020 affected489 at risk
Renal failure acute	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0001 affected496 at risk EG0010 affected494 at risk EG0020 affected489 at risk

ID	Term
D003704	Dementia
D001927	Brain Diseases
D002493	Central Nervous System Diseases
D009422	Nervous System Diseases
D024801	Tauopathies
D019636	Neurodegenerative Diseases
D019965	Neurocognitive Disorders
D001523	Mental Disorders

ID	Term
D007189	Indans
D007192	Indenes
D011084	Polycyclic Aromatic Hydrocarbons
D006841	Hydrocarbons, Aromatic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons
D009930	Organic Chemicals
D010880	Piperidines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D011083	Polycyclic Compounds

ID	Title	Description
BG000	Placebo	Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.
BG001	2mg Rosiglitazone Extended Release	Participants received rosiglitazone extended release 2 milligram (mg) tablet orally, once daily until Week 48 followed by placebo tablet orally once daily until Week 54.
BG002	8mg Rosiglitazone Extended Release	Participants received rosiglitazone extended release 4 mg tablet orally, once daily until Week 4 followed by 8 mg tablet orally once daily from Week 4 until Week 48 followed by placebo tablet orally once daily until Week 54.
BG003	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Participants received rosiglitazone extended release matching placebo tablet orally, once daily until Week 54.	12	496	62	496	11	496
EG001	2mg Rosiglitazone Extended Release	Participants received rosiglitazone extended release 2 mg tablet orally, once daily until Week 48 followed by placebo tablet orally once daily until Week 54.	6	494	45	494	29	494
EG002	8mg Rosiglitazone Extended Release	Participants received rosiglitazone extended release 4 mg tablet orally, once daily until Week 4 followed by 8 mg tablet orally once daily from Week 4 until Week 48 followed by placebo tablet orally once daily until Week 54.	8	489	50	489	69	489