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

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ClinicalTrials.gov Identifier: NCT00348309
Recruitment Status : Completed
First Posted : July 4, 2006
Results First Posted : November 28, 2017
Last Update Posted : November 28, 2017
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Alzheimer's Disease
Interventions Drug: Rosiglitazone Extended Release 2mg
Drug: Rosiglitazone Extended Release 8mg
Other: Placebo
Other: Donepezil
Enrollment 1496
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 Details 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
Hide 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
Reason Not Completed
Adverse Event             56             28             63
Lost to Follow-up             6             7             4
Protocol Violation             7             12             7
Withdrawal by Subject             33             37             40
Non-compliance             8             6             8
Death of caregiver             1             0             1
Lack of insight, dementia             1             0             0
Wrong bottle allocated             1             0             0
Caregiver sick             1             0             0
Use of prohibited medication             5             2             2
Caregiver withdrawal             3             0             7
Unable to complete ET visit             1             0             0
PI closing medical practice             1             0             0
Principal investigator's decision             1             0             0
No disponibility of medication             1             0             0
Worsened neurodegenerative disease             1             0             0
Cognitive and behaviour worsening             2             0             0
Worsening of alzheimer             1             0             1
Did not appear in time for Visit 3             1             0             0
Participant died             2             1             1
Decision of sponsor             1             0             0
Ineffectiveness of treatment             0             1             0
A foul of exclusion criteria             0             1             0
Participant was hospitalized             0             1             0
Sponsor refuseal             0             1             1
Forgot often medication             0             1             0
Medical Monitor decision             0             0             1
Increased dose of Aricept             0             0             1
Site closure             0             0             1
Adverse event not attended             0             0             1
ECG abnormal             0             0             2
Cardiologist recommendations             0             0             1
HCV career             0             0             1
Arm/Group Title Placebo 2mg Rosiglitazone Extended Release 8mg Rosiglitazone Extended Release Total
Hide 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 Number of Baseline Participants 496 494 489 1479
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 496 participants 494 participants 489 participants 1479 participants
74.2  (7.95) 74.5  (8.06) 74.4  (7.83) 74.4  (7.94)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 496 participants 494 participants 489 participants 1479 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  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 496 participants 494 participants 489 participants 1479 participants
Hispanic or Latino 97 86 82 265
Not Hispanic or Latino 399 408 407 1214
1.Primary Outcome
Title Change From Baseline in Alzheimer’s Disease Assessment Scale – Cognitive Subscale (ADAS-Cog) Total Score at Week 48
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 461 473 459
Least Squares Mean (Standard Error)
Unit of Measure: Score on a scale
APOE4 negatives Number Analyzed 153 participants 172 participants 141 participants
2.9  (0.54) 1.6  (0.42) 2.7  (0.56)
All except E4/E4s Number Analyzed 317 participants 350 participants 285 participants
3.1  (0.36) 2.1  (0.29) 3.1  (0.37)
Full populations Number Analyzed 356 participants 391 participants 333 participants
3.4  (0.35) 2.4  (0.30) 3.2  (0.35)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, 2mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.049
Comments APOE4 negatives
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.3
Confidence Interval (2-Sided) 95%
-2.7 to -0.0
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, 8mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.808
Comments APOE4 negatives
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.2
Confidence Interval (2-Sided) 95%
-1.7 to 1.3
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, 2mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.035
Comments All except E4/E4s
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.0
Confidence Interval (2-Sided) 95%
-1.9 to -0.1
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, 8mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.999
Comments All except E4/E4s
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-1.0 to 1.0
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, 2mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.020
Comments Full population
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.0
Confidence Interval (2-Sided) 95%
-1.9 to -0.2
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, 8mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.661
Comments Full population
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.2
Confidence Interval (2-Sided) 95%
-1.2 to 0.7
Estimation Comments [Not Specified]
2.Primary Outcome
Title Change From Baseline in Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) at Week 48 for APOE E4
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 461 473 459
Least Squares Mean (Standard Error)
Unit of Measure: Score on a scale
APOE4 negatives Number Analyzed 146 participants 169 participants 139 participants
1.3  (0.21) 0.8  (0.16) 1.5  (0.20)
All except E4/E4s Number Analyzed 309 participants 343 participants 283 participants
1.5  (0.14) 1.0  (0.12) 1.7  (0.14)
Full population Number Analyzed 347 participants 384 participants 331 participants
1.6  (0.14) 1.0  (0.12) 1.7  (0.13)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, 2mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.056
Comments APOE4 negatives
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.5
Confidence Interval (2-Sided) 95%
-1.0 to 0.0
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, 8mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.587
Comments APOE4 negatives
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.2
Confidence Interval (2-Sided) 95%
-0.4 to 0.7
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, 2mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.004
Comments All except E4/E4s
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.5
Confidence Interval (2-Sided) 95%
-0.9 to -0.2
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, 8mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.402
Comments All except E4/E4s
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.2
Confidence Interval (2-Sided) 95%
-0.2 to 0.6
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, 2mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.002
Comments Full population
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.5
Confidence Interval (2-Sided) 95%
-0.9 to -0.2
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, 8mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.478
Comments Full population
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.1
Confidence Interval (2-Sided) 95%
-0.2 to 0.5
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline in Disability Assessment for Dementia Scale (DAD) Total Score
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 436 458 441
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
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)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, 2mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.340
Comments Week 8
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.6
Confidence Interval (2-Sided) 95%
-2.0 to 0.7
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, 8mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.079
Comments Week 8
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.2
Confidence Interval (2-Sided) 95%
-2.5 to 0.1
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, 2mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.910
Comments Week 16
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-1.7 to 1.5
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, 8mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.521
Comments Week 16
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.5
Confidence Interval (2-Sided) 95%
-2.1 to 1.0
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, 2mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.154
Comments Week 24
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.3
Confidence Interval (2-Sided) 95%
-0.5 to 3.0
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, 8mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.836
Comments Week 24
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.2
Confidence Interval (2-Sided) 95%
-1.6 to 2.0
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, 2mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.061
Comments Week 48
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.1
Confidence Interval (2-Sided) 95%
-0.1 to 4.2
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, 8mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.566
Comments Week 48
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.7
Confidence Interval (2-Sided) 95%
-2.9 to 1.6
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 461 473 459
Least Squares Mean (Standard Error)
Unit of Measure: Score on a scale
At Week 8 Number Analyzed 440 participants 458 participants 442 participants
-0.3  (0.39) -0.7  (0.32) -0.3  (0.39)
At Week 16 Number Analyzed 425 participants 442 participants 415 participants
-0.3  (0.43) -0.6  (0.36) 0.1  (0.43)
At Week 24 Number Analyzed 411 participants 425 participants 390 participants
0.4  (0.47) -0.2  (0.39) 0.2  (0.48)
At Week 48 Number Analyzed 359 participants 395 participants 345 participants
1.6  (0.61) 0.1  (0.44) 1.8  (0.55)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, 2mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.414
Comments Week 8
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.4
Confidence Interval (2-Sided) 95%
-1.3 to 0.5
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, 8mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.931
Comments Week 8
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-1.0 to 1.1
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, 2mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.485
Comments Week 16
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.4
Confidence Interval (2-Sided) 95%
-1.4 to 0.7
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, 8mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.550
Comments Week 16
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.3
Confidence Interval (2-Sided) 95%
-0.8 to 1.5
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, 2mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.264
Comments Week 24
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.6
Confidence Interval (2-Sided) 95%
-1.8 to 0.5
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, 8mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.732
Comments Week 24
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.2
Confidence Interval (2-Sided) 95%
-1.5 to 1.0
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, 2mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.043
Comments Week 48
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.5
Confidence Interval (2-Sided) 95%
-2.9 to -0.0
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, 8mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.814
Comments Week 48
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.2
Confidence Interval (2-Sided) 95%
-1.4 to 1.8
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change From Screening in Mini Mental State Examination (MMSE) Total Score
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 348 388 335
Least Squares Mean (Standard Error)
Unit of Measure: Score on a scale
-1.6  (0.21) -1.6  (0.20) -1.7  (0.21)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, 2mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.870
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-0.5 to 0.6
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, 8mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.617
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-0.7 to 0.4
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Change From Baseline in the Domains of the Resource Utilization in Dementia Scale (RUD)
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 461 473 459
Least Squares Mean (Standard Error)
Unit of Measure: hours
Q1: Week 12 Number Analyzed 386 participants 408 participants 379 participants
1.6  (2.25) 2.4  (2.50) -0.1  (3.18)
Q1: Week 24 Number Analyzed 386 participants 380 participants 347 participants
10.7  (3.52) 3.4  (1.84) 7.0  (4.06)
Q1: Week 36 Number Analyzed 342 participants 361 participants 327 participants
16.3  (3.60) 10.0  (3.43) 15.2  (4.95)
Q1: Week 48 Number Analyzed 320 participants 351 participants 310 participants
21.7  (4.16) 17.0  (4.17) 18.1  (4.72)
Q2: Week 12 Number Analyzed 171 participants 183 participants 162 participants
-6.4  (4.64) 2.4  (4.16) 1.5  (4.50)
Q2: Week 24 Number Analyzed 162 participants 170 participants 150 participants
0.3  (4.89) 1.6  (4.17) 6.5  (4.88)
Q2: Week 36 Number Analyzed 153 participants 162 participants 141 participants
5.0  (5.34) 4.6  (4.44) 13.3  (5.35)
Q2: Week 48 Number Analyzed 139 participants 157 participants 137 participants
10.8  (5.51) 8.4  (4.88) 27.0  (6.24)
Show Statistical Analysis 1 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.789
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.8
Confidence Interval (2-Sided) 95%
-5.2 to 6.9
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, 8mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.643
Comments Week 12Q1
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.7
Confidence Interval (2-Sided) 95%
-9.0 to 5.6
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, 2mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.052
Comments Week 24 Q1
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -7.3
Confidence Interval (2-Sided) 95%
-14.7 to 0.1
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, 8mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.481
Comments Week 24 Q1
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.7
Confidence Interval (2-Sided) 95%
-14.0 to 6.6
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, 2mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.195
Comments Week 36 Q1
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -6.2
Confidence Interval (2-Sided) 95%
-15.6 to 3.2
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, 8mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.857
Comments Week 36 Q1
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.1
Confidence Interval (2-Sided) 95%
-12.9 to 10.7
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, 2mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.422
Comments Week 48 Q1
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -4.6
Confidence Interval (2-Sided) 95%
-15.9 to 6.7
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, 8mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.562
Comments Week 48 Q1
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.6
Confidence Interval (2-Sided) 95%
-15.7 to 8.6
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Placebo, 2mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.129
Comments Week 12 Q2
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 8.8
Confidence Interval (2-Sided) 95%
-2.6 to 20.2
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Placebo, 8mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.194
Comments Week 12 Q2
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 7.9
Confidence Interval (2-Sided) 95%
-4.0 to 19.9
Estimation Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Placebo, 2mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.832
Comments Week 24 Q2
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.3
Confidence Interval (2-Sided) 95%
-10.5 to 13.1
Estimation Comments [Not Specified]
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Placebo, 8mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.351
Comments Week 24 Q2
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 6.1
Confidence Interval (2-Sided) 95%
-6.8 to 19.1
Estimation Comments [Not Specified]
Show Statistical Analysis 13 Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Placebo, 2mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.949
Comments Week 36 Q2
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.4
Confidence Interval (2-Sided) 95%
-13.3 to 12.5
Estimation Comments [Not Specified]
Show Statistical Analysis 14 Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Placebo, 8mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.253
Comments Week 36 Q2
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 8.3
Confidence Interval (2-Sided) 95%
-6.0 to 22.6
Estimation Comments [Not Specified]
Show Statistical Analysis 15 Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Placebo, 2mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.735
Comments Week 48 Q2
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.4
Confidence Interval (2-Sided) 95%
-16.2 to 11.4
Estimation Comments [Not Specified]
Show Statistical Analysis 16 Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Placebo, 8mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.046
Comments Week 48 Q2
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 16.2
Confidence Interval (2-Sided) 95%
0.3 to 32.0
Estimation Comments [Not Specified]
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
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 461 473 459
Least Squares Mean (Standard Error)
Unit of Measure: Score on a scale
Thermometer: Week 12 Number Analyzed 425 participants 449 participants 413 participants
0.5  (0.84) 0.3  (0.82) -0.5  (0.94)
Thermometer: Week 36 Number Analyzed 381 participants 404 participants 362 participants
0.8  (0.95) -1.6  (0.97) -2.1  (1.03)
Thermometer: Week 48 Number Analyzed 352 participants 389 participants 337 participants
-1.5  (1.05) -0.3  (0.96) -2.4  (1.08)
Utility: Week 12 Number Analyzed 425 participants 448 participants 414 participants
0.01  (0.009) 0.02  (0.009) -0.01  (0.010)
Utility: Week 36 Number Analyzed 381 participants 403 participants 363 participants
-0.02  (0.011) -0.01  (0.010) -0.04  (0.012)
Utility: Week 48 Number Analyzed 351 participants 389 participants 337 participants
-0.04  (0.012) -0.02  (0.011) -0.05  (0.013)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, 2mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.914
Comments Week 12 Thermometer
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-2.3 to 2.0
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, 8mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.415
Comments Week 12 Thermometer
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.0
Confidence Interval (2-Sided) 95%
-3.3 to 1.4
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, 2mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.063
Comments Week 36 Thermometer
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.4
Confidence Interval (2-Sided) 95%
-4.9 to 0.1
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, 8mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.030
Comments Week 36 Thermometer
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.9
Confidence Interval (2-Sided) 95%
-5.6 to -0.3
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, 2mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.392
Comments Week 48 Thermometer
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.2
Confidence Interval (2-Sided) 95%
-1.5 to 3.8
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, 8mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.557
Comments Week 48 Thermometer
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.9
Confidence Interval (2-Sided) 95%
-3.7 to 2.0
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, 2mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.320
Comments Week 12 Utility
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.01
Confidence Interval (2-Sided) 95%
-0.01 to 0.03
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, 8mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.180
Comments Week 12 Utility
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.02
Confidence Interval (2-Sided) 95%
-0.04 to 0.01
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Placebo, 2mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.498
Comments Week 36 Utility
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.01
Confidence Interval (2-Sided) 95%
-0.02 to 0.04
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Placebo, 8mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.081
Comments Week 36 Utility
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.03
Confidence Interval (2-Sided) 95%
-0.06 to 0.00
Estimation Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Placebo, 2mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.077
Comments Week 48 Utility
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.03
Confidence Interval (2-Sided) 95%
-0.00 to 0.06
Estimation Comments [Not Specified]
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Placebo, 8mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.640
Comments Week 48 Utility
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.01
Confidence Interval (2-Sided) 95%
-0.04 to 0.03
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Change From Baseline in ADAS-Cog Total Score for Observed Cases at Weeks 8, 16, 24, 36 and 48
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 461 473 459
Mean (Standard Deviation)
Unit of Measure: Score on a scale
Week 8 Number Analyzed 435 participants 457 participants 437 participants
-0.2  (4.21) -0.6  (4.57) -0.2  (4.44)
Week 16 Number Analyzed 422 participants 441 participants 411 participants
-0.1  (5.09) -0.5  (4.76) 0.1  (5.13)
Week 24 Number Analyzed 404 participants 425 participants 386 participants
1.0  (5.86) -0.2  (5.17) 0.8  (5.66)
Week 36 Number Analyzed 378 participants 402 participants 362 participants
1.8  (6.08) 1.3  (5.79) 2.2  (6.40)
Week 48 Number Analyzed 358 participants 393 participants 333 participants
2.9  (6.85) 2.1  (6.25) 2.6  (6.76)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, 2mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.105
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.7
Confidence Interval (2-Sided) 95%
-1.6 to 0.2
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, 8mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.483
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.3
Confidence Interval (2-Sided) 95%
-1.3 to 0.6
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Change From Baseline in CDR-SB Score for Observed Cases at Weeks 12, 24, 36 and 48
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 461 473 459
Mean (Standard Deviation)
Unit of Measure: Score on a scale
Week 12 Number Analyzed 423 participants 446 participants 414 participants
0.4  (1.55) 0.3  (1.36) 0.3  (1.40)
Week 24 Number Analyzed 402 participants 421 participants 382 participants
0.7  (2.01) 0.5  (1.67) 0.8  (1.83)
Week 36 Number Analyzed 374 participants 400 participants 357 participants
1.0  (2.26) 0.7  (2.06) 1.2  (2.30)
Week 48 Number Analyzed 349 participants 385 participants 331 participants
1.5  (2.68) 1.0  (2.28) 1.6  (2.56)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, 2mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.004
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.5
Confidence Interval (2-Sided) 95%
-0.9 to -0.2
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, 8mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.554
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.1
Confidence Interval (2-Sided) 95%
-0.3 to 0.5
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Change in ADAS-Cog Total Score for Observed Cases at Week 54 Compared to Week 48
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 332 366 305
Least Squares Mean (Standard Error)
Unit of Measure: Score on a scale
0.7  (0.28) 1.1  (0.27) 1.1  (0.29)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, 2mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.292
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.4
Confidence Interval (2-Sided) 95%
-0.3 to 1.1
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, 8mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.297
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.4
Confidence Interval (2-Sided) 95%
-0.3 to 1.1
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Change in CDR-SB Total Score at Week 54 Compared to Week 48
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 328 364 302
Least Squares Mean (Standard Error)
Unit of Measure: Score on a scale
0.2  (0.07) 0.2  (0.07) 0.1  (0.07)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, 2mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.598
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-0.2 to 0.1
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, 8mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.073
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.2
Confidence Interval (2-Sided) 95%
-0.4 to 0.0
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 48
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 321 352 313
Least Squares Mean (Standard Error)
Unit of Measure: Percentage of total hemoglobin
0.14  (0.020) 0.21  (0.020) 0.18  (0.020)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, 2mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.006
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.07
Confidence Interval (2-Sided) 95%
0.02 to 0.12
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, 8mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.140
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.04
Confidence Interval (2-Sided) 95%
-0.01 to 0.09
Estimation Comments [Not Specified]
13.Secondary Outcome
Title Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 496 494 489
Measure Type: Number
Unit of Measure: Participants
Any TEAEs 304 273 327
Any SAEs 62 45 50
14.Secondary Outcome
Title Mean Change From Baseline in Systolic and Diastolic Blood Pressure (BP)
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 477 481 470
Mean (Standard Deviation)
Unit of Measure: Millimeter of mercury (mmHg)
Systolic BP Week 4 Number Analyzed 457 participants 469 participants 457 participants
-0.7  (15.21) -1.0  (13.21) -2.3  (13.43)
Systolic BP Week 8 Number Analyzed 436 participants 460 participants 434 participants
-0.3  (15.49) -0.7  (14.55) -2.9  (14.49)
Systolic BP Week 12 Number Analyzed 431 participants 454 participants 415 participants
-0.5  (16.48) -2.5  (14.49) -4.2  (15.25)
Systolic BP Week 16 Number Analyzed 425 participants 442 participants 411 participants
-0.8  (15.80) -1.7  (14.80) -3.7  (15.75)
Systolic BP Week 24 Number Analyzed 413 participants 431 participants 392 participants
-1.2  (15.95) -1.0  (15.22) -3.5  (14.74)
Systolic BP Week 36 Number Analyzed 384 participants 406 participants 367 participants
-1.6  (16.65) -0.3  (15.79) -2.7  (15.97)
Systolic BP Week 48 Number Analyzed 363 participants 397 participants 345 participants
-1.0  (17.08) -0.6  (15.05) -2.5  (16.55)
Systolic BP Week 54 Number Analyzed 345 participants 385 participants 321 participants
0.0  (17.24) -1.1  (14.95) -2.3  (15.56)
Diastolic BP Week 4 Number Analyzed 457 participants 469 participants 457 participants
-0.4  (9.54) -0.7  (9.21) -1.2  (8.51)
Diastolic BP Week 8 Number Analyzed 436 participants 460 participants 434 participants
-0.0  (9.55) -0.9  (9.20) -2.1  (9.21)
Diastolic BP Week 12 Number Analyzed 431 participants 454 participants 415 participants
0.0  (9.63) -1.3  (9.25) -2.5  (9.49)
Diastolic BP Week 16 Number Analyzed 425 participants 442 participants 411 participants
-0.7  (9.78) -1.3  (9.16) -3.0  (9.62)
Diastolic BP Week 24 Number Analyzed 413 participants 431 participants 392 participants
-1.1  (9.87) -1.2  (9.55) -2.6  (9.48)
Diastolic BP Week 36 Number Analyzed 384 participants 406 participants 367 participants
-1.2  (10.27) -0.6  (9.94) -3.3  (10.68)
Diastolic BP Week 48 Number Analyzed 363 participants 397 participants 345 participants
-0.8  (10.85) -0.5  (10.02) -1.9  (11.07)
Diastolic BP Week 54 Number Analyzed 345 participants 385 participants 321 participants
-0.9  (10.35) -0.4  (9.62) -1.8  (10.04)
15.Secondary Outcome
Title Mean Change From Baseline in Heart Rate
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 477 481 470
Mean (Standard Deviation)
Unit of Measure: beats per min (bpm)
Week 4 Number Analyzed 457 participants 468 participants 457 participants
0.8  (8.42) 1.1  (7.95) 0.6  (8.36)
Week 8 Number Analyzed 435 participants 459 participants 434 participants
1.5  (8.98) 1.3  (9.19) 1.0  (8.91)
Week 12 Number Analyzed 430 participants 453 participants 414 participants
1.6  (9.06) 1.8  (9.04) 0.7  (9.68)
Week 16 Number Analyzed 425 participants 441 participants 411 participants
1.0  (9.23) 1.3  (9.18) 0.8  (9.52)
Week 24 Number Analyzed 413 participants 431 participants 392 participants
0.9  (9.41) 1.3  (8.70) 0.8  (10.19)
Week 36 Number Analyzed 382 participants 406 participants 367 participants
0.9  (9.30) 1.8  (9.42) 1.1  (9.58)
Week 48 Number Analyzed 361 participants 397 participants 344 participants
1.2  (9.10) 1.4  (8.92) 0.7  (9.43)
Week 54 Number Analyzed 344 participants 384 participants 321 participants
0.5  (10.10) 1.4  (9.55) 0.0  (11.05)
16.Secondary Outcome
Title Mean Change From Baseline in Weight
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 477 481 470
Mean (Standard Deviation)
Unit of Measure: kilogram (kg)
Week 4 Number Analyzed 456 participants 471 participants 458 participants
0.1  (2.04) 0.2  (1.66) 0.3  (1.88)
Week 8 Number Analyzed 436 participants 460 participants 435 participants
0.2  (2.35) 0.3  (1.95) 0.7  (2.37)
Week 12 Number Analyzed 430 participants 453 participants 414 participants
0.2  (2.50) 0.3  (2.09) 0.9  (2.33)
Week 16 Number Analyzed 425 participants 441 participants 412 participants
0.1  (2.88) 0.3  (2.44) 1.0  (2.56)
Week 24 Number Analyzed 413 participants 430 participants 391 participants
0.1  (2.88) 0.6  (2.77) 0.9  (3.26)
Week 36 Number Analyzed 384 participants 405 participants 367 participants
0.0  (3.37) 0.7  (3.00) 1.3  (3.92)
Week 48 Number Analyzed 363 participants 396 participants 346 participants
0.4  (3.54) 0.8  (3.47) 1.3  (4.13)
Week 54 Number Analyzed 346 participants 384 participants 322 participants
0.3  (3.74) 0.7  (3.69) 0.8  (4.53)
17.Secondary Outcome
Title Change From Baseline in Hemoglobin Values
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 496 494 489
Mean (Standard Deviation)
Unit of Measure: grams per litre (g/L)
Week 4 Number Analyzed 453 participants 457 participants 457 participants
-0.4  (6.45) -2.5  (6.92) -3.7  (6.19)
Week 16 Number Analyzed 423 participants 444 participants 407 participants
-0.6  (7.01) -6.2  (7.76) -11.9  (8.65)
Week 36 Number Analyzed 382 participants 398 participants 363 participants
-2.0  (7.25) -6.4  (8.04) -12.5  (9.38)
Week 48 Number Analyzed 346 participants 377 participants 334 participants
-1.9  (7.86) -6.5  (8.45) -12.2  (10.62)
18.Secondary Outcome
Title Change From Baseline in Hematocrit Values
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 496 494 489
Mean (Standard Deviation)
Unit of Measure: litre
Week 4 Number Analyzed 453 participants 457 participants 457 participants
-0.0007  (0.02133) -0.0068  (0.02189) -0.0115  (0.01994)
Week 16 Number Analyzed 423 participants 444 participants 407 participants
-0.0003  (0.02318) -0.0174  (0.02460) -0.0339  (0.02697)
Week 36 Number Analyzed 382 participants 398 participants 363 participants
-0.0037  (0.02246) -0.0167  (0.02471) -0.0352  (0.02834)
Week 48 Number Analyzed 346 participants 377 participants 334 participants
-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
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 461 473 459
Mean (Standard Deviation)
Unit of Measure: Score on a scale
Week 8 Number Analyzed 430 participants 455 participants 431 participants
-0.3  (2.71) -0.4  (3.03) -0.3  (2.76)
Week 16 Number Analyzed 416 participants 433 participants 404 participants
-0.4  (2.93) -0.7  (2.92) -0.4  (3.07)
Week 24 Number Analyzed 402 participants 418 participants 377 participants
0.1  (2.96) -0.4  (3.03) -0.1  (3.06)
Week 36 Number Analyzed 372 participants 393 participants 358 participants
0.4  (2.79) 0.3  (3.18) 0.7  (3.04)
Week 48 Number Analyzed 356 participants 383 participants 329 participants
0.6  (3.01) 0.3  (3.07) 0.4  (3.06)
Week 54 Number Analyzed 333 participants 367 participants 305 participants
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
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 145 150 127
Mean (Standard Deviation)
Unit of Measure: Percent of total hemoglobin
Week 12 Number Analyzed 82 participants 78 participants 81 participants
0.01  (0.336) 0.14  (0.634) 0.16  (0.407)
Week 24 Number Analyzed 145 participants 150 participants 124 participants
0.07  (0.401) 0.12  (0.422) 0.06  (0.551)
Week 36 Number Analyzed 140 participants 145 participants 127 participants
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
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 496 494 489
Measure Type: Number
Unit of Measure: participants
Eosinophils high Number Analyzed 471 participants 486 participants 477 participants
0 3 0
Hematocrit low Number Analyzed 471 participants 486 participants 477 participants
2 2 5
Hemoglobin high Number Analyzed 471 participants 486 participants 477 participants
2 0 0
Hemoglobin low Number Analyzed 471 participants 486 participants 477 participants
8 11 31
Lymphocytes high Number Analyzed 471 participants 486 participants 477 participants
0 1 2
Lymphocytes low Number Analyzed 471 participants 486 participants 477 participants
8 10 13
Mean CH high Number Analyzed 471 participants 486 participants 477 participants
0 0 1
Mean CH low Number Analyzed 471 participants 486 participants 477 participants
2 2 0
Mean CV high Number Analyzed 471 participants 486 participants 477 participants
0 0 1
Mean CV low Number Analyzed 471 participants 486 participants 477 participants
2 1 0
Monocytes low Number Analyzed 471 participants 486 participants 477 participants
81 55 65
Platelet count high Number Analyzed 471 participants 486 participants 475 participants
4 2 7
Platelet count low Number Analyzed 471 participants 486 participants 475 participants
1 2 4
RDW high Number Analyzed 471 participants 486 participants 475 participants
18 31 86
RBC high Number Analyzed 471 participants 486 participants 477 participants
0 1 0
RBC low Number Analyzed 471 participants 486 participants 477 participants
0 1 8
SN high Number Analyzed 471 participants 486 participants 477 participants
8 2 4
SN low Number Analyzed 471 participants 486 participants 477 participants
2 6 13
TN high Number Analyzed 471 participants 486 participants 477 participants
4 1 2
TN low Number Analyzed 471 participants 486 participants 477 participants
2 6 13
WBC high Number Analyzed 471 participants 486 participants 477 participants
4 1 3
WBC low Number Analyzed 471 participants 486 participants 477 participants
1 5 12
22.Secondary Outcome
Title Change From Baseline in Alzheimer’s Carer Quality of Life Instrument (ACQLI) Total Score
Hide 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
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Hide 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
Hide 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.
Overall Number of Participants Analyzed 461 473 459
Least Squares Mean (Standard Error)
Unit of Measure: Score on a scale
Week 12 Number Analyzed 387 participants 405 participants 377 participants
0.5  (0.23) -0.2  (0.23) -0.0  (0.22)
Week 36 Number Analyzed 341 participants 363 participants 327 participants
1.0  (0.28) 0.6  (0.27) 0.6  (0.26)
Week 48 Number Analyzed 315 participants 350 participants 309 participants
1.2  (0.30) 0.3  (0.28) 1.1  (0.31)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, 2mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.027
Comments Week 12
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.7
Confidence Interval (2-Sided) 95%
-1.2 to -0.1
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, 8mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.091
Comments Week 12
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.5
Confidence Interval (2-Sided) 95%
-1.1 to 0.1
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, 2mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.268
Comments Week 36
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.4
Confidence Interval (2-Sided) 95%
-1.1 to 0.3
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, 8mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.318
Comments Week 36
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.4
Confidence Interval (2-Sided) 95%
-1.1 to 0.4
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, 2mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.030
Comments Week 48
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.9
Confidence Interval (2-Sided) 95%
-1.6 to -0.1
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, 8mg Rosiglitazone Extended Release
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.797
Comments Week 48
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-0.9 to 0.7
Estimation Comments [Not Specified]
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
Hide 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 (%) Affected / at Risk (%) Affected / at Risk (%)
Total   12/496 (2.42%)      6/494 (1.21%)      8/489 (1.64%)    
Show Serious Adverse Events Hide 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 (12.50%)      45/494 (9.11%)      50/489 (10.22%)    
Blood and lymphatic system disorders       
Iron deficiency anaemia  1  1/496 (0.20%)  1/494 (0.20%)  0/489 (0.00%) 
Anaemia  1  0/496 (0.00%)  0/494 (0.00%)  1/489 (0.20%) 
Normochromic normocytic anaemia  1  0/496 (0.00%)  0/494 (0.00%)  1/489 (0.20%) 
Cardiac disorders       
Myocardial infarction  1  5/496 (1.01%)  1/494 (0.20%)  0/489 (0.00%) 
Cardiac arrest  1  2/496 (0.40%)  2/494 (0.40%)  1/489 (0.20%) 
Angina pectoris  1  1/496 (0.20%)  1/494 (0.20%)  0/489 (0.00%) 
Atrial fibrillation  1  0/496 (0.00%)  0/494 (0.00%)  2/489 (0.41%) 
Bradycardia  1  0/496 (0.00%)  1/494 (0.20%)  1/489 (0.20%) 
Cardiac failure congestive  1  1/496 (0.20%)  1/494 (0.20%)  0/489 (0.00%) 
Coronary artery stenosis  1  0/496 (0.00%)  1/494 (0.20%)  1/489 (0.20%) 
Myocardial ischaemia  1  0/496 (0.00%)  0/494 (0.00%)  2/489 (0.41%) 
Acute myocardial infarction  1  1/496 (0.20%)  0/494 (0.00%)  0/489 (0.00%) 
Cardiac failure  1  0/496 (0.00%)  0/494 (0.00%)  1/489 (0.20%) 
Cardio-respiratory arrest  1  1/496 (0.20%)  0/494 (0.00%)  0/489 (0.00%) 
Coronary artery disease  1  0/496 (0.00%)  1/494 (0.20%)  0/489 (0.00%) 
Sick sinus syndrome  1  0/496 (0.00%)  0/494 (0.00%)  1/489 (0.20%) 
Tachyarrhythmia  1  0/496 (0.00%)  1/494 (0.20%)  0/489 (0.00%) 
Ear and labyrinth disorders       
Vertigo  1  0/496 (0.00%)  1/494 (0.20%)  0/489 (0.00%) 
Eye disorders       
Angle closure glaucoma  1  0/496 (0.00%)  1/494 (0.20%)  0/489 (0.00%) 
Cataract  1  1/496 (0.20%)  0/494 (0.00%)  0/489 (0.00%) 
Gastrointestinal disorders       
Inguinal hernia  1  0/496 (0.00%)  2/494 (0.40%)  0/489 (0.00%) 
Colonic polyp  1  1/496 (0.20%)  0/494 (0.00%)  0/489 (0.00%) 
Diarrhoea  1  0/496 (0.00%)  0/494 (0.00%)  1/489 (0.20%) 
Diverticulum intestinal  1  0/496 (0.00%)  0/494 (0.00%)  1/489 (0.20%) 
Duodenal ulcer haemorrhage  1  0/496 (0.00%)  0/494 (0.00%)  1/489 (0.20%) 
Haemorrhoids  1  1/496 (0.20%)  0/494 (0.00%)  0/489 (0.00%) 
Large intestine perforation  1  1/496 (0.20%)  0/494 (0.00%)  0/489 (0.00%) 
Peptic ulcer perforation  1  0/496 (0.00%)  0/494 (0.00%)  1/489 (0.20%) 
Rectal haemorrhage  1  1/496 (0.20%)  0/494 (0.00%)  0/489 (0.00%) 
Rectal polyp  1  0/496 (0.00%)  0/494 (0.00%)  1/489 (0.20%) 
General disorders       
Malaise  1  1/496 (0.20%)  0/494 (0.00%)  1/489 (0.20%) 
Death  1  0/496 (0.00%)  0/