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Rosiglitazone (Extended Release Tablets) As Adjunctive Therapy In Subjects With Mild To Moderate Alzheimer's Disease (REFLECT-3)

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ClinicalTrials.gov Identifier: NCT00348140
Recruitment Status : Completed
First Posted : July 4, 2006
Results First Posted : September 5, 2017
Last Update Posted : September 5, 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
Enrollment 1468
Recruitment Details A total of 1485 participants with Alzheimer’s disease (AD) who were being treated with an approved Acetylcholinesterase inhibitor (AChEI) were randomized in the study and stratified by Apolipoprotein E gene (APOE) ε4 allele status. Total of 1468 were included in safety population and 1429 in the intent-to-treat population (ITT).
Pre-assignment Details  
Arm/Group Title Placebo RSG XR 2mg RSG XR 8mg
Hide Arm/Group Description Participants randomized to this arm received matching Rosiglitazone extended release (RSG XR) placebo tablets once daily which remained constant throughout the 48 Week treatment period. From Week 48 all the participants received single-blind placebo treatment as one tablet daily until Visit 10 (Week 54) Participants randomized to this arm received RSG XR 2 milligrams (mg) once daily which remained constant throughout the 48 Week treatment period. From Week 48 all the participants received single-blind placebo treatment as one tablet daily until Visit 10 (Week 54) Participants randomized to this arm received RSG XR 8 mg one 4mg tablet once daily for the first 4 weeks of treatment. From Visit 3 (Week 4) onwards, these participants received one 8mg tablet once daily for the remaining 44 weeks of double-blind treatment. From Week 48 all participants received single-blind placebo treatment as one tablet daily, until Visit 10 (Week 54)
Period Title: Overall Study
Started 487 490 491
Completed 361 351 328
Not Completed 126 139 163
Reason Not Completed
Adverse Event             46             49             78
Lost to Follow-up             4             4             4
Protocol Violation             12             13             14
Withdrawal by Subject             32             40             40
Non-compliance             8             13             5
Participant at risk due to study drug             2             0             0
Conditional medication increased dose             1             0             0
Caregiver related             4             7             3
Participant hospitalised             3             0             0
Efficacy related             1             1             0
Administration related             3             1             1
Unmet inclusion-exclusion criteria             1             0             1
Participant unwell             1             0             0
Screen failure             1             0             0
Investigator decided to discontinue             4             1             4
Decided to discontinue on their own             1             4             1
Use of prohibited drug             1             0             2
Disease progression             1             2             5
Increased risk of cardiac infarction             0             1             0
Serious adverse event             0             1             0
Abnormal ECG             0             1             3
Participant died             0             1             0
Exclusion criteria met             0             0             1
Memory declined             0             0             1
Arm/Group Title Placebo RSG XR 2mg RSG XR 8mg Total
Hide Arm/Group Description Participants randomized to this arm received matching RSG XR placebo tablets once daily which remained constant throughout the 48 Week treatment period. From Week 48 all the participants received single-blind placebo treatment as one tablet daily until Visit 10 (Week 54) Participants randomized to this arm received RSG XR 2 mg once daily which remained constant throughout the 48 Week treatment period. From Week 48 all the participants received single-blind placebo treatment as one tablet daily until Visit 10 (Week 54) Participants randomized to this arm received RSG XR 8 mg one 4mg tablet once daily for the first 4 weeks of treatment. From Visit 3 (Week 4) onwards, these participants received one 8mg tablet once daily for the remaining 44 weeks of double-blind treatment. From Week 48 all participants received single-blind placebo treatment as one tablet daily, until Visit 10 (Week 54) Total of all reporting groups
Overall Number of Baseline Participants 487 490 491 1468
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 487 participants 490 participants 491 participants 1468 participants
72.8  (8.19) 73.4  (8.19) 73.6  (8.40) 73.3  (8.26)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 487 participants 490 participants 491 participants 1468 participants
Female
272
  55.9%
276
  56.3%
268
  54.6%
816
  55.6%
Male
215
  44.1%
214
  43.7%
223
  45.4%
652
  44.4%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 487 participants 490 participants 491 participants 1468 participants
Hispanic or Latino
16
   3.3%
14
   2.9%
18
   3.7%
48
   3.3%
Not Hispanic or Latino
467
  95.9%
473
  96.5%
470
  95.7%
1410
  96.0%
Missing
4
   0.8%
3
   0.6%
3
   0.6%
10
   0.7%
1.Primary Outcome
Title Change From Baseline in Alzheimer's Disease Assessment Scale – Cognitive Subscale (ADAS-Cog) Total Score at Week 48, as a Function of APOE ε4 Status in APOE4 Negatives Cohort
Hide Description The 11-item ADAS-Cog assessed a range of cognitive abilities including memory, comprehension, orientation in time and place and spontaneous speech. Most items were evaluated by tests, but some were dependent on clinician ratings on a five point scale. Scores range from 0 to 70 with higher scores indicating greater dysfunction. 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. A hierarchical testing procedure was used to control for statistical tests in the two RSG dose groups and the genetic subgroups.
Time Frame Baseline (Week 0) and Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population comprised of all participants randomized to treatment, who had taken at least one dose of study medication and who had at least one post baseline efficacy assessment. Number of participants with observed data contributing to the analysis have been presented.
Arm/Group Title Placebo RSG XR 2mg RSG XR 8mg
Hide Arm/Group Description:
Participants randomized to this arm received matching RSG XR placebo tablets once daily which remained constant throughout the 48 Week treatment period. From Week 48 all the participants received single-blind placebo treatment as one tablet daily until Visit 10 (Week 54)
Participants randomized to this arm received RSG XR 2 mg once daily which remained constant throughout the 48 Week treatment period. From Week 48 all the participants received single-blind placebo treatment as one tablet daily until Visit 10 (Week 54)
Participants randomized to this arm received RSG XR 8 mg one 4mg tablet once daily for the first 4 weeks of treatment. From Visit 3 (Week 4) onwards, these participants received one 8mg tablet once daily for the remaining 44 weeks of double-blind treatment. From Week 48 all participants received single-blind placebo treatment as one tablet daily, until Visit 10 (Week 54)
Overall Number of Participants Analyzed 145 142 137
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
3.2  (0.54) 3.5  (0.53) 4.0  (0.63)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 2mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.739
Comments [Not Specified]
Method Mixed model for repeated measures
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.3
Confidence Interval (2-Sided) 95%
-1.2 to 1.8
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of participants with evaluable data
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 8mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.343
Comments [Not Specified]
Method Mixed model for repeated measures
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.8
Confidence Interval (2-Sided) 95%
-0.8 to 2.4
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of participants with evaluable data
2.Primary Outcome
Title Change From Baseline in ADAS-Cog Total Score at Week 48, as a Function of APOE ε4 Status in All Except E4/E4s Cohort
Hide Description The 11-item ADAS-Cog assessed a range of cognitive abilities including memory, comprehension, orientation in time and place and spontaneous speech. Most items were evaluated by tests, but some were dependent on clinician ratings on a five point scale. Scores range from 0 to 70 with higher scores indicating greater dysfunction. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value a t Week 0. Estimated value was calculated by Active treatment minus Placebo. The adjusted means were presented. A hierarchical testing procedure was used to control for statistical tests in the two RSG dose groups and the genetic subgroups.
Time Frame Baseline (Week 0) and Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Number of participants with observed data contributing to the analysis have been presented.
Arm/Group Title Placebo RSG XR 2mg RSG XR 8mg
Hide Arm/Group Description:
Participants randomized to this arm received matching RSG XR placebo tablets once daily which remained constant throughout the 48 Week treatment period. From Week 48 all the participants received single-blind placebo treatment as one tablet daily until Visit 10 (Week 54)
Participants randomized to this arm received RSG XR 2 mg once daily which remained constant throughout the 48 Week treatment period. From Week 48 all the participants received single-blind placebo treatment as one tablet daily until Visit 10 (Week 54)
Participants randomized to this arm received RSG XR 8 mg one 4mg tablet once daily for the first 4 weeks of treatment. From Visit 3 (Week 4) onwards, these participants received one 8mg tablet once daily for the remaining 44 weeks of double-blind treatment. From Week 48 all participants received single-blind placebo treatment as one tablet daily, until Visit 10 (Week 54)
Overall Number of Participants Analyzed 303 302 274
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
3.8  (0.38) 3.6  (0.35) 3.8  (0.41)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 2mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.783
Comments [Not Specified]
Method Mixed model for repeated measures
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-1.1 to 0.9
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of participants with evaluable data
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 8mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.940
Comments [Not Specified]
Method Mixed model for repeated measures
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-1.1 to 1.1
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of participants with evaluable data
3.Primary Outcome
Title Change From Baseline in ADAS-Cog Total Score at Week 48, as a Function of APOE ε4 Status in Full Population Cohort
Hide Description The 11-item ADAS-Cog assessed a range of cognitive abilities including memory, comprehension, orientation in time and place and spontaneous speech. Most items were evaluated by tests, but some were dependent on clinician ratings on a five point scale. Scores range from 0 to 70 with higher scores indicating greater dysfunction. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value a t Week 0. Estimated value was calculated by Active treatment minus Placebo. The adjusted means were presented. A hierarchical testing procedure was used to control for statistical tests in the two RSG dose groups and the genetic subgroups.
Time Frame Baseline (Week 0) and Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Number of participants with observed data contributing to the analysis have been presented.
Arm/Group Title Placebo RSG XR 2mg RSG XR 8mg
Hide Arm/Group Description:
Participants randomized to this arm received matching RSG XR placebo tablets once daily which remained constant throughout the 48 Week treatment period. From Week 48 all the participants received single-blind placebo treatment as one tablet daily until Visit 10 (Week 54)
Participants randomized to this arm received RSG XR 2 mg once daily which remained constant throughout the 48 Week treatment period. From Week 48 all the participants received single-blind placebo treatment as one tablet daily until Visit 10 (Week 54)
Participants randomized to this arm received RSG XR 8 mg one 4mg tablet once daily for the first 4 weeks of treatment. From Visit 3 (Week 4) onwards, these participants received one 8mg tablet once daily for the remaining 44 weeks of double-blind treatment. From Week 48 all participants received single-blind placebo treatment as one tablet daily, until Visit 10 (Week 54)
Overall Number of Participants Analyzed 361 343 331
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
3.9  (0.35) 3.8  (0.33) 3.8  (0.36)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 2mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.763
Comments [Not Specified]
Method Mixed model for repeated measures
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-1.1 to 0.8
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of participants with evaluable data
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 8mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.800
Comments [Not Specified]
Method Mixed model for repeated measures
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-1.1 to 0.9
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of participants with evaluable data
4.Primary Outcome
Title Change From Baseline in Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) Score at Week 48, as a Function of APOE ε4 Status in APOE4 Negatives Cohort
Hide Description The CDR-SB was a validated clinical assessment of global function in patients with AD. Impairment was scored in each of 6 cognitive categories on a scale in which none = 0, questionable = 0.5, mild = 1, moderate = 2, and severe = 3. The 6 individual category ratings, or “box scores”, can be added together to give the CDR-Sum of Boxes which ranges from 0 to 18 (severe impairment). Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value a t Week 0. Estimated value was calculated by Active treatment minus Placebo. The adjusted means were presented. Primary inference will be based on the week 48 treatment differences obtained from the MMRM model. A hierarchical testing procedure was used to control for statistical tests in the two RSG dose groups and the genetic subgroups.
Time Frame Baseline (Week 0) and Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Number of participants with observed data contributing to the analysis have been presented.
Arm/Group Title Placebo RSG XR 2mg RSG XR 8mg
Hide Arm/Group Description:
Participants randomized to this arm received matching RSG XR placebo tablets once daily which remained constant throughout the 48 Week treatment period. From Week 48 all the participants received single-blind placebo treatment as one tablet daily until Visit 10 (Week 54)
Participants randomized to this arm received RSG XR 2 mg once daily which remained constant throughout the 48 Week treatment period. From Week 48 all the participants received single-blind placebo treatment as one tablet daily until Visit 10 (Week 54)
Participants randomized to this arm received RSG XR 8 mg one 4mg tablet once daily for the first 4 weeks of treatment. From Visit 3 (Week 4) onwards, these participants received one 8mg tablet once daily for the remaining 44 weeks of double-blind treatment. From Week 48 all participants received single-blind placebo treatment as one tablet daily, until Visit 10 (Week 54)
Overall Number of Participants Analyzed 146 144 138
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
1.8  (0.20) 1.7  (0.20) 1.7  (0.17)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 2mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.611
Comments [Not Specified]
Method Mixed model for repeated measures
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-0.7 to 0.4
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of participants with evaluable data
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 8mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.741
Comments [Not Specified]
Method Mixed model for repeated measures
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-0.6 to 0.4
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of participants with evaluable data
5.Primary Outcome
Title Change From Baseline in CDR-SB Score at Week 48, as a Function of APOE ε4 Status in All Except E4/E4s Cohort
Hide Description The CDR-SB was a validated clinical assessment of global function in patients with AD. Impairment was scored in each of 6 cognitive categories on a scale in which none = 0, questionable = 0.5, mild = 1, moderate = 2, and severe = 3. The 6 individual category ratings, or “box scores”, can be added together to give the CDR-Sum of Boxes which ranges from 0 to 18 (severe impairment). Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value a t Week 0. Estimated value was calculated by Active treatment minus Placebo. The adjusted means were presented. Primary inference will be based on the week 48 treatment differences obtained from the MMRM model. A hierarchical testing procedure was used to control for statistical tests in the two RSG dose groups and the genetic subgroups.
Time Frame Baseline (Week 0) and Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Number of participants with observed data contributing to the analysis have been presented.
Arm/Group Title Placebo RSG XR 2mg RSG XR 8mg
Hide Arm/Group Description:
Participants randomized to this arm received matching RSG XR placebo tablets once daily which remained constant throughout the 48 Week treatment period. From Week 48 all the participants received single-blind placebo treatment as one tablet daily until Visit 10 (Week 54)
Participants randomized to this arm received RSG XR 2 mg once daily which remained constant throughout the 48 Week treatment period. From Week 48 all the participants received single-blind placebo treatment as one tablet daily until Visit 10 (Week 54)
Participants randomized to this arm received RSG XR 8 mg one 4mg tablet once daily for the first 4 weeks of treatment. From Visit 3 (Week 4) onwards, these participants received one 8mg tablet once daily for the remaining 44 weeks of double-blind treatment. From Week 48 all participants received single-blind placebo treatment as one tablet daily, until Visit 10 (Week 54)
Overall Number of Participants Analyzed 302 311 272
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
1.8  (0.13) 1.8  (0.13) 1.7  (0.13)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 2mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.913
Comments [Not Specified]
Method Mixed model for repeated measures
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-0.4 to 0.3
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of participants with evaluable data
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 8mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.481
Comments [Not Specified]
Method Mixed model for repeated measures
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-0.5 to 0.2
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of participants with evaluable data
6.Primary Outcome
Title Change From Baseline in CDR-SB Score at Week 48, as a Function of APOE ε4 Status in Full Population Cohort
Hide Description The CDR-SB was a validated clinical assessment of global function in patients with AD. Impairment was scored in each of 6 cognitive categories on a scale in which none = 0, questionable = 0.5, mild = 1, moderate = 2, and severe = 3. The 6 individual category ratings, or “box scores”, can be added together to give the CDR-Sum of Boxes which ranges from 0 to 18 (severe impairment). Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value a t Week 0. Estimated value was calculated by Active treatment minus Placebo. The adjusted means were presented. Primary inference will be based on the week 48 treatment differences obtained from the MMRM model. A hierarchical testing procedure was used to control for statistical tests in the two RSG dose groups and the genetic subgroups.
Time Frame Baseline (Week 0) and Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Number of participants with observed data contributing to the analysis have been presented.
Arm/Group Title Placebo RSG XR 2mg RSG XR 8mg
Hide Arm/Group Description:
Participants randomized to this arm received matching RSG XR placebo tablets once daily which remained constant throughout the 48 Week treatment period. From Week 48 all the participants received single-blind placebo treatment as one tablet daily until Visit 10 (Week 54)
Participants randomized to this arm received RSG XR 2 mg once daily which remained constant throughout the 48 Week treatment period. From Week 48 all the participants received single-blind placebo treatment as one tablet daily until Visit 10 (Week 54)
Participants randomized to this arm received RSG XR 8 mg one 4mg tablet once daily for the first 4 weeks of treatment. From Visit 3 (Week 4) onwards, these participants received one 8mg tablet once daily for the remaining 44 weeks of double-blind treatment. From Week 48 all participants received single-blind placebo treatment as one tablet daily, until Visit 10 (Week 54)
Overall Number of Participants Analyzed 360 349 331
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
1.9  (0.12) 1.8  (0.13) 1.8  (0.12)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 2mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.557
Comments [Not Specified]
Method Mixed model for repeated measures
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-0.4 to 0.2
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of participants with evaluable data
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 8mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.404
Comments [Not Specified]
Method Mixed model for repeated measures
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-0.5 to 0.2
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of participants with evaluable data
7.Secondary Outcome
Title Change From Baseline in ADAS-Cog Total Score at Weeks 8, 16, 24 and 36
Hide Description The 11-item ADAS-Cog assessed a range of cognitive abilities including memory, comprehension, orientation in time and place and spontaneous speech. Most items were evaluated by tests, but some were dependent on clinician ratings on a five point scale. Scores range from 0 to 70 with higher scores indicating greater dysfunction. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value a t Week 0. It was calculated at Weeks 8, 16, 24 and 36. Full population data was presented.
Time Frame Baseline (Week 0) and Week 8, 16, 24, 36
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Number of participants with observed data contributing to the analysis.
Arm/Group Title Placebo RSG XR 2mg RSG XR 8mg
Hide Arm/Group Description:
Participants randomized to this arm received matching RSG XR placebo tablets once daily which remained constant throughout the 48 Week treatment period. From Week 48 all the participants received single-blind placebo treatment as one tablet daily until Visit 10 (Week 54)
Participants randomized to this arm received RSG XR 2 mg once daily which remained constant throughout the 48 Week treatment period. From Week 48 all the participants received single-blind placebo treatment as one tablet daily until Visit 10 (Week 54)
Participants randomized to this arm received RSG XR 8 mg one 4mg tablet once daily for the first 4 weeks of treatment. From Visit 3 (Week 4) onwards, these participants received one 8mg tablet once daily for the remaining 44 weeks of double-blind treatment. From Week 48 all participants received single-blind placebo treatment as one tablet daily, until Visit 10 (Week 54)
Overall Number of Participants Analyzed 479 480 470
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
Week 8 Number Analyzed 460 participants 451 participants 440 participants
0.1  (0.23) 0.2  (0.23) 0.3  (0.23)
Week 16 Number Analyzed 440 participants 430 participants 411 participants
0.2  (0.24) 0.3  (0.23) 0.2  (0.24)
Week 24 Number Analyzed 422 participants 408 participants 379 participants
1.1  (0.26) 1.5  (0.28) 1.1  (0.27)
Week 36 Number Analyzed 383 participants 381 participants 352 participants
2.6  (0.31) 2.8  (0.29) 2.6  (0.31)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 2mg
Comments For Week 8
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.633
Comments [Not Specified]
Method Mixed model for repeated measures
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.1
Confidence Interval (2-Sided) 95%
-0.5 to 0.8
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of participants with evaluable data
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 8mg
Comments For Week 8
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.575
Comments [Not Specified]
Method Mixed model for repeated measures
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.2
Confidence Interval (2-Sided) 95%
-0.4 to 0.8
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of participants with evaluable data
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 2mg
Comments For Week 16
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.820
Comments [Not Specified]
Method Mixed model for repeated measures
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.1
Confidence Interval (2-Sided) 95%
-0.6 to 0.7
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of participants with evaluable data
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 8mg
Comments For Week 16
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.908
Comments [Not Specified]
Method Mixed model for repeated measures
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-0.7 to 0.6
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of participants with evaluable data
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 2mg
Comments For Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.292
Comments [Not Specified]
Method Mixed model for repeated measures
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.4
Confidence Interval (2-Sided) 95%
-0.3 to 1.1
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of participants with evaluable data
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 8mg
Comments For Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.978
Comments [Not Specified]
Method Mixed model for repeated measures
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-0.7 to 0.7
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of participants with evaluable data
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 2mg
Comments For Week 36
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.691
Comments [Not Specified]
Method Mixed model for repeated measures
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.2
Confidence Interval (2-Sided) 95%
-0.6 to 1.0
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of participants with evaluable data
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 8mg
Comments For Week 36
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.849
Comments [Not Specified]
Method Mixed model for repeated measures
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-0.9 to 0.8
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of participants with evaluable data
8.Secondary Outcome
Title Change From Baseline in CDR-SB Score at Weeks 12, 24 and 36
Hide Description The CDR-SB was a validated clinical assessment of global function in patients with AD. Impairment was scored in each of 6 cognitive categories on a scale in which none = 0, questionable = 0.5, mild = 1, moderate = 2, and severe = 3. The 6 individual category ratings, or “box scores”, can be added together to give the CDR-Sum of Boxes which ranges from 0 to 18 (severe impairment). Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value a t Week 0. Estimated value was calculated by Active treatment minus Placebo. The adjusted means were presented. It was calculated at Weeks 12, 24 and 36. Full population data was presented.
Time Frame Baseline (Week 0) and Week 12, 24, 36
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Number of participants with observed data contributing to the analysis.
Arm/Group Title Placebo RSG XR 2mg RSG XR 8mg
Hide Arm/Group Description:
Participants randomized to this arm received matching RSG XR placebo tablets once daily which remained constant throughout the 48 Week treatment period. From Week 48 all the participants received single-blind placebo treatment as one tablet daily until Visit 10 (Week 54)
Participants randomized to this arm received RSG XR 2 mg once daily which remained constant throughout the 48 Week treatment period. From Week 48 all the participants received single-blind placebo treatment as one tablet daily until Visit 10 (Week 54)
Participants randomized to this arm received RSG XR 8 mg one 4mg tablet once daily for the first 4 weeks of treatment. From Visit 3 (Week 4) onwards, these participants received one 8mg tablet once daily for the remaining 44 weeks of double-blind treatment. From Week 48 all participants received single-blind placebo treatment as one tablet daily, until Visit 10 (Week 54)
Overall Number of Participants Analyzed 479 480 470
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
Week 12 Number Analyzed 437 participants 432 participants 422 participants
0.3  (0.07) 0.4  (0.08) 0.3  (0.07)
Week 24 Number Analyzed 413 participants 400 participants 376 participants
0.9  (0.10) 0.8  (0.10) 0.9  (0.09)
Week 36 Number Analyzed 382 participants 374 participants 350 participants
1.4  (0.11) 1.3  (0.11) 1.3  (0.10)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 2mg
Comments For Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.938
Comments [Not Specified]
Method Mixed model for repeated measures
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-0.2 to 0.2
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of participants with evaluable data
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 8mg
Comments For Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.887
Comments [Not Specified]
Method Mixed model for repeated measures
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-0.2 to 0.2
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of participants with evaluable data
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 2mg
Comments For Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.465
Comments [Not Specified]
Method Mixed model for repeated measures
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-0.4 to 0.2
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of participants with evaluable data
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 8mg
Comments For Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.596
Comments [Not Specified]
Method Mixed model for repeated measures
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.1
Confidence Interval (2-Sided) 95%
-0.2 to 0.3
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of participants with evaluable data
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 2mg
Comments For Week 36
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.452
Comments [Not Specified]
Method Mixed model for repeated measures
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-0.4 to 0.2
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of participants with evaluable data
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 8mg
Comments For Week 36
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.429
Comments [Not Specified]
Method Mixed model for repeated measures
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-0.4 to 0.2
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of participants with evaluable data
9.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. Scores range from 0 to 30, with lower scores indicating greater cognitive impairment. The scale is completed by the investigator, based on the performance of the participant. Change from screening was calculated as value at scheduled time point minus screening value. Baseline was defined as value a t Week 0. Estimated value was calculated by Active treatment minus Placebo. The adjusted means were presented. Full population data was presented.
Time Frame Screening (Week -4) and Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Only those participants available at that particular time point were analyzed.
Arm/Group Title Placebo RSG XR 2mg RSG XR 8mg
Hide Arm/Group Description:
Participants randomized to this arm received matching RSG XR placebo tablets once daily which remained constant throughout the 48 Week treatment period. From Week 48 all the participants received single-blind placebo treatment as one tablet daily until Visit 10 (Week 54)
Participants randomized to this arm received RSG XR 2 mg once daily which remained constant throughout the 48 Week treatment period. From Week 48 all the participants received single-blind placebo treatment as one tablet daily until Visit 10 (Week 54)
Participants randomized to this arm received RSG XR 8 mg one 4mg tablet once daily for the first 4 weeks of treatment. From Visit 3 (Week 4) onwards, these participants received one 8mg tablet once daily for the remaining 44 weeks of double-blind treatment. From Week 48 all participants received single-blind placebo treatment as one tablet daily, until Visit 10 (Week 54)
Overall Number of Participants Analyzed 366 356 336
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
-2.0  (0.21) -2.3  (0.22) -2.0  (0.22)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 2mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.386
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.3
Confidence Interval (2-Sided) 95%
-0.8 to 0.3
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 8mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.999
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-0.6 to 0.6
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Change From Baseline in Disability Assessment for Dementia (DAD) Total Score
Hide Description The DAD assessed the ability of a participant to execute basic and instrumental activities of daily living (ADL) and leisure activities. The scale consists of 40 questions assessing basic and instrumental ADLs. This scale assessed 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. Each item was scored as yes: 1, no: 0 and N/A: not applicable. Higher scores indicate less disability with a score of 100 indicating no disability and 0 indicating no functional ability. The percentage score was calculated as (DAD Total score /Total number of applicable items) multiplied by 100. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at Week 0. Full population data was presented.
Time Frame Baseline (Week 0) and Week 8, 16, 24, 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Number of participants with observed data contributing to the analysis.
Arm/Group Title Placebo RSG XR 2mg RSG XR 8mg
Hide Arm/Group Description:
Participants randomized to this arm received matching RSG XR placebo tablets once daily which remained constant throughout the 48 Week treatment period. From Week 48 all the participants received single-blind placebo treatment as one tablet daily until Visit 10 (Week 54)
Participants randomized to this arm received RSG XR 2 mg once daily which remained constant throughout the 48 Week treatment period. From Week 48 all the participants received single-blind placebo treatment as one tablet daily until Visit 10 (Week 54)
Participants randomized to this arm received RSG XR 8 mg one 4mg tablet once daily for the first 4 weeks of treatment. From Visit 3 (Week 4) onwards, these participants received one 8mg tablet once daily for the remaining 44 weeks of double-blind treatment. From Week 48 all participants received single-blind placebo treatment as one tablet daily, until Visit 10 (Week 54)
Overall Number of Participants Analyzed 479 480 470
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
Week 8 Number Analyzed 464 participants 455 participants 442 participants
-2.3  (0.50) -1.2  (0.50) -2.3  (0.46)
Week 16 Number Analyzed 443 participants 433 participants 417 participants
-3.0  (0.57) -2.3  (0.55) -3.9  (0.59)
Week 24 Number Analyzed 427 participants 412 participants 387 participants
-4.6  (0.60) -2.8  (0.62) -4.7  (0.63)
Week 48 Number Analyzed 373 participants 359 participants 342 participants
-9.5  (0.81) -9.4  (0.81) -10.4  (0.82)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 2mg
Comments For Week 8
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.090
Comments [Not Specified]
Method Mixed model for repeated measures
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.1
Confidence Interval (2-Sided) 95%
-0.2 to 2.5
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of participants with evaluable data
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 8mg
Comments For Week 8
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.957
Comments [Not Specified]
Method Mixed model for repeated measures
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-1.3 to 1.3
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of participants with evaluable data
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 2mg
Comments For Week 16
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.395
Comments [Not Specified]
Method Mixed model for repeated measures
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.7
Confidence Interval (2-Sided) 95%
-0.9 to 2.2
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of participants with evaluable data
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 8mg
Comments For Week 16
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.275
Comments [Not Specified]
Method Mixed model for repeated measures
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.9
Confidence Interval (2-Sided) 95%
-2.5 to 0.7
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of participants with evaluable data
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 2mg
Comments For Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.039
Comments [Not Specified]
Method Mixed model for repeated measures
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.7
Confidence Interval (2-Sided) 95%
0.1 to 3.4
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of participants with evaluable data
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 8mg
Comments For Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.895
Comments [Not Specified]
Method Mixed model for repeated measures
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-1.8 to 1.6
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of participants with evaluable data
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 2mg
Comments For Week 48
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.914
Comments [Not Specified]
Method Mixed model for repeated measures
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.1
Confidence Interval (2-Sided) 95%
-2.1 to 2.3
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of participants with evaluable data
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 8mg
Comments For Week 48
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.430
Comments [Not Specified]
Method Mixed model for repeated measures
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.9
Confidence Interval (2-Sided) 95%
-3.2 to 1.3
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of participants with evaluable data
11.Secondary Outcome
Title Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score
Hide Description NPI is an assessment of frequency and severity of behavioral disturbances in dementia that comprised of 10 dimensions: delusions, hallucinations, dysphoria, apathy, euphoria, disinhibition, aggressiveness and agitation, irritability, anxiety, aberrant motor activity. Participant’s caregiver asked about behavior in participant. If “Yes”, informant then rated both severity on a 3-point scale, 1-mild to 3-severe (total range: 0-36) and frequency using a 4-point scale, 1-occasionally to 4-very frequently. Total score was frequency × severity. Distress was scored on 5-point scale, 0-no distress to 5-very severe or extreme. Total NPI score was calculated by adding all domain scores; NPI total score: 0-144 and NPI distress score: 0-60, higher scores indicated more severe behavioral disturbance. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at Week 0. Adjusted means were presented. Full population data was presented.
Time Frame Baseline (Week 0) and Week 8, 16, 24, 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Number of participants with observed data contributing to the analysis.
Arm/Group Title Placebo RSG XR 2mg RSG XR 8mg
Hide Arm/Group Description:
Participants randomized to this arm received matching RSG XR placebo tablets once daily which remained constant throughout the 48 Week treatment period. From Week 48 all the participants received single-blind placebo treatment as one tablet daily until Visit 10 (Week 54)
Participants randomized to this arm received RSG XR 2 mg once daily which remained constant throughout the 48 Week treatment period. From Week 48 all the participants received single-blind placebo treatment as one tablet daily until Visit 10 (Week 54)
Participants randomized to this arm received RSG XR 8 mg one 4mg tablet once daily for the first 4 weeks of treatment. From Visit 3 (Week 4) onwards, these participants received one 8mg tablet once daily for the remaining 44 weeks of double-blind treatment. From Week 48 all participants received single-blind placebo treatment as one tablet daily, until Visit 10 (Week 54)
Overall Number of Participants Analyzed 479 480 470
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
Week 8 Number Analyzed 464 participants 457 participants 443 participants
-0.0  (0.32) -0.3  (0.33) -0.2  (0.31)
Week 16 Number Analyzed 443 participants 433 participants 417 participants
0.1  (0.34) 0.2  (0.37) 0.1  (0.37)
Week 24 Number Analyzed 428 participants 413 participants 384 participants
1.3  (0.43) 0.3  (0.41) 0.2  (0.39)
Week 48 Number Analyzed 374 participants 360 participants 342 participants
2.6  (0.52) 1.5  (0.49) 1.9  (0.50)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 2mg
Comments For Week 8
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.583
Comments [Not Specified]
Method Mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.2
Confidence Interval (2-Sided) 95%
-1.1 to 0.6
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 8mg
Comments For Week 8
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.631
Comments [Not Specified]
Method Mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.2
Confidence Interval (2-Sided) 95%
-1.1 to 0.6
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 2mg
Comments For Week 16
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.812
Comments [Not Specified]
Method Mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.1
Confidence Interval (2-Sided) 95%
-0.8 to 1.1
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 8mg
Comments For Week 16
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.952
Comments [Not Specified]
Method Mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-0.9 to 1.0
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 2mg
Comments For Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.117
Comments [Not Specified]
Method Mixed model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.9
Confidence Interval (2-Sided) 95%
-2.1 to 0.2
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 8mg
Comments For Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.074
Comments [Not Specified]
Method Mixed model for repeated measures
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.0
Confidence Interval (2-Sided) 95%
-2.1 to 0.1
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of participants with evaluable data
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 2mg
Comments For Week 48
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.141
Comments [Not Specified]
Method Mixed model for repeated measures
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.0
Confidence Interval (2-Sided) 95%
-2.4 to 0.3
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of participants with evaluable data
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 8mg
Comments For Week 48
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.331
Comments [Not Specified]
Method Mixed model for repeated measures
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.7
Confidence Interval (2-Sided) 95%
-2.1 to 0.7
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of participants with evaluable data
12.Secondary Outcome
Title Change From Baseline in Domains of the Resource Utilization in Dementia Scale (RUD)- Q1 and Q2 Caregiver Hours
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. Full population data was presented.
Time Frame Baseline (Week 0) and Week 12, 24, 36, 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Number of participants with observed data contributing to the analysis.
Arm/Group Title Placebo RSG XR 2mg RSG XR 8mg
Hide Arm/Group Description:
Participants randomized to this arm received matching RSG XR placebo tablets once daily which remained constant throughout the 48 Week treatment period. From Week 48 all the participants received single-blind placebo treatment as one tablet daily until Visit 10 (Week 54)
Participants randomized to this arm received RSG XR 2 mg once daily which remained constant throughout the 48 Week treatment period. From Week 48 all the participants received single-blind placebo treatment as one tablet daily until Visit 10 (Week 54)
Participants randomized to this arm received RSG XR 8 mg one 4mg tablet once daily for the first 4 weeks of treatment. From Visit 3 (Week 4) onwards, these participants received one 8mg tablet once daily for the remaining 44 weeks of double-blind treatment. From Week 48 all participants received single-blind placebo treatment as one tablet daily, until Visit 10 (Week 54)
Overall Number of Participants Analyzed 479 480 470
Least Squares Mean (Standard Error)
Unit of Measure: Caregiver hours
Q1 Week 12 Number Analyzed 449 participants 441 participants 425 participants
-2.4  (2.72) 1.8  (2.56) 3.5  (2.68)
Q1 Week 24 Number Analyzed 427 participants 411 participants 385 participants
7.4  (3.43) 9.0  (2.92) 10.9  (3.69)
Q1 Week 36 Number Analyzed 393 participants 383 participants 359 participants
11.2  (4.36) 12.7  (3.70) 13.4  (4.09)
Q1 Week 48 Number Analyzed 371 participants 357 participants 341 participants
15.7  (4.14) 19.7  (4.06) 19.2  (4.54)
Q2 Week 12 Number Analyzed 448 participants 440 participants 425 participants
-1.1  (4.06) 5.8  (3.70) 6.4  (4.04)
Q2 Week 24 Number Analyzed 427 participants 410 participants 385 participants
5.6  (4.41) 15.6  (4.90) 12.3  (4.79)
Q2 Week 36 Number Analyzed 393 participants 382 participants 359 participants
16.4  (5.52) 23.4  (6.10) 15.2  (4.53)
Q2 Week 48 Number Analyzed 371 participants 356 participants 341 participants
21.8  (5.62) 26.0  (5.69) 21.6  (4.92)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 2mg
Comments Q1 Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.251
Comments [Not Specified]
Method Mixed model for repeated measures
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 4.1
Confidence Interval (2-Sided) 95%
-2.9 to 11.2
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of participants with evaluable data
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 8mg
Comments Q1 Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.113
Comments [Not Specified]
Method Mixed model for repeated measures
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 5.9
Confidence Interval (2-Sided) 95%
-1.4 to 13.2
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of participants with evaluable data
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 2mg
Comments Q1 Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.723
Comments [Not Specified]
Method Mixed model for repeated measures
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.6
Confidence Interval (2-Sided) 95%
-7.1 to 10.2
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of participants with evaluable data
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 8mg
Comments Q1 Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.482
Comments [Not Specified]
Method Mixed model for repeated measures
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 3.5
Confidence Interval (2-Sided) 95%
-6.3 to 13.2
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of participants with evaluable data
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 2mg
Comments Q1 Week 36
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.785
Comments [Not Specified]
Method Mixed model for repeated measures
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.5
Confidence Interval (2-Sided) 95%
-9.5 to 12.6
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of participants with evaluable data
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 8mg
Comments Q1 Week 36
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.711
Comments [Not Specified]
Method Mixed model for repeated measures
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 2.2
Confidence Interval (2-Sided) 95%
-9.4 to 13.8
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of participants with evaluable data
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 2mg
Comments Q1 Week 48
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.484
Comments [Not Specified]
Method Mixed model for repeated measures
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 4.0
Confidence Interval (2-Sided) 95%
-7.2 to 15.2
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of participants with evaluable data
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 8mg
Comments Q1 Week 48
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.572
Comments [Not Specified]
Method Mixed model for repeated measures
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 3.4
Confidence Interval (2-Sided) 95%
-8.5 to 15.4
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of participants with evaluable data
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 2mg
Comments Q2 Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.197
Comments [Not Specified]
Method Mixed model for repeated measures
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 6.8
Confidence Interval (2-Sided) 95%
-3.6 to 17.3
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of participants with evaluable data
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 8mg
Comments Q2 Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.183
Comments [Not Specified]
Method Mixed model for repeated measures
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 7.4
Confidence Interval (2-Sided) 95%
-3.5 to 18.4
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of participants with evaluable data
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 2mg
Comments Q2 Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.121
Comments [Not Specified]
Method Mixed model for repeated measures
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 10.0
Confidence Interval (2-Sided) 95%
-2.6 to 22.6
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of participants with evaluable data
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 8mg
Comments Q2 Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.291
Comments [Not Specified]
Method Mixed model for repeated measures
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 6.8
Confidence Interval (2-Sided) 95%
-5.8 to 19.3
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of participants with evaluable data
Show Statistical Analysis 13 Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 2mg
Comments Q2 Week 36
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.389
Comments [Not Specified]
Method Mixed model for repeated measures
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 7.0
Confidence Interval (2-Sided) 95%
-8.9 to 22.9
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of participants with evaluable data
Show Statistical Analysis 14 Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 8mg
Comments Q2 Week 36
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.865
Comments [Not Specified]
Method Mixed model for repeated measures
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.2
Confidence Interval (2-Sided) 95%
-15.0 to 12.6
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of participants with evaluable data
Show Statistical Analysis 15 Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 2mg
Comments Q2 Week 48
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.596
Comments [Not Specified]
Method Mixed model for repeated measures
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 4.2
Confidence Interval (2-Sided) 95%
-11.3 to 19.6
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of participants with evaluable data
Show Statistical Analysis 16 Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 8mg
Comments Q2 Week 48
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.975
Comments [Not Specified]
Method Mixed model for repeated measures
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.2
Confidence Interval (2-Sided) 95%
-14.7 to 14.2
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of participants with evaluable data
13.Secondary Outcome
Title Change From Baseline in European Quality of Life -5 Dimensions (EQ-5D) Scale Total Score- Thermometer Score
Hide Description The EQ-5D Proxy is an assessment of quality of life and utility benefit. The EQ-5D Proxy is composed of two parts: part two is the visual analogue scale ‘Thermometer’. Caregivers are asked to respond as they feel the participant would on dimensions of mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The 'Thermometer' has endpoints of 100 (best imaginable health state) and 0 (worst imaginable health state). Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value a t Week 0. Estimated value was calculated by Active treatment minus Placebo. The adjusted means were presented. Full population data was presented.
Time Frame Baseline (Week 0) and Week 12, 36, 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Number of participants with observed data contributing to the analysis.
Arm/Group Title Placebo RSG XR 2mg RSG XR 8mg
Hide Arm/Group Description:
Participants randomized to this arm received matching RSG XR placebo tablets once daily which remained constant throughout the 48 Week treatment period. From Week 48 all the participants received single-blind placebo treatment as one tablet daily until Visit 10 (Week 54)
Participants randomized to this arm received RSG XR 2 mg once daily which remained constant throughout the 48 Week treatment period. From Week 48 all the participants received single-blind placebo treatment as one tablet daily until Visit 10 (Week 54)
Participants randomized to this arm received RSG XR 8 mg one 4mg tablet once daily for the first 4 weeks of treatment. From Visit 3 (Week 4) onwards, these participants received one 8mg tablet once daily for the remaining 44 weeks of double-blind treatment. From Week 48 all participants received single-blind placebo treatment as one tablet daily, until Visit 10 (Week 54)
Overall Number of Participants Analyzed 479 480 470
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
Thermometer score Week 12 Number Analyzed 442 participants 439 participants 424 participants
2.4  (0.82) -0.0  (0.89) 0.1  (0.87)
Thermometer score Week 36 Number Analyzed 396 participants 383 participants 361 participants
1.7  (0.87) 1.3  (0.94) -0.4  (0.95)
Thermometer score Week 48 Number Analyzed 366 participants 354 participants 342 participants
2.1  (0.91) -0.5  (1.00) -1.4  (0.96)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 2mg
Comments Thermometer score Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.043
Comments [Not Specified]
Method Mixed model for repeated measures
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -2.4
Confidence Interval (2-Sided) 95%
-4.7 to -0.1
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of participants with evaluable data
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 8mg
Comments Thermometer score Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.056
Comments [Not Specified]
Method Mixed model for repeated measures
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -2.2
Confidence Interval (2-Sided) 95%
-4.5 to 0.1
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of participants with evaluable data
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 2mg
Comments Thermometer score Week 36
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.758
Comments [Not Specified]
Method Mixed model for repeated measures
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.4
Confidence Interval (2-Sided) 95%
-2.8 to 2.1
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of participants with evaluable data
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 8mg
Comments Thermometer score Week 36
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.109
Comments [Not Specified]
Method Mixed model for repeated measures
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -2.0
Confidence Interval (2-Sided) 95%
-4.5 to 0.5
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of participants with evaluable data
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 2mg
Comments Thermometer score Week 48
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.050
Comments [Not Specified]
Method Mixed model for repeated measures
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -2.6
Confidence Interval (2-Sided) 95%
-5.2 to -0.0
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of participants with evaluable data
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 8mg
Comments Thermometer score Week 48
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.009
Comments [Not Specified]
Method Mixed model for repeated measures
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -3.4
Confidence Interval (2-Sided) 95%
-6.0 to -0.9
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of participants with evaluable data
14.Secondary Outcome
Title Change From Baseline in EQ-5D Scale Total Score- Utility Score
Hide Description The EQ-5D Proxy is an assessment of quality of life and utility benefit. The EQ-5D Proxy is composed of two parts: part one is the five dimensional Health State Classification. The Utility score is a caregiver rating of health status on dimensions of mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Answers to each question were responded to on a 3-point scale which indicates the level of impairment (level 1= no problem; level 2=some or moderate problem(s) and level 3=unable, or extreme problem with higher scores indicating greater dysfunction. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value a t Week 0. Estimated value was calculated by Active treatment minus Placebo. The adjusted means were presented. Full population data was presented.
Time Frame Baseline (Week 0) and Week 12, 36, 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Number of participants with observed data contributing to the analysis.
Arm/Group Title Placebo RSG XR 2mg RSG XR 8mg
Hide Arm/Group Description:
Participants randomized to this arm received matching RSG XR placebo tablets once daily which remained constant throughout the 48 Week treatment period. From Week 48 all the participants received single-blind placebo treatment as one tablet daily until Visit 10 (Week 54)
Participants randomized to this arm received RSG XR 2 mg once daily which remained constant throughout the 48 Week treatment period. From Week 48 all the participants received single-blind placebo treatment as one tablet daily until Visit 10 (Week 54)
Participants randomized to this arm received RSG XR 8 mg one 4mg tablet once daily for the first 4 weeks of treatment. From Visit 3 (Week 4) onwards, these participants received one 8mg tablet once daily for the remaining 44 weeks of double-blind treatment. From Week 48 all participants received single-blind placebo treatment as one tablet daily, until Visit 10 (Week 54)
Overall Number of Participants Analyzed 479 480 470
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
Ultility score Week 12 Number Analyzed 442 participants 441 participants 423 participants
-0.02  (0.009) -0.01  (0.009) -0.03  (0.009)
Utility score Week 36 Number Analyzed 397 participants 385 participants 362 participants
-0.03  (0.011) -0.03  (0.011) -0.06  (0.010)
Utility score Week 48 Number Analyzed 368 participants 355 participants 342 participants
-0.03  (0.011) -0.05  (0.012) -0.04  (0.010)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 2mg
Comments Ultility score Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.662
Comments [Not Specified]
Method Mixed model for repeated measures
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.01
Confidence Interval (2-Sided) 95%
-0.02 to 0.03
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of participants with evaluable data
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 8mg
Comments Ultility score Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.503
Comments [Not Specified]
Method Mixed model for repeated measures
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.01
Confidence Interval (2-Sided) 95%
-0.03 to 0.02
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of participants with evaluable data
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 2mg
Comments Utility score Week 36
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.892
Comments [Not Specified]
Method Mixed model for repeated measures
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.00
Confidence Interval (2-Sided) 95%
-0.03 to 0.03
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of participants with evaluable data
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 8mg
Comments Utility score Week 36
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.083
Comments [Not Specified]
Method Mixed model for repeated measures
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.03
Confidence Interval (2-Sided) 95%
-0.05 to 0.00
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of participants with evaluable data
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 2mg
Comments Utility score Week 48
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.366
Comments [Not Specified]
Method Mixed model for repeated measures
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.01
Confidence Interval (2-Sided) 95%
-0.05 to 0.02
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of participants with evaluable data
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 8mg
Comments Utility score Week 48
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.769
Comments [Not Specified]
Method Mixed model for repeated measures
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.00
Confidence Interval (2-Sided) 95%
-0.03 to 0.02
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of participants with evaluable data
15.Secondary Outcome
Title Change From Baseline in Alzheimer’s Carer’s Quality of Life Instrument (ACQLI) Score
Hide Description The ACQLI is an assessment of caregiver quality of life. This instrument consisted of 30 questions exploring various aspects of carer’s quality of life. Each of the questions had two point response, and the 30 questions were summed to provide a total score. Items were assumed to be unidimensional (i.e., represent a single variable) and were scored 0/1 (false/true) before summation into a total score with a 0–30 range. To ease comparisons between scales, ACQLI scores were transformed to range between 0–100 (100: worse). Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value a t Week 0. Estimated value was calculated by Active treatment minus Placebo. The adjusted means were presented. Full population data was presented.
Time Frame Baseline (Week 0) and Week 12, 36, 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Number of participants with observed data contributing to the analysis.
Arm/Group Title Placebo RSG XR 2mg RSG XR 8mg
Hide Arm/Group Description:
Participants randomized to this arm received matching RSG XR placebo tablets once daily which remained constant throughout the 48 Week treatment period. From Week 48 all the participants received single-blind placebo treatment as one tablet daily until Visit 10 (Week 54)
Participants randomized to this arm received RSG XR 2 mg once daily which remained constant throughout the 48 Week treatment period. From Week 48 all the participants received single-blind placebo treatment as one tablet daily until Visit 10 (Week 54)
Participants randomized to this arm received RSG XR 8 mg one 4mg tablet once daily for the first 4 weeks of treatment. From Visit 3 (Week 4) onwards, these participants received one 8mg tablet once daily for the remaining 44 weeks of double-blind treatment. From Week 48 all participants received single-blind placebo treatment as one tablet daily, until Visit 10 (Week 54)
Overall Number of Participants Analyzed 479 480 470
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
Week 12 Number Analyzed 447 participants 443 participants 419 participants
0.3  (0.19) 0.1  (0.19) 0.2  (0.21)
Week 36 Number Analyzed 400 participants 384 participants 361 participants
1.2  (0.24) 0.8  (0.25) 1.4  (0.25)
Week 48 Number Analyzed 373 participants 356 participants 341 participants
1.1  (0.27) 1.3  (0.29) 1.2  (0.27)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 2mg
Comments Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.529
Comments [Not Specified]
Method Mixed model for repeated measures
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.2
Confidence Interval (2-Sided) 95%
-0.7 to 0.3
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of participants with evaluable data
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 8mg
Comments Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.620
Comments [Not Specified]
Method Mixed model for repeated measures
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-0.7 to 0.4
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of participants with evaluable data
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 2mg
Comments Week 36
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.284
Comments [Not Specified]
Method Mixed model for repeated measures
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.4
Confidence Interval (2-Sided) 95%
-1.0 to 0.3
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of participants with evaluable data
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 8mg
Comments Week 36
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.488
Comments [Not Specified]
Method Mixed model for repeated measures
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.2
Confidence Interval (2-Sided) 95%
-0.4 to 0.9
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of participants with evaluable data
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 2mg
Comments Week 48
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.549
Comments [Not Specified]
Method Mixed model for repeated measures
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.2
Confidence Interval (2-Sided) 95%
-0.5 to 1.0
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of participants with evaluable data
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 8mg
Comments For Week 48
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.780
Comments [Not Specified]
Method Mixed model for repeated measures
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.1
Confidence Interval (2-Sided) 95%
-0.6 to 0.9
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of participants with evaluable data
16.Secondary Outcome
Title Change in ADAS-Cog Total Score for Observed Cases at Week 54 Compared to Week 48
Hide Description The 11-item ADAS-Cog assessed a range of cognitive abilities including memory, comprehension, orientation in time and place and spontaneous speech. Most items were evaluated by tests, but some were dependent on clinician ratings on a five point scale. Scores range from 0 to 70 with higher scores indicating greater dysfunction. It was of interest to compare the single blind phase data between the treatment groups defined based on the double blind treatment group. This analysis only included participants who received at least one dose of single-blind medication. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at Week 0. Full population data was presented.
Time Frame Week 48 and Week 54
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. This analysis will only include participants who received at least one dose of single-blind medication. Only those participants available at that particular time point were analyzed.
Arm/Group Title Placebo RSG XR 2mg RSG XR 8mg
Hide Arm/Group Description:
Participants randomized to this arm received matching RSG XR placebo tablets once daily which remained constant throughout the 48 Week treatment period. From Week 48 all the participants received single-blind placebo treatment as one tablet daily until Visit 10 (Week 54)
Participants randomized to this arm received RSG XR 2 mg once daily which remained constant throughout the 48 Week treatment period. From Week 48 all the participants received single-blind placebo treatment as one tablet daily until Visit 10 (Week 54)
Participants randomized to this arm received RSG XR 8 mg one 4mg tablet once daily for the first 4 weeks of treatment. From Visit 3 (Week 4) onwards, these participants received one 8mg tablet once daily for the remaining 44 weeks of double-blind treatment. From Week 48 all participants received single-blind placebo treatment as one tablet daily, until Visit 10 (Week 54)
Overall Number of Participants Analyzed 338 319 307
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
1.0  (0.27) 0.4  (0.28) 0.5  (0.28)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 2mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.106
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.6
Confidence Interval (2-Sided) 95%
-1.3 to 0.1
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 8mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.229
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.4
Confidence Interval (2-Sided) 95%
-1.2 to 0.3
Estimation Comments [Not Specified]
17.Secondary Outcome
Title Change in CDR-SB Total Score for Observed Cases at Week 54 Compared to Week 48
Hide Description The CDR-SB was a validated clinical assessment of global function in participants with AD. Impairment was scored in each of 6 cognitive categories on a scale in which none = 0, questionable = 0.5, mild = 1, moderate = 2, and severe = 3. The 6 individual category ratings, or “box scores”, can be added together to give the CDR-Sum of Boxes which ranges from 0 to 18 (severe impairment). It was of interest to compare the single blind phase data between the treatment groups defined based on the double blind treatment group. This analysis only included participants who received at least one dose of single-blind medication. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at Week 0. Full population data was presented.
Time Frame Week 48 and Week 54
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Only those participants available at that particular time point were analyzed.
Arm/Group Title Placebo RSG XR 2mg RSG XR 8mg
Hide Arm/Group Description:
Participants randomized to this arm received matching RSG XR placebo tablets once daily which remained constant throughout the 48 Week treatment period. From Week 48 all the participants received single-blind placebo treatment as one tablet daily until Visit 10 (Week 54)
Participants randomized to this arm received RSG XR 2 mg once daily which remained constant throughout the 48 Week treatment period. From Week 48 all the participants received single-blind placebo treatment as one tablet daily until Visit 10 (Week 54)
Participants randomized to this arm received RSG XR 8 mg one 4mg tablet once daily for the first 4 weeks of treatment. From Visit 3 (Week 4) onwards, these participants received one 8mg tablet once daily for the remaining 44 weeks of double-blind treatment. From Week 48 all participants received single-blind placebo treatment as one tablet daily, until Visit 10 (Week 54)
Overall Number of Participants Analyzed 335 316 303
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
0.3  (0.07) 0.2  (0.08) 0.3  (0.08)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 2mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.324
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-0.3 to 0.1
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 8mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.987
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-0.2 to 0.2
Estimation Comments [Not Specified]
18.Secondary Outcome
Title Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 48
Hide Description Blood samples were collected for assessments of HbA1c levels at Baseline and up to Week 48. Change from Baseline was calculated as value at scheduled time point minus Baseline value . Baseline was defined as value at Week 0. Endpoint treatment differences which were adjusted to take account of missing data are derived. Full population data was presented.
Time Frame Baseline (Week 0) and Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Only those participants available at that particular time point were analyzed.
Arm/Group Title Placebo RSG XR 2mg RSG XR 8mg
Hide Arm/Group Description:
Participants randomized to this arm received matching RSG XR placebo tablets once daily which remained constant throughout the 48 Week treatment period. From Week 48 all the participants received single-blind placebo treatment as one tablet daily until Visit 10 (Week 54)
Participants randomized to this arm received RSG XR 2 mg once daily which remained constant throughout the 48 Week treatment period. From Week 48 all the participants received single-blind placebo treatment as one tablet daily until Visit 10 (Week 54)
Participants randomized to this arm received RSG XR 8 mg one 4mg tablet once daily for the first 4 weeks of treatment. From Visit 3 (Week 4) onwards, these participants received one 8mg tablet once daily for the remaining 44 weeks of double-blind treatment. From Week 48 all participants received single-blind placebo treatment as one tablet daily, until Visit 10 (Week 54)
Overall Number of Participants Analyzed 337 326 309
Least Squares Mean (Standard Error)
Unit of Measure: Percentage
0.13  (0.018) 0.18  (0.019) 0.26  (0.019)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 2mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.038
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.05
Confidence Interval (2-Sided) 95%
0.00 to 0.10
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 8mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.13
Confidence Interval (2-Sided) 95%
0.08 to 0.18
Estimation Comments [Not Specified]
19.Secondary Outcome
Title Number of Participants With On-treatment Adverse Events (AEs), Serious Adverse Events (SAEs) and Severity of AEs
Hide Description AE was defined as any untoward medical occurrence in a participant temporarily associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE was any untoward medical occurrence that, at any dose results in death, was life threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, was a congenital anomaly/birth defect or was considered as medically significant.
Time Frame Upto Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population consisted of all participants randomized to treatment who had taken at least one dose of study medication. This population was used for analysis of safety data.
Arm/Group Title Placebo RSG XR 2mg RSG XR 8mg
Hide Arm/Group Description:
Participants randomized to this arm received matching RSG XR placebo tablets once daily which remained constant throughout the 48 Week treatment period. From Week 48 all the participants received single-blind placebo treatment as one tablet daily until Visit 10 (Week 54)
Participants randomized to this arm received RSG XR 2 mg once daily which remained constant throughout the 48 Week treatment period. From Week 48 all the participants received single-blind placebo treatment as one tablet daily until Visit 10 (Week 54)
Participants randomized to this arm received RSG XR 8 mg one 4mg tablet once daily for the first 4 weeks of treatment. From Visit 3 (Week 4) onwards, these participants received one 8mg tablet once daily for the remaining 44 weeks of double-blind treatment. From Week 48 all participants received single-blind placebo treatment as one tablet daily, until Visit 10 (Week 54)
Overall Number of Participants Analyzed 487 490 491
Measure Type: Count of Participants
Unit of Measure: Participants
On treatment AEs
275
  56.5%
298
  60.8%
319
  65.0%
On treatment SAEs
60
  12.3%
58
  11.8%
66
  13.4%
Mild AEs
109
  22.4%
119
  24.3%
112
  22.8%
Moderate AEs
111
  22.8%
128
  26.1%
158
  32.2%
Severe AEs
55
  11.3%
50
  10.2%
48
   9.8%
20.Secondary Outcome
Title Number of Participants With Change From Baseline in Vital Signs of Clinical Concern at Any Time on Treatment- Weight
Hide Description Body weight was measured at all visits, without shoes and wearing light clothing. The assessment was performed a t Baseline and up to Week 54. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at Week 0. Full population data was presented.
Time Frame Upto Week 54
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population. Only those participants available at the indicated time point were analyzed.
Arm/Group Title Placebo RSG XR 2mg RSG XR 8mg
Hide Arm/Group Description:
Participants randomized to this arm received matching RSG XR placebo tablets once daily which remained constant throughout the 48 Week treatment period. From Week 48 all the participants received single-blind placebo treatment as one tablet daily until Visit 10 (Week 54)
Participants randomized to this arm received RSG XR 2 mg once daily which remained constant throughout the 48 Week treatment period. From Week 48 all the participants received single-blind placebo treatment as one tablet daily until Visit 10 (Week 54)
Participants randomized to this arm received RSG XR 8 mg one 4mg tablet once daily for the first 4 weeks of treatment. From Visit 3 (Week 4) onwards, these participants received one 8mg tablet once daily for the remaining 44 weeks of double-blind treatment. From Week 48 all participants received single-blind placebo treatment as one tablet daily, until Visit 10 (Week 54)
Overall Number of Participants Analyzed 355 342 318
Measure Type: Count of Participants
Unit of Measure: Participants
Increase from Baseline >=7%
33
   9.3%
31
   9.1%
47
  14.8%
Decrease from Baseline >=7%
28
   7.9%
32
   9.4%
23
   7.2%
21.Secondary Outcome
Title Number of Participants With Change From Baseline in Vital Signs of Clinical Concern at Any Time on Treatment- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Hide Description SBP and DBP of participants were recorded in sitting posture as vital sign at each visit. The blood pressure (BP) values were identified as of potential clinical concern if the values were out of the reference range (for SBP, 90 to 140 mmHg and DBP, 50 to 90 mmHg) or meet a change from baseline criterion. The change from baseline criterion for SBP, was increase from Baseline (high) if increased by more than or equal to (>=) 40 mm Hg from Baseline; decrease from Baseline (low) if decreased by >= 30 mmHg from Baseline. For DBP, increase from baseline (high) if increased by >=30 mmHg from baseline; decrease from Baseline (low) if decreased by >= 20 mmHg from Baseline. Baseline was defined as value at Week 0.
Time Frame Upto Week 54
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population. Only those participants available at the indicated time points were analyzed.
Arm/Group Title Placebo RSG XR 2mg RSG XR 8mg
Hide Arm/Group Description:
Participants randomized to this arm received matching RSG XR placebo tablets once daily which remained constant throughout the 48 Week treatment period. From Week 48 all the participants received single-blind placebo treatment as one tablet daily until Visit 10 (Week 54)
Participants randomized to this arm received RSG XR 2 mg once daily which remained constant throughout the 48 Week treatment period. From Week 48 all the participants received single-blind placebo treatment as one tablet daily until Visit 10 (Week 54)
Participants randomized to this arm received RSG XR 8 mg one 4mg tablet once daily for the first 4 weeks of treatment. From Visit 3 (Week 4) onwards, these participants received one 8mg tablet once daily for the remaining 44 weeks of double-blind treatment. From Week 48 all participants received single-blind placebo treatment as one tablet daily, until Visit 10 (Week 54)
Overall Number of Participants Analyzed 487 490 491
Measure Type: Count of Participants
Unit of Measure: Participants
SBP >140 or <90 Number Analyzed 356 participants 343 participants 322 participants
67
  18.8%
72
  21.0%
86
  26.7%
SBP Increase from Baseline>=40 Number Analyzed 356 participants 343 participants 322 participants
1
   0.3%
3
   0.9%
3
   0.9%
SBP Decrease from Baseline>=30 Number Analyzed 356 participants 343 participants 322 participants
19
   5.3%
19
   5.5%
14
   4.3%
DBP >90 or <50 Number Analyzed 356 participants 343 participants 322 participants
8
   2.2%
15
   4.4%
12
   3.7%
DBP Increase from Baseline>=30 Number Analyzed 356 participants 343 participants 322 participants
0
   0.0%
0
   0.0%
1
   0.3%
DBP Decrease from Baseline >=20 Number Analyzed 356 participants 343 participants 322 participants
12
   3.4%
18
   5.2%
13
   4.0%
22.Secondary Outcome
Title Number of Participants With Change From Baseline in Vital Signs of Clinical Concern at Any Time on Treatment- Heart Rate (HR)
Hide Description HR of participants were recorded in sitting posture as vital sign at each visit. The HR values were identified as of potential clinical concern if the values were out of the reference range (50 to 100 beats per minute) or meet a change from baseline criterion. The change from baseline criterion for HR, was increase from Baseline (high) if increased by more than or equal to (>=) 30 from Baseline; decrease from Baseline (low) if decreased by >= 30 from Baseline. Baseline was defined as value at Week 0. Full population data was presented.
Time Frame Upto Week 54
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population. Only those participants available at the indicated time points were analyzed.
Arm/Group Title Placebo RSG XR 2mg RSG XR 8mg
Hide Arm/Group Description:
Participants randomized to this arm received matching RSG XR placebo tablets once daily which remained constant throughout the 48 Week treatment period. From Week 48 all the participants received single-blind placebo treatment as one tablet daily until Visit 10 (Week 54)
Participants randomized to this arm received RSG XR 2 mg once daily which remained constant throughout the 48 Week treatment period. From Week 48 all the participants received single-blind placebo treatment as one tablet daily until Visit 10 (Week 54)
Participants randomized to this arm received RSG XR 8 mg one 4mg tablet once daily for the first 4 weeks of treatment. From Visit 3 (Week 4) onwards, these participants received one 8mg tablet once daily for the remaining 44 weeks of double-blind treatment. From Week 48 all participants received single-blind placebo treatment as one tablet daily, until Visit 10 (Week 54)
Overall Number of Participants Analyzed 355 344 322
Measure Type: Count of Participants
Unit of Measure: Participants
>100 or <50
12
   3.4%
5
   1.5%
5
   1.6%
Increase from Baseline >=30
0
   0.0%
0
   0.0%
4
   1.2%
Decrease from Baseline >=30
2
   0.6%
0
   0.0%
1
   0.3%
23.Secondary Outcome
Title Change From Baseline in Weight
Hide Description Body weight was measured at all visits, without shoes and wearing light clothing. The assessment was performed at Baseline, Weeks 4, 8, 12, 16, 24, 36, 48, 54. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at Week 0. Full population data was presented.
Time Frame Baseline (Week 0) and Weeks 4, 8, 12, 16, 24, 36, 48, 54
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population. Only those participants available at the indicated time points were analyzed.
Arm/Group Title Placebo RSG XR 2mg RSG XR 8mg
Hide Arm/Group Description:
Participants randomized to this arm received matching RSG XR placebo tablets once daily which remained constant throughout the 48 Week treatment period. From Week 48 all the participants received single-blind placebo treatment as one tablet daily until Visit 10 (Week 54)
Participants randomized to this arm received RSG XR 2 mg once daily which remained constant throughout the 48 Week treatment period. From Week 48 all the participants received single-blind placebo treatment as one tablet daily until Visit 10 (Week 54)
Participants randomized to this arm received RSG XR 8 mg one 4mg tablet once daily for the first 4 weeks of treatment. From Visit 3 (Week 4) onwards, these participants received one 8mg tablet once daily for the remaining 44 weeks of double-blind treatment. From Week 48 all participants received single-blind placebo treatment as one tablet daily, until Visit 10 (Week 54)
Overall Number of Participants Analyzed 487 490 491
Mean (Standard Deviation)
Unit of Measure: Kilograms (Kg)
Week 4 Number Analyzed 470 participants 471 participants 469 participants
-0.1  (1.95) 0.1  (1.61) 0.5  (1.70)
Week 8 Number Analyzed 459 participants 447 participants 443 participants
0.1  (2.10) 0.2  (2.15) 0.9  (2.34)
Week 12 Number Analyzed 447 participants 436 participants 420 participants
0.0  (2.35) 0.1  (2.66) 1.2  (2.50)
Week 16 Number Analyzed 440 participants 428 participants 416 participants
0.0  (2.88) 0.2  (2.85) 1.3  (2.78)
Week 24 Number Analyzed 428 participants 412 participants 387 participants
0.1  (2.85) 0.1  (3.28) 1.2  (3.59)
Week 36 Number Analyzed 397 participants 389 participants 359 participants
-0.0  (4.53) 0.2  (3.69) 1.5  (3.28)
Week 48 Number Analyzed 375 participants 358 participants 341 participants
0.1  (3.51) 0.2  (4.33) 1.9  (3.69)
Week 54 Number Analyzed 355 participants 342 participants 318 participants
0.1  (3.70) 0.1  (5.88) 1.2  (3.57)
24.Secondary Outcome
Title Change From Baseline in Hemoglobin
Hide Description Hematology parameters were assessed at Baseline, Weeks 4, 16, 36, 48. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at Week 0. Full population data was presented.
Time Frame Baseline (Week 0) and Weeks 4, 16, 36, 48
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population. Only those participants available at the indicated time points were analyzed.
Arm/Group Title Placebo RSG XR 2mg RSG XR 8mg
Hide Arm/Group Description:
Participants randomized to this arm received matching RSG XR placebo tablets once daily which remained constant throughout the 48 Week treatment period. From Week 48 all the participants received single-blind placebo treatment as one tablet daily until Visit 10 (Week 54)
Participants randomized to this arm received RSG XR 2 mg once daily which remained constant throughout the 48 Week treatment period. From Week 48 all the participants received single-blind placebo treatment as one tablet daily until Visit 10 (Week 54)
Participants randomized to this arm received RSG XR 8 mg one 4mg tablet once daily for the first 4 weeks of treatment. From Visit 3 (Week 4) onwards, these participants received one 8mg tablet once daily for the remaining 44 weeks of double-blind treatment. From Week 48 all participants received single-blind placebo treatment as one tablet daily, until Visit 10 (Week 54)
Overall Number of Participants Analyzed 487 490 491
Mean (Standard Deviation)
Unit of Measure: Gram\Liter (G\L)
Week 4 Number Analyzed 460 participants 453 participants 461 participants
-0.5  (6.50) -2.9  (6.76) -3.9  (6.80)
Week 16 Number Analyzed 428 participants 422 participants 403 participants
-0.6  (7.37) -6.1  (7.79) -11.2  (9.37)
Week 36 Number Analyzed 381 participants 376 participants 343 participants
-0.7  (7.78) -6.2  (8.73) -10.6  (9.67)
Week 48 Number Analyzed 362 participants 336 participants 332 participants
-0.7  (9.10) -5.8  (8.66) -10.7  (10.15)
25.Secondary Outcome
Title Change From Baseline in Hematocrit
Hide Description Hematology parameters were assessed at Baseline and up to Week 48. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at Week 0.
Time Frame Baseline (Week 0) and Weeks 4, 16, 36, 48
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population. Only those participants available at the indicated time points were analyzed.
Arm/Group Title Placebo RSG XR 2mg RSG XR 8mg
Hide Arm/Group Description:
Participants randomized to this arm received matching RSG XR placebo tablets once daily which remained constant throughout the 48 Week treatment period. From Week 48 all the participants received single-blind placebo treatment as one tablet daily until Visit 10 (Week 54)
Participants randomized to this arm received RSG XR 2 mg once daily which remained constant throughout the 48 Week treatment period. From Week 48 all the participants received single-blind placebo treatment as one tablet daily until Visit 10 (Week 54)
Participants randomized to this arm received RSG XR 8 mg one 4mg tablet once daily for the first 4 weeks of treatment. From Visit 3 (Week 4) onwards, these participants received one 8mg tablet once daily for the remaining 44 weeks of double-blind treatment. From Week 48 all participants received single-blind placebo treatment as one tablet daily, until Visit 10 (Week 54)
Overall Number of Participants Analyzed 487 490 491
Mean (Standard Deviation)
Unit of Measure: Ratio
Week 4 Number Analyzed 459 participants 453 participants 461 participants
-0.0020  (0.02050) -0.0088  (0.02150) -0.0121  (0.02128)
Week 16 Number Analyzed 428 participants 422 participants 403 participants
-0.0018  (0.02340) -0.0166  (0.02442) -0.0320  (0.02922)
Week 36 Number Analyzed 381 participants 376 participants 343 participants
-0.0017  (0.02428) -0.0174  (0.02705) -0.0300  (0.02880)
Week 48 Number Analyzed 362 participants 336 participants 332 participants
-0.0026  (0.02776) -0.0167  (0.02683) -0.0303  (0.03015)