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Rosiglitazone (Extended Release Tablets) As Monotherapy In Subjects With Mild To Moderate Alzheimer's Disease

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ClinicalTrials.gov Identifier: NCT00428090
Recruitment Status : Completed
First Posted : January 29, 2007
Results First Posted : May 19, 2017
Last Update Posted : May 19, 2017
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Alzheimer's Disease
Intervention Drug: Rosiglitazone
Enrollment 862
Recruitment Details Participants (par.) were enrolled across 134 centres Austria, Bulgaria, Chile, China, Crotia, Estonia, Germany, Greece, Hungry, Korea, Mexico, New Zealand, Pakistan, Peru, Philippines, Puerto Rico, Russia, the United Kingdom and the United States from February 2007 to September 2008. The total study duration was 30 weeks (W).
Pre-assignment Details Total of 639 par. were screened out of which 581 were randomized and 58 were placebo run-in failures. Analysis population included 579 par. of 581 randomized participants as 2 par. did not take study drug: 1 from placebo and 1 from donepezil arm.
Arm/Group Title Placebo RSG XR 2 mg RSG XR 8 mg Donepezil 10 mg
Hide Arm/Group Description Par. in this arm received RSG placebo tablet along with dummy donepezil capsule once daily for 24W. For par. in this arm, the dosage were remain constant throughout the 24W treatment period. Study treatment were taken in the evening with or without food. Par. in this arm received rosiglitazone extended release (RSGXR) 2 milligram (mg) tablet along with dummy donepezil capsule once daily for 24W. For par. in this arm, the dosage were remain constant throughout the 24W treatment period. Study treatment were taken in the evening with or without food. Par. in this arm received RSGXR 4 mg tablet along with dummy donepezil capsule once daily for the first 4W of treatment. From Visit 4 (W4) onwards, these par. received 8 mg RSGXR tablet along with dummy donepezil capsule once daily for the remaining 20W of double-blind treatment. Study treatment were taken in the evening with or without food. Par. in this arm received donepezil 5 mg capsule along with dummy RSGXR tablet once daily for the first 4W of treatment. From Visit 4 (W4) onwards, these par. received donepezil 10 mg capsule along with dummy RSGXR tablet once daily for the remaining 20W of double-blind treatment. Study treatment were taken in the evening with or without food.
Period Title: Overall Study
Started 165 166 165 83
Completed 131 135 127 55
Not Completed 34 31 38 28
Reason Not Completed
Adverse Event             10             8             10             11
Lost to Follow-up             3             6             1             4
Protocol Violation             3             1             3             3
Withdrawal by Subject             10             12             15             5
Sponsor terminated study             0             1             0             0
Non-compliance             4             0             1             3
Par. did not returned to visit             1             0             0             1
Follow-Up visit not possible             1             0             0             0
Prohibited medication used for SAE             1             0             0             0
Death of par.             1             0             1             0
Visit 7 exceed the visit window             0             1             0             0
Medical monitor terminated par.             0             1             0             0
Mental status of par. was             0             1             0             0
Worsening of AD             0             0             1             0
Excluded for concerning QTc value             0             0             1             0
Insufficient AD documentation             0             0             1             0
High MMSE scores             0             0             1             0
Deterioration of cognitive status             0             0             1             0
Serious adverse event             0             0             1             0
Excluded for heart insufficiency             0             0             1             0
Raised Creatinine Value             0             0             0             1
Arm/Group Title Placebo RSG XR 2 mg RSG XR 8 mg Donepezil 10 mg Total
Hide Arm/Group Description Par. in this arm received RSG placebo tablet along with dummy donepezil capsule once daily for 24W. For par. in this arm, the dosage were remain constant throughout the 24W treatment period. Study treatment were taken in the evening with or without food. Par. in this arm received RSGXR 2 milligram (mg) tablet along with dummy donepezil capsule once daily for 24W. For par. in this arm, the dosage were remain constant throughout the 24W treatment period. Study treatment were taken in the evening with or without food. Par. in this arm received RSGXR 4 mg tablet along with dummy donepezil capsule once daily for the first 4W of treatment. From Visit 4 (W4) onwards, these par. received 8 mg RSGXR tablet along with dummy donepezil capsule once daily for the remaining 20W of double-blind treatment. Study treatment were taken in the evening with or without food. Par. in this arm received donepezil 5 mg capsule along with dummy RSGXR tablet once daily for the first 4W of treatment. From Visit 4 (W4) onwards, these par. received donepezil 10 mg capsule along with dummy RSGXR tablet once daily for the remaining 20W of double-blind treatment. Study treatment were taken in the evening with or without food. Total of all reporting groups
Overall Number of Baseline Participants 159 162 156 76 553
Hide Baseline Analysis Population Description
The intent-to-treat (ITT) population was used and consist of all par. randomized to treatment, who have taken at least one dose of study medication and who have at least one post baseline efficacy assessment. The ITT population included 553 participants.
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 159 participants 162 participants 156 participants 76 participants 553 participants
72.5  (8.56) 71.7  (7.91) 72.6  (8.63) 72.9  (7.97) 72.4  (8.30)
[1]
Measure Description: Baseline data are presented for intention-to-Treat (ITT) population which defined as par. randomized to treatment, who have taken at least one dose of study medication and who have at least one post baseline efficacy assessment (Alzheimer’s Disease Assessment Scale – Cognitive subscale [ADAS-Cog] or Clinician’s Interview-Based Impression of Change Plus [CIBIC+]).
Sex: Female, Male   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 159 participants 162 participants 156 participants 76 participants 553 participants
Female
95
  59.7%
103
  63.6%
101
  64.7%
48
  63.2%
347
  62.7%
Male
64
  40.3%
59
  36.4%
55
  35.3%
28
  36.8%
206
  37.3%
[1]
Measure Description: ITT Population
Race (NIH/OMB)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 159 participants 162 participants 156 participants 76 participants 553 participants
American Indian or Alaska Native
1
   0.6%
1
   0.6%
2
   1.3%
0
   0.0%
4
   0.7%
Asian
33
  20.8%
50
  30.9%
37
  23.7%
14
  18.4%
134
  24.2%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
1
   0.6%
1
   0.6%
2
   1.3%
3
   3.9%
7
   1.3%
White
123
  77.4%
109
  67.3%
112
  71.8%
57
  75.0%
401
  72.5%
More than one race
1
   0.6%
1
   0.6%
3
   1.9%
2
   2.6%
7
   1.3%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
[1]
Measure Description: ITT Population
1.Primary Outcome
Title Change From Baseline (W0) in Mean ADAS-Cog Total Score at W24 as a Function of APOE e4 Status in Apolipoprotein epsilon4 (APOE e4) Negative 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. Items were evaluated by tests and clinician ratings on a 5-point scale. Scores ranged from 0-70 with higher scores indicates more dysfunction. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline is defined as value at W0. Estimated value was calculated by Active treatment minus Placebo. The adjusted means were presented. A hierarchical testing procedure was used to control for the two rosiglitazone dose groups and the three genetic subgroups. There was no adjustment for the donepezil versus placebo comparisons, which were included to assess the sensitivity of the trial to detect a treatment effect.
Time Frame Baseline (W0) and W24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those par. available at the indicated time points were analyzed. These comparisons were conducted for APOE e4 negative (neg) par. (e2/e2, e2/e3, and e3/e3) cohort
Arm/Group Title Placebo RSG XR 2 mg RSG XR 8 mg Donepezil 10 mg
Hide Arm/Group Description:
Par. randomized to this arm received RSG placebo tablet along with dummy donepezil capsule once daily for 24W. For par. in this arm, the dosage were remain constant throughout the 24W treatment period. Study treatment were taken in the evening with or without food.
Par. randomized to this arm received RSGXR 2 milligram (mg) tablet along with dummy donepezil capsule once daily for 24W. For par. in this arm, the dosage were remain constant throughout the 24W treatment period. Study treatment were taken in the evening with or without food.
Par. randomized to this arm received RSGXR 4 mg tablet along with dummy donepezil capsule once daily for the first 4 weeks of treatment. From Visit 4 (Week 4) onwards, these par. received 8 mg RSGXR tablet along with dummy donepezil capsule once daily for the remaining 20W of double-blind treatment. Study treatment were taken in the evening with or without food.
Par. randomized to this arm received donepezil 5 mg capsule along with dummy RSGXR tablet once daily for the first 4 weeks of treatment. From Visit 4 (Week 4) onwards, these par. received donepezil 10 mg capsule along with dummy RSGXR tablet once daily for the remaining 20W of double-blind treatment. Study treatment were taken in the evening with or without food.
Overall Number of Participants Analyzed 63 69 65 28
Least Squares Mean (Standard Error)
Unit of Measure: Score on a scale
1.6  (0.78) -0.2  (0.67) 0.6  (0.67) 0.9  (1.16)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 2 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.074
Comments Comparison between Placebo and RSG XR 2 mg in APOE e4 neg cohort
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 (Final Values)
Estimated Value -1.8
Confidence Interval (2-Sided) 95%
-3.8 to 0.2
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 8 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.338
Comments Comparison between Placebo and RSG XR 8 mg in APOE e4 neg cohort
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 (Final Values)
Estimated Value -1.0
Confidence Interval (2-Sided) 95%
-3.0 to 1.0
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Donepezil 10 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.602
Comments Comparison between Placebo and Donepezil 10mg in APOE e4 neg cohort
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 (Final Values)
Estimated Value -0.7
Confidence Interval (2-Sided) 95%
-3.5 to 2.1
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
2.Primary Outcome
Title Change From Baseline (W0) in Mean ADAS-Cog Total Score at W24 as a Function of APOE e4 Status in All Except e4/e4’s 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. Items were evaluated by tests and clinician ratings on a 5-point scale. Scores ranged from 0-70 with higher scores indicates more dysfunction. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline is defined as value at W0. Estimated value was calculated by Active treatment minus Placebo. A hierarchical testing procedure was used to control for the two rosiglitazone dose groups and the three genetic subgroups. There was no adjustment for the donepezil versus placebo comparisons, which were included to assess the sensitivity of the trial to detect a treatment effect.
Time Frame Baseline (W0) and W24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those par. available at the indicated time points were analyzed. These comparisons were conducted in all except e4/e4’s: comprised of APOE e4 neg par. (e2/e2, e2/e3, and e3/e3) and APOE e4 heterozygote par. (e2/e4, e3/e4)
Arm/Group Title Placebo RSG XR 2 mg RSG XR 8 mg Donepezil 10 mg
Hide Arm/Group Description:
Par. randomized to this arm received RSG placebo tablet along with dummy donepezil capsule once daily for 24W. For par. in this arm, the dosage were remain constant throughout the 24W treatment period. Study treatment were taken in the evening with or without food.
Par. randomized to this arm received RSGXR 2 milligram (mg) tablet along with dummy donepezil capsule once daily for 24W. For par. in this arm, the dosage were remain constant throughout the 24W treatment period. Study treatment were taken in the evening with or without food.
Par. randomized to this arm received RSGXR 4 mg tablet along with dummy donepezil capsule once daily for the first 4 weeks of treatment. From Visit 4 (Week 4) onwards, these par. received 8 mg RSGXR tablet along with dummy donepezil capsule once daily for the remaining 20W of double-blind treatment. Study treatment were taken in the evening with or without food.
Par. randomized to this arm received donepezil 5 mg capsule along with dummy RSGXR tablet once daily for the first 4 weeks of treatment. From Visit 4 (Week 4) onwards, these par. received donepezil 10 mg capsule along with dummy RSGXR tablet once daily for the remaining 20W of double-blind treatment. Study treatment were taken in the evening with or without food.
Overall Number of Participants Analyzed 117 115 112 49
Least Squares Mean (Standard Error)
Unit of Measure: Score on a scale
1.5  (0.58) 0.3  (0.54) 0.7  (0.57) -0.1  (0.79)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 2 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.131
Comments Comparison between Placebo and RSG XR 2 mg in All except e4/e4’s cohort
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 (Final Values)
Estimated Value -1.2
Confidence Interval (2-Sided) 95%
-2.7 to 0.4
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 8 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.315
Comments Comparison between Placebo and RSG XR 8 mg in All except e4/e4’s cohort
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 (Final Values)
Estimated Value -0.8
Confidence Interval (2-Sided) 95%
-2.4 to 0.8
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Donepezil 10 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.105
Comments Comparison between Placebo and Donepezil 10 mg in All except e4/e4’s cohort
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 (Final Values)
Estimated Value -1.6
Confidence Interval (2-Sided) 95%
-3.5 to 0.3
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
3.Primary Outcome
Title Change From Baseline (W0) in Mean ADAS-Cog Total Score at W24 as a Function of APOE e4 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. Items were evaluated by tests and clinician ratings on a 5-point scale. Scores ranged from 0-70 with higher scores indicates more dysfunction. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline is defined as value at W0. Estimated value was calculated by Active treatment minus Placebo. A hierarchical testing procedure was used to control for the two rosiglitazone dose groups and the three genetic subgroups. There was no adjustment for the donepezil versus placebo comparisons, which were included to assess the sensitivity of the trial to detect a treatment effect.
Time Frame Baseline (W0) and W24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Placebo RSG XR 2 mg RSG XR 8 mg Donepezil 10 mg
Hide Arm/Group Description:
Par. randomized to this arm received RSG placebo tablet along with dummy donepezil capsule once daily for 24W. For par. in this arm, the dosage were remain constant throughout the 24W treatment period. Study treatment were taken in the evening with or without food.
Par. randomized to this arm received RSGXR 2 milligram (mg) tablet along with dummy donepezil capsule once daily for 24W. For par. in this arm, the dosage were remain constant throughout the 24W treatment period. Study treatment were taken in the evening with or without food.
Par. randomized to this arm received RSGXR 4 mg tablet along with dummy donepezil capsule once daily for the first 4 weeks of treatment. From Visit 4 (Week 4) onwards, these par. received 8 mg RSGXR tablet along with dummy donepezil capsule once daily for the remaining 20W of double-blind treatment. Study treatment were taken in the evening with or without food.
Par. randomized to this arm received donepezil 5 mg capsule along with dummy RSGXR tablet once daily for the first 4 weeks of treatment. From Visit 4 (Week 4) onwards, these par. received donepezil 10 mg capsule along with dummy RSGXR tablet once daily for the remaining 20W of double-blind treatment. Study treatment were taken in the evening with or without food.
Overall Number of Participants Analyzed 131 130 125 56
Least Squares Mean (Standard Error)
Unit of Measure: Score on a scale
2.0  (0.56) 1.2  (0.53) 1.2  (0.55) 0.6  (0.74)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 2 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.272
Comments Comparison between Placebo and RSG XR 2 mg in Full population cohort
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 (Final Values)
Estimated Value -0.8
Confidence Interval (2-Sided) 95%
-2.2 to 0.6
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 8 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.297
Comments Comparison between Placebo and RSG XR 8 mg in Full population cohort
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 (Final Values)
Estimated Value -0.8
Confidence Interval (2-Sided) 95%
-2.2 to 0.7
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Donepezil 10 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.131
Comments Comparison between Placebo and Donepezil 10 mg in Full population cohort
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 (Final Values)
Estimated Value -1.3
Confidence Interval (2-Sided) 95%
-3.1 to 0.4
Estimation Comments [Not Specified]
4.Primary Outcome
Title Change From Baseline (W0) in Mean CIBIC+ Global Functioning Total Score at W24 as a Function of APOE e4 Status in APOE4 Negative Cohort
Hide Description The CIBIC+ assessment comprised of a 7-point rating of severity (at baseline) and change (at indicated time points). It was rated on a scale of 1 to 7 as 1: markedly improved, 2.: moderately improved, 3: minimally improved, 4: no change, 5: minimally worse, 6: moderately worse and 7: markedly worse; higher score means greater dysfunction. It was based on interviews with the par. and caregiver by an independent rater. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at W0. Endpoint treatment differences which were adjusted to take account of missing data are derived. Estimated value was calculated by Active treatment minus Placebo. A hierarchical testing procedure was used to control for the two rosiglitazone dose groups and the three genetic subgroups. There was no adjustment for the donepezil versus placebo comparisons, which were included to assess the sensitivity of the trial to detect a treatment effect.
Time Frame Baseline (W0) and W24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those par. available at the indicated time points were analyzed. These comparisons were conducted in APOE e4 negative (neg) par. (e2/e2, e2/e3, and e3/e3).
Arm/Group Title Placebo RSG XR 2 mg RSG XR 8 mg Donepezil 10 mg
Hide Arm/Group Description:
Par. randomized to this arm received RSG placebo tablet along with dummy donepezil capsule once daily for 24W. For par. in this arm, the dosage were remain constant throughout the 24W treatment period. Study treatment were taken in the evening with or without food.
Par. randomized to this arm received RSGXR 2 milligram (mg) tablet along with dummy donepezil capsule once daily for 24W. For par. in this arm, the dosage were remain constant throughout the 24W treatment period. Study treatment were taken in the evening with or without food.
Par. randomized to this arm received RSGXR 4 mg tablet along with dummy donepezil capsule once daily for the first 4 weeks of treatment. From Visit 4 (Week 4) onwards, these par. received 8 mg RSGXR tablet along with dummy donepezil capsule once daily for the remaining 20W of double-blind treatment. Study treatment were taken in the evening with or without food.
Par. randomized to this arm received donepezil 5 mg capsule along with dummy RSGXR tablet once daily for the first 4 weeks of treatment. From Visit 4 (Week 4) onwards, these par. received donepezil 10 mg capsule along with dummy RSGXR tablet once daily for the remaining 20W of double-blind treatment. Study treatment were taken in the evening with or without food.
Overall Number of Participants Analyzed 63 71 66 28
Least Squares Mean (Standard Error)
Unit of Measure: Score on a scale
4.2  (0.14) 4.2  (0.12) 4.1  (0.11) 3.9  (0.22)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 2 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.663
Comments Comparison between Placebo and RSG XR 2 mg in APOE e4 neg cohort
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 (Final Values)
Estimated Value 0.1
Confidence Interval (2-Sided) 95%
-0.3 to 0.4
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 8 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.891
Comments Comparison between Placebo and RSG XR 8 mg in APOE e4 neg cohort
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 (Final Values)
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 par. with evaluable data
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Donepezil 10 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.414
Comments Comparison between Placebo and Donepezil 10 mg in APOE e4 neg cohort
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 (Final Values)
Estimated Value -0.2
Confidence Interval (2-Sided) 95%
-0.7 to 0.3
Estimation Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
5.Primary Outcome
Title Change From Baseline (W0) in Mean CIBIC+ Global Functioning Total Score at W24 as a Function of APOE e4 Status in All Except e4/e4’s Cohort
Hide Description The CIBIC+ assessment comprised of a 7-point rating of severity (at baseline) and change (at indicated time points). It was rated on a scale of 1 to 7 as 1: markedly improved, 2.: moderately improved, 3: minimally improved, 4: no change, 5: minimally worse, 6: moderately worse and 7: markedly worse; higher score means greater dysfunction. It was based on interviews with the par. and caregiver by an independent rater. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at W0. Endpoint treatment differences which were adjusted to take account of missing data are derived. Estimated value was calculated by Active treatment minus Placebo. A hierarchical testing procedure was used to control for the two rosiglitazone dose groups and the three genetic subgroups. There was no adjustment for the donepezil versus placebo comparisons, which were included to assess the sensitivity of the trial to detect a treatment effect.
Time Frame Baseline (W0) and W24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those par. available at the indicated time points were analyzed. These comparisons were conducted in all except e4/e4’s: comprised of APOE e4 neg par. (e2/e2, e2/e3, and e3/e3) and APOE e4 heterozygote par. (e2/e4, e3/e4)
Arm/Group Title Placebo RSG XR 2 mg RSG XR 8 mg Donepezil 10 mg
Hide Arm/Group Description:
Par. randomized to this arm received RSG placebo tablet along with dummy donepezil capsule once daily for 24W. For par. in this arm, the dosage were remain constant throughout the 24W treatment period. Study treatment were taken in the evening with or without food.
Par. randomized to this arm received RSGXR 2 milligram (mg) tablet along with dummy donepezil capsule once daily for 24W. For par. in this arm, the dosage were remain constant throughout the 24W treatment period. Study treatment were taken in the evening with or without food.
Par. randomized to this arm received RSGXR 4 mg tablet along with dummy donepezil capsule once daily for the first 4 weeks of treatment. From Visit 4 (Week 4) onwards, these par. received 8 mg RSGXR tablet along with dummy donepezil capsule once daily for the remaining 20W of double-blind treatment. Study treatment were taken in the evening with or without food.
Par. randomized to this arm received donepezil 5 mg capsule along with dummy RSGXR tablet once daily for the first 4 weeks of treatment. From Visit 4 (Week 4) onwards, these par. received donepezil 10 mg capsule along with dummy RSGXR tablet once daily for the remaining 20W of double-blind treatment. Study treatment were taken in the evening with or without food.
Overall Number of Participants Analyzed 117 117 114 49
Least Squares Mean (Standard Error)
Unit of Measure: Score on a scale
4.3  (0.10) 4.3  (0.10) 4.1  (0.10) 3.8  (0.17)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 2 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.913
Comments Comparison between Placebo and RSG XR 2 mg in All except e4/e4’s cohort
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 (Final Values)
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-0.3 to 0.3
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 8 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.276
Comments Comparison between Placebo and RSG XR 8 mg in All except e4/e4’s cohort
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 (Final Values)
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-0.4 to 0.1
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Donepezil 10 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.025
Comments Comparison between Placebo and Donepezil 10 mg in All except e4/e4’s cohort
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 (Final Values)
Estimated Value -0.5
Confidence Interval (2-Sided) 95%
-0.8 to -0.1
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
6.Primary Outcome
Title Change From Baseline (W0) in Mean CIBIC+ Global Functioning Total Score at W24 as a Function of APOE e4 Status in Full Population Cohort
Hide Description The CIBIC+ assessment comprised of a 7-point rating of severity (at baseline) and change (at indicated time points). It was rated on a scale of 1 to 7 as 1: markedly improved, 2.: moderately improved, 3: minimally improved, 4: no change, 5: minimally worse, 6: moderately worse and 7: markedly worse; higher score means greater dysfunction. It was based on interviews with the par. and caregiver by an independent rater. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at W0. Endpoint treatment differences which were adjusted to take account of missing data are derived. Estimated value was calculated by Active treatment minus Placebo. A hierarchical testing procedure was used to control for the two rosiglitazone dose groups and the three genetic subgroups. There was no adjustment for the donepezil versus placebo comparisons, which were included to assess the sensitivity of the trial to detect a treatment effect.
Time Frame Baseline (W0) and W24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those par. available at the indicated time points were analyzed. These comparisons were conducted in full population.
Arm/Group Title Placebo RSG XR 2 mg RSG XR 8 mg Donepezil 10 mg
Hide Arm/Group Description:
Par. randomized to this arm received RSG placebo tablet along with dummy donepezil capsule once daily for 24W. For par. in this arm, the dosage were remain constant throughout the 24W treatment period. Study treatment were taken in the evening with or without food.
Par. randomized to this arm received RSGXR 2 milligram (mg) tablet along with dummy donepezil capsule once daily for 24W. For par. in this arm, the dosage were remain constant throughout the 24W treatment period. Study treatment were taken in the evening with or without food.
Par. randomized to this arm received RSGXR 4 mg tablet along with dummy donepezil capsule once daily for the first 4 weeks of treatment. From Visit 4 (Week 4) onwards, these par. received 8 mg RSGXR tablet along with dummy donepezil capsule once daily for the remaining 20W of double-blind treatment. Study treatment were taken in the evening with or without food.
Par. randomized to this arm received donepezil 5 mg capsule along with dummy RSGXR tablet once daily for the first 4 weeks of treatment. From Visit 4 (Week 4) onwards, these par. received donepezil 10 mg capsule along with dummy RSGXR tablet once daily for the remaining 20W of double-blind treatment. Study treatment were taken in the evening with or without food.
Overall Number of Participants Analyzed 131 133 127 56
Least Squares Mean (Standard Error)
Unit of Measure: Score on a scale
4.3  (0.09) 4.3  (0.09) 4.2  (0.10) 3.8  (0.16)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 2 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.939
Comments Comparison between Placebo and RSG XR 2 mg in Full population cohort
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 (Final Values)
Estimated Value 0.0
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 par. with evaluable data
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 8 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.307
Comments Comparison between Placebo and RSG XR 8 mg in Full population cohort
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 (Final Values)
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-0.4 to 0.1
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Donepezil 10 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.009
Comments Comparison between Placebo and Donepezil 10 mg in Full population cohort
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 (Final Values)
Estimated Value -0.5
Confidence Interval (2-Sided) 95%
-0.8 to -0.1
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
7.Secondary Outcome
Title Change From Baseline (W0) in Mean ADAS-Cog Total Score at W8, W16, W24
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 5-point scale. Scores ranged from 0-70 with higher scores indicating greater dysfunction. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline is defined as value at W0. Endpoint treatment differences were adjusted to take account of missing data. It was evaluated at Baseline, W8, W16 and W24.
Time Frame Baseline (W0) and up to W24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants available at the specified time points were analyzed (represented as n=x,x,x,x in the category titles).
Arm/Group Title Placebo RSG XR 2 mg RSG XR 8 mg Donepezil 10 mg
Hide Arm/Group Description:
Par. in this arm received RSG placebo tablet along with dummy donepezil capsule once daily for 24W. For par. in this arm, the dosage were remain constant throughout the 24W treatment period. Study treatment were taken in the evening with or without food.
Par. in this arm received RSGXR 2 milligram (mg) tablet along with dummy donepezil capsule once daily for 24W. For par. in this arm, the dosage were remain constant throughout the 24W treatment period. Study treatment were taken in the evening with or without food.
Par. in this arm received RSGXR 4 mg tablet along with dummy donepezil capsule once daily for the first 4W of treatment. From Visit 4 (W4) onwards, these par. received 8 mg RSGXR tablet along with dummy donepezil capsule once daily for the remaining 20W of double-blind treatment. Study treatment were taken in the evening with or without food.
Par. in this arm received donepezil 5 mg capsule along with dummy RSGXR tablet once daily for the first 4W of treatment. From Visit 4 (W4) onwards, these par. received donepezil 10 mg capsule along with dummy RSGXR tablet once daily for the remaining 20W of double-blind treatment. Study treatment were taken in the evening with or without food.
Overall Number of Participants Analyzed 159 162 156 76
Least Squares Mean (Standard Error)
Unit of Measure: Score on a scale
ADAS-Cog, W8, n=153, 155,147,67 0.4  (0.42) -0.5  (0.45) 0.5  (0.43) -0.3  (0.63)
ADAS-Cog, W16, n=143,145,132,62 0.5  (0.46) 0.6  (0.49) 1.3  (0.45) -1.1  (0.80)
ADAS-Cog, W24, n=131, 130,125,156 2.0  (0.56) 1.2  (0.53) 1.2  (0.55) 0.6  (0.74)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 2 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.116
Comments Comparison between Placebo and RSG XR 2 mg at Week 8 in Full population cohort
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 (Final Values)
Estimated Value -0.9
Confidence Interval (2-Sided) 95%
-2.0 to 0.2
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 8 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.816
Comments Comparison between Placebo and RSG XR 8 mg at Week 8 in Full population cohort
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 (Final Values)
Estimated Value 0.1
Confidence Interval (2-Sided) 95%
-0.9 to 1.2
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Donepezil 10 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.318
Comments Comparison between Placebo and Donepezil 10 mg at Week 8 in Full population cohort
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 (Final Values)
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 par. with evaluable data
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 2 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.839
Comments Comparison between Placebo and RSG XR 2 mg in at Week 16 Full population cohort
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 (Final Values)
Estimated Value 0.1
Confidence Interval (2-Sided) 95%
-1.1 to 1.3
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 8 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.165
Comments Comparison between Placebo and RSG XR 8 mg at Week 16 in Full population cohort
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 (Final Values)
Estimated Value 0.8
Confidence Interval (2-Sided) 95%
-0.3 to 2.0
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, Donepezil 10 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.073
Comments Comparison between Placebo and Donepezil 10 mg at Week 16 in Full population cohort
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 (Final Values)
Estimated Value -1.6
Confidence Interval (2-Sided) 95%
-3.4 to 0.2
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 2 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.272
Comments Comparison between Placebo and RSG XR 2 mg at Week 24 in Full population cohort
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 (Final Values)
Estimated Value -0.8
Confidence Interval (2-Sided) 95%
-2.2 to 0.6
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 8 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.297
Comments Comparison between Placebo and RSG XR 8 mg at Week 24 in Full population cohort
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 (Final Values)
Estimated Value -0.8
Confidence Interval (2-Sided) 95%
-2.2 to 0.7
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Placebo, Donepezil 10 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.131
Comments Comparison between Placebo and Donepezil 10 mg at Week 24 in Full population cohort
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 (Final Values)
Estimated Value -1.3
Confidence Interval (2-Sided) 95%
-3.1 to 0.4
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
8.Secondary Outcome
Title Change From Baseline (W0) in Mean CIBIC+ Global Functioning Total Score at W8, W16, W24
Hide Description The CIBIC+ assessment comprised of a 7-point rating of severity (at baseline) and change (at indicated time points). It was rated on a scale of 1 to 7 as 1: markedly improved, 2.: moderately improved, 3: minimally improved, 4: no change, 5: minimally worse, 6: moderately worse and 7: markedly worse; higher score means more dysfunction. The scale was based on interviews with the par. and caregiver and was completed by an independent rater. It required separate structured 15-20 minute interviews with the par. and caregiver. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at W0. Endpoint treatment differences which were adjusted to take account of missing data are derived. It was evaluated at Baseline, W8, W16 and W24.
Time Frame Baseline (W0) and up to W24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants available at the specified time points were analyzed (represented as n=x,x,x,x in the category titles).
Arm/Group Title Placebo RSG XR 2 mg RSG XR 8 mg Donepezil 10 mg
Hide Arm/Group Description:
Par. in this arm received RSG placebo tablet along with dummy donepezil capsule once daily for 24W. For par. in this arm, the dosage were remain constant throughout the 24W treatment period. Study treatment were taken in the evening with or without food.
Par. in this arm received RSGXR 2 milligram (mg) tablet along with dummy donepezil capsule once daily for 24W. For par. in this arm, the dosage were remain constant throughout the 24W treatment period. Study treatment were taken in the evening with or without food.
Par. in this arm received RSGXR 4 mg tablet along with dummy donepezil capsule once daily for the first 4W of treatment. From Visit 4 (W4) onwards, these par. received 8 mg RSGXR tablet along with dummy donepezil capsule once daily for the remaining 20W of double-blind treatment. Study treatment were taken in the evening with or without food.
Par. in this arm received donepezil 5 mg capsule along with dummy RSGXR tablet once daily for the first 4W of treatment. From Visit 4 (W4) onwards, these par. received donepezil 10 mg capsule along with dummy RSGXR tablet once daily for the remaining 20W of double-blind treatment. Study treatment were taken in the evening with or without food.
Overall Number of Participants Analyzed 159 162 156 76
Least Squares Mean (Standard Error)
Unit of Measure: Score on a scale
CIBIC+, W8, n=150, 156,147,67 4.1  (0.07) 3.9  (0.08) 4.1  (0.08) 3.9  (0.12)
CIBIC+, W16, n=144,145,127,61 4.2  (0.08) 4.0  (0.08) 4.1  (0.09) 3.8  (0.14)
CIBIC+, W24, n=131,133, 127, 56 4.3  (0.09) 4.3  (0.09) 4.2  (0.10) 3.8  (0.16)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 2 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.133
Comments Comparison between Placebo and RSG XR 2 mg at Week 8 in Full population cohort
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 (Final Values)
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-0.3 to 0.0
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 8 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.958
Comments Comparison between Placebo and RSG XR 8 mg at Week 8 in Full population cohort
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 (Final Values)
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 par. with evaluable data
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Donepezil 10 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.085
Comments Comparison between Placebo and Donepezil 10 mg at Week 8 in Full population cohort
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 (Final Values)
Estimated Value -0.2
Confidence Interval (2-Sided) 95%
-0.5 to 0.0
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 2 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.102
Comments Comparison between Placebo and RSG XR 2 mg at Week 16 in Full population cohort
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 (Final Values)
Estimated Value -0.2
Confidence Interval (2-Sided) 95%
-0.4 to 0.0
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 8 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.380
Comments Comparison between Placebo and RSG XR 8 mg at Week 16 in Full population cohort
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 (Final Values)
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-0.3 to 0.1
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, Donepezil 10 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.006
Comments Comparison between Placebo and Donepezil 10 mg at Week 16 in Full population cohort
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 (Final Values)
Estimated Value -0.4
Confidence Interval (2-Sided) 95%
-0.7 to -0.1
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 2 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.939
Comments Comparison between Placebo and RSG XR 2 mg at Week 24 in Full population cohort
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 (Final Values)
Estimated Value 0.0
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 par. with evaluable data
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 8 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.307
Comments Comparison between Placebo and RSG XR 8 mg at Week 24 in Full population cohort
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 (Final Values)
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-0.4 to 0.1
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Placebo, Donepezil 10 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.009
Comments Comparison between Placebo and Donepezil 10 mg at Week 24 in Full population cohort
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 (Final Values)
Estimated Value -0.5
Confidence Interval (2-Sided) 95%
-0.8 to -0.1
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
9.Secondary Outcome
Title Change From Baseline (W0) in Mean Neuropsychiatric Inventory (NPI) Total Score at W8, W16, W24
Hide Description The NPI assessed behavioral disturbances comprises 10 dimensions: delusions, hallucinations, dysphoria, apathy, euphoria, disinhibition, aggressiveness and agitation, irritability, anxiety and aberrant motor activity. The par. caregiver asked about behavior in the par. If “Yes”, the informant then rates both the severity on a 3-point scale, 1: mild to 3: severe (total range: 0-36) and the frequency using a 4-point scale, 1: occasionally to 4: very frequently. The total domain score was frequency × severity. The distress was scored on 5-point scale, 0: no distress to 5 - very severe or extreme. A total NPI score can be calculated by adding all domain scores together; NPI total score: from 0-144 and NPI distress score: from 0-60, all with higher scores indicating more severe behavioral disturbance. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at W0.
Time Frame Baseline (W0) and up to W24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants available at the specified time points were analyzed (represented as n=x,x,x,x in the category titles). Endpoint treatment differences which were adjusted to take account of missing data are derived.
Arm/Group Title Placebo RSG XR 2 mg RSG XR 8 mg Donepezil 10 mg
Hide Arm/Group Description:
Par. in this arm received RSG placebo tablet along with dummy donepezil capsule once daily for 24W. For par. in this arm, the dosage were remain constant throughout the 24W treatment period. Study treatment were taken in the evening with or without food.
Par. in this arm received RSGXR 2 milligram (mg) tablet along with dummy donepezil capsule once daily for 24W. For par. in this arm, the dosage were remain constant throughout the 24W treatment period. Study treatment were taken in the evening with or without food.
Par. in this arm received RSGXR 4 mg tablet along with dummy donepezil capsule once daily for the first 4 weeks of treatment. From Visit 4 (Week 4) onwards, these par. received 8 mg RSGXR tablet along with dummy donepezil capsule once daily for the remaining 20W of double-blind treatment. Study treatment were taken in the evening with or without food.
Par. in this arm received donepezil 5 mg capsule along with dummy RSGXR tablet once daily for the first 4 weeks of treatment. From Visit 4 (Week 4) onwards, these par. received donepezil 10 mg capsule along with dummy RSGXR tablet once daily for the remaining 20W of double-blind treatment. Study treatment were taken in the evening with or without food.
Overall Number of Participants Analyzed 159 162 156 76
Least Squares Mean (Standard Error)
Unit of Measure: Score on a scale
NPI, W8, n=146,151,144,65 0.2  (0.59) 0.1  (0.63) 0.5  (0.81) -0.1  (0.87)
NPI, W16, n=139,142,131,59 -0.1  (0.69) -0.0  (0.69) -0.1  (0.90) 0.5  (0.97)
NPI, W24, n=129,133,127,55 1.2  (1.04) 1.6  (0.74) 1.1  (1.01) -0.6  (1.12)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 2 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.957
Comments Comparison between Placebo and RSG XR 2mg at Week 8 in Full population cohort
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 (Final Values)
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-1.6 to 1.5
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 8 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.693
Comments Comparison between Placebo and RSG XR 8 mg at Week 8 in Full population cohort
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 (Final Values)
Estimated Value 0.4
Confidence Interval (2-Sided) 95%
-1.4 to 2.2
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Donepezil 10 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.798
Comments Comparison between Placebo and Donepezil 10 mg at Week 8 in Full population cohort
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 (Final Values)
Estimated Value -0.3
Confidence Interval (2-Sided) 95%
-2.2 to 1.7
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 2 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.958
Comments Comparison between Placebo and RSG XR 2 mg at Week 16 in Full population cohort
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 (Final Values)
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-1.7 to 1.8
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 8 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.998
Comments Comparison between Placebo and RSG XR 8 mg at Week 16 in Full population cohort
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 (Final Values)
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-2.1 to 2.1
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, Donepezil 10 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.639
Comments Comparison between Placebo and Donepezil 10 mg at Week 16 in Full population cohort
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 (Final Values)
Estimated Value 0.5
Confidence Interval 95%
-1.7 to 2.8
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 2 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.797
Comments Comparison between Placebo and RSG XR 2 mg at Week 24 in Full population cohort
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 (Final Values)
Estimated Value 0.3
Confidence Interval (2-Sided) 95%
-2.1 to 2.7
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 8 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.942
Comments Comparison between Placebo and RSG XR 8 mg at Week 24 in Full population cohort
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 (Final Values)
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-2.9 to 2.7
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Placebo, Donepezil 10 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.213
Comments Comparison between Placebo and Donepezil 10 mg at Week 24 in Full population cohort
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 (Final Values)
Estimated Value -1.9
Confidence Interval (2-Sided) 95%
-4.8 to 1.1
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
10.Secondary Outcome
Title Change From Baseline (W0) in Mean Disability Assessment for Dementia (DAD) Scale Total Score at W8, W16, W24
Hide Description The DAD, assessed the ability of a par. 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 assesses a participants’ ability to initiate, plan, and perform activities related to hygiene, dressing, continence, eating, meal preparation, telephoning, going on an outing, finance and correspondence, medications, leisure, and housework. 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. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at W0. The percentage score was calculated as (DAD total score/total number of applicable items) multiplied by 100. Endpoint treatment differences which were adjusted to take account of missing data are derived.
Time Frame Baseline (W0) and up to W24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those par. available at the specified time points were analyzed (represented as n=x,x,x,x in the category titles).
Arm/Group Title Placebo RSG XR 2 mg RSG XR 8 mg Donepezil 10 mg
Hide Arm/Group Description:
Par. in this arm received RSG placebo tablet along with dummy donepezil capsule once daily for 24W. For par. in this arm, the dosage were remain constant throughout the 24W treatment period. Study treatment were taken in the evening with or without food.
Par. in this arm received RSGXR 2 milligram (mg) tablet along with dummy donepezil capsule once daily for 24W. For par. in this arm, the dosage were remain constant throughout the 24W treatment period. Study treatment were taken in the evening with or without food.
Par. in this arm received RSGXR 4 mg tablet along with dummy donepezil capsule once daily for the first 4W of treatment. From Visit 4 (W4) onwards, these par. received 8 mg RSGXR tablet along with dummy donepezil capsule once daily for the remaining 20W of double-blind treatment. Study treatment were taken in the evening with or without food.
Par. in this arm received donepezil 5 mg capsule along with dummy RSGXR tablet once daily for the first 4W of treatment. From Visit 4 (W4) onwards, these par. received donepezil 10 mg capsule along with dummy RSGXR tablet once daily for the remaining 20W of double-blind treatment. Study treatment were taken in the evening with or without food.
Overall Number of Participants Analyzed 159 162 156 76
Least Squares Mean (Standard Error)
Unit of Measure: Score on a scale
DAD, W8, n=147,152, 144, 65 -0.8  (0.80) -0.6  (0.94) -0.3  (0.78) 0.5  (1.00)
DAD, W16, n=141,143,131,59 -2.6  (0.98) -1.7  (1.07) -1.7  (1.05) 1.1  (1.40)
DAD, W24, n=129,133,127,55 -3.7  (0.97) -2.4  (1.21) -3.8  (1.19) -0.2  (1.81)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 2 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.919
Comments Comparison between Placebo and RSG XR 2 mg at Week 8 in Full population cohort
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 (Final Values)
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 par. with evaluable data
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 8 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.649
Comments Comparison between Placebo and RSG XR 8 mg at Week 8 in Full population cohort
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 (Final Values)
Estimated Value 0.5
Confidence Interval (2-Sided) 95%
-1.5 to 2.4
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Donepezil 10 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.279
Comments Comparison between Placebo and Donepezil 10 mg at Week 8 in Full population cohort
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 (Final Values)
Estimated Value 1.3
Confidence Interval (2-Sided) 95%
-1.1 to 3.6
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 2 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.498
Comments Comparison between Placebo and RSG XR 2 mg at Week 16 in Full population cohort
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 (Final Values)
Estimated Value 0.9
Confidence Interval (2-Sided) 95%
-1.8 to 3.6
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 8 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.489
Comments Comparison between Placebo and RSG XR 8 mg in at Week 16 Full population cohort
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 (Final Values)
Estimated Value 0.9
Confidence Interval (2-Sided) 95%
-1.7 to 3.6
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, Donepezil 10 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.024
Comments Comparison between Placebo and Donepezil 10 mg at Week 16 in Full population cohort
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 (Final Values)
Estimated Value 3.7
Confidence Interval (2-Sided) 95%
0.5 to 7.0
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 2 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.385
Comments Comparison between Placebo and RSG XR 2 mg at Week 24 in Full population cohort
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 (Final Values)
Estimated Value 1.3
Confidence Interval (2-Sided) 95%
-1.6 to 4.2
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 8 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.944
Comments Comparison between Placebo and RSG XR 8 mg at Week 24 in Full population cohort
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 (Final Values)
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-3.0 to 2.8
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Placebo, Donepezil 10 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.078
Comments Comparison between Placebo and Donepezil 10 mg at Week 24 in Full population cohort
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 (Final Values)
Estimated Value 3.6
Confidence Interval (2-Sided) 95%
-0.4 to 7.5
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
11.Secondary Outcome
Title Change From Baseline (W0) in Mean Short Term Memory Assessment Total Score (ADAS-Cog Q1 Plus Q7) at W8, W16, W24
Hide Description Change from Baseline in short term memory assessment score was assessed from a combined analysis of items 1 (word recall task) and 7 (word recognition task) of ADAS-Cog scale. Word recall task consist of the participants score was the mean number of words not recalled on three trials (maximum score 10) and word recognition task, to score this item the number of incorrect responses was counted (maximum error score was 12). Higher score indicating greater dysfunction. Total score is sum of individual score. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at W0. Endpoint treatment differences which were adjusted to take account of missing data are derived.
Time Frame Baseline (W0) and up to W24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those par. available at the specified time points were analyzed (represented as n=x,x,x,x in the category titles).
Arm/Group Title Placebo RSG XR 2 mg RSG XR 8 mg Donepezil 10 mg
Hide Arm/Group Description:
Par. in this arm received RSG placebo tablet along with dummy donepezil capsule once daily for 24W. For par. in this arm, the dosage were remain constant throughout the 24W treatment period. Study treatment were taken in the evening with or without food.
Par. in this arm received RSGXR 2 milligram (mg) tablet along with dummy donepezil capsule once daily for 24W. For par. in this arm, the dosage were remain constant throughout the 24W treatment period. Study treatment were taken in the evening with or without food.
Par. in this arm received RSGXR 4 mg tablet along with dummy donepezil capsule once daily for the first 4W of treatment. From Visit 4 (W4) onwards, these par. received 8 mg RSGXR tablet along with dummy donepezil capsule once daily for the remaining 20W of double-blind treatment. Study treatment were taken in the evening with or without food.
Par. in this arm received donepezil 5 mg capsule along with dummy RSGXR tablet once daily for the first 4W of treatment. From Visit 4 (W4) onwards, these par. received donepezil 10 mg capsule along with dummy RSGXR tablet once daily for the remaining 20W of double-blind treatment. Study treatment were taken in the evening with or without food.
Overall Number of Participants Analyzed 159 162 156 76
Least Squares Mean (Standard Error)
Unit of Measure: Score on a scale
ADAS-Cog Q1 plus Q7, W8, n=152,155,146,67 0.1  (0.25) -0.1  (0.27) 0.5  (0.25) -0.4  (0.40)
ADAS-Cog Q1 plus Q7, W16, n=143,143,130,62 0.1  (0.27) 0.6  (0.26) 0.8  (0.24) -0.6  (0.45)
ADAS-Cog Q1 plus Q7, W24, n=131,128,123,56 0.7  (0.27) 0.3  (0.30) 0.6  (0.29) 0.2  (0.43)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 2 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.635
Comments Comparison between Placebo and RSG XR 2 mg at Week 8 in Full population cohort
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 (Final Values)
Estimated Value -0.2
Confidence Interval (2-Sided) 95%
-0.8 to 0.5
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 8 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.194
Comments Comparison between Placebo and RSG XR 8 mg at Week 8 in Full population cohort
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 (Final Values)
Estimated Value 0.4
Confidence Interval (2-Sided) 95%
-0.2 to 1.1
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Donepezil 10 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.325
Comments Comparison between Placebo and Donepezil 10 mg at Week 8 in Full population cohort
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 (Final Values)
Estimated Value -0.4
Confidence Interval (2-Sided) 95%
-1.3 to 0.4
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 2 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.109
Comments Comparison between Placebo and RSG XR 2 mg at Week 16 in Full population cohort
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 (Final Values)
Estimated Value 0.6
Confidence Interval (2-Sided) 95%
-0.1 to 1.2
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 8 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.032
Comments Comparison between Placebo and RSG XR 8 mg at Week 16 in Full population cohort
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 (Final Values)
Estimated Value 0.7
Confidence Interval (2-Sided) 95%
0.1 to 1.4
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, Donepezil 10 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.189
Comments Comparison between Placebo and Donepezil 10 mg at Week 16 in Full population cohort
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 (Final Values)
Estimated Value -0.7
Confidence Interval (2-Sided) 95%
-1.7 to 0.3
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 2 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.288
Comments Comparison between Placebo and RSG XR 2 mg at Week 24 in Full population cohort
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 (Final Values)
Estimated Value -0.4
Confidence Interval (2-Sided) 95%
-1.1 to 0.3
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 8 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.819
Comments Comparison between Placebo and RSG XR 8 mg at Week 24 in Full population cohort
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 (Final Values)
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-0.8 to 0.6
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Placebo, Donepezil 10 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.306
Comments Comparison between Placebo and Donepezil 10 mg at Week 24 in Full population cohort
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 (Final Values)
Estimated Value -0.5
Confidence Interval (2-Sided) 95%
-1.5 to 0.5
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
12.Secondary Outcome
Title Change From Baseline (W0) in Mean European Quality of Life -5 Dimensions Proxy Version (EQ-5D Proxy) Total Score at W12, W24 Assessed by Utility
Hide Description The EQ-5D Proxy was a 2 part scale used to assess the quality of life and utility benefit. The data for Part 1 is presented. It is a 5 dimensional Health State Classification. Caregivers were asked to respond as they feel the par. would on dimensions of mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Answers to each question were recorded 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. EQ-5D Proxy assessments was performed at Baseline, W12 and W24. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at W0. Endpoint treatment differences which were adjusted to take account of missing data are derived.
Time Frame Baseline (W0) and up to W24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those par. available at the specified time points were analyzed (represented as n=x,x,x,x in the category titles).
Arm/Group Title Placebo RSG XR 2 mg RSG XR 8 mg Donepezil 10 mg
Hide Arm/Group Description:
Par. in this arm received RSG placebo tablet along with dummy donepezil capsule once daily for 24W. For par. in this arm, the dosage were remain constant throughout the 24W treatment period. Study treatment were taken in the evening with or without food.
Par. in this arm received RSGXR 2 milligram (mg) tablet along with dummy donepezil capsule once daily for 24W. For par. in this arm, the dosage were remain constant throughout the 24W treatment period. Study treatment were taken in the evening with or without food.
Par. in this arm received RSGXR 4 mg tablet along with dummy donepezil capsule once daily for the first 4 weeks of treatment. From Visit 4 (Week 4) onwards, these par. received 8 mg RSGXR tablet along with dummy donepezil capsule once daily for the remaining 20W of double-blind treatment. Study treatment were taken in the evening with or without food.
Par. in this arm received donepezil 5 mg capsule along with dummy RSGXR tablet once daily for the first 4 weeks of treatment. From Visit 4 (Week 4) onwards, these par. received donepezil 10 mg capsule along with dummy RSGXR tablet once daily for the remaining 20W of double-blind treatment. Study treatment were taken in the evening with or without food.
Overall Number of Participants Analyzed 159 162 156 76
Least Squares Mean (Standard Error)
Unit of Measure: Score on a scale
EQ-5D Proxy Utility, W12, n=141,146, 135, 62 -0.02  (0.017) 0.00  (0.016) 0.01  (0.016) 0.01  (0.021)
EQ-5D Proxy Utility, W24, n=128, 130, 125, 55 -0.02  (0.017) 0.02  (0.016) -0.02  (0.019) 0.00  (0.018)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 2 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.199
Comments Comparison between Placebo and RSG XR 2 mg at Week 12 in Full population cohort
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 (Final Values)
Estimated Value 0.03
Confidence Interval (2-Sided) 95%
-0.01 to 0.07
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 8 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.094
Comments Comparison between Placebo and RSG XR 8 mg at Week 12 in Full population cohort
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 (Final Values)
Estimated Value 0.04
Confidence Interval (2-Sided) 95%
-0.01 to 0.08
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Donepezil 10 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.187
Comments Comparison between Placebo and Donepezil 10 mg at Week 12 in Full population cohort
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 (Final Values)
Estimated Value 0.03
Confidence Interval (2-Sided) 95%
-0.02 to 0.09
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 2 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.134
Comments Comparison between Placebo and RSG XR 2 mg at Week 24 in Full population cohort
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 (Final Values)
Estimated Value 0.03
Confidence Interval (2-Sided) 95%
-0.01 to 0.07
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 8 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.958
Comments Comparison between Placebo and RSG XR 8 mg at Week 24 in Full population cohort
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 (Final Values)
Estimated Value 0.00
Confidence Interval (2-Sided) 95%
-0.05 to 0.05
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, Donepezil 10 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.374
Comments Comparison between Placebo and Donepezil 10 mg at Week 24 in Full population cohort
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 (Final Values)
Estimated Value 0.02
Confidence Interval (2-Sided) 95%
-0.03 to 0.07
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
13.Secondary Outcome
Title Change From Baseline (W0) in Mean European Quality of Life -5 Dimensions Proxy Version (EQ-5D Proxy) Total Score at W12, W24 Assessed by Thermometer (Visual Analog Scale [VAS])
Hide Description The EQ-5D Proxy is a 2 part scale used to assess the quality of life and utility benefit. The data for Part 2 is presented. It is a the visual analogue scale Thermometer which assessed caregiver's impression of par. overall health. The Thermometer has endpoints of 100 (best imaginable health state) and 0 (worst imaginable health state). EQ-5D Proxy assessments was performed at Baseline, W12 and W24. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at W0. Endpoint treatment differences which were adjusted to take account of missing data are derived.
Time Frame Baseline (W0) and up to W24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those par. available at the specified time points were analyzed (represented as n=x,x,x,x in the category titles).
Arm/Group Title Placebo RSG XR 2 mg RSG XR 8 mg Donepezil 10 mg
Hide Arm/Group Description:
Par. in this arm received RSG placebo tablet along with dummy donepezil capsule once daily for 24W. For par. in this arm, the dosage were remain constant throughout the 24W treatment period. Study treatment were taken in the evening with or without food.
Par. in this arm received RSGXR 2 milligram (mg) tablet along with dummy donepezil capsule once daily for 24W. For par. in this arm, the dosage were remain constant throughout the 24W treatment period. Study treatment were taken in the evening with or without food.
Par. in this arm received RSGXR 4 mg tablet along with dummy donepezil capsule once daily for the first 4W of treatment. From Visit 4 (W4) onwards, these par. received 8 mg RSGXR tablet along with dummy donepezil capsule once daily for the remaining 20W of double-blind treatment. Study treatment were taken in the evening with or without food.
Par. in this arm received donepezil 5 mg capsule along with dummy RSGXR tablet once daily for the first 4W of treatment. From Visit 4 (W4) onwards, these par. received donepezil 10 mg capsule along with dummy RSGXR tablet once daily for the remaining 20W of double-blind treatment. Study treatment were taken in the evening with or without food.
Overall Number of Participants Analyzed 159 162 156 76
Least Squares Mean (Standard Error)
Unit of Measure: Score on a scale
EQ-5D Proxy Thermometer, W12, n=141, 146, 135, 62 1.4  (1.35) 0.3  (1.37) 1.7  (1.41) -2.6  (2.41)
EQ-5D Proxy Thermometer, W24, n=128, 130, 126, 55 1.9  (1.56) -0.7  (1.52) 0.2  (1.71) 1.5  (2.40)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 2 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.493
Comments Comparison between Placebo and RSG XR 2 mg at Week 12 in Full population cohort
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 (Final Values)
Estimated Value -1.2
Confidence Interval (2-Sided) 95%
-4.6 to 2.2
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 8 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.883
Comments Comparison between Placebo and RSG XR 8 mg at Week 12 in Full population cohort
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 (Final Values)
Estimated Value 0.3
Confidence Interval (2-Sided) 95%
-3.2 to 3.7
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Donepezil 10 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.130
Comments Comparison between Placebo and Donepezil 10 mg at Week 12 in Full population cohort
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 (Final Values)
Estimated Value -4.0
Confidence Interval (2-Sided) 95%
-9.3 to 1.2
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 2 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.198
Comments Comparison between Placebo and RSG XR 2 mg at Week 24 in Full population cohort
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 (Final Values)
Estimated Value -2.6
Confidence Interval (2-Sided) 95%
-6.6 to 1.4
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 8 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.441
Comments Comparison between Placebo and RSG XR 8 mg at Week 24 in Full population cohort
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 (Final Values)
Estimated Value -1.7
Confidence Interval (2-Sided) 95%
-5.9 to 2.6
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, Donepezil 10 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.898
Comments Comparison between Placebo and Donepezil 10 mg at Week 24 in Full population cohort
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 (Final Values)
Estimated Value -0.4
Confidence Interval (2-Sided) 95%
-5.8 to 5.1
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
14.Secondary Outcome
Title Time Spent Caring for Basic and Instrumental Activities Resource Utilization in Dementia (RUD) Scale at W12 and W24
Hide Description The RUD instrument was developed as a comprehensive tool to assess the amount of resource use among demented par. RUD assess both formal and informal resource use of the par. and the primary caregiver, making it possible to calculate costs from a societal perspective. Q1 relates to assisting par. with basic activities of daily living and Q2 relates to instrumental activities of daily living. The assessments was performed at Baseline, W12 and W24. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at W0. Endpoint treatment differences which were adjusted to take account of missing data are derived.
Time Frame Baseline (W0) and up to W24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those par. available at the specified time points were analyzed (represented as n=x,x,x,x in the category titles).
Arm/Group Title Placebo RSG XR 2 mg RSG XR 8 mg Donepezil 10 mg
Hide Arm/Group Description:
Par. in this arm received RSG placebo tablet along with dummy donepezil capsule once daily for 24W. For par. in this arm, the dosage were remain constant throughout the 24W treatment period. Study treatment were taken in the evening with or without food.
Par. in this arm received RSGXR 2 milligram (mg) tablet along with dummy donepezil capsule once daily for 24W. For par. in this arm, the dosage were remain constant throughout the 24W treatment period. Study treatment were taken in the evening with or without food.
Par. in this arm received RSGXR 4 mg tablet along with dummy donepezil capsule once daily for the first 4 weeks of treatment. From Visit 4 (Week 4) onwards, these par. received 8 mg RSGXR tablet along with dummy donepezil capsule once daily for the remaining 20W of double-blind treatment. Study treatment were taken in the evening with or without food.
Par. in this arm received donepezil 5 mg capsule along with dummy RSGXR tablet once daily for the first 4 weeks of treatment. From Visit 4 (Week 4) onwards, these par. received donepezil 10 mg capsule along with dummy RSGXR tablet once daily for the remaining 20W of double-blind treatment. Study treatment were taken in the evening with or without food.
Overall Number of Participants Analyzed 159 162 156 76
Mean (Standard Deviation)
Unit of Measure: Hours
RUD Q1, W12, n=141, 149, 137, 69 2.3  (43.31) 4.5  (81.21) -9.8  (77.44) -5.7  (70.19)
RUD Q1, W24, n=128, 133, 127, 55 19.4  (109.41) -0.6  (58.72) -2.7  (86.26) 3.7  (19.26)
RUD Q2, W12, n=141, 149, 137, 62 13.7  (73.94) 9.0  (60.54) 4.9  (80.97) -5.3  (56.50)
RUD Q2, W24, n=128, 133, 127, 55 17.1  (75.45) 9.7  (47.96) 11.6  (107.52) 1.1  (61.49)
15.Secondary Outcome
Title Change From Baseline (W0) in Alzheimer’s Carer’s Quality of Life Instrument (ACQLI) Score at W12 and W24.
Hide Description The ACQLI was an assessment of caregiver quality of life. This instrument consists of 30 questions exploring various aspects of carer’s quality of life. Each of the questions had a two point response and the 30 questions were summed to provide a total score. Items are assumed to be unidimensional (i.e., represent a single variable) and are scored 0/1 (false/true) before summation into a total score with a 0–30 range. To ease comparisons between scales, ACQLI scores were transformed to range between 0–100 (100: worse). The assessments was performed at Baseline, W12 and W24. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at W0. Endpoint treatment differences which were adjusted to take account of missing data are derived.
Time Frame Baseline (W0) and up to W24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those par. available at the specified time points were analyzed (represented as n=x,x,x,x in the category titles).
Arm/Group Title Placebo RSG XR 2 mg RSG XR 8 mg Donepezil 10 mg
Hide Arm/Group Description:
Par. in this arm received RSG placebo tablet along with dummy donepezil capsule once daily for 24W. For par. in this arm, the dosage were remain constant throughout the 24W treatment period. Study treatment were taken in the evening with or without food.
Par. in this arm received RSGXR 2 milligram (mg) tablet along with dummy donepezil capsule once daily for 24W. For par. in this arm, the dosage were remain constant throughout the 24W treatment period. Study treatment were taken in the evening with or without food.
Par. in this arm received RSGXR 4 mg tablet along with dummy donepezil capsule once daily for the first 4W of treatment. From Visit 4 (W4) onwards, these par. received 8 mg RSGXR tablet along with dummy donepezil capsule once daily for the remaining 20W of double-blind treatment. Study treatment were taken in the evening with or without food.
Par. in this arm received donepezil 5 mg capsule along with dummy RSGXR tablet once daily for the first 4W of treatment. From Visit 4 (W4) onwards, these par. received donepezil 10 mg capsule along with dummy RSGXR tablet once daily for the remaining 20W of double-blind treatment. Study treatment were taken in the evening with or without food.
Overall Number of Participants Analyzed 159 162 156 76
Least Squares Mean (Standard Error)
Unit of Measure: Score on a scale
ACQLI, W12, n=141, 148, 137, 60 0.5  (0.38) -0.6  (0.41) -0.1  (0.46) 0.5  (0.50)
ACQLI, W24, n=128, 132, 126, 54 0.6  (0.45) -0.2  (0.49) 0.0  (0.54) -0.0  (0.69)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 2 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.027
Comments Comparison between Placebo and RSG XR 2 mg at Week 12 in Full population cohort
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 (Final Values)
Estimated Value -1.1
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 par. with evaluable data
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 8 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.278
Comments Comparison between Placebo and RSG XR 8 mg at Week 12 in Full population cohort
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 (Final Values)
Estimated Value -0.6
Confidence Interval (2-Sided) 95%
-1.6 to 0.5
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Donepezil 10 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.993
Comments Comparison between Placebo and Donepezil 10 mg at Week 12 in Full population cohort
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 (Final Values)
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-1.2 to 1.1
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 2 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.196
Comments Comparison between Placebo and RSG XR 2 mg at Week 24 in Full population cohort
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 (Final Values)
Estimated Value -0.8
Confidence Interval (2-Sided) 95%
-2.0 to 0.4
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 8 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.353
Comments Comparison between Placebo and RSG XR 8 mg at Week 24 in Full population cohort
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 (Final Values)
Estimated Value -0.6
Confidence Interval (2-Sided) 95%
-1.9 to 0.7
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, Donepezil 10 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.427
Comments Comparison between Placebo and Donepezil 10 mg at Week 24 in Full population cohort
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 (Final Values)
Estimated Value -0.6
Confidence Interval (2-Sided) 95%
-2.2 to 0.9
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
16.Secondary Outcome
Title Change From Baseline (W0) in Mini Mental State Examination (MMSE) Total Score at W24.
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 par. and takes approximately 5 to 10 minutes to administer. The assessments was performed at Baseline and W24. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at W0. Endpoint treatment differences which were adjusted to take account of missing data are derived
Time Frame Baseline (W0) and W24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those par. available at the specified time points were analyzed (represented as n=x,x,x,x in the category titles).
Arm/Group Title Placebo RSG XR 2 mg RSG XR 8 mg Donepezil 10 mg
Hide Arm/Group Description:
Par. in this arm received RSG placebo tablet along with dummy donepezil capsule once daily for 24W. For par. in this arm, the dosage were remain constant throughout the 24W treatment period. Study treatment were taken in the evening with or without food.
Par. in this arm received RSGXR 2 milligram (mg) tablet along with dummy donepezil capsule once daily for 24W. For par. in this arm, the dosage were remain constant throughout the 24W treatment period. Study treatment were taken in the evening with or without food.
Par. in this arm received RSGXR 4 mg tablet along with dummy donepezil capsule once daily for the first 4W of treatment. From Visit 4 (W4) onwards, these par. received 8 mg RSGXR tablet along with dummy donepezil capsule once daily for the remaining 20W of double-blind treatment. Study treatment were taken in the evening with or without food.
Par. in this arm received donepezil 5 mg capsule along with dummy RSGXR tablet once daily for the first 4W of treatment. From Visit 4 (W4) onwards, these par. received donepezil 10 mg capsule along with dummy RSGXR tablet once daily for the remaining 20W of double-blind treatment. Study treatment were taken in the evening with or without food.
Overall Number of Participants Analyzed 131 133 127 56
Least Squares Mean (Standard Error)
Unit of Measure: Score on a scale
-0.5  (0.27) -0.6  (0.27) -0.7  (0.28) 0.4  (0.38)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 2 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.886
Comments [Not Specified]
Method ANCOVA
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Final Values)
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 par. with evaluable data
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 8 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.710
Comments [Not Specified]
Method ANCOVA
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-0.8 to 0.6
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Donepezil 10 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.030
Comments [Not Specified]
Method ANCOVA
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.0
Confidence Interval (2-Sided) 95%
0.1 to 1.8
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
17.Secondary Outcome
Title Change From Baseline (W0) in Glycosylated Hemoglobin (HbA1c) at W24.
Hide Description The blood sample was collected for assessments of HbA1c levels at Baseline and W24. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at W0. Endpoint treatment differences which were adjusted to take account of missing data are derived.
Time Frame Baseline (W0) and W24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those par. available at the specified time points were analyzed (represented as n=x,x,x,x in the category titles).
Arm/Group Title Placebo RSG XR 2 mg RSG XR 8 mg Donepezil 10 mg
Hide Arm/Group Description:
Par. in this arm received RSG placebo tablet along with dummy donepezil capsule once daily for 24W. For par. in this arm, the dosage were remain constant throughout the 24W treatment period. Study treatment were taken in the evening with or without food.
Par. in this arm received RSGXR 2 milligram (mg) tablet along with dummy donepezil capsule once daily for 24W. For par. in this arm, the dosage were remain constant throughout the 24W treatment period. Study treatment were taken in the evening with or without food.
Par. in this arm received RSGXR 4 mg tablet along with dummy donepezil capsule once daily for the first 4W of treatment. From Visit 4 (W4) onwards, these par. received 8 mg RSGXR tablet along with dummy donepezil capsule once daily for the remaining 20W of double-blind treatment. Study treatment were taken in the evening with or without food.
Par. in this arm received donepezil 5 mg capsule along with dummy RSGXR tablet once daily for the first 4Wof treatment. From Visit 4 (W4) onwards, these par. received donepezil 10 mg capsule along with dummy RSGXR tablet once daily for the remaining 20W of double-blind treatment. Study treatment were taken in the evening with or without food.
Overall Number of Participants Analyzed 123 120 117 52
Least Squares Mean (Standard Error)
Unit of Measure: Percentage (%)
0.1  (0.05) 0.2  (0.05) 0.1  (0.05) 0.1  (0.07)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 2 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.139
Comments [Not Specified]
Method ANCOVA
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.1
Confidence Interval (2-Sided) 95%
-0.0 to 0.2
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, RSG XR 8 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.846
Comments [Not Specified]
Method ANCOVA
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-0.1 to 0.1
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Donepezil 10 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.864
Comments [Not Specified]
Method ANCOVA
Comments Mixed model for repeated measures with restricted maximum likelihood estimation and an unstructured covariance matrix
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-0.1 to 0.2
Estimation Comments Difference in adjusted least square means was shown (Active treatment minus Placebo); n = Number of par. with evaluable data
18.Secondary Outcome
Title Number of Participants With Adverse Events Defined by Severity
Hide Description An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE included significant or unexpected worsening or exacerbation of the condition/indication under study, exacerbation of a chronic or intermittent pre-existing condition, new conditions detected or diagnosed, signs, symptoms, or the clinical sequelae of a suspected overdose of either investigational product or a concurrent medication. Number of participants with any AE and as per severity were reported. Refer to the general AE/SAE module for a list of AEs and SAEs.
Time Frame Up to W24
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population: This included all par. randomized to treatment who have taken at least one dose of study medication.
Arm/Group Title Placebo RSG XR 2 mg RSG XR 8 mg Donepezil 10 mg
Hide Arm/Group Description:
Par. in this arm received RSG placebo tablet along with dummy donepezil capsule once daily for 24W. For par. in this arm, the dosage were remain constant throughout the 24W treatment period. Study treatment were taken in the evening with or without food.
Par. in this arm received RSGXR 2 milligram (mg) tablet along with dummy donepezil capsule once daily for 24W. For par. in this arm, the dosage were remain constant throughout the 24W treatment period. Study treatment were taken in the evening with or without food.
Par. in this arm received RSGXR 4 mg tablet along with dummy donepezil capsule once daily for the first 4W of treatment. From Visit 4 (W4) onwards, these par. received 8 mg RSGXR tablet along with dummy donepezil capsule once daily for the remaining 20W of double-blind treatment. Study treatment were taken in the evening with or without food.
Par. in this arm received donepezil 5 mg capsule along with dummy RSGXR tablet once daily for the first 4W of treatment. From Visit 4 (W4) onwards, these par. received donepezil 10 mg capsule along with dummy RSGXR tablet once daily for the remaining 20W of double-blind treatment. Study treatment were taken in the evening with or without food.
Overall Number of Participants Analyzed 165 166 165 83
Measure Type: Number
Unit of Measure: Participants
Any AE 62 60 69 42
Mild AE 32 35 37 22
Moderate AE 25 22 30 15
Severe AE 5 3 2 5
19.Secondary Outcome
Title Number of Participants With Systolic and Diastolic Blood Pressure (SBP and DBP), Heart Rate (HR) and Weight Values of Potential Clinical Concern (PCC) Any Time on Treatment (ATOT).
Hide Description SBP, DBP and HR of par. were recorded in sitting posture as vital signs, while body weight was measured without shoes and wearing light clothing at each visit. The blood pressure (BP) and HR values were identified as of PCC if the vales were out of the reference range (for SBP, 90 to 140 millimeters of mercury (mmHg), DBP, 50 to 90 mmHg, and HR >100 or <50 beats per minute [bpm]) or meet a change from Baseline criterion. For SBP it was increase from Baseline (high) if increased by more than or equal to (>=) 40 mmHg; decrease from Baseline (low) if decreased by >=30 mmHg. For DBP, increase from Baseline (high) if increased by >=30 mmHg; decrease from Baseline (low) if decreased by >=20 mmHg. For HR, increase from Baseline (high) if increased by >=30 bpm; decrease from Baseline (low) if decreased by >=30 bpm. For weight, increase from Baseline (high) if increased by >=7%; decrease from Baseline (low) if decreased by >=7%. Baseline was defined as value at W0.
Time Frame Up to W24
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those par. available at the specified time points were analyzed (represented as n=x,x,x,x in the category titles).
Arm/Group Title Placebo RSG XR 2 mg RSG XR 8 mg Donepezil 10 mg
Hide Arm/Group Description:
Par. in this arm received RSG placebo tablet along with dummy donepezil capsule once daily for 24W. For par. in this arm, the dosage were remain constant throughout the 24W treatment period. Study treatment were taken in the evening with or without food.
Par. in this arm received RSGXR 2 milligram (mg) tablet along with dummy donepezil capsule once daily for 24W. For par. in this arm, the dosage were remain constant throughout the 24W treatment period. Study treatment were taken in the evening with or without food.
Par. in this arm received RSGXR 4 mg tablet along with dummy donepezil capsule once daily for the first 4W of treatment. From Visit 4 (W4) onwards, these par. received 8 mg RSGXR tablet along with dummy donepezil capsule once daily for the remaining 20W of double-blind treatment. Study treatment were taken in the evening with or without food.
Par.in this arm received donepezil 5 mg capsule along with dummy RSGXR tablet once daily for the first 4W of treatment. From Visit 4 (W4) onwards, these par. received donepezil 10 mg capsule along with dummy RSGXR tablet once daily for the remaining 20W of double-blind treatment. Study treatment were taken in the evening with or without food.
Overall Number of Participants Analyzed 160 162 154 79
Measure Type: Number
Unit of Measure: Participants
SBP, >140 or <90 52 61 41 24
SBP, Increase from Baseline >=40 1 3 3 3
SBP, Decrease from Baseline >=30 7 9 15 6
DBP, >90 or <50 17 16 13 8
DBP, Increase from Baseline >=30 4 1 1 1
DBP, Decrease from Baseline >=20 8 12 25 8
HR, >100 or <50 2 4 4 2
HR, Increase from Baseline >=30 1 3 3 1
HR, Decrease from Baseline >=30 3 0 0 1
Weight, Increase from Baseline >=7% 9 21 25 1
Weight, Decrease from Baseline >=7% 7 4 3 5
20.Secondary Outcome
Title Change From Baseline (W0) in 12-lead Electrocardiogram (ECG)
Hide Description Triplicate 12-lead ECG measures was obtained digitally, approximately one minute apart after the par. had rested in the supine position in a quiet room (no TV, minimal talking) for at least 10 minutes. Conduction intervals from the 12-lead ECGs were manually read and confirmed by an external cardiologist/vendor. The ECG parameters includes PR interval, QRS duration, QT – uncorrected interval, QTc Bazett (QTcB), QTc Fridericia (QTcF) and RR interval of Central Cardiologist are reported. The assessments was performed at Baseline and W24. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at Screening/Visit 1/W-6.
Time Frame Baseline (W0) and up to W24
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those par. available at the specified time points were analyzed (represented as n=x,x,x,x in the category titles).
Arm/Group Title Placebo RSG XR 2 mg RSG XR 8 mg Donepezil 10 mg
Hide Arm/Group Description:
Par. in this arm received RSG placebo tablet along with dummy donepezil capsule once daily for 24W. For par. in this arm, the dosage were remain constant throughout the 24W treatment period. Study treatment were taken in the evening with or without food.
Par. in this arm received RSGXR 2 milligram (mg) tablet along with dummy donepezil capsule once daily for 24W. For par. in this arm, the dosage were remain constant throughout the 24W treatment period. Study treatment were taken in the evening with or without food.
Par. in this arm received RSGXR 4 mg tablet along with dummy donepezil capsule once daily for the first 4W of treatment. From Visit 4 (W4) onwards, these par. received 8 mg RSGXR tablet along with dummy donepezil capsule once daily for the remaining 20W of double-blind treatment. Study treatment were taken in the evening with or without food.
Par. in this arm received donepezil 5 mg capsule along with dummy RSGXR tablet once daily for the first 4W of treatment. From Visit 4 (W4) onwards, these par. received donepezil 10 mg capsule along with dummy RSGXR tablet once daily for the remaining 20W of double-blind treatment. Study treatment were taken in the evening with or without food.
Overall Number of Participants Analyzed 165 166 165 83
Mean (Standard Deviation)
Unit of Measure: milliseconds (MSEC)
PR Interval, n=16,11, 14, 4 2.2  (14.39) 6.9  (30.44) 6.0  (19.98) -5.5  (8.50)
QRS Duration, n=17, 11, 14, 5 1.1  (8.28) 0.7  (5.50) 3.6  (6.14) 0.9  (9.04)
QT Interval, n=17, 11, 14, 5 5.3  (27.69) 15.6  (25.06) 19.8  (22.17) 15.9  (22.57)
QTcB, n=17, 11, 14, 5 10.2  (18.21) 7.1  (22.69) 20.0  (13.54) -0.2  (17.22)
QTcF, n=17, 11, 14, 5 8.1  (17.12) 10.0  (21.47) 20.1  (12.71) 4.9  (15.50)
RR Interval -12.3  (107.35) 43.8  (89.52) -0.5  (107.49) 76.5  (109.43)
21.Secondary Outcome
Title Change From Baseline (W0) in Heart Rate (HR) Measured From 12-lead Electrocardiogram (ECG)
Hide Description Triplicate 12-lead ECG measures was obtained digitally, approximately one minute apart after the par. had rested in the supine position in a quiet room (no TV, minimal talking) for at least 10 minutes. Conduction intervals from the 12-lead ECGs were manually read and confirmed by an external cardiologist/vendor. The ECG HR of Central Cardiologist reported. The assessments was performed at Baseline and W24. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at Screening/Visit 1/W-6.
Time Frame Baseline (W0) and up to W24
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those par. available at the specified time points were analyzed (represented as n=x,x,x,x in the category titles).
Arm/Group Title Placebo RSG XR 2 mg RSG XR 8 mg Donepezil 10 mg
Hide Arm/Group Description:
Par. in this arm received RSG placebo tablet along with dummy donepezil capsule once daily for 24W. For par. in this arm, the dosage were remain constant throughout the 24W treatment period. Study treatment were taken in the evening with or without food.
Par. in this arm received RSGXR 2 milligram (mg) tablet along with dummy donepezil capsule once daily for 24W. For par. in this arm, the dosage were remain constant throughout the 24W treatment period. Study treatment were taken in the evening with or without food.
Par. in this arm received RSGXR 4 mg tablet along with dummy donepezil capsule once daily for the first 4W of treatment. From Visit 4 (W4) onwards, these par. received 8 mg RSGXR tablet along with dummy donepezil capsule once daily for the remaining 20W of double-blind treatment. Study treatment were taken in the evening with or without food.
Par. in this arm received donepezil 5 mg capsule along with dummy RSGXR tablet once daily for the first 4W of treatment. From Visit 4 (W4) onwards, these par. received donepezil 10 mg capsule along with dummy RSGXR tablet once daily for the remaining 20W of double-blind treatment. Study treatment were taken in the evening with or without food.
Overall Number of Participants Analyzed 17 11 14 5
Mean (Standard Deviation)
Unit of Measure: Beats per minute
2.1  (12.08) -2.8  (7.77) -0.3  (8.39) -4.7  (9.23)
22.Secondary Outcome
Title Change From Baseline (W0) in Body Weight
Hide Description Body weight will be measured at all visits, without shoes and wearing light clothing. The assessments was performed at Baseline, W4, W8, W12, W16, and W24. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at W0.
Time Frame Baseline (W0) and up to W24
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those par. available at the specified time points were analyzed (represented as n=x,x,x,x in the category titles).
Arm/Group Title Placebo RSG XR 2 mg RSG XR 8 mg Donepezil 10 mg
Hide Arm/Group Description:
Par. in this arm received RSG placebo tablet along with dummy donepezil capsule once daily for 24W. For par. in this arm, the dosage were remain constant throughout the 24W treatment period. Study treatment were taken in the evening with or without food.
Par. in this arm received RSGXR 2 milligram (mg) tablet along with dummy donepezil capsule once daily for 24W. For par. in this arm, the dosage were remain constant throughout the 24W treatment period. Study treatment were taken in the evening with or without food.
Par. in this arm received RSGXR 4 mg tablet along with dummy donepezil capsule once daily for the first 4W of treatment. From Visit 4 (W4) onwards, these par. received 8 mg RSGXR tablet along with dummy donepezil capsule once daily for the remaining 20W of double-blind treatment. Study treatment were taken in the evening with or without food.
Par. in this arm received donepezil 5 mg capsule along with dummy RSGXR tablet once daily for the first 4W of treatment. From Visit 4 (W4) onwards, these par. received donepezil 10 mg capsule along with dummy RSGXR tablet once daily for the remaining 20W of double-blind treatment. Study treatment were taken in the evening with or without food.
Overall Number of Participants Analyzed 165 166 165 83
Mean (Standard Deviation)
Unit of Measure: Kilogram (Kg)
Week 4, n=160, 161, 153, 79 0.1  (1.59) 0.4  (1.76) 0.3  (1.61) -0.1  (1.39)
Week 8, n=150, 157, 147, 66 -0.0  (2.56) 0.5  (1.73) 0.8  (2.16) -0.4  (1.46)
Week 12, n=143, 149, 136, 61 0.0  (2.12) 0.6  (2.06) 0.9  (2.03) -0.9  (1.71)
Week 16, n=143, 146, 132, 61 -0.0  (2.05) 0.7  (2.20) 1.1  (2.08) -1.0  (2.05)
Week 24, 133, 132, 125, 55 -0.3  (2.53) 0.8  (2.63) 0.8  (2.54) -0.8  (2.28)
23.Secondary Outcome
Title Change From Baseline (W0) in Hemoglobin