ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 27 of 31 for:    alzheimer dijon

Open-Label Extension Study Of Rosiglitazone XR As Adjunctive Therapy In Subjects With Mild-to-Moderate Alzheimers

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00490568
Recruitment Status : Terminated (Based on preliminary parent study results)
First Posted : June 22, 2007
Results First Posted : November 13, 2017
Last Update Posted : November 13, 2017
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition: Alzheimer's Disease
Intervention: Drug: Rosiglitazone XR

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
A open-label extension study to evaluate the long-term safety and tolerability of rosiglitazone extended-release (RSG XR) tablets in participants with mild-to moderate Alzheimer’s Disease conducted in a total of 29 countries across 267 centers from 08 August 2007 to 30 May 2009.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Approximately 1800 participants were planned to be enrolled however a total of 1461 participants (after completing parent studies AVA102670/AVA102672) were enrolled and received open-label RSG-XR tablets.

Reporting Groups
  Description
RSG XR Eligible participants who completed studies AVA102670 or AVA102672 entered in this open-label extension study. Participants received open-label RSG XR throughout the treatment period as adjunctive therapy to their existing dose of Acetylcholinesterase Inhibitor (AChEI) for Alzheimer’s disease treatment. Participants took one tablet of study medication daily in the morning with or without food. All participants received oral 4 milligram (mg) once daily RSG XR for the first 4 weeks of the study (only for the first 4 weeks of the study). The RSG XR dose was then increased to 8 mg once daily from Week 4 through Week 52. The dose of RSG XR was reduced to 2mg once daily if the 8 mg dose was not well tolerated. Participants were not permitted to titrate back to 8 mg RSG XR.

Participant Flow:   Overall Study
    RSG XR
STARTED   1461 
COMPLETED   97 
NOT COMPLETED   1364 
Adverse Event                116 
Lost to Follow-up                13 
Protocol Violation                45 
Withdrawal by Subject                135 
Still in the study at termination                974 
Other                1 
Exclusion criteria met                1 
Caregiver related                20 
Abnormal ECG                25 
Participant refused follow-up                9 
Legal representative withdrew consent                1 
Disease progression                4 
Unmet inclusion-exclusion criteria                5 
Investigator decision                3 
Non-Compliance                7 
Efficacy related                3 
Participant died                1 
Participant withdrawal due to surgery                1 



  Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
RSG XR (AVA102675) Eligible participants who completed studies AVA102670 or AVA102672 entered in this open-label extension study. Participants received open-label RSG XR throughout the treatment period as adjunctive therapy to their existing dose of AChEI for Alzheimer’s disease treatment. Participants took one tablet of study medication daily in the morning with or without food. All participants received 4 mg once daily RSG XR for the first 4 weeks of the study (only for the first 4 weeks of the study). The RSG XR dose was then increased to 8 mg once daily from Week 4 through Week 52. The dose of RSG XR was reduced to 2mg once daily if the 8 mg dose was not well tolerated. Participants were not permitted to titrate back to 8 mg RSG XR.

Baseline Measures
   RSG XR (AVA102675) 
Overall Participants Analyzed 
[Units: Participants]
 1461 
Age 
[Units: Years]
Mean (Standard Deviation)
 73.9  (7.96) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
 
Female      843  57.7% 
Male      618  42.3% 
Race (NIH/OMB) 
[Units: Participants]
Count of Participants
 
American Indian or Alaska Native      6   0.4% 
Asian      52   3.6% 
Native Hawaiian or Other Pacific Islander      0   0.0% 
Black or African American      7   0.5% 
White      1396  95.6% 
More than one race      0   0.0% 
Unknown or Not Reported      0   0.0% 


  Outcome Measures

1.  Primary:   Number of Participants With Any Adverse Events (AEs) and Severity of AEs   [ Time Frame: Up to 76 Weeks ]

Measure Type Primary
Measure Title Number of Participants With Any Adverse Events (AEs) and Severity of AEs
Measure Description An AE is defined as any untoward medical occurrence in a patient or clinical investigation participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. The severity of the AE'S was categorized as mild, moderate and severe. Number of participants reporting AEs during the on treatment phase of the study.
Time Frame Up to 76 Weeks  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All Subjects (Full population), comprised of all participants who took at least one dose of open-label study medication.

Reporting Groups
  Description
RSG XR Eligible participants who completed studies AVA102670 or AVA102672 entered in this open-label extension study. Participants received open-label RSG XR throughout the treatment period as adjunctive therapy to their existing dose of AChEI for Alzheimer’s disease treatment. Participants took one tablet of study medication daily in the morning with or without food. All participants received 4 mg once daily RSG XR for the first 4 weeks of the study (only for the first 4 weeks of the study). The RSG XR dose was then increased to 8 mg once daily from Week 4 through Week 52. The dose of RSG XR was reduced to 2mg once daily if the 8 mg dose was not well tolerated. Participants were not permitted to titrate back to 8 mg RSG XR..

Measured Values
   RSG XR 
Participants Analyzed   1461 
Number of Participants With Any Adverse Events (AEs) and Severity of AEs 
[Units: Participants]
Count of Participants
 
Any AE   724 
Mild AE   345 
Moderate AE   289 
Severe AE   88 

No statistical analysis provided for Number of Participants With Any Adverse Events (AEs) and Severity of AEs



2.  Secondary:   Number Participants With Serious Adverse Events (SAEs) and Deaths   [ Time Frame: Up to 76 Weeks ]

Measure Type Secondary
Measure Title Number Participants With Serious Adverse Events (SAEs) and Deaths
Measure Description A SAE is defined as any untoward medical occurrence that, at any dose results in death, is a life-threatening condition, requires hospitalization or prolongation of existing hospitalization, results in disability or incapacity, or a congenital anomaly or birth defect. Number of participants with SAEs and deaths were reported for treatment duration of the study.
Time Frame Up to 76 Weeks  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All subject (Full population)

Reporting Groups
  Description
RSG XR Eligible participants who completed studies AVA102670 or AVA102672 entered in this open-label extension study. Participants received open-label RSG XR throughout the treatment period as adjunctive therapy to their existing dose of AChEI for Alzheimer’s disease treatment. Participants took one tablet of study medication daily in the morning with or without food. All participants received 4 mg once daily RSG XR for the first 4 weeks of the study (only for the first 4 weeks of the study). The RSG XR dose was then increased to 8 mg once daily from Week 4 through Week 52. The dose of RSG XR was reduced to 2mg once daily if the 8 mg dose was not well tolerated. Participants were not permitted to titrate back to 8 mg RSG XR.

Measured Values
   RSG XR 
Participants Analyzed   1461 
Number Participants With Serious Adverse Events (SAEs) and Deaths 
[Units: Participants]
Count of Participants
 
Any SAE   126 
Deaths   20 

No statistical analysis provided for Number Participants With Serious Adverse Events (SAEs) and Deaths



3.  Secondary:   Number of Participants With Adverse Event of Oedema   [ Time Frame: Up to 76 Weeks ]

Measure Type Secondary
Measure Title Number of Participants With Adverse Event of Oedema
Measure Description Oedema was considered as adverse event of special interest (AESI). The process for AESI selection was based on RSG's pharmacologic class and relevant AEs potentially associated with RSG. The number of participants and their percentage for the adverse event of the various types of oedema were reported.
Time Frame Up to 76 Weeks  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All subject (Full population)

Reporting Groups
  Description
RSG XR Eligible participants who completed studies AVA102670 or AVA102672 entered in this open-label extension study. Participants received open-label RSG XR throughout the treatment period as adjunctive therapy to their existing dose of AChEI for Alzheimer’s disease treatment. Participants took one tablet of study medication daily in the morning with or without food. All participants received 4 mg once daily RSG XR for the first 4 weeks of the study (only for the first 4 weeks of the study). The RSG XR dose was then increased to 8 mg once daily from Week 4 through Week 52. The dose of RSG XR was reduced to 2mg once daily if the 8 mg dose was not well tolerated. Participants were not permitted to titrate back to 8 mg RSG XR.

Measured Values
   RSG XR 
Participants Analyzed   1461 
Number of Participants With Adverse Event of Oedema 
[Units: Participants]
Count of Participants
 
Oedema peripheral   130 
Face oedema   8 
Pitting oedema   5 
Oedema   3 
Pulmonary oedema   1 
Eyelid oedema   1 

No statistical analysis provided for Number of Participants With Adverse Event of Oedema



4.  Secondary:   Change From Baseline in Vital Sign Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)   [ Time Frame: Up to 70 Weeks (including follow up) ]

Measure Type Secondary
Measure Title Change From Baseline in Vital Sign Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Measure Description Vital signs SBP and DBP were measured at each visit. All measurements were made on the participant non-dominant arm supported at heart level, using the same cuff size and same equipment. Blood pressure was measured once, after the participant sat quietly for at least 5 minutes. DBP was measured at the disappearance of Korotkoff sounds (Phase V). If the participant was a smoker or used tobacco products, a period of 30 minutes without tobacco was allowed before taking these measurements. Baseline for the open-label study was the latest assessment from Week 48 of parent studies to the first dose of open-label medication. Change from Baseline was measured as the blood pressure value recorded at specified visit minus the Baseline value.
Time Frame Up to 70 Weeks (including follow up)  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All subject (Full population). Only those participants available at the specified time points were analyzed.

Reporting Groups
  Description
RSG XR Eligible participants who completed studies AVA102670 or AVA102672 entered in this open-label extension study. Participants received open-label RSG XR throughout the treatment period as adjunctive therapy to their existing dose of AChEI for Alzheimer’s disease treatment. Participants took one tablet of study medication daily in the morning with or without food. All participants received 4 mg once daily RSG XR for the first 4 weeks of the study (only for the first 4 weeks of the study). The RSG XR dose was then increased to 8 mg once daily from Week 4 through Week 52. The dose of RSG XR was reduced to 2mg once daily if the 8 mg dose was not well tolerated. Participants were not permitted to titrate back to 8 mg RSG XR..

Measured Values
   RSG XR 
Participants Analyzed   1461 
Change From Baseline in Vital Sign Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) 
[Units: Millimeters of mercury (mmHg)]
Mean (Standard Deviation)
 
SBP at Week 4   
Participants Analyzed   1395 
SBP at Week 4   -1.4  (14.10) 
SBP at Week 8   
Participants Analyzed   1274 
SBP at Week 8   -2.4  (14.73) 
SBP at Week 12   
Participants Analyzed   1146 
SBP at Week 12   -2.7  (14.73) 
SBP at Week 16   
Participants Analyzed   1061 
SBP at Week 16   -3.7  (15.02) 
SBP at Week 24   
Participants Analyzed   892 
SBP at Week 24   -2.1  (15.51) 
SBP at Week 36   
Participants Analyzed   666 
SBP at Week 36   -1.4  (15.14) 
SBP at Week 52   
Participants Analyzed   251 
SBP at Week 52   -1.7  (16.18) 
SBP at Week 64   
Participants Analyzed   15 
SBP at Week 64   -2.2  (13.78) 
SBP at Follow-up   
Participants Analyzed   1280 
SBP at Follow-up   -1.8  (15.60) 
DBP at Week 4   
Participants Analyzed   1395 
DBP at Week 4   -1.4  (9.41) 
DBP at Week 8   
Participants Analyzed   1274 
DBP at Week 8   -2.0  (9.53) 
DBP at Week 12   
Participants Analyzed   1146 
DBP at Week 12   -2.1  (9.74) 
DBP at Week 16   
Participants Analyzed   1061 
DBP at Week 16   -2.4  (9.62) 
DBP at Week 24   
Participants Analyzed   892 
DBP at Week 24   -2.4  (9.48) 
DBP at Week 36   
Participants Analyzed   666 
DBP at Week 36   -2.0  (9.85) 
DBP at Week 52   
Participants Analyzed   251 
DBP at Week 52   -3.6  (9.94) 
DBP at Week 64   
Participants Analyzed   15 
DBP at Week 64   -6.3  (6.72) 
DBP at Follow-up   
Participants Analyzed   1280 
DBP at Follow-up   -0.9  (10.23) 

No statistical analysis provided for Change From Baseline in Vital Sign Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)



5.  Secondary:   Change From Baseline in Vital Sign Heart Rate (HR)   [ Time Frame: Up to 70 Weeks (including follow up) ]

Measure Type Secondary
Measure Title Change From Baseline in Vital Sign Heart Rate (HR)
Measure Description Vital sign HR was measured at each visit. HR was measured once, after the participant sat quietly for at least 5 minutes. Baseline for the open-label study was the latest assessment from Week 48 of parent studies to the first dose of open-label medication. Change from Baseline was measured as the HR at specified visit minus the Baseline value.
Time Frame Up to 70 Weeks (including follow up)  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All subject (Full population). Only those participants available at the specified time points were analyzed.

Reporting Groups
  Description
RSG XR Eligible participants who completed studies AVA102670 or AVA102672 entered in this open-label extension study. Participants received open-label RSG XR throughout the treatment period as adjunctive therapy to their existing dose of AChEI for Alzheimer’s disease treatment. Participants took one tablet of study medication daily in the morning with or without food. All participants received 4 mg once daily RSG XR for the first 4 weeks of the study (only for the first 4 weeks of the study). The RSG XR dose was then increased to 8 mg once daily from Week 4 through Week 52. The dose of RSG XR was reduced to 2mg once daily if the 8 mg dose was not well tolerated. Participants were not permitted to titrate back to 8 mg RSG XR.

Measured Values
   RSG XR 
Participants Analyzed   1461 
Change From Baseline in Vital Sign Heart Rate (HR) 
[Units: Beats per minute (bpm)]
Mean (Standard Deviation)
 
HR at Week 4   
Participants Analyzed   1391 
HR at Week 4   1.0  (8.95) 
HR at Week 8   
Participants Analyzed   1271 
HR at Week 8   1.8  (9.60) 
HR at Week 12   
Participants Analyzed   1142 
HR at Week 12   1.6  (9.77) 
HR at Week 16   
Participants Analyzed   1061 
HR at Week 16   1.6  (9.66) 
HR at Week 24   
Participants Analyzed   888 
HR at Week 24   0.9  (9.99) 
HR at Week 36   
Participants Analyzed   665 
HR at Week 36   1.3  (9.86) 
HR at Week 52   
Participants Analyzed   251 
HR at Week 52   0.7  (8.54) 
HR at Week 64   
Participants Analyzed   15 
HR at Week 64   1.0  (8.02) 
HR at Follow-up   
Participants Analyzed   1276 
HR at Follow-up   0.9  (10.03) 

No statistical analysis provided for Change From Baseline in Vital Sign Heart Rate (HR)



6.  Secondary:   Change From Baseline in Vital Sign Body Weight (BW)   [ Time Frame: Up to 70 Weeks (including follow up) ]

Measure Type Secondary
Measure Title Change From Baseline in Vital Sign Body Weight (BW)
Measure Description BW was measured at all visits, without shoes and wearing light clothing. Baseline for the open-label study was the latest assessment from Week 48 of parent studies to the first dose of open-label medication. Change from Baseline was measured as the body weight at specified visit minus the Baseline value.
Time Frame Up to 70 Weeks (including follow up)  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All subject (Full population). Only those participants available at the specified time points were analyzed.

Reporting Groups
  Description
RSG XR Eligible participants who completed studies AVA102670 or AVA102672 entered in this open-label extension study. Participants received open-label RSG XR throughout the treatment period as adjunctive therapy to their existing dose of AChEI for Alzheimer’s disease treatment. Participants took one tablet of study medication daily in the morning with or without food. All participants received 4 mg once daily RSG XR for the first 4 weeks of the study (only for the first 4 weeks of the study). The RSG XR dose was then increased to 8 mg once daily from Week 4 through Week 52. The dose of RSG XR was reduced to 2mg once daily if the 8 mg dose was not well tolerated. Participants were not permitted to titrate back to 8 mg RSG XR.

Measured Values
   RSG XR 
Participants Analyzed   1461 
Change From Baseline in Vital Sign Body Weight (BW) 
[Units: Kg]
Mean (Standard Deviation)
 
BW at Week 4   
Participants Analyzed   1391 
BW at Week 4   0.3  (2.04) 
BW at Week 8   
Participants Analyzed   1263 
BW at Week 8   0.6  (2.45) 
BW at Week 12   
Participants Analyzed   1139 
BW at Week 12   0.6  (2.43) 
BW at Week 16   
Participants Analyzed   1057 
BW at Week 16   0.7  (3.53) 
BW at Week 24   
Participants Analyzed   889 
BW at Week 24   0.6  (2.95) 
BW at Week 36   
Participants Analyzed   666 
BW at Week 36   1.0  (4.08) 
BW at Week 52   
Participants Analyzed   251 
BW at Week 52   1.2  (3.82) 
BW at Week 64   
Participants Analyzed   15 
BW at Week 64   1.4  (2.52) 
BW at Follow-up   
Participants Analyzed   1268 
BW at Follow-up   0.5  (3.15) 

No statistical analysis provided for Change From Baseline in Vital Sign Body Weight (BW)



7.  Secondary:   Change From Baseline in Non-fasting Measures of Lipid Metabolism Namely Total Cholesterol (TC), High Density Lipoprotein (HDL), Low Density Lipoprotein (LDL), Triglycerides   [ Time Frame: Up to 82 Weeks (including follow up) ]

Measure Type Secondary
Measure Title Change From Baseline in Non-fasting Measures of Lipid Metabolism Namely Total Cholesterol (TC), High Density Lipoprotein (HDL), Low Density Lipoprotein (LDL), Triglycerides
Measure Description The clinical chemistry data included non-fasting measures of lipid metabolism (TC,HDL,LDL,triglycerides). Baseline for the open-label study was the latest assessment from Week 48 of parent studies to the first dose of open-label medication. Change from Baseline was measured as the lipids (TC,HDL,LDL,triglycerides) value recorded at specified visit minus the Baseline value.
Time Frame Up to 82 Weeks (including follow up)  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All subject (Full population). Only those participants available at the specified time points were analyzed.

Reporting Groups
  Description
RSG XR Eligible participants who completed studies AVA102670 or AVA102672 entered in this open-label extension study. Participants received open-label RSG XR throughout the treatment period as adjunctive therapy to their existing dose of AChEI for Alzheimer’s disease treatment. Participants took one tablet of study medication daily in the morning with or without food. All participants received 4 mg once daily RSG XR for the first 4 weeks of the study (only for the first 4 weeks of the study). The RSG XR dose was then increased to 8 mg once daily from Week 4 through Week 52. The dose of RSG XR was reduced to 2mg once daily if the 8 mg dose was not well tolerated. Participants were not permitted to titrate back to 8 mg RSG XR.

Measured Values
   RSG XR 
Participants Analyzed   1461 
Change From Baseline in Non-fasting Measures of Lipid Metabolism Namely Total Cholesterol (TC), High Density Lipoprotein (HDL), Low Density Lipoprotein (LDL), Triglycerides 
[Units: Millimole per litre (mmol/l)]
Mean (Standard Deviation)
 
TC at Week 4   
Participants Analyzed   1313 
TC at Week 4   0.076  (0.6828) 
TC at Week 16   
Participants Analyzed   1038 
TC at Week 16   0.201  (0.8666) 
TC at Week 36   
Participants Analyzed   639 
TC at Week 36   0.246  (0.9649) 
TC at Week 52   
Participants Analyzed   234 
TC at Week 52   0.174  (1.1437) 
TC at Week 76   
Participants Analyzed   2 
TC at Week 76   -0.715  (0.3041) 
TC at follow up   
Participants Analyzed   888 
TC at follow up   0.093  (0.9377) 
HDL at Week 4   
Participants Analyzed   1313 
HDL at Week 4   0.007  (0.2008) 
HDL at Week 16   
Participants Analyzed   1036 
HDL at Week 16   -0.014  (0.2427) 
HDL at Week 36   
Participants Analyzed   639 
HDL at Week 36   -0.026  (0.2487) 
HDL at Week 52   
Participants Analyzed   234 
HDL at Week 52   -0.035  (0.2512) 
HDL at Week 76   
Participants Analyzed   1 
HDL at Week 76   0.050 [1] 
HDL at follow up   
Participants Analyzed   887 
HDL at follow up   -0.058  (0.2605) 
LDL at Week 4   
Participants Analyzed   1263 
LDL at Week 4   0.062  (0.6207) 
LDL at Week 16   
Participants Analyzed   1008 
LDL at Week 16   0.210  (0.7782) 
LDL at Week 36   
Participants Analyzed   623 
LDL at Week 36   0.281  (0.8863) 
LDL at Week 52   
Participants Analyzed   226 
LDL at Week 52   0.228  (1.0563) 
LDL at Week 76   
Participants Analyzed   1 
LDL at Week 76   -0.200 [1] 
LDL at follow up   
Participants Analyzed   853 
LDL at follow up   0.148  (0.8336) 
Triglycerides at Week 4   
Participants Analyzed   1313 
Triglycerides at Week 4   0.004  (0.7845) 
Triglycerides at Week 16   
Participants Analyzed   1038 
Triglycerides at Week 16   -0.025  (0.8053) 
Triglycerides at Week 36   
Participants Analyzed   639 
Triglycerides at Week 36   -0.062  (0.8053) 
Triglycerides at Week 52   
Participants Analyzed   234 
Triglycerides at Week 52   -0.092  (0.8521) 
Triglycerides at Week 76   
Participants Analyzed   2 
Triglycerides at Week 76   -0.150  (0.9758) 
Triglycerides at follow up   
Participants Analyzed   888 
Triglycerides at follow up   -0.035  (0.8295) 
[1] Standard deviation could not be calculated as a single participant was analyzed.

No statistical analysis provided for Change From Baseline in Non-fasting Measures of Lipid Metabolism Namely Total Cholesterol (TC), High Density Lipoprotein (HDL), Low Density Lipoprotein (LDL), Triglycerides



8.  Secondary:   Number of Participants With SBP and DBP Values of Potential Clinical Concern (PCC)   [ Time Frame: Up to 70 Weeks (including follow up) ]

Measure Type Secondary
Measure Title Number of Participants With SBP and DBP Values of Potential Clinical Concern (PCC)
Measure Description The frequency of participant vital sign sitting blood pressure was obtained to check if the values lie outside of a pre-determined reference range (RR) for SBP 90-140 mmHg, DBP 50-90 mmHg or have a change from Baseline of PCC for SBP increase from Baseline (IFB) >=40, decrease from Baseline (DFB) >= 30 for and for DBP (IFB) >= 30 ,DFB >= 20. The number of participants with values of PCC at any time on treatment (ATOT) and follow up were reported.
Time Frame Up to 70 Weeks (including follow up)  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All subject (Full population). Only those participants available at the specified time points were analyzed.

Reporting Groups
  Description
RSG XR Eligible participants who completed studies AVA102670 or AVA102672 entered in this open-label extension study. Participants received open-label RSG XR throughout the treatment period as adjunctive therapy to their existing dose of AChEI for Alzheimer’s disease treatment. Participants took one tablet of study medication daily in the morning with or without food. All participants received 4 mg once daily RSG XR for the first 4 weeks of the study (only for the first 4 weeks of the study). The RSG XR dose was then increased to 8 mg once daily from Week 4 through Week 52. The dose of RSG XR was reduced to 2mg once daily if the 8 mg dose was not well tolerated. Participants were not permitted to titrate back to 8 mg RSG XR.

Measured Values
   RSG XR 
Participants Analyzed   1461 
Number of Participants With SBP and DBP Values of Potential Clinical Concern (PCC) 
[Units: Participants]
Count of Participants
 
ATOT,SBP(RR)>140 or <90   
Participants Analyzed   1409 
ATOT,SBP(RR)>140 or <90   520 
ATOT,SBP(IFB)>=40   
Participants Analyzed   1409 
ATOT,SBP(IFB)>=40   33 
ATOT,SBP(DFB)>=30   
Participants Analyzed   1409 
ATOT,SBP(DFB)>=30   179 
Follow up,SBP(RR)>140 or <90   
Participants Analyzed   1280 
Follow up,SBP(RR)>140 or <90   240 
Follow up,SBP(IFB)>=40   
Participants Analyzed   1280 
Follow up,SBP(IFB)>=40   13 
Follow up,SBP(DFB)>=30   
Participants Analyzed   1280 
Follow up,SBP(DFB)>=30   63 
ATOT,DBP(RR)>90 or<50   
Participants Analyzed   1409 
ATOT,DBP(RR)>90 or<50   141 
ATOT,DBP(IFB)>=30   
Participants Analyzed   1409 
ATOT,DBP(IFB)>=30   20 
ATOT,DBP(DFB)>= 20   
Participants Analyzed   1409 
ATOT,DBP(DFB)>= 20   211 
Follow up,DBP(RR)>90 or<50   
Participants Analyzed   1280 
Follow up,DBP(RR)>90 or<50   54 
Follow up,DBP(IFB)>=30   
Participants Analyzed   1280 
Follow up,DBP(IFB)>=30   5 
Follow up, DBP(DFB)>= 20   
Participants Analyzed   1280 
Follow up, DBP(DFB)>= 20   67 

No statistical analysis provided for Number of Participants With SBP and DBP Values of Potential Clinical Concern (PCC)



9.  Secondary:   Number of Participants With HR Values of PCC ATOT   [ Time Frame: Up to 70 Weeks (including follow up) ]

Measure Type Secondary
Measure Title Number of Participants With HR Values of PCC ATOT
Measure Description HR was measured once, after the participant sat quietly for at least 5 minutes. The frequency of participant vital sign heart rate was obtained to check if the values lie outside of a pre-determined reference range (RR) 50-100 bpm or have a change from Baseline of PCC IFB >=30 and DFB >=30. The number of participants with values of PCC including follow up were reported.
Time Frame Up to 70 Weeks (including follow up)  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All subject (Full population). Only those participants available at the specified time points were analyzed.

Reporting Groups
  Description
RSG XR Eligible participants who completed studies AVA102670 or AVA102672 entered in this open-label extension study. Participants received open-label RSG XR throughout the treatment period as adjunctive therapy to their existing dose of AChEI for Alzheimer’s disease treatment. Participants took one tablet of study medication daily in the morning with or without food. All participants received 4 mg once daily RSG XR for the first 4 weeks of the study (only for the first 4 weeks of the study). The RSG XR dose was then increased to 8 mg once daily from Week 4 through Week 52. The dose of RSG XR was reduced to 2mg once daily if the 8 mg dose was not well tolerated. Participants were not permitted to titrate back to 8 mg RSG XR.

Measured Values
   RSG XR 
Participants Analyzed   1461 
Number of Participants With HR Values of PCC ATOT 
[Units: Participants]
Count of Participants
 
ATOT,HR (RR)>100 or <50   
Participants Analyzed   1409 
ATOT,HR (RR)>100 or <50   55 
ATOT,HR (IFB)>=30   
Participants Analyzed   1409 
ATOT,HR (IFB)>=30   25 
ATOT,HR (DFB)>=30   
Participants Analyzed   1409 
ATOT,HR (DFB)>=30   14 
Follow up,HR (RR)>100 or <50   
Participants Analyzed   1276 
Follow up,HR (RR)>100 or <50   18 
Follow up,HR (IFB)>=30   
Participants Analyzed   1276 
Follow up,HR (IFB)>=30   11 
Follow up,HR (DFB)>=30   
Participants Analyzed   1276 
Follow up,HR (DFB)>=30   6 

No statistical analysis provided for Number of Participants With HR Values of PCC ATOT



10.  Secondary:   Number of Participants With BW Values of PCC ATOT   [ Time Frame: Up to 70 Weeks (including follow up) ]

Measure Type Secondary
Measure Title Number of Participants With BW Values of PCC ATOT
Measure Description The frequency of participant vital sign weight was obtained to check if the values have CFB of PCC IFB >=7 percent. With the exception of Week 4, when participants were first titrated to the 8mg RSG XR dose, at every time point in the study where weight was measured the percentage of participants experienced an increase in BW of PCC was approximately 2 times greater than the percentage of participants experiencing an decrease in BW of PCC DFB >=7 percent. The number of participants with values of PCC including follow up were reported.
Time Frame Up to 70 Weeks (including follow up)  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All subject (Full population). Only those participants available at the specified time points were analyzed.

Reporting Groups
  Description
RSG XR Eligible participants who completed studies AVA102670 or AVA102672 entered in this open-label extension study. Participants received open-label RSG XR throughout the treatment period as adjunctive therapy to their existing dose of AChEI for Alzheimer’s disease treatment. Participants took one tablet of study medication daily in the morning with or without food. All participants received 4 mg once daily RSG XR for the first 4 weeks of the study (only for the first 4 weeks of the study). The RSG XR dose was then increased to 8 mg once daily from Week 4 through Week 52. The dose of RSG XR was reduced to 2mg once daily if the 8 mg dose was not well tolerated. Participants were not permitted to titrate back to 8 mg RSG XR.

Measured Values
   RSG XR 
Participants Analyzed   1461 
Number of Participants With BW Values of PCC ATOT 
[Units: Participants]
Count of Participants
 
ATOT, BW(IFB)>=7 percent   
Participants Analyzed   1408 
ATOT, BW(IFB)>=7 percent   188 
ATOT, BW(DFB)>= 7 percent   
Participants Analyzed   1408 
ATOT, BW(DFB)>= 7 percent   83 
Follow up, BW(IFB)>=7 percent   
Participants Analyzed   1270 
Follow up, BW(IFB)>=7 percent   90 
Follow up, BW(DFB)>= 7 percent   
Participants Analyzed   1270 
Follow up, BW(DFB)>= 7 percent   51 

No statistical analysis provided for Number of Participants With BW Values of PCC ATOT



11.  Secondary:   Number of Participants With Hematology Parameters of PCC ATOT   [ Time Frame: Up to Week 82 (including follow up) ]

Measure Type Secondary
Measure Title Number of Participants With Hematology Parameters of PCC ATOT
Measure Description The hematology data included eosinophils, haematocrit, haemoglobin, lymphocytes, mean corpuscular haemoglobin (MCH), mean corpuscular volume (MCV), monocytes, platelet count, red cell distribution width (RDW), red blood cell (RBC) count, segmented neutrophils (SN), total neutrophils (TN), white blood cell (WBC) count. The number of participants with values of PCC (defined as high and low) ATOT were reported.
Time Frame Up to Week 82 (including follow up)  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All subject (Full population). Only those participants available at the specified time points were analyzed.

Reporting Groups
  Description
RSG XR Eligible participants who completed studies AVA102670 or AVA102672 entered in this open-label extension study. Participants received open-label RSG XR throughout the treatment period as adjunctive therapy to their existing dose of AChEI for Alzheimer’s disease treatment. Participants took one tablet of study medication daily in the morning with or without food. All participants received 4 mg once daily RSG XR for the first 4 weeks of the study (only for the first 4 weeks of the study). The RSG XR dose was then increased to 8 mg once daily from Week 4 through Week 52. The dose of RSG XR was reduced to 2mg once daily if the 8 mg dose was not well tolerated. Participants were not permitted to titrate back to 8 mg RSG XR.

Measured Values
   RSG XR 
Participants Analyzed   1461 
Number of Participants With Hematology Parameters of PCC ATOT 
[Units: Participants]
Count of Participants
 
ATOT, Eosinophils (high)   
Participants Analyzed   1384 
ATOT, Eosinophils (high)   2 
ATOT, Haematocrit (low)   
Participants Analyzed   1385 
ATOT, Haematocrit (low)   8 
Follow up, Haematocrit (low)   
Participants Analyzed   910 
Follow up, Haematocrit (low)   6 
ATOT, Haemoglobin (high)   
Participants Analyzed   1385 
ATOT, Haemoglobin (high)   2 
ATOT, Haemoglobin (low)   
Participants Analyzed   1385 
ATOT, Haemoglobin (low)   74 
Follow up, Hemoglobin (high)   
Participants Analyzed   910 
Follow up, Hemoglobin (high)   2 
Follow up, Hemoglobin (low)   
Participants Analyzed   910 
Follow up, Hemoglobin (low)   25 
ATOT, Lymphocytes (high)   
Participants Analyzed   1384 
ATOT, Lymphocytes (high)   3 
ATOT, Lymphocytes (low)   
Participants Analyzed   1384 
ATOT, Lymphocytes (low)   21 
Follow up, Lymphocytes (high)   
Participants Analyzed   909 
Follow up, Lymphocytes (high)   3 
Follow up, Lymphocytes (low)   
Participants Analyzed   909 
Follow up, Lymphocytes (low)   9 
ATOT, MCH (low)   
Participants Analyzed   1211 
ATOT, MCH (low)   5 
Follow up, MCH (low)   
Participants Analyzed   785 
Follow up, MCH (low)   1 
ATOT, MCV (low)   
Participants Analyzed   1385 
ATOT, MCV (low)   1 
ATOT, monocytes (high)   
Participants Analyzed   1384 
ATOT, monocytes (high)   1 
ATOT, monocytes (low)   
Participants Analyzed   1384 
ATOT, monocytes (low)   61 
Follow up, monocytes (low)   
Participants Analyzed   909 
Follow up, monocytes (low)   23 
ATOT, platelet count (high)   
Participants Analyzed   1381 
ATOT, platelet count (high)   7 
ATOT, platelet count (low)   
Participants Analyzed   1381 
ATOT, platelet count (low)   5 
ATOT, RDW (high)   
Participants Analyzed   1385 
ATOT, RDW (high)   158 
Follow up, RDW (high)   
Participants Analyzed   910 
Follow up, RDW (high)   45 
ATOT, RBC (low)   
Participants Analyzed   1385 
ATOT, RBC (low)   12 
Follow up, RBC (low)   
Participants Analyzed   910 
Follow up, RBC (low)   4 
ATOT, SN (high)   
Participants Analyzed   1384 
ATOT, SN (high)   6 
ATOT, SN (low)   
Participants Analyzed   1384 
ATOT, SN (low)   15 
Follow up, SN (high)   
Participants Analyzed   909 
Follow up, SN (high)   3 
Follow up, SN (low)   
Participants Analyzed   909 
Follow up, SN (low)   3 
ATOT, TN (high)   
Participants Analyzed   1384 
ATOT, TN (high)   3 
ATOT, TN (low)   
Participants Analyzed   1384 
ATOT, TN (low)   15 
Follow up, TN (high)   
Participants Analyzed   909 
Follow up, TN (high)   2 
Follow up, TN (low)   
Participants Analyzed   909 
Follow up, TN (low)   3 
ATOT, WBC (high)   
Participants Analyzed   1384 
ATOT, WBC (high)   5 
ATOT, WBC (low)   
Participants Analyzed   1384 
ATOT, WBC (low)   22 
Follow up, WBC (high)   
Participants Analyzed   909 
Follow up, WBC (high)   3 
Follow up, WBC (low)   
Participants Analyzed   909 
Follow up, WBC (low)   11 

No statistical analysis provided for Number of Participants With Hematology Parameters of PCC ATOT



12.  Secondary:   Number of Participants With Clinical Chemistry Parameters (Including Lipids) of PCC ATOT   [ Time Frame: Up to Week 82 (including follow up) ]

Measure Type Secondary
Measure Title Number of Participants With Clinical Chemistry Parameters (Including Lipids) of PCC ATOT
Measure Description The clinical chemistry data included alanine amino transferase (ALT), albumin, aldolase, asparatate amino transferase (AST), BUN/creatinine ratio, carbon dioxide(CO2) content, chloride, cholesterol, creatinine kinase (CK), creatinine, direct bilirubin (DB), gamma glutamyl transferase (GGT), glucose, glycosylated Hemoglobin (HbA1C), HDL, LDL, lactate dehydrogenase (LD), magnesium, potassium, sodium, total bilirubin (TB), triglycerides, troponin I, urea. The number of participants with values of PCC (defined as high and low) ATOT were reported.
Time Frame Up to Week 82 (including follow up)  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All subject population (Full population). Only those participants available at the specified time points were analyzed.

Reporting Groups
  Description
RSG XR Eligible participants who completed studies AVA102670 or AVA102672 entered in this open-label extension study. Participants received open-label RSG XR throughout the treatment period as adjunctive therapy to their existing dose of AChEI for Alzheimer’s disease treatment. Participants took one tablet of study medication daily in the morning with or without food. All participants received 4 mg once daily RSG XR for the first 4 weeks of the study (only for the first 4 weeks of the study). The RSG XR dose was then increased to 8 mg once daily from Week 4 through Week 52. The dose of RSG XR was reduced to 2mg once daily if the 8 mg dose was not well tolerated. Participants were not permitted to titrate back to 8 mg RSG XR.

Measured Values
   RSG XR 
Participants Analyzed   1461 
Number of Participants With Clinical Chemistry Parameters (Including Lipids) of PCC ATOT 
[Units: Participants]
Count of Participants
 
Follow up, ALT (high)   
Participants Analyzed   908 
Follow up, ALT (high)   2 
Follow up, Albumin (low)   
Participants Analyzed   909 
Follow up, Albumin (low)   1 
ATOT, Aldolase (high)   
Participants Analyzed   464 
ATOT, Aldolase (high)   16 
ATOT, Aldolase (low)   
Participants Analyzed   464 
ATOT, Aldolase (low)   78 
Follow up, Aldolase (high)   
Participants Analyzed   146 
Follow up, Aldolase (high)   3 
Follow up, Aldolase (low)   
Participants Analyzed   146 
Follow up, Aldolase (low)   14 
ATOT, AST (high)   
Participants Analyzed   1385 
ATOT, AST (high)   2 
Follow up, AST (high)   
Participants Analyzed   908 
Follow up, AST (high)   3 
ATOT, BUN/creatinine ratio (high)   
Participants Analyzed   1385 
ATOT, BUN/creatinine ratio (high)   87 
Follow up, BUN/creatinine ratio (high)   
Participants Analyzed   908 
Follow up, BUN/creatinine ratio (high)   37 
ATOT, CO2 content (low)   
Participants Analyzed   1384 
ATOT, CO2 content (low)   2 
Follow up, CO2 content (low)   
Participants Analyzed   908 
Follow up, CO2 content (low)   3 
ATOT, chloride (high)   
Participants Analyzed   1385 
ATOT, chloride (high)   1 
ATOT, cholesterol (high)   
Participants Analyzed   1383 
ATOT, cholesterol (high)   175 
Follow up, cholesterol (high)   
Participants Analyzed   907 
Follow up, cholesterol (high)   50 
ATOT, CK (high)   
Participants Analyzed   1385 
ATOT, CK (high)   131 
Follow up, CK (high)   
Participants Analyzed   908 
Follow up, CK (high)   40 
ATOT, Creatinine (high)   
Participants Analyzed   1385 
ATOT, Creatinine (high)   27 
Follow up, creatinine (high)   
Participants Analyzed   908 
Follow up, creatinine (high)   10 
ATOT, DB (high)   
Participants Analyzed   1385 
ATOT, DB (high)   4 
ATOT, GGT (high)   
Participants Analyzed   1385 
ATOT, GGT (high)   7 
Follow up, GGT (high)   
Participants Analyzed   908 
Follow up, GGT (high)   2 
ATOT, Glucose (high)   
Participants Analyzed   1385 
ATOT, Glucose (high)   100 
ATOT, Glucose (low)   
Participants Analyzed   1385 
ATOT, Glucose (low)   40 
Follow up, glucose (high)   
Participants Analyzed   908 
Follow up, glucose (high)   31 
Follow up, glucose (low)   
Participants Analyzed   908 
Follow up, glucose (low)   13 
ATOT, HbA1c (high)   
Participants Analyzed   742 
ATOT, HbA1c (high)   2 
ATOT, HDL (low)   
Participants Analyzed   1383 
ATOT, HDL (low)   11 
Follow up, HDL (low)   
Participants Analyzed   906 
Follow up, HDL (low)   7 
ATOT, LDL (low)   
Participants Analyzed   1368 
ATOT, LDL (low)   469 
Follow up, LDL (low)   
Participants Analyzed   888 
Follow up, LDL (low)   211 
ATOT, LD (high)   
Participants Analyzed   1384 
ATOT, LD (high)   1 
Follow up, LD (high)   
Participants Analyzed   909 
Follow up, LD (high)   1 
ATOT, Magnesium (low)   
Participants Analyzed   1385 
ATOT, Magnesium (low)   1 
Follow up, Magnesium (low)   
Participants Analyzed   909 
Follow up, Magnesium (low)   1 
ATOT, Potassium (high)   
Participants Analyzed   1384 
ATOT, Potassium (high)   17 
ATOT, Potassium (low)   
Participants Analyzed   1384 
ATOT, Potassium (low)   1 
Follow up, Potassium (high)   
Participants Analyzed   909 
Follow up, Potassium (high)   2 
Follow up, Potassium (low)   
Participants Analyzed   909 
Follow up, Potassium (low)   1 
ATOT, Sodium (high)   
Participants Analyzed   1385 
ATOT, Sodium (high)   2 
ATOT, Sodium (low)   
Participants Analyzed   1385 
ATOT, Sodium (low)   4 
Follow up, Sodium (low)   
Participants Analyzed   909 
Follow up, Sodium (low)   1 
ATOT, TB (high)   
Participants Analyzed   1386 
ATOT, TB (high)   1 
Follow up, TB (high)   
Participants Analyzed   908 
Follow up, TB (high)   1 
ATOT, Triglycerides (high)   
Participants Analyzed   1383 
ATOT, Triglycerides (high)   1 
ATOT, Troponin I (high)   
Participants Analyzed   426 
ATOT, Troponin I (high)   13 
Follow up, Troponin I (high)   
Participants Analyzed   142 
Follow up, Troponin I (high)   2 
ATOT, Urea (high)   
Participants Analyzed   1385 
ATOT, Urea (high)   97 
Follow up, Urea (high)   
Participants Analyzed   909 
Follow up, Urea (high)   42 

No statistical analysis provided for Number of Participants With Clinical Chemistry Parameters (Including Lipids) of PCC ATOT



13.  Secondary:   Change From Baseline in Alzheimer's Disease Assessment Scale – Cognitive (ADAS-cog) Total Score as a Function of Apolipoprotein E (APOE) ε4 Status.   [ Time Frame: Baseline (Week 0) and Week 24, 52 ]

Measure Type Secondary
Measure Title Change From Baseline in Alzheimer's Disease Assessment Scale – Cognitive (ADAS-cog) Total Score as a Function of Apolipoprotein E (APOE) ε4 Status.
Measure Description The 11-item ADAS-Cog assessed a range of cognitive abilities including memory, comprehension, orientation in time and place and spontaneous speech. Most items were evaluated by tests, but some were dependent on clinician ratings on a five point scale. Scores ranged from 0 to 70 with higher scores indicating greater dysfunction. Baseline for the open-label study was the latest assessment from Week 48 of parent studies to the first dose of open-label medication (Week 0). Change from Baseline was calculated as the Baseline value minus the value at the specified time point.
Time Frame Baseline (Week 0) and Week 24, 52  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All subject (Full population). Only those participants available at the specified time points were analyzed. The analysis was done on the full population and was repeated for APOE subgroups (negative, positive, homozygotes, heterozygotes).

Reporting Groups
  Description
RSG XR Eligible participants who completed studies AVA102670 or AVA102672 entered in this open-label extension study. Participants received open-label RSG XR throughout the treatment period as adjunctive therapy to their existing dose of AChEI for Alzheimer’s disease treatment. Participants took one tablet of study medication daily in the morning with or without food. All participants received 4 mg once daily RSG XR for the first 4 weeks of the study (only for the first 4 weeks of the study). The RSG XR dose was then increased to 8 mg once daily from Week 4 through Week 52. The dose of RSG XR was reduced to 2mg once daily if the 8 mg dose was not well tolerated. Participants were not permitted to titrate back to 8 mg RSG XR.

Measured Values
   RSG XR 
Participants Analyzed   1461 
Change From Baseline in Alzheimer's Disease Assessment Scale – Cognitive (ADAS-cog) Total Score as a Function of Apolipoprotein E (APOE) ε4 Status. 
[Units: Scores on scale]
Mean (Standard Deviation)
 
Week 24 (Full population)   
Participants Analyzed   973 
Week 24 (Full population)   2.5  (5.51) 
Week 52 (Full population)   
Participants Analyzed   308 
Week 52 (Full population)   5.1  (6.82) 
Week 24 (APOE4 negatives)   
Participants Analyzed   404 
Week 24 (APOE4 negatives)   2.3  (5.28) 
Week 52 (APOE4 negatives)   
Participants Analyzed   135 
Week 52 (APOE4 negatives)   4.8  (6.44) 
Week 24 (APOE4 positives)   
Participants Analyzed   569 
Week 24 (APOE4 positives)   2.6  (5.66) 
Week 52(APOE4 positives)   
Participants Analyzed   173 
Week 52(APOE4 positives)   5.4  (7.11) 
Week 24 (APOE4 E4 homozygotes)   
Participants Analyzed   126 
Week 24 (APOE4 E4 homozygotes)   2.7  (5.77) 
Week 52 (APOE4 E4 homozygotes)   
Participants Analyzed   39 
Week 52 (APOE4 E4 homozygotes)   5.2  (7.49) 
Week 24 (APOE4 E4 heterozygotes)   
Participants Analyzed   443 
Week 24 (APOE4 E4 heterozygotes)   2.6  (5.63) 
Week 52 (APOE4 E4 heterozygotes)   
Participants Analyzed   134 
Week 52 (APOE4 E4 heterozygotes)   5.4  (7.02) 

No statistical analysis provided for Change From Baseline in Alzheimer's Disease Assessment Scale – Cognitive (ADAS-cog) Total Score as a Function of Apolipoprotein E (APOE) ε4 Status.



14.  Secondary:   Change From Baseline in Clinical Dementia Rating Scale–Sum of Boxes (CDR-SB) Score as a Function of APOE ε4 Status.   [ Time Frame: Baseline (Week 0) and Week 24, 52 ]

Measure Type Secondary
Measure Title Change From Baseline in Clinical Dementia Rating Scale–Sum of Boxes (CDR-SB) Score as a Function of APOE ε4 Status.
Measure Description The CDR-SB is a validated clinical assessment of global function in par. with Alzheimer’s disease (AD). Impairment was scored in each of 6 cognitive categories on a scale in which none = 0, questionable = 0.5, mild = 1, moderate = 2, and severe = 3. The 6 individual category ratings, or box scores, were added together to give the CDR-Sum of Boxes which ranged from 0 to 18 (severe impairment). Baseline for the open-label study was the latest assessment from Week 48 of parent studies to the first dose of open-label medication (Week 0). Change from Baseline was calculated as the Baseline value minus the value at the specified time point.
Time Frame Baseline (Week 0) and Week 24, 52  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All subject population. Only those participants available at the specified time points were analyzed. The analysis was done on the full population and was repeated for APOE subgroups (negatives, positives, homozygotes, heterozygotes).

Reporting Groups
  Description
RSG XR Eligible participants who completed studies AVA102670 or AVA102672 entered in this open-label extension study. Participants received open-label RSG XR throughout the treatment period as adjunctive therapy to their existing dose of AChEI for Alzheimer’s disease treatment. Participants took one tablet of study medication daily in the morning with or without food. All participants received 4 mg once daily RSG XR for the first 4 weeks of the study (only for the first 4 weeks of the study). The RSG XR dose was then increased to 8 mg once daily from Week 4 through Week 52. The dose of RSG XR was reduced to 2mg once daily if the 8 mg dose was not well tolerated. Participants were not permitted to titrate back to 8 mg RSG XR.

Measured Values
   RSG XR 
Participants Analyzed   1461 
Change From Baseline in Clinical Dementia Rating Scale–Sum of Boxes (CDR-SB) Score as a Function of APOE ε4 Status. 
[Units: Scores on scale]
Mean (Standard Deviation)
 
Week 24 (Full population)   
Participants Analyzed   988 
Week 24 (Full population)   0.7  (1.84) 
Week 52 (Full population)   
Participants Analyzed   313 
Week 52 (Full population)   1.6  (2.26) 
Week 24 (APOE4 negatives)   
Participants Analyzed   409 
Week 24 (APOE4 negatives)   0.6  (1.76) 
Week 52 (APOE4 negatives)   
Participants Analyzed   139 
Week 52 (APOE4 negatives)   1.3  (2.19) 
Week 24 (APOE4 positives)   
Participants Analyzed   579 
Week 24 (APOE4 positives)   0.7  (1.89) 
Week 52 (APOE4 positives)   
Participants Analyzed   174 
Week 52 (APOE4 positives)   1.9  (2.30) 
Week 24 (APOE4 E4 homozygotes)   
Participants Analyzed   127 
Week 24 (APOE4 E4 homozygotes)   0.9  (1.90) 
Week 52 (APOE4 E4 homozygotes)   
Participants Analyzed   39 
Week 52 (APOE4 E4 homozygotes)   1.9  (2.32) 
Week 24 (APOE4 E4 heterozygotes)   
Participants Analyzed   452 
Week 24 (APOE4 E4 heterozygotes)   0.7  (1.89) 
Week 52 (APOE4 E4 heterozygotes)   
Participants Analyzed   135 
Week 52 (APOE4 E4 heterozygotes)   1.9  (2.30) 

No statistical analysis provided for Change From Baseline in Clinical Dementia Rating Scale–Sum of Boxes (CDR-SB) Score as a Function of APOE ε4 Status.



15.  Secondary:   Change From Baseline in Mini Mental State Examination (MMSE) Total Score as a Function of APOE ε4 Status.   [ Time Frame: Baseline (Week 0) and Week 24, 52 ]

Measure Type Secondary
Measure Title Change From Baseline in Mini Mental State Examination (MMSE) Total Score as a Function of APOE ε4 Status.
Measure Description The MMSE consisted of 11 tests of orientation, memory (recent and immediate), concentration, language and praxis. Scores ranged from 0 to 30, with lower scores indicating greater cognitive impairment. Baseline for the open-label study was the latest assessment from Week 48 of parent studies to the first dose of open-label medication (Week 0). Change from Baseline was calculated as the Baseline value minus the value at the specified time point.
Time Frame Baseline (Week 0) and Week 24, 52  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All subject (Full population). Only those participants available at the specified time points were analyzed. The analysis was done on the full population and was repeated for APOE subgroups (negatives, positives, homozygotes, heterozygotes).

Reporting Groups
  Description
RSG XR Eligible participants who completed studies AVA102670 or AVA102672 entered in this open-label extension study. Participants received open-label RSG XR throughout the treatment period as adjunctive therapy to their existing dose of AChEI for Alzheimer’s disease treatment. Participants took one tablet of study medication daily in the morning with or without food. All participants received 4 mg once daily RSG XR for the first 4 weeks of the study (only for the first 4 weeks of the study). The RSG XR dose was then increased to 8 mg once daily from Week 4 through Week 52. The dose of RSG XR was reduced to 2mg once daily if the 8 mg dose was not well tolerated. Participants were not permitted to titrate back to 8 mg RSG XR.

Measured Values
   RSG XR 
Participants Analyzed   1461 
Change From Baseline in Mini Mental State Examination (MMSE) Total Score as a Function of APOE ε4 Status. 
[Units: Scores on scale]
Mean (Standard Deviation)
 
Week 24 (Full population)   
Participants Analyzed   833 
Week 24 (Full population)   -1.2  (2.84) 
Week 52 (Full population)   
Participants Analyzed   184 
Week 52 (Full population)   -2.3  (3.39) 
Week 24 (APOE4 negatives)   
Participants Analyzed   353 
Week 24 (APOE4 negatives)   -0.7  (2.74) 
Week 52 (APOE4 negatives)   
Participants Analyzed   77 
Week 52 (APOE4 negatives)   -1.5  (3.56) 
Week 24 (APOE4 positives)   
Participants Analyzed   480 
Week 24 (APOE4 positives)   -1.5  (2.87) 
Week 52 (APOE4 positives)   
Participants Analyzed   107 
Week 52 (APOE4 positives)   -2.8  (3.17) 
Week 24 (APOE4 E4 homozygotes)   
Participants Analyzed   104 
Week 24 (APOE4 E4 homozygotes)   -1.5  (3.07) 
Week 52 (APOE4 E4 homozygotes)   
Participants Analyzed   23 
Week 52 (APOE4 E4 homozygotes)   -2.5  (3.16) 
Week 24 (APOE4 E4 heterozygotes)   
Participants Analyzed   376 
Week 24 (APOE4 E4 heterozygotes)   -1.5  (2.82) 
Week 52 (APOE4 E4 heterozygotes)   
Participants Analyzed   84 
Week 52 (APOE4 E4 heterozygotes)   -2.9  (3.18) 

No statistical analysis provided for Change From Baseline in Mini Mental State Examination (MMSE) Total Score as a Function of APOE ε4 Status.



16.  Secondary:   Change From Baseline in Disability Assessment for Dementia Scale (DAD) Total Score as a Function of APOE ε4 Status.   [ Time Frame: Baseline (Week 0) and Week 24, 52 ]

Measure Type Secondary
Measure Title Change From Baseline in Disability Assessment for Dementia Scale (DAD) Total Score as a Function of APOE ε4 Status.
Measure Description DAD, assessed the ability of a participant to execute basic and instrumental activities of daily living (ADL) and leisure activities. The scale consists of 40 questions assessing basic and instrumental ADLs. This scale assesses a participant’s ability to initiate, plan, and perform activities related to hygiene, dressing, continence, eating, meal preparation, telephoning, going on an outing, finance and correspondence, medications, leisure, and housework. Each item was scored as yes: 1, no: 0 and N/A: not applicable. Higher scores indicate less disability with a score of 100 indicating no disability and 0 indicating no functional ability. The percentage score was calculated as (DAD total score/total number of applicable items) * 100. Baseline for the open-label study was the latest assessment from Week 48 of parent studies to the first dose of open-label medication (Week 0). Change from Baseline was calculated as the Baseline value minus the value at the specified time point.
Time Frame Baseline (Week 0) and Week 24, 52  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All subject (Full population). Only those participants available at the specified time points were analyzed.The analysis was done on the full population and was repeated for APOE subgroups (negatives, positives, homozygotes, heterozygotes).

Reporting Groups
  Description
RSG XR Eligible participants who completed studies AVA102670 or AVA102672 entered in this open-label extension study. Participants received open-label RSG XR throughout the treatment period as adjunctive therapy to their existing dose of AChEI for Alzheimer’s disease treatment. Participants took one tablet of study medication daily in the morning with or without food. All participants received 4 mg once daily RSG XR for the first 4 weeks of the study (only for the first 4 weeks of the study). The RSG XR dose was then increased to 8 mg once daily from Week 4 through Week 52. The dose of RSG XR was reduced to 2mg once daily if the 8 mg dose was not well tolerated. Participants were not permitted to titrate back to 8 mg RSG XR.

Measured Values
   RSG XR 
Participants Analyzed   1461 
Change From Baseline in Disability Assessment for Dementia Scale (DAD) Total Score as a Function of APOE ε4 Status. 
[Units: Scores on scale]
Mean (Standard Deviation)
 
Week 24 (Full population)   
Participants Analyzed   837 
Week 24 (Full population)   -5.6  (12.36) 
Week 52 (Full population)   
Participants Analyzed   183 
Week 52 (Full population)   -10.8  (15.07) 
Week 24 (APOE4 negatives)   
Participants Analyzed   354 
Week 24 (APOE4 negatives)   -4.6  (11.57) 
Week 52 (APOE4 negatives)   
Participants Analyzed   77 
Week 52 (APOE4 negatives)   -10.9  (14.90) 
Week 24 (APOE4 positives)   
Participants Analyzed   483 
Week 24 (APOE4 positives)   -6.2  (12.88) 
Week 52 (APOE4 positives)   
Participants Analyzed   106 
Week 52 (APOE4 positives)   -10.7  (15.26) 
Week 24 (APOE4 E4 homozygotes)   
Participants Analyzed   106 
Week 24 (APOE4 E4 homozygotes)   -5.6  (12.16) 
Week 52 (APOE4 E4 homozygotes)   
Participants Analyzed   24 
Week 52 (APOE4 E4 homozygotes)   -12.6  (11.84) 
Week 24 (APOE4 E4 heterozygotes)   
Participants Analyzed   377 
Week 24 (APOE4 E4 heterozygotes)   -6.4  (13.08) 
Week 52 (APOE4 E4 heterozygotes)   
Participants Analyzed   82 
Week 52 (APOE4 E4 heterozygotes)   -10.1  (16.14) 

No statistical analysis provided for Change From Baseline in Disability Assessment for Dementia Scale (DAD) Total Score as a Function of APOE ε4 Status.



17.  Secondary:   Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score as a Function of APOE ε4 Status.   [ Time Frame: Baseline (Week 0) and Week 24, 52 ]

Measure Type Secondary
Measure Title Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score as a Function of APOE ε4 Status.
Measure Description 12-domain caregiver assessment of behavioral disturbances occurring in dementia: delusions, hallucinations, agitation, depression, anxiety, euphoria, apathy, disinhibition, irritability, motor disturbance, appetite, nighttime behavior. A screening question is asked about each sub-domain. If the responses to these questions=participant has problems with a particular sub-domain of behavior, the caregiver asked all the questions about that domain, rating the frequency (1=occasionally to 4=very frequently) on a 4-point scale, their severity (1=Mild to 3=Severe) on a 3-point scale, and the distress on a 5-point scale. Total score=sum of each domain score(range 0-144);higher score=greater behavioral disturbances. Baseline for the open-label study was the latest assessment from Week 48 of parent studies to the first dose of open-label medication (Week 0). Change from Baseline was calculated as the Baseline value minus the value at the specified time point.
Time Frame Baseline (Week 0) and Week 24, 52  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All subject (Full population). Only those participants available at the specified time points were analyzed.The analysis was done on the full population and was repeated for APOE subgroups (negatives, positives, homozygotes, heterozygotes).

Reporting Groups
  Description
RSG XR Eligible participants who completed studies AVA102670 or AVA102672 entered in this open-label extension study. Participants received open-label RSG XR throughout the treatment period as adjunctive therapy to their existing dose of AChEI for Alzheimer’s disease treatment. Participants took one tablet of study medication daily in the morning with or without food. All participants received 4 mg once daily RSG XR for the first 4 weeks of the study (only for the first 4 weeks of the study). The RSG XR dose was then increased to 8 mg once daily from Week 4 through Week 52. The dose of RSG XR was reduced to 2mg once daily if the 8 mg dose was not well tolerated. Participants were not permitted to titrate back to 8 mg RSG XR.

Measured Values
   RSG XR 
Participants Analyzed   1461 
Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score as a Function of APOE ε4 Status. 
[Units: Score on scale]
Mean (Standard Deviation)
 
Week 24 (Full population)   
Participants Analyzed   835 
Week 24 (Full population)   1.4  (7.87) 
Week 52 (Full population)   
Participants Analyzed   183 
Week 52 (Full population)   3.2  (10.90) 
Week 24 (APOE4 negatives)   
Participants Analyzed   353 
Week 24 (APOE4 negatives)   1.0  (7.26) 
Week 52 (APOE4 negatives)   
Participants Analyzed   77 
Week 52 (APOE4 negatives)   2.4  (7.74) 
Week 24 (APOE4 positives)   
Participants Analyzed   482 
Week 24 (APOE4 positives)   1.7  (8.29) 
Week 52 (APOE4 positives)   
Participants Analyzed   106 
Week 52 (APOE4 positives)   3.8  (12.71) 
Week 24 (APOE4 E4 homozygotes)   
Participants Analyzed   105 
Week 24 (APOE4 E4 homozygotes)   1.8  (7.75) 
Week 52 (APOE4 E4 homozygotes)   
Participants Analyzed   24 
Week 52 (APOE4 E4 homozygotes)   4.2  (14.19) 
Week 24 (APOE4 E4 heterozygotes)   
Participants Analyzed   377 
Week 24 (APOE4 E4 heterozygotes)   1.6  (8.45) 
Week 52 (APOE4 E4 heterozygotes)   
Participants Analyzed   82 
Week 52 (APOE4 E4 heterozygotes)   3.7  (12.34) 

No statistical analysis provided for Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score as a Function of APOE ε4 Status.




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
phone: 866-435-7343


Publications:

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00490568     History of Changes
Other Study ID Numbers: AVA102675
First Submitted: June 21, 2007
First Posted: June 22, 2007
Results First Submitted: September 5, 2017
Results First Posted: November 13, 2017
Last Update Posted: November 13, 2017