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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

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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
Enrollment 1461
Recruitment Details 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 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.
Arm/Group Title RSG XR
Hide Arm/Group Description 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.
Period Title: Overall Study
Started 1461
Completed 97
Not Completed 1364
Reason Not Completed
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
Arm/Group Title RSG XR (AVA102675)
Hide Arm/Group Description 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.
Overall Number of Baseline Participants 1461
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 1461 participants
73.9  (7.96)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1461 participants
Female
843
  57.7%
Male
618
  42.3%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1461 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%
1.Primary Outcome
Title Number of Participants With Any Adverse Events (AEs) and Severity of AEs
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All Subjects (Full population), comprised of all participants who took at least one dose of open-label study medication.
Arm/Group Title RSG XR
Hide Arm/Group Description:
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..
Overall Number of Participants Analyzed 1461
Measure Type: Count of Participants
Unit of Measure: Participants
Any AE
724
  49.6%
Mild AE
345
  23.6%
Moderate AE
289
  19.8%
Severe AE
88
   6.0%
2.Secondary Outcome
Title Number Participants With Serious Adverse Events (SAEs) and Deaths
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All subject (Full population)
Arm/Group Title RSG XR
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 1461
Measure Type: Count of Participants
Unit of Measure: Participants
Any SAE
126
   8.6%
Deaths
20
   1.4%
3.Secondary Outcome
Title Number of Participants With Adverse Event of Oedema
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All subject (Full population)
Arm/Group Title RSG XR
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 1461
Measure Type: Count of Participants
Unit of Measure: Participants
Oedema peripheral
130
   8.9%
Face oedema
8
   0.5%
Pitting oedema
5
   0.3%
Oedema
3
   0.2%
Pulmonary oedema
1
   0.1%
Eyelid oedema
1
   0.1%
4.Secondary Outcome
Title Change From Baseline in Vital Sign Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All subject (Full population). Only those participants available at the specified time points were analyzed.
Arm/Group Title RSG XR
Hide Arm/Group Description:
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..
Overall Number of Participants Analyzed 1461
Mean (Standard Deviation)
Unit of Measure: millimeters of mercury (mmHg)
SBP at Week 4 Number Analyzed 1395 participants
-1.4  (14.10)
SBP at Week 8 Number Analyzed 1274 participants
-2.4  (14.73)
SBP at Week 12 Number Analyzed 1146 participants
-2.7  (14.73)
SBP at Week 16 Number Analyzed 1061 participants
-3.7  (15.02)
SBP at Week 24 Number Analyzed 892 participants
-2.1  (15.51)
SBP at Week 36 Number Analyzed 666 participants
-1.4  (15.14)
SBP at Week 52 Number Analyzed 251 participants
-1.7  (16.18)
SBP at Week 64 Number Analyzed 15 participants
-2.2  (13.78)
SBP at Follow-up Number Analyzed 1280 participants
-1.8  (15.60)
DBP at Week 4 Number Analyzed 1395 participants
-1.4  (9.41)
DBP at Week 8 Number Analyzed 1274 participants
-2.0  (9.53)
DBP at Week 12 Number Analyzed 1146 participants
-2.1  (9.74)
DBP at Week 16 Number Analyzed 1061 participants
-2.4  (9.62)
DBP at Week 24 Number Analyzed 892 participants
-2.4  (9.48)
DBP at Week 36 Number Analyzed 666 participants
-2.0  (9.85)
DBP at Week 52 Number Analyzed 251 participants
-3.6  (9.94)
DBP at Week 64 Number Analyzed 15 participants
-6.3  (6.72)
DBP at Follow-up Number Analyzed 1280 participants
-0.9  (10.23)
5.Secondary Outcome
Title Change From Baseline in Vital Sign Heart Rate (HR)
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All subject (Full population). Only those participants available at the specified time points were analyzed.
Arm/Group Title RSG XR
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 1461
Mean (Standard Deviation)
Unit of Measure: beats per minute (bpm)
HR at Week 4 Number Analyzed 1391 participants
1.0  (8.95)
HR at Week 8 Number Analyzed 1271 participants
1.8  (9.60)
HR at Week 12 Number Analyzed 1142 participants
1.6  (9.77)
HR at Week 16 Number Analyzed 1061 participants
1.6  (9.66)
HR at Week 24 Number Analyzed 888 participants
0.9  (9.99)
HR at Week 36 Number Analyzed 665 participants
1.3  (9.86)
HR at Week 52 Number Analyzed 251 participants
0.7  (8.54)
HR at Week 64 Number Analyzed 15 participants
1.0  (8.02)
HR at Follow-up Number Analyzed 1276 participants
0.9  (10.03)
6.Secondary Outcome
Title Change From Baseline in Vital Sign Body Weight (BW)
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All subject (Full population). Only those participants available at the specified time points were analyzed.
Arm/Group Title RSG XR
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 1461
Mean (Standard Deviation)
Unit of Measure: kg
BW at Week 4 Number Analyzed 1391 participants
0.3  (2.04)
BW at Week 8 Number Analyzed 1263 participants
0.6  (2.45)
BW at Week 12 Number Analyzed 1139 participants
0.6  (2.43)
BW at Week 16 Number Analyzed 1057 participants
0.7  (3.53)
BW at Week 24 Number Analyzed 889 participants
0.6  (2.95)
BW at Week 36 Number Analyzed 666 participants
1.0  (4.08)
BW at Week 52 Number Analyzed 251 participants
1.2  (3.82)
BW at Week 64 Number Analyzed 15 participants
1.4  (2.52)
BW at Follow-up Number Analyzed 1268 participants
0.5  (3.15)
7.Secondary Outcome
Title Change From Baseline in Non-fasting Measures of Lipid Metabolism Namely Total Cholesterol (TC), High Density Lipoprotein (HDL), Low Density Lipoprotein (LDL), Triglycerides
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All subject (Full population). Only those participants available at the specified time points were analyzed.
Arm/Group Title RSG XR
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 1461
Mean (Standard Deviation)
Unit of Measure: millimole per litre (mmol/l)
TC at Week 4 Number Analyzed 1313 participants
0.076  (0.6828)
TC at Week 16 Number Analyzed 1038 participants
0.201  (0.8666)
TC at Week 36 Number Analyzed 639 participants
0.246  (0.9649)
TC at Week 52 Number Analyzed 234 participants
0.174  (1.1437)
TC at Week 76 Number Analyzed 2 participants
-0.715  (0.3041)
TC at follow up Number Analyzed 888 participants
0.093  (0.9377)
HDL at Week 4 Number Analyzed 1313 participants
0.007  (0.2008)
HDL at Week 16 Number Analyzed 1036 participants
-0.014  (0.2427)
HDL at Week 36 Number Analyzed 639 participants
-0.026  (0.2487)
HDL at Week 52 Number Analyzed 234 participants
-0.035  (0.2512)
HDL at Week 76 Number Analyzed 1 participants
0.050 [1]   (NA)
HDL at follow up Number Analyzed 887 participants
-0.058  (0.2605)
LDL at Week 4 Number Analyzed 1263 participants
0.062  (0.6207)
LDL at Week 16 Number Analyzed 1008 participants
0.210  (0.7782)
LDL at Week 36 Number Analyzed 623 participants
0.281  (0.8863)
LDL at Week 52 Number Analyzed 226 participants
0.228  (1.0563)
LDL at Week 76 Number Analyzed 1 participants
-0.200 [1]   (NA)
LDL at follow up Number Analyzed 853 participants
0.148  (0.8336)
Triglycerides at Week 4 Number Analyzed 1313 participants
0.004  (0.7845)
Triglycerides at Week 16 Number Analyzed 1038 participants
-0.025  (0.8053)
Triglycerides at Week 36 Number Analyzed 639 participants
-0.062  (0.8053)
Triglycerides at Week 52 Number Analyzed 234 participants
-0.092  (0.8521)
Triglycerides at Week 76 Number Analyzed 2 participants
-0.150  (0.9758)
Triglycerides at follow up Number Analyzed 888 participants
-0.035  (0.8295)
[1]
Standard deviation could not be calculated as a single participant was analyzed.
8.Secondary Outcome
Title Number of Participants With SBP and DBP Values of Potential Clinical Concern (PCC)
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All subject (Full population). Only those participants available at the specified time points were analyzed.
Arm/Group Title RSG XR
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 1461
Measure Type: Count of Participants
Unit of Measure: Participants
ATOT,SBP(RR)>140 or <90 Number Analyzed 1409 participants
520
  36.9%
ATOT,SBP(IFB)>=40 Number Analyzed 1409 participants
33
   2.3%
ATOT,SBP(DFB)>=30 Number Analyzed 1409 participants
179
  12.7%
Follow up,SBP(RR)>140 or <90 Number Analyzed 1280 participants
240
  18.8%
Follow up,SBP(IFB)>=40 Number Analyzed 1280 participants
13
   1.0%
Follow up,SBP(DFB)>=30 Number Analyzed 1280 participants
63
   4.9%
ATOT,DBP(RR)>90 or<50 Number Analyzed 1409 participants
141
  10.0%
ATOT,DBP(IFB)>=30 Number Analyzed 1409 participants
20
   1.4%
ATOT,DBP(DFB)>= 20 Number Analyzed 1409 participants
211
  15.0%
Follow up,DBP(RR)>90 or<50 Number Analyzed 1280 participants
54
   4.2%
Follow up,DBP(IFB)>=30 Number Analyzed 1280 participants
5
   0.4%
Follow up, DBP(DFB)>= 20 Number Analyzed 1280 participants
67
   5.2%
9.Secondary Outcome
Title Number of Participants With HR Values of PCC ATOT
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All subject (Full population). Only those participants available at the specified time points were analyzed.
Arm/Group Title RSG XR
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 1461
Measure Type: Count of Participants
Unit of Measure: Participants
ATOT,HR (RR)>100 or <50 Number Analyzed 1409 participants
55
   3.9%
ATOT,HR (IFB)>=30 Number Analyzed 1409 participants
25
   1.8%
ATOT,HR (DFB)>=30 Number Analyzed 1409 participants
14
   1.0%
Follow up,HR (RR)>100 or <50 Number Analyzed 1276 participants
18
   1.4%
Follow up,HR (IFB)>=30 Number Analyzed 1276 participants
11
   0.9%
Follow up,HR (DFB)>=30 Number Analyzed 1276 participants
6
   0.5%
10.Secondary Outcome
Title Number of Participants With BW Values of PCC ATOT
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All subject (Full population). Only those participants available at the specified time points were analyzed.
Arm/Group Title RSG XR
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 1461
Measure Type: Count of Participants
Unit of Measure: Participants
ATOT, BW(IFB)>=7 percent Number Analyzed 1408 participants
188
  13.4%
ATOT, BW(DFB)>= 7 percent Number Analyzed 1408 participants
83
   5.9%
Follow up, BW(IFB)>=7 percent Number Analyzed 1270 participants
90
   7.1%
Follow up, BW(DFB)>= 7 percent Number Analyzed 1270 participants
51
   4.0%
11.Secondary Outcome
Title Number of Participants With Hematology Parameters of PCC ATOT
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All subject (Full population). Only those participants available at the specified time points were analyzed.
Arm/Group Title RSG XR
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 1461
Measure Type: Count of Participants
Unit of Measure: Participants
ATOT, Eosinophils (high) Number Analyzed 1384 participants
2
   0.1%
ATOT, Haematocrit (low) Number Analyzed 1385 participants
8
   0.6%
Follow up, Haematocrit (low) Number Analyzed 910 participants
6
   0.7%
ATOT, Haemoglobin (high) Number Analyzed 1385 participants
2
   0.1%
ATOT, Haemoglobin (low) Number Analyzed 1385 participants
74
   5.3%
Follow up, Hemoglobin (high) Number Analyzed 910 participants
2
   0.2%
Follow up, Hemoglobin (low) Number Analyzed 910 participants
25
   2.7%
ATOT, Lymphocytes (high) Number Analyzed 1384 participants
3
   0.2%
ATOT, Lymphocytes (low) Number Analyzed 1384 participants
21
   1.5%
Follow up, Lymphocytes (high) Number Analyzed 909 participants
3
   0.3%
Follow up, Lymphocytes (low) Number Analyzed 909 participants
9
   1.0%
ATOT, MCH (low) Number Analyzed 1211 participants
5
   0.4%
Follow up, MCH (low) Number Analyzed 785 participants
1
   0.1%
ATOT, MCV (low) Number Analyzed 1385 participants
1
   0.1%
ATOT, monocytes (high) Number Analyzed 1384 participants
1
   0.1%
ATOT, monocytes (low) Number Analyzed 1384 participants
61
   4.4%
Follow up, monocytes (low) Number Analyzed 909 participants
23
   2.5%
ATOT, platelet count (high) Number Analyzed 1381 participants
7
   0.5%
ATOT, platelet count (low) Number Analyzed 1381 participants
5
   0.4%
ATOT, RDW (high) Number Analyzed 1385 participants
158
  11.4%
Follow up, RDW (high) Number Analyzed 910 participants
45
   4.9%
ATOT, RBC (low) Number Analyzed 1385 participants
12
   0.9%
Follow up, RBC (low) Number Analyzed 910 participants
4
   0.4%
ATOT, SN (high) Number Analyzed 1384 participants
6
   0.4%
ATOT, SN (low) Number Analyzed 1384 participants
15
   1.1%
Follow up, SN (high) Number Analyzed 909 participants
3
   0.3%
Follow up, SN (low) Number Analyzed 909 participants
3
   0.3%
ATOT, TN (high) Number Analyzed 1384 participants
3
   0.2%
ATOT, TN (low) Number Analyzed 1384 participants
15
   1.1%
Follow up, TN (high) Number Analyzed 909 participants
2
   0.2%
Follow up, TN (low) Number Analyzed 909 participants
3
   0.3%
ATOT, WBC (high) Number Analyzed 1384 participants
5
   0.4%
ATOT, WBC (low) Number Analyzed 1384 participants
22
   1.6%
Follow up, WBC (high) Number Analyzed 909 participants
3
   0.3%
Follow up, WBC (low) Number Analyzed 909 participants
11
   1.2%
12.Secondary Outcome
Title Number of Participants With Clinical Chemistry Parameters (Including Lipids) of PCC ATOT
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All subject population (Full population). Only those participants available at the specified time points were analyzed.
Arm/Group Title RSG XR
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 1461
Measure Type: Count of Participants
Unit of Measure: Participants
Follow up, ALT (high) Number Analyzed 908 participants
2
   0.2%
Follow up, Albumin (low) Number Analyzed 909 participants
1
   0.1%
ATOT, Aldolase (high) Number Analyzed 464 participants
16
   3.4%
ATOT, Aldolase (low) Number Analyzed 464 participants
78
  16.8%
Follow up, Aldolase (high) Number Analyzed 146 participants
3
   2.1%
Follow up, Aldolase (low) Number Analyzed 146 participants
14
   9.6%
ATOT, AST (high) Number Analyzed 1385 participants
2
   0.1%
Follow up, AST (high) Number Analyzed 908 participants
3
   0.3%
ATOT, BUN/creatinine ratio (high) Number Analyzed 1385 participants
87
   6.3%
Follow up, BUN/creatinine ratio (high) Number Analyzed 908 participants
37
   4.1%
ATOT, CO2 content (low) Number Analyzed 1384 participants
2
   0.1%
Follow up, CO2 content (low) Number Analyzed 908 participants
3
   0.3%
ATOT, chloride (high) Number Analyzed 1385 participants
1
   0.1%
ATOT, cholesterol (high) Number Analyzed 1383 participants
175
  12.7%
Follow up, cholesterol (high) Number Analyzed 907 participants
50
   5.5%
ATOT, CK (high) Number Analyzed 1385 participants
131
   9.5%
Follow up, CK (high) Number Analyzed 908 participants
40
   4.4%
ATOT, Creatinine (high) Number Analyzed 1385 participants
27
   1.9%
Follow up, creatinine (high) Number Analyzed 908 participants
10
   1.1%
ATOT, DB (high) Number Analyzed 1385 participants
4
   0.3%
ATOT, GGT (high) Number Analyzed 1385 participants
7
   0.5%
Follow up, GGT (high) Number Analyzed 908 participants
2
   0.2%
ATOT, Glucose (high) Number Analyzed 1385 participants
100
   7.2%
ATOT, Glucose (low) Number Analyzed 1385 participants
40
   2.9%
Follow up, glucose (high) Number Analyzed 908 participants
31
   3.4%
Follow up, glucose (low) Number Analyzed 908 participants
13
   1.4%
ATOT, HbA1c (high) Number Analyzed 742 participants
2
   0.3%
ATOT, HDL (low) Number Analyzed 1383 participants
11
   0.8%
Follow up, HDL (low) Number Analyzed 906 participants
7
   0.8%
ATOT, LDL (low) Number Analyzed 1368 participants
469
  34.3%
Follow up, LDL (low) Number Analyzed 888 participants
211
  23.8%
ATOT, LD (high) Number Analyzed 1384 participants
1
   0.1%
Follow up, LD (high) Number Analyzed 909 participants
1
   0.1%
ATOT, Magnesium (low) Number Analyzed 1385 participants
1
   0.1%
Follow up, Magnesium (low) Number Analyzed 909 participants
1
   0.1%
ATOT, Potassium (high) Number Analyzed 1384 participants
17
   1.2%
ATOT, Potassium (low) Number Analyzed 1384 participants
1
   0.1%
Follow up, Potassium (high) Number Analyzed 909 participants
2
   0.2%
Follow up, Potassium (low) Number Analyzed 909 participants
1
   0.1%
ATOT, Sodium (high) Number Analyzed 1385 participants
2
   0.1%
ATOT, Sodium (low) Number Analyzed 1385 participants
4
   0.3%
Follow up, Sodium (low) Number Analyzed 909 participants
1
   0.1%
ATOT, TB (high) Number Analyzed 1386 participants
1
   0.1%
Follow up, TB (high) Number Analyzed 908 participants
1
   0.1%
ATOT, Triglycerides (high) Number Analyzed 1383 participants
1
   0.1%
ATOT, Troponin I (high) Number Analyzed 426 participants
13
   3.1%
Follow up, Troponin I (high) Number Analyzed 142 participants
2
   1.4%
ATOT, Urea (high) Number Analyzed 1385 participants
97
   7.0%
Follow up, Urea (high) Number Analyzed 909 participants
42
   4.6%
13.Secondary Outcome
Title Change From Baseline in Alzheimer's Disease Assessment Scale – Cognitive (ADAS-cog) Total Score as a Function of Apolipoprotein E (APOE) ε4 Status.
Hide Description The 11-item ADAS-Cog assessed a range of cognitive abilities including memory, comprehension, orientation in time and place and spontaneous speech. Most items were evaluated by tests, but some were dependent on clinician ratings on a five point scale. Scores 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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).
Arm/Group Title RSG XR
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 1461
Mean (Standard Deviation)
Unit of Measure: Scores on scale
Week 24 (Full population) Number Analyzed 973 participants
2.5  (5.51)
Week 52 (Full population) Number Analyzed 308 participants
5.1  (6.82)
Week 24 (APOE4 negatives) Number Analyzed 404 participants
2.3  (5.28)
Week 52 (APOE4 negatives) Number Analyzed 135 participants
4.8  (6.44)
Week 24 (APOE4 positives) Number Analyzed 569 participants
2.6  (5.66)
Week 52(APOE4 positives) Number Analyzed 173 participants
5.4  (7.11)
Week 24 (APOE4 E4 homozygotes) Number Analyzed 126 participants
2.7  (5.77)
Week 52 (APOE4 E4 homozygotes) Number Analyzed 39 participants
5.2  (7.49)
Week 24 (APOE4 E4 heterozygotes) Number Analyzed 443 participants
2.6  (5.63)
Week 52 (APOE4 E4 heterozygotes) Number Analyzed 134 participants
5.4  (7.02)
14.Secondary Outcome
Title Change From Baseline in Clinical Dementia Rating Scale–Sum of Boxes (CDR-SB) Score as a Function of APOE ε4 Status.
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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).
Arm/Group Title RSG XR
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 1461
Mean (Standard Deviation)
Unit of Measure: Scores on scale
Week 24 (Full population) Number Analyzed 988 participants
0.7  (1.84)
Week 52 (Full population) Number Analyzed 313 participants
1.6  (2.26)
Week 24 (APOE4 negatives) Number Analyzed 409 participants
0.6  (1.76)
Week 52 (APOE4 negatives) Number Analyzed 139 participants
1.3  (2.19)
Week 24 (APOE4 positives) Number Analyzed 579 participants
0.7  (1.89)
Week 52 (APOE4 positives) Number Analyzed 174 participants
1.9  (2.30)
Week 24 (APOE4 E4 homozygotes) Number Analyzed 127 participants
0.9  (1.90)
Week 52 (APOE4 E4 homozygotes) Number Analyzed 39 participants
1.9  (2.32)
Week 24 (APOE4 E4 heterozygotes) Number Analyzed 452 participants
0.7  (1.89)
Week 52 (APOE4 E4 heterozygotes) Number Analyzed 135 participants
1.9  (2.30)
15.Secondary Outcome
Title Change From Baseline in Mini Mental State Examination (MMSE) Total Score as a Function of APOE ε4 Status.
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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).
Arm/Group Title RSG XR
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 1461
Mean (Standard Deviation)
Unit of Measure: Scores on scale
Week 24 (Full population) Number Analyzed 833 participants
-1.2  (2.84)
Week 52 (Full population) Number Analyzed 184 participants
-2.3  (3.39)
Week 24 (APOE4 negatives) Number Analyzed 353 participants
-0.7  (2.74)
Week 52 (APOE4 negatives) Number Analyzed 77 participants
-1.5  (3.56)
Week 24 (APOE4 positives) Number Analyzed 480 participants
-1.5  (2.87)
Week 52 (APOE4 positives) Number Analyzed 107 participants
-2.8  (3.17)
Week 24 (APOE4 E4 homozygotes) Number Analyzed 104 participants
-1.5  (3.07)
Week 52 (APOE4 E4 homozygotes) Number Analyzed 23 participants
-2.5  (3.16)
Week 24 (APOE4 E4 heterozygotes) Number Analyzed 376 participants
-1.5  (2.82)
Week 52 (APOE4 E4 heterozygotes) Number Analyzed 84 participants
-2.9  (3.18)
16.Secondary Outcome
Title Change From Baseline in Disability Assessment for Dementia Scale (DAD) Total Score as a Function of APOE ε4 Status.
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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).
Arm/Group Title RSG XR
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 1461
Mean (Standard Deviation)
Unit of Measure: Scores on scale
Week 24 (Full population) Number Analyzed 837 participants
-5.6  (12.36)
Week 52 (Full population) Number Analyzed 183 participants
-10.8  (15.07)
Week 24 (APOE4 negatives) Number Analyzed 354 participants
-4.6  (11.57)
Week 52 (APOE4 negatives) Number Analyzed 77 participants
-10.9  (14.90)
Week 24 (APOE4 positives) Number Analyzed 483 participants
-6.2  (12.88)
Week 52 (APOE4 positives) Number Analyzed 106 participants
-10.7  (15.26)
Week 24 (APOE4 E4 homozygotes) Number Analyzed 106 participants
-5.6  (12.16)
Week 52 (APOE4 E4 homozygotes) Number Analyzed 24 participants
-12.6  (11.84)
Week 24 (APOE4 E4 heterozygotes) Number Analyzed 377 participants
-6.4  (13.08)
Week 52 (APOE4 E4 heterozygotes) Number Analyzed 82 participants
-10.1  (16.14)
17.Secondary Outcome
Title Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score as a Function of APOE ε4 Status.
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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).
Arm/Group Title RSG XR
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 1461
Mean (Standard Deviation)
Unit of Measure: Score on scale
Week 24 (Full population) Number Analyzed 835 participants
1.4  (7.87)
Week 52 (Full population) Number Analyzed 183 participants
3.2  (10.90)
Week 24 (APOE4 negatives) Number Analyzed 353 participants
1.0  (7.26)
Week 52 (APOE4 negatives) Number Analyzed 77 participants
2.4  (7.74)
Week 24 (APOE4 positives) Number Analyzed 482 participants
1.7  (8.29)
Week 52 (APOE4 positives) Number Analyzed 106 participants
3.8  (12.71)
Week 24 (APOE4 E4 homozygotes) Number Analyzed 105 participants
1.8  (7.75)
Week 52 (APOE4 E4 homozygotes) Number Analyzed 24 participants
4.2  (14.19)
Week 24 (APOE4 E4 heterozygotes) Number Analyzed 377 participants
1.6  (8.45)
Week 52 (APOE4 E4 heterozygotes) Number Analyzed 82 participants
3.7  (12.34)
Time Frame Up to 76 Weeks
Adverse Event Reporting Description All subject (Full population) was used for analysis.
 
Arm/Group Title RSG XR
Hide Arm/Group Description 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.
All-Cause Mortality
RSG XR
Affected / at Risk (%)
Total   20/1461 (1.37%) 
Show Serious Adverse Events Hide Serious Adverse Events
RSG XR
Affected / at Risk (%)
Total   126/1461 (8.62%) 
Blood and lymphatic system disorders   
Anaemia  1  5/1461 (0.34%) 
Iron deficiency anaemia  1  1/1461 (0.07%) 
Cardiac disorders   
Myocardial infarction  1  3/1461 (0.21%) 
Acute myocardial infarction  1  2/1461 (0.14%) 
Atrial fibrillation  1  2/1461 (0.14%) 
Angina pectoris  1  1/1461 (0.07%) 
Atrial flutter  1  1/1461 (0.07%) 
Cardiac failure congestive  1  1/1461 (0.07%) 
Cardio-respiratory arrest  1  1/1461 (0.07%) 
Coronary artery disease  1  1/1461 (0.07%) 
Myocardial ischaemia  1  1/1461 (0.07%) 
Sinus arrhythmia  1  1/1461 (0.07%) 
Gastrointestinal disorders   
Haematemesis  1  1/1461 (0.07%) 
Intestinal obstruction  1  1/1461 (0.07%) 
Large intestine perforation  1  1/1461 (0.07%) 
Lumbar hernia  1  1/1461 (0.07%) 
Peritonitis  1  1/1461 (0.07%) 
Colonic polyp  1  1/1461 (0.07%) 
General disorders   
Death  1  1/1461 (0.07%) 
General physical health deterioration  1  1/1461 (0.07%) 
Oedema peripheral  1  1/1461 (0.07%) 
Hepatobiliary disorders   
Bile duct stone  1  1/1461 (0.07%) 
Cholangitis  1  1/1461 (0.07%) 
Cholecystitis  1  1/1461 (0.07%) 
Infections and infestations   
Pneumonia  1  5/1461 (0.34%) 
Bronchopneumonia  1  2/1461 (0.14%) 
Urinary tract infection  1  2/1461 (0.14%) 
Cellulitis  1  1/1461 (0.07%) 
Diverticulitis  1  1/1461 (0.07%) 
Respiratory tract infection viral  1  1/1461 (0.07%) 
Injury, poisoning and procedural complications   
Fall  1  4/1461 (0.27%) 
Femur fracture  1  3/1461 (0.21%) 
Humerus fracture  1  2/1461 (0.14%) 
Skin laceration  1  2/1461 (0.14%) 
Spinal compression fracture  1  2/1461 (0.14%) 
Drug toxicity  1  1/1461 (0.07%) 
Femoral neck fracture  1  1/1461 (0.07%) 
Fracture  1  1/1461 (0.07%) 
Head injury  1  1/1461 (0.07%) 
Hip fracture  1  1/1461 (0.07%) 
Injury  1  1/1461 (0.07%) 
Lumbar vertebral fracture  1  1/1461 (0.07%) 
Pacemaker complication  1  1/1461 (0.07%) 
Soft tissue injury  1  1/1461 (0.07%) 
Subdural haematoma  1  1/1461 (0.07%) 
Subdural haemorrhage  1  1/1461 (0.07%) 
Traumatic fracture  1  1/1461 (0.07%) 
Upper limb fracture  1  1/1461 (0.07%) 
Wrist fracture  1  1/1461 (0.07%) 
Investigations   
Blood sodium increased  1  1/1461 (0.07%) 
Weight increased  1  1/1461 (0.07%) 
Metabolism and nutrition disorders   
Dehydration  1  1/1461 (0.07%) 
Hypokalaemia  1  1/1461 (0.07%) 
Musculoskeletal and connective tissue disorders   
Osteoarthritis  1  2/1461 (0.14%) 
Foot deformity  1  1/1461 (0.07%) 
Osteoporotic fracture  1  1/1461 (0.07%) 
Synovial disorder  1  1/1461 (0.07%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Breast cancer  1  2/1461 (0.14%) 
Brain cancer metastatic  1  1/1461 (0.07%) 
Brain neoplasm  1  1/1461 (0.07%) 
Colon cancer  1  1/1461 (0.07%) 
Endometrial cancer  1  1/1461 (0.07%) 
Lung neoplasm  1  1/1461 (0.07%) 
Metastases to bone  1  1/1461 (0.07%) 
Ovarian cancer  1  1/1461 (0.07%) 
Paget's disease of the breast  1  1/1461 (0.07%) 
Prostate cancer  1  1/1461 (0.07%) 
Refractory anaemia  1  1/1461 (0.07%) 
Nervous system disorders   
Cerebrovascular accident  1  4/1461 (0.27%) 
Syncope  1  4/1461 (0.27%) 
Dementia  1  2/1461 (0.14%) 
Dementia Alzheimer's type  1  2/1461 (0.14%) 
Transient ischaemic attack  1  2/1461 (0.14%) 
Cerebral haemorrhage  1  1/1461 (0.07%) 
Coma  1  1/1461 (0.07%) 
Convulsion  1  1/1461 (0.07%) 
Dizziness  1  1/1461 (0.07%) 
Epilepsy  1  1/1461 (0.07%) 
Ischaemic stroke  1  1/1461 (0.07%) 
Loss of consciousness  1  1/1461 (0.07%) 
Nerve root compression  1  1/1461 (0.07%) 
Optic neuritis  1  1/1461 (0.07%) 
Subarachnoid haemorrhage  1  1/1461 (0.07%) 
Thalamic infarction  1  1/1461 (0.07%) 
Psychiatric disorders   
Aggression  1  3/1461 (0.21%) 
Delirium  1  2/1461 (0.14%) 
Agitation  1  1/1461 (0.07%) 
Behavioural and psychiatric symptoms of dementia  1  1/1461 (0.07%) 
Confusional state  1  1/1461 (0.07%) 
Hallucination  1  1/1461 (0.07%) 
Mental status changes  1  1/1461 (0.07%) 
Panic disorder  1  1/1461 (0.07%) 
Sleep disorder  1  1/1461 (0.07%) 
Renal and urinary disorders   
Nephrotic syndrome  1  1/1461 (0.07%) 
Urinary retention  1  1/1461 (0.07%) 
Reproductive system and breast disorders   
Benign prostatic hyperplasia  1  1/1461 (0.07%) 
Uterine prolapse  1  1/1461 (0.07%) 
Respiratory, thoracic and mediastinal disorders   
Lung disorder  1  1/1461 (0.07%) 
Pulmonary embolism  1  1/1461 (0.07%) 
Skin and subcutaneous tissue disorders   
Skin ulcer  1  1/1461 (0.07%) 
Vascular disorders   
Circulatory collapse  1  2/1461 (0.14%) 
Peripheral arterial occlusive disease  1  1/1461 (0.07%) 
Post thrombotic syndrome  1  1/1461 (0.07%) 
1
Term from vocabulary, MedDRA
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
RSG XR
Affected / at Risk (%)
Total   130/1461 (8.90%) 
General disorders   
Oedema peripheral  1  130/1461 (8.90%) 
1
Term from vocabulary, MedDRA
Indicates events were collected by systematic assessment
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.
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Results Point of Contact
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
Phone: 866-435-7343
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