Trial Outcomes & Findings for Study Of Rosiglitazone XR In Subjects With Mild-to-Moderate Alzheimers (NCT NCT00550420)

Last Updated: 2017-11-08

Results Overview

AE was defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. The drug related-AEs of special interest (AESI) was reported. The severity of the AESI was categorized as mild, moderate and severe. Number of participants with AEs were reported for treatment duration of the study.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

331 participants

Primary outcome timeframe

Up to Week 82

Results posted on

2017-11-08

Participant Flow

A total of 331 participants who had completed the double-blind treatment phase in AVA105640 were enrolled. Only 26 participants completed the study as it was early terminated, 206 participants were still enrolled at the time of study termination while 97 participants withdrew prematurely. The study completion status of 2 participants was missing.

The enrolled participants had successfully completed Visit 8 of AVA105640 without safety/tolerability issues. For safety endpoints, 'baseline' referred to the current study baseline assessment, (AVA102677 Visit 1). For efficacy endpoints, the term 'baseline' referred to the baseline assessment of the parent study (AVA105640), Visit 3.

Participant milestones

Participant milestones
Measure	RSG XR 8 mg Participants received rosiglitazone extended-release (RSG XR) 4 milligram (mg) tablet once daily, orally for the first 4 weeks of the study followed by RSG XR 8mg tablet once daily, orally up to 52 weeks. If a participant and caregiver chose to extend treatment beyond the first 52 weeks, following re-consent, participants were allowed to continue the treatment and attended visits at the following time points every year: 12, 24, 36 and 52 weeks.
Overall Study STARTED	331
Overall Study COMPLETED	26
Overall Study NOT COMPLETED	305

Reasons for withdrawal

Reasons for withdrawal
Measure	RSG XR 8 mg Participants received rosiglitazone extended-release (RSG XR) 4 milligram (mg) tablet once daily, orally for the first 4 weeks of the study followed by RSG XR 8mg tablet once daily, orally up to 52 weeks. If a participant and caregiver chose to extend treatment beyond the first 52 weeks, following re-consent, participants were allowed to continue the treatment and attended visits at the following time points every year: 12, 24, 36 and 52 weeks.
Overall Study Adverse Event	28
Overall Study Lost to Follow-up	8
Overall Study Protocol Violation	11
Overall Study Withdrawal by Subject	30
Overall Study Still in study at termination	206
Overall Study Missing	2
Overall Study Prolonged QT Interval Electrocardiogram	12
Overall Study Investigators opinion	1
Overall Study Lack of curative effect	1
Overall Study Unethical stop of enrollment	2
Overall Study Caregiver's decision to withdraw	1
Overall Study Out of Electrocardiogram criteria	1
Overall Study Exclusion criteria	1
Overall Study Prohibited medicine	1

Baseline Characteristics

Study Of Rosiglitazone XR In Subjects With Mild-to-Moderate Alzheimers

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	RSG XR 8 mg n=331 Participants Participants received RSG XR 4mg tablet once daily, orally for the first 4 weeks of the study followed by RSG XR 8mg tablet once daily, orally up to 52 weeks. If a participant and caregiver chose to extend treatment beyond the first 52 weeks, following re-consent, participants were allowed to continue the treatment and attended visits at the following time points every year: 12, 24, 36 and 52 weeks.
Age, Continuous	72.8 Years STANDARD_DEVIATION 7.95 • n=5 Participants
Sex: Female, Male Female	206 Participants n=5 Participants
Sex: Female, Male Male	125 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	3 Participants n=5 Participants
Race (NIH/OMB) Asian	85 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	242 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to Week 82

Population: All subject population was comprised of all participants who took at least one dose of open-label study medication.

Outcome measures

Outcome measures
Measure	RSG XR 8 mg n=331 Participants Participants received RSG XR 4mg tablet once daily, orally for the first 4 weeks of the study followed by RSG XR 8mg tablet once daily, orally up to 52 weeks. If a participant and caregiver chose to extend treatment beyond the first 52 weeks, following re-consent, participants were allowed to continue the treatment and attended visits at the following time points every year: 12, 24, 36 and 52 weeks.
Number of Participants With Any Adverse Events (AEs) and Severity of AEs Any AEs	125 Participants
Number of Participants With Any Adverse Events (AEs) and Severity of AEs Total Drug-Related AESI	46 Participants
Number of Participants With Any Adverse Events (AEs) and Severity of AEs Mild AESI	31 Participants
Number of Participants With Any Adverse Events (AEs) and Severity of AEs Moderate AESI	13 Participants
Number of Participants With Any Adverse Events (AEs) and Severity of AEs Severe AESI	2 Participants

SECONDARY outcome

Timeframe: Up to Week 82

Population: All subject population

A serious adverse event is defined as any untoward medical occurrence that, at any dose results in death, life-threatening condition, requires hospitalization or prolongation of existing hospitalization, results in disability or incapacity, or a congenital anomaly or birth defect. The SAEs and deaths are reported from Visit 1 (W0) till end of the follow-up period (W110)

Outcome measures

Outcome measures
Measure	RSG XR 8 mg n=331 Participants Participants received RSG XR 4mg tablet once daily, orally for the first 4 weeks of the study followed by RSG XR 8mg tablet once daily, orally up to 52 weeks. If a participant and caregiver chose to extend treatment beyond the first 52 weeks, following re-consent, participants were allowed to continue the treatment and attended visits at the following time points every year: 12, 24, 36 and 52 weeks.
Number of Participants With Serious AEs and Deaths Death	3 Participants
Number of Participants With Serious AEs and Deaths Any SAE	8 Participants

SECONDARY outcome

Timeframe: Up to 82 Weeks

Population: All subject population

Edema 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. Percentage of participants reported with edema as AESI were reported.

Outcome measures

Outcome measures
Measure	RSG XR 8 mg n=331 Participants Participants received RSG XR 4mg tablet once daily, orally for the first 4 weeks of the study followed by RSG XR 8mg tablet once daily, orally up to 52 weeks. If a participant and caregiver chose to extend treatment beyond the first 52 weeks, following re-consent, participants were allowed to continue the treatment and attended visits at the following time points every year: 12, 24, 36 and 52 weeks.
Percentage of Participants With AEs of Edema	13 Percentage of participants

SECONDARY outcome

Timeframe: Baseline (Visit 1, W0), W4, W8, W12, W16, W24, W36, W52, W64 and Follow-up (W82)

Population: All subjects population. Only those participants available at the indicated time points were analyzed.

SBP and DBP of participant were recorded in sitting posture as vital sign at each visit. The blood pressure (BP) values were identified as of potential clinical concern if the vales were out of the reference range (for SBP, 90 to 140 mmHg and DBP, 50 to 90 mmHg) or meet a change from Baseline criterion. The change from Baseline criterion for SBP, was increase from Baseline (high) if increased by more than or equal to (\>=) 40 mmHg from Baseline; decrease from Baseline (low) if decreased by \>= 30 mmHg from Baseline. For DBP, increase form Baseline (high) if increased by \>= 30 mmHg from Baseline; decrease from Baseline (low) if decreased by \>= 20 mmHg from Baseline. The Baseline assessments were referred to assessments at Visit 1 (W 0). Change from Baseline was measured as the blood pressure value recorded at specified visit minus the Baseline value.

Outcome measures

Outcome measures
Measure	RSG XR 8 mg n=331 Participants Participants received RSG XR 4mg tablet once daily, orally for the first 4 weeks of the study followed by RSG XR 8mg tablet once daily, orally up to 52 weeks. If a participant and caregiver chose to extend treatment beyond the first 52 weeks, following re-consent, participants were allowed to continue the treatment and attended visits at the following time points every year: 12, 24, 36 and 52 weeks.
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, W4	-0.2 millimeter of mercury (mmHg) Standard Deviation 11.61
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, W8	-1.1 millimeter of mercury (mmHg) Standard Deviation 11.83
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, W12	-0.7 millimeter of mercury (mmHg) Standard Deviation 13.80
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, W16	-1.3 millimeter of mercury (mmHg) Standard Deviation 13.66
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, W24	-1.2 millimeter of mercury (mmHg) Standard Deviation 13.30
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, W36	-3.0 millimeter of mercury (mmHg) Standard Deviation 15.37
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, W52	0.3 millimeter of mercury (mmHg) Standard Deviation 12.85
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Year 2 W12	-0.1 millimeter of mercury (mmHg) Standard Deviation 16.93
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Follow-up	-0.5 millimeter of mercury (mmHg) Standard Deviation 12.32
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, W4	-0.8 millimeter of mercury (mmHg) Standard Deviation 7.59
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, W8	-2.1 millimeter of mercury (mmHg) Standard Deviation 8.52
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, W12	-2.0 millimeter of mercury (mmHg) Standard Deviation 8.74
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, W16	-2.2 millimeter of mercury (mmHg) Standard Deviation 9.00
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, W24	-2.1 millimeter of mercury (mmHg) Standard Deviation 8.53
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, W36	-3.0 millimeter of mercury (mmHg) Standard Deviation 9.11
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, W52	-1.4 millimeter of mercury (mmHg) Standard Deviation 8.26
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Year 2 W12	2.8 millimeter of mercury (mmHg) Standard Deviation 9.86
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Follow-up	-0.9 millimeter of mercury (mmHg) Standard Deviation 9.04

SECONDARY outcome

Timeframe: Baseline (Visit 1, W0), W4, W8, W12, W16, W24, W36, W52, W64 and Follow-up (W82)

Population: All subject population. Only those participants available at the indicated time points were analyzed.

HR of participants was recorded as vital sign at each visit. The HR values were identified as of potential clinical concern if the vales were out of the reference range 50 to 100 beats per minute (BPM) or meet a change from Baseline criterion. The change from Baseline criterion was as, increase in HR (high) from Baseline if HR was increased by \>= 30 bpm or decrease in HR (Low) from Baseline if HR was decreased by \>= 30 bpm from Baseline. The Baseline assessments were referred to assessments at Visit 1 (W 0). Change from Baseline was measured as the HR at specified visit minus the Baseline value.

Outcome measures

Outcome measures
Measure	RSG XR 8 mg n=331 Participants Participants received RSG XR 4mg tablet once daily, orally for the first 4 weeks of the study followed by RSG XR 8mg tablet once daily, orally up to 52 weeks. If a participant and caregiver chose to extend treatment beyond the first 52 weeks, following re-consent, participants were allowed to continue the treatment and attended visits at the following time points every year: 12, 24, 36 and 52 weeks.
Change From Baseline in Heart Rate (HR) HR, W4	1.1 BPM Standard Deviation 7.19
Change From Baseline in Heart Rate (HR) HR, W8	1.8 BPM Standard Deviation 7.44
Change From Baseline in Heart Rate (HR) HR, W12	2.2 BPM Standard Deviation 8.70
Change From Baseline in Heart Rate (HR) HR, W16	1.2 BPM Standard Deviation 7.89
Change From Baseline in Heart Rate (HR) HR, W24	1.0 BPM Standard Deviation 7.87
Change From Baseline in Heart Rate (HR) HR, W36	1.7 BPM Standard Deviation 7.60
Change From Baseline in Heart Rate (HR) HR, W52	-0.8 BPM Standard Deviation 8.87
Change From Baseline in Heart Rate (HR) HR, Year 2 W12	2.9 BPM Standard Deviation 10.64
Change From Baseline in Heart Rate (HR) HR, Follow-up	1.6 BPM Standard Deviation 8.17

SECONDARY outcome

Timeframe: Up to 82 weeks

Population: All subjects population. Only those participants available at the indicated time points were analyzed.

Outcome measures

Outcome measures
Measure	RSG XR 8 mg n=331 Participants Participants received RSG XR 4mg tablet once daily, orally for the first 4 weeks of the study followed by RSG XR 8mg tablet once daily, orally up to 52 weeks. If a participant and caregiver chose to extend treatment beyond the first 52 weeks, following re-consent, participants were allowed to continue the treatment and attended visits at the following time points every year: 12, 24, 36 and 52 weeks.
Number of Participants With Abnormal SBP and DBP at Any Time During Treatment Period SBP, Increase from Baseline >=40,	8 Participants
Number of Participants With Abnormal SBP and DBP at Any Time During Treatment Period SBP, Decrease from Baseline >=30,	22 Participants
Number of Participants With Abnormal SBP and DBP at Any Time During Treatment Period DBP, >90 or <50,	23 Participants
Number of Participants With Abnormal SBP and DBP at Any Time During Treatment Period DBP, Increase from Baseline >=30,	2 Participants
Number of Participants With Abnormal SBP and DBP at Any Time During Treatment Period DBP, Decrease from Baseline >=20,	31 Participants
Number of Participants With Abnormal SBP and DBP at Any Time During Treatment Period SBP, >140 or <90,	84 Participants

SECONDARY outcome

Timeframe: Up to 82 weeks

Population: All subject population. Only those participants available at the indicated time points were analyzed.

Outcome measures

Outcome measures
Measure	RSG XR 8 mg n=319 Participants Participants received RSG XR 4mg tablet once daily, orally for the first 4 weeks of the study followed by RSG XR 8mg tablet once daily, orally up to 52 weeks. If a participant and caregiver chose to extend treatment beyond the first 52 weeks, following re-consent, participants were allowed to continue the treatment and attended visits at the following time points every year: 12, 24, 36 and 52 weeks.
Number of Participants With Abnormal HR at Any Time During Treatment Period HR, >100 or <50	3 Participants
Number of Participants With Abnormal HR at Any Time During Treatment Period HR, Increase from baseline >=30	2 Participants

SECONDARY outcome

Timeframe: Baseline (Visit 1, W0), W4, W8, W12, W16, W24, W36, W52, W64 and Follow-up (W82)

Population: All subject population. Only those participants available at the indicated time points were analyzed.

BW of participants were recorded as vital sign at each visit. The BW were identified as of potential clinical concern if the vales were increased or decreased from Baseline by \>=7%. The Baseline assessments were referred to assessments at Visit 1 (W0). Change from Baseline was measured as the BW at specified visit minus the Baseline value.

Outcome measures

Outcome measures
Measure	RSG XR 8 mg n=331 Participants Participants received RSG XR 4mg tablet once daily, orally for the first 4 weeks of the study followed by RSG XR 8mg tablet once daily, orally up to 52 weeks. If a participant and caregiver chose to extend treatment beyond the first 52 weeks, following re-consent, participants were allowed to continue the treatment and attended visits at the following time points every year: 12, 24, 36 and 52 weeks.
Change From Baseline in Body Weight (BW) BW, W4	0.2 Kilograms (kg) Standard Deviation 1.57
Change From Baseline in Body Weight (BW) BW, W8	0.4 Kilograms (kg) Standard Deviation 2.42
Change From Baseline in Body Weight (BW) BW, W12	0.5 Kilograms (kg) Standard Deviation 2.06
Change From Baseline in Body Weight (BW) BW, W16	0.5 Kilograms (kg) Standard Deviation 2.59
Change From Baseline in Body Weight (BW) BW, W24	0.6 Kilograms (kg) Standard Deviation 2.80
Change From Baseline in Body Weight (BW) BW, W36	0.5 Kilograms (kg) Standard Deviation 3.60
Change From Baseline in Body Weight (BW) BW, W52	-0.0 Kilograms (kg) Standard Deviation 3.75
Change From Baseline in Body Weight (BW) BW, Year 2 W12	0.5 Kilograms (kg) Standard Deviation 3.92
Change From Baseline in Body Weight (BW) BW, Follow-up	0.5 Kilograms (kg) Standard Deviation 3.04

SECONDARY outcome

Timeframe: Baseline (Visit 1, W0) to W 52

Population: All subject population. Only those participants available at the indicated time points were analyzed.

BW of participants were recorded as vital sign at each visit. The BW were identified as of potential clinical concern if the vales were increased or decreased from Baseline by \>=7%. The Baseline assessments were referred to assessments at Visit 1 (W0). Change from Baseline in BW was measured as the BW value at specified visit minus the Baseline BW value. Number of participants with abnormal BW at any time during treatment period were reported.

Outcome measures

Outcome measures
Measure	RSG XR 8 mg n=318 Participants Participants received RSG XR 4mg tablet once daily, orally for the first 4 weeks of the study followed by RSG XR 8mg tablet once daily, orally up to 52 weeks. If a participant and caregiver chose to extend treatment beyond the first 52 weeks, following re-consent, participants were allowed to continue the treatment and attended visits at the following time points every year: 12, 24, 36 and 52 weeks.
Number of Participants With Abnormal BW at Any Time During Treatment Period Decrease from Baseline >=7%	16 Participants
Number of Participants With Abnormal BW at Any Time During Treatment Period Increase from Baseline >=7%	30 Participants

SECONDARY outcome

Timeframe: Baseline (Visit 1, W0), W4, W16, W36, W52, W76, and W82

Population: All subject population. Only those participants available at the indicated time points were analyzed.

Non-fasting measures of lipid metabolism including cholesterol (TC), high density lipoprotein (HDL), low density lipoprotein (LDL), triglycerides (TG) were measured at Baseline (W0), W4, W16, W36, W52, Year 2 W24 and Follow-up. The Baseline assessments were referred to assessments at Visit 1 (W0). Change from Baseline was calculated as the value at the indicated visit minus the Baseline value.

Outcome measures

Outcome measures
Measure	RSG XR 8 mg n=331 Participants Participants received RSG XR 4mg tablet once daily, orally for the first 4 weeks of the study followed by RSG XR 8mg tablet once daily, orally up to 52 weeks. If a participant and caregiver chose to extend treatment beyond the first 52 weeks, following re-consent, participants were allowed to continue the treatment and attended visits at the following time points every year: 12, 24, 36 and 52 weeks.
Change From Baseline in Non-fasting Measures of Lipid Metabolism Including Total Cholesterol, High Density Lipoprotein, Low Density Lipoprotein and Triglycerides at Indicated Timepoints. TC, W4	0.106 Millimoles per litre Standard Deviation 0.7341
Change From Baseline in Non-fasting Measures of Lipid Metabolism Including Total Cholesterol, High Density Lipoprotein, Low Density Lipoprotein and Triglycerides at Indicated Timepoints. TC, W16	0.200 Millimoles per litre Standard Deviation 0.9713
Change From Baseline in Non-fasting Measures of Lipid Metabolism Including Total Cholesterol, High Density Lipoprotein, Low Density Lipoprotein and Triglycerides at Indicated Timepoints. TC, W36	0.140 Millimoles per litre Standard Deviation 1.0659
Change From Baseline in Non-fasting Measures of Lipid Metabolism Including Total Cholesterol, High Density Lipoprotein, Low Density Lipoprotein and Triglycerides at Indicated Timepoints. TC, W52	0.333 Millimoles per litre Standard Deviation 1.2454
Change From Baseline in Non-fasting Measures of Lipid Metabolism Including Total Cholesterol, High Density Lipoprotein, Low Density Lipoprotein and Triglycerides at Indicated Timepoints. TC, Year 2 W24	1.163 Millimoles per litre Standard Deviation 0.6604
Change From Baseline in Non-fasting Measures of Lipid Metabolism Including Total Cholesterol, High Density Lipoprotein, Low Density Lipoprotein and Triglycerides at Indicated Timepoints. TC, Follow-up	0.069 Millimoles per litre Standard Deviation 0.9649
Change From Baseline in Non-fasting Measures of Lipid Metabolism Including Total Cholesterol, High Density Lipoprotein, Low Density Lipoprotein and Triglycerides at Indicated Timepoints. HDL, W4	-0.035 Millimoles per litre Standard Deviation 0.2217
Change From Baseline in Non-fasting Measures of Lipid Metabolism Including Total Cholesterol, High Density Lipoprotein, Low Density Lipoprotein and Triglycerides at Indicated Timepoints. HDL, W16	-0.030 Millimoles per litre Standard Deviation 0.2597
Change From Baseline in Non-fasting Measures of Lipid Metabolism Including Total Cholesterol, High Density Lipoprotein, Low Density Lipoprotein and Triglycerides at Indicated Timepoints. HDL, W36	-0.069 Millimoles per litre Standard Deviation 0.2711
Change From Baseline in Non-fasting Measures of Lipid Metabolism Including Total Cholesterol, High Density Lipoprotein, Low Density Lipoprotein and Triglycerides at Indicated Timepoints. HDL, W52	-0.020 Millimoles per litre Standard Deviation 0.3420
Change From Baseline in Non-fasting Measures of Lipid Metabolism Including Total Cholesterol, High Density Lipoprotein, Low Density Lipoprotein and Triglycerides at Indicated Timepoints. HDL, Year 2 W24	-0.150 Millimoles per litre Standard Deviation 0.4104
Change From Baseline in Non-fasting Measures of Lipid Metabolism Including Total Cholesterol, High Density Lipoprotein, Low Density Lipoprotein and Triglycerides at Indicated Timepoints. HDL, Follow-up	-0.057 Millimoles per litre Standard Deviation 0.2325
Change From Baseline in Non-fasting Measures of Lipid Metabolism Including Total Cholesterol, High Density Lipoprotein, Low Density Lipoprotein and Triglycerides at Indicated Timepoints. LDL, W4	0.088 Millimoles per litre Standard Deviation 0.6689
Change From Baseline in Non-fasting Measures of Lipid Metabolism Including Total Cholesterol, High Density Lipoprotein, Low Density Lipoprotein and Triglycerides at Indicated Timepoints. LDL, W16	0.211 Millimoles per litre Standard Deviation 0.9151
Change From Baseline in Non-fasting Measures of Lipid Metabolism Including Total Cholesterol, High Density Lipoprotein, Low Density Lipoprotein and Triglycerides at Indicated Timepoints. LDL, W36	0.163 Millimoles per litre Standard Deviation 0.9484
Change From Baseline in Non-fasting Measures of Lipid Metabolism Including Total Cholesterol, High Density Lipoprotein, Low Density Lipoprotein and Triglycerides at Indicated Timepoints. LDL, W52	0.385 Millimoles per litre Standard Deviation 1.0346
Change From Baseline in Non-fasting Measures of Lipid Metabolism Including Total Cholesterol, High Density Lipoprotein, Low Density Lipoprotein and Triglycerides at Indicated Timepoints. LDL, Year 2 W24	1.051 Millimoles per litre Standard Deviation 0.5836
Change From Baseline in Non-fasting Measures of Lipid Metabolism Including Total Cholesterol, High Density Lipoprotein, Low Density Lipoprotein and Triglycerides at Indicated Timepoints. LDL, Follow-up	0.133 Millimoles per litre Standard Deviation 0.8985
Change From Baseline in Non-fasting Measures of Lipid Metabolism Including Total Cholesterol, High Density Lipoprotein, Low Density Lipoprotein and Triglycerides at Indicated Timepoints. TG, W4	0.084 Millimoles per litre Standard Deviation 0.6918
Change From Baseline in Non-fasting Measures of Lipid Metabolism Including Total Cholesterol, High Density Lipoprotein, Low Density Lipoprotein and Triglycerides at Indicated Timepoints. TG, W16	0.027 Millimoles per litre Standard Deviation 0.8355
Change From Baseline in Non-fasting Measures of Lipid Metabolism Including Total Cholesterol, High Density Lipoprotein, Low Density Lipoprotein and Triglycerides at Indicated Timepoints. TG, W36	0.050 Millimoles per litre Standard Deviation 0.8774
Change From Baseline in Non-fasting Measures of Lipid Metabolism Including Total Cholesterol, High Density Lipoprotein, Low Density Lipoprotein and Triglycerides at Indicated Timepoints. TG, W52	-0.179 Millimoles per litre Standard Deviation 1.0565
Change From Baseline in Non-fasting Measures of Lipid Metabolism Including Total Cholesterol, High Density Lipoprotein, Low Density Lipoprotein and Triglycerides at Indicated Timepoints. TG, Year 2 W24	0.573 Millimoles per litre Standard Deviation 0.8992
Change From Baseline in Non-fasting Measures of Lipid Metabolism Including Total Cholesterol, High Density Lipoprotein, Low Density Lipoprotein and Triglycerides at Indicated Timepoints. TG, Follow-up	-0.062 Millimoles per litre Standard Deviation 0.7616

SECONDARY outcome

Timeframe: Up to 82 weeks

Population: All subject population. Only those participants available at the indicated time points were analyzed.

The hematological parameters including eosinophils, lymphocytes, monocytes, platelet count, Segmented Neutrophils, total neutrophils, white blood cell (WBC), red blood cell (RBC) counts, hemoglobin, hematocrit count, mean corpuscle hemoglobin (MCH) and mean corpuscle volume (MCV) were analyzed as safety parameters. The number of participants with values outside the reference range (potential clinical concern ) at any time on treatment (ATOT) and follow-up period were reported. The treatment period was till W104 followed by 6 weeks of follow-up period till W110 of study.

Outcome measures

Outcome measures
Measure	RSG XR 8 mg n=331 Participants Participants received RSG XR 4mg tablet once daily, orally for the first 4 weeks of the study followed by RSG XR 8mg tablet once daily, orally up to 52 weeks. If a participant and caregiver chose to extend treatment beyond the first 52 weeks, following re-consent, participants were allowed to continue the treatment and attended visits at the following time points every year: 12, 24, 36 and 52 weeks.
Number of Participants With Hematological Parameters of Potential Clinical Concern Eosinophils, ATOT, High	1 Participants
Number of Participants With Hematological Parameters of Potential Clinical Concern Hematocrit, ATOT, Low	2 Participants
Number of Participants With Hematological Parameters of Potential Clinical Concern Hematocrit, Follow-up, Low	1 Participants
Number of Participants With Hematological Parameters of Potential Clinical Concern Hemoglobin, ATOT, High	1 Participants
Number of Participants With Hematological Parameters of Potential Clinical Concern Hemoglobin, ATOT, Low	20 Participants
Number of Participants With Hematological Parameters of Potential Clinical Concern Hemoglobin, Follow-Up, Low	8 Participants
Number of Participants With Hematological Parameters of Potential Clinical Concern Lymphocytes, ATOT, Low	5 Participants
Number of Participants With Hematological Parameters of Potential Clinical Concern Lymphocytes, Follow-Up, Low	3 Participants
Number of Participants With Hematological Parameters of Potential Clinical Concern MCH, ATOT, High	1 Participants
Number of Participants With Hematological Parameters of Potential Clinical Concern MCH, Follow-Up, High	1 Participants
Number of Participants With Hematological Parameters of Potential Clinical Concern MCV, ATOT, High	1 Participants
Number of Participants With Hematological Parameters of Potential Clinical Concern MCV, Follow-Up, High	1 Participants
Number of Participants With Hematological Parameters of Potential Clinical Concern Monocytes, ATOT, Low	17 Participants
Number of Participants With Hematological Parameters of Potential Clinical Concern Monocytes, ATOT, High	5 Participants
Number of Participants With Hematological Parameters of Potential Clinical Concern Platelet count, ATOT, High	1 Participants
Number of Participants With Hematological Parameters of Potential Clinical Concern Platelet count, ATOT, Low	2 Participants
Number of Participants With Hematological Parameters of Potential Clinical Concern Red Cell Distribution Width, ATOT, High	30 Participants
Number of Participants With Hematological Parameters of Potential Clinical Concern Red Cell Distribution Width,Follow-up, High	8 Participants
Number of Participants With Hematological Parameters of Potential Clinical Concern Red Blood Cell count, ATOT, Low	4 Participants
Number of Participants With Hematological Parameters of Potential Clinical Concern Red Blood Cell count, Follow-up, Low	4 Participants
Number of Participants With Hematological Parameters of Potential Clinical Concern Segmented Neutrophils, ATOT, High	1 Participants
Number of Participants With Hematological Parameters of Potential Clinical Concern Segmented Neutrophils, ATOT, Low	14 Participants
Number of Participants With Hematological Parameters of Potential Clinical Concern Segmented Neutrophils, Follow-up, Low	2 Participants
Number of Participants With Hematological Parameters of Potential Clinical Concern Total Neutrophils, ATOT, High	1 Participants
Number of Participants With Hematological Parameters of Potential Clinical Concern Total Neutrophils, ATOT, Low	14 Participants
Number of Participants With Hematological Parameters of Potential Clinical Concern Total Neutrophils, Follow-Up, Low	2 Participants
Number of Participants With Hematological Parameters of Potential Clinical Concern WBC, ATOT, Low	9 Participants

SECONDARY outcome

Timeframe: Up to 82 weeks

Population: All subject population. Only those participants available at the indicated time points were analyzed.

The clinical chemistry parameters including alanine amino transferase (ALT), aldolase, aspartate amino transferase (AST), blood urea nitrogen /creatinine (BUN/Creat) ratio, cholesterol (Chol), creatine kinase, creatinine, direct bilirubin, gamma glutamyl transferase (GGT), glucose, high density lipid (HDL), low density lipid (LDL), potassium, troponin 1, and urea were assessed as safety parameters. The number of participants with values outside the reference range (potential clinical concern ) at any time on treatment (ATOT) and follow-up period were reported. The treatment period was till W104 followed by 6 weeks of follow-up period till W110 of study.

Outcome measures

Outcome measures
Measure	RSG XR 8 mg n=331 Participants Participants received RSG XR 4mg tablet once daily, orally for the first 4 weeks of the study followed by RSG XR 8mg tablet once daily, orally up to 52 weeks. If a participant and caregiver chose to extend treatment beyond the first 52 weeks, following re-consent, participants were allowed to continue the treatment and attended visits at the following time points every year: 12, 24, 36 and 52 weeks.
Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern ALT, ATOT, High	1 Participants
Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern ALT, Follow-up, High	1 Participants
Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern Aldolase, ATOT, High	3 Participants
Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern Aldolase, ATOT, Low	7 Participants
Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern Aldolase, Follow-up, Low	3 Participants
Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern AST, ATOT, High	2 Participants
Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern AST, Follow-up, High	1 Participants
Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern BUN/Creat ratio, ATOT, High	18 Participants
Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern BUN/Creat ratio, Follow-up, High	1 Participants
Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern Chol, ATOT, High	52 Participants
Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern Chol, Follow-up, High	13 Participants
Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern Creatine Kinase, ATOT, High	32 Participants
Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern Creatine Kinase, Follow-up, High	7 Participants
Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern Creatinin, ATOT, High	4 Participants
Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern Creatinin, Follow-up, High	5 Participants
Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern Direct Bilirubin, ATOT, High	1 Participants
Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern GGT, ATOT, High	308 Participants
Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern GGT, Follow-up, High	142 Participants
Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern Glucose, ATOT, High	19 Participants
Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern Glucose, ATOT, Low	5 Participants
Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern Glucose, Follow-up, High	8 Participants
Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern HDL, ATOT, Low	1 Participants
Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern LDL, ATOT, High	135 Participants
Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern LDL, Follow-up, High	45 Participants
Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern Potassium, ATOT, High	4 Participants
Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern Potassium, ATOT, Low	1 Participants
Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern Troponin I, ATOT, High	2 Participants
Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern Urea, ATOT, High	19 Participants
Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern Urea, Follow-up, High	7 Participants

SECONDARY outcome

Timeframe: Baseline (Visit 1, W0), W24 and W52

Population: All subject population. All subject population was further stratified to 4 different cohorts based upon APOE 4 status as APOE 4 negative, APOE 4 positive, APOE 4 heterozygus and APOE 4 homozygus. Only those participants available at the indicated time points were analyzed.

The 11-item ADAS-cog was used to 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 was referred to Visit 1 (W0)assessments. Change from Baseline was calculated as value at scheduled time point minus Baseline value.

Outcome measures

Outcome measures
Measure	RSG XR 8 mg n=331 Participants Participants received RSG XR 4mg tablet once daily, orally for the first 4 weeks of the study followed by RSG XR 8mg tablet once daily, orally up to 52 weeks. If a participant and caregiver chose to extend treatment beyond the first 52 weeks, following re-consent, participants were allowed to continue the treatment and attended visits at the following time points every year: 12, 24, 36 and 52 weeks.
Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive (ADAS-Cog) Total Score as a Function of Apolipoprotein E (APOE) 4 Status at W24 and W52 All subject population, W24	1.9 Score on scale Standard Deviation 5.23
Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive (ADAS-Cog) Total Score as a Function of Apolipoprotein E (APOE) 4 Status at W24 and W52 All subject population, W52	2.5 Score on scale Standard Deviation 5.69
Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive (ADAS-Cog) Total Score as a Function of Apolipoprotein E (APOE) 4 Status at W24 and W52 APOE4, Neg, W24	2.1 Score on scale Standard Deviation 5.29
Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive (ADAS-Cog) Total Score as a Function of Apolipoprotein E (APOE) 4 Status at W24 and W52 APOE4, Neg, W52	3.0 Score on scale Standard Deviation 5.40
Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive (ADAS-Cog) Total Score as a Function of Apolipoprotein E (APOE) 4 Status at W24 and W52 APOEe4, Pos, W24	1.8 Score on scale Standard Deviation 5.19
Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive (ADAS-Cog) Total Score as a Function of Apolipoprotein E (APOE) 4 Status at W24 and W52 APOEe4, Pos, W52	1.8 Score on scale Standard Deviation 6.07

SECONDARY outcome

Timeframe: Baseline (Visit 1, W0), W 24 and W 52

The CIBIC+ score used for global functioning assessment. The CIBIC+ assessment comprised of a 7-point rating of severity. It was rated on a scale of 1 to 7 as 1: markedly improved, 2.: moderately improved, 3: minimally improved, 4: no change, 5: minimally worse, 6: moderately worse and 7: markedly worse; The lower score indicated betterment in functioning and higher score means greater dysfunction. The scale was based on interviews with the participant and the caregiver and was completed by an independent rater.

Outcome measures

Outcome measures
Measure	RSG XR 8 mg n=331 Participants Participants received RSG XR 4mg tablet once daily, orally for the first 4 weeks of the study followed by RSG XR 8mg tablet once daily, orally up to 52 weeks. If a participant and caregiver chose to extend treatment beyond the first 52 weeks, following re-consent, participants were allowed to continue the treatment and attended visits at the following time points every year: 12, 24, 36 and 52 weeks.
Mean Clinician Interview-Based Impression of Change Plus Caregiver Input (CIBIC+) Score as a Function of APOE 4 Status APOEe4, Neg, W52	4.7 Score on scale Standard Deviation 1.16
Mean Clinician Interview-Based Impression of Change Plus Caregiver Input (CIBIC+) Score as a Function of APOE 4 Status APOEe4, Pos, W24	4.3 Score on scale Standard Deviation 1.05
Mean Clinician Interview-Based Impression of Change Plus Caregiver Input (CIBIC+) Score as a Function of APOE 4 Status APOEe4, Pos, W52	4.3 Score on scale Standard Deviation 0.99
Mean Clinician Interview-Based Impression of Change Plus Caregiver Input (CIBIC+) Score as a Function of APOE 4 Status All subject population, W24	4.3 Score on scale Standard Deviation 1.05
Mean Clinician Interview-Based Impression of Change Plus Caregiver Input (CIBIC+) Score as a Function of APOE 4 Status All subject population, W52	4.5 Score on scale Standard Deviation 1.10
Mean Clinician Interview-Based Impression of Change Plus Caregiver Input (CIBIC+) Score as a Function of APOE 4 Status APOEe4, Neg, W24	4.3 Score on scale Standard Deviation 1.04

SECONDARY outcome

Timeframe: Baseline (Visit 1, W0), W 24 and W52

The MMSE consisted of 11 tests of orientation, memory (recent and immediate), concentration, language and praxis. Scores range from 0 to 30, with lower scores indicating greater cognitive impairment. The scale was completed by the investigator, based on the performance of the participant, and took approximately 5 to 10 minutes to administer. Change from parent Baseline in MMSE was analyzed using a mixed model for repeated measures (MMRM). Baseline was referred to Visit 1 (W0)assessments. Change from Baseline was calculated as value at scheduled time point minus Baseline value.

Outcome measures

Outcome measures
Measure	RSG XR 8 mg n=331 Participants Participants received RSG XR 4mg tablet once daily, orally for the first 4 weeks of the study followed by RSG XR 8mg tablet once daily, orally up to 52 weeks. If a participant and caregiver chose to extend treatment beyond the first 52 weeks, following re-consent, participants were allowed to continue the treatment and attended visits at the following time points every year: 12, 24, 36 and 52 weeks.
Change From Baseline in Mini Mental State Examination (MMSE) Total Score as a Function of APOE 4 Status at W24 and W52 APOEe4, Pos, W24	-0.7 Score on scale Standard Deviation 2.63
Change From Baseline in Mini Mental State Examination (MMSE) Total Score as a Function of APOE 4 Status at W24 and W52 APOEe4, Pos, W52	-2.1 Score on scale Standard Deviation 2.03
Change From Baseline in Mini Mental State Examination (MMSE) Total Score as a Function of APOE 4 Status at W24 and W52 All subject population, W24	-0.7 Score on scale Standard Deviation 2.65
Change From Baseline in Mini Mental State Examination (MMSE) Total Score as a Function of APOE 4 Status at W24 and W52 All subject population, W52	-1.6 Score on scale Standard Deviation 2.85
Change From Baseline in Mini Mental State Examination (MMSE) Total Score as a Function of APOE 4 Status at W24 and W52 APOEe4, Neg, W24	-0.7 Score on scale Standard Deviation 2.70
Change From Baseline in Mini Mental State Examination (MMSE) Total Score as a Function of APOE 4 Status at W24 and W52 APOEe4, Neg, W52	-1.2 Score on scale Standard Deviation 3.37

SECONDARY outcome

Timeframe: Baseline (Visit 1, W0), W24 and W52

The DAD, assessed the ability of a participant to execute basic and instrumental activities of daily living (ADL) and leisure activities. The scale consists of 40 questions assessing basic and instrumental ADLs. This scale 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) multiplied by 100. The DAD was conducted as an interview with the caregiver and took approximately 20 minutes. Baseline was referred to Visit 1 (W0) assessments. Change from Baseline was calculated as value at scheduled time point minus Baseline value.

Outcome measures

Outcome measures
Measure	RSG XR 8 mg n=331 Participants Participants received RSG XR 4mg tablet once daily, orally for the first 4 weeks of the study followed by RSG XR 8mg tablet once daily, orally up to 52 weeks. If a participant and caregiver chose to extend treatment beyond the first 52 weeks, following re-consent, participants were allowed to continue the treatment and attended visits at the following time points every year: 12, 24, 36 and 52 weeks.
Change From Baseline in Disability Assessment for Dementia Scale (DAD) Total Score as a Function of APOEe 4 Status All subject population, W24	-3.2 Score on scale Standard Deviation 10.23
Change From Baseline in Disability Assessment for Dementia Scale (DAD) Total Score as a Function of APOEe 4 Status All subject population, W52	-5.2 Score on scale Standard Deviation 18.21
Change From Baseline in Disability Assessment for Dementia Scale (DAD) Total Score as a Function of APOEe 4 Status APOEe4, Neg, W24	-4.5 Score on scale Standard Deviation 11.57
Change From Baseline in Disability Assessment for Dementia Scale (DAD) Total Score as a Function of APOEe 4 Status APOEe4, Neg, W52	-6.2 Score on scale Standard Deviation 22.66
Change From Baseline in Disability Assessment for Dementia Scale (DAD) Total Score as a Function of APOEe 4 Status APOEe4, Pos, W24	-2.2 Score on scale Standard Deviation 8.91
Change From Baseline in Disability Assessment for Dementia Scale (DAD) Total Score as a Function of APOEe 4 Status APOEe4, Pos, W52	-3.8 Score on scale Standard Deviation 10.73

SECONDARY outcome

Timeframe: Baseline (Visit 1, W0), W24 and W52

The NPI assessed behavioural disturbances comprises 10 dimensions: delusions, hallucinations, dysphoria, apathy, euphoria, disinhibition, aggressiveness and agitation, irritability, anxiety and aberrant motor activity. The participant caregiver asked about behaviour in the participant. If "Yes", the informant then rates both the severity on a 3-point scale, 1: mild to 3: severe (total range: 0-36) and the frequency using a 4-point scale, 1: occasionally to 4: very frequently. The total domain score was frequency × severity. The distress was scored on 5-point scale, 0: no distress to 5 - very severe or extreme. A total NPI score was calculated by adding all domain scores together: NPI total score (from 0-144) and NPI distress score (from 0-60), with higher scores indicating more severe behavioral disturbance. Baseline was referred to Visit 1 (W0) assessments. Change from Baseline was calculated as value at scheduled time point minus Baseline value.

Outcome measures

Outcome measures
Measure	RSG XR 8 mg n=331 Participants Participants received RSG XR 4mg tablet once daily, orally for the first 4 weeks of the study followed by RSG XR 8mg tablet once daily, orally up to 52 weeks. If a participant and caregiver chose to extend treatment beyond the first 52 weeks, following re-consent, participants were allowed to continue the treatment and attended visits at the following time points every year: 12, 24, 36 and 52 weeks.
Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score as a Function of APOE 4 Status at W24 and W52 All subject population, W24	1.1 Score on scale Standard Deviation 7.07
Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score as a Function of APOE 4 Status at W24 and W52 All subject population, W52	2.1 Score on scale Standard Deviation 9.55
Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score as a Function of APOE 4 Status at W24 and W52 APOEe4, Neg, W24	1.9 Score on scale Standard Deviation 8.24
Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score as a Function of APOE 4 Status at W24 and W52 APOEe4, Neg, W52	1.5 Score on scale Standard Deviation 9.41
Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score as a Function of APOE 4 Status at W24 and W52 APOEe4, Pos, W24	0.4 Score on scale Standard Deviation 5.91
Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score as a Function of APOE 4 Status at W24 and W52 APOEe4, Pos, W52	2.8 Score on scale Standard Deviation 10.35

SECONDARY outcome

Timeframe: Baseline (Vsit 1 W0), W12, W24, W36, W52, W76 and Follow-up (W82)

Population: All subject population. Only those participants available at the indicated time points were analyzed.

HbA1c was evaluated as safety parameter in this study. The values of change from Baseline was presented. The Baseline assessments were referred to assessments at Visit 1 (W0). Change from Baseline was measured as the BW at specified visit minus the Baseline value.

Outcome measures

Outcome measures
Measure	RSG XR 8 mg n=331 Participants Participants received RSG XR 4mg tablet once daily, orally for the first 4 weeks of the study followed by RSG XR 8mg tablet once daily, orally up to 52 weeks. If a participant and caregiver chose to extend treatment beyond the first 52 weeks, following re-consent, participants were allowed to continue the treatment and attended visits at the following time points every year: 12, 24, 36 and 52 weeks.
Change From Baseline in Glycosylated Haemoglobin (HbA1c) Follow-up	0.07 Percent HbA1c Standard Deviation 0.540
Change From Baseline in Glycosylated Haemoglobin (HbA1c) W12	-0.02 Percent HbA1c Standard Deviation 0.573
Change From Baseline in Glycosylated Haemoglobin (HbA1c) W24	0.08 Percent HbA1c Standard Deviation 0.512
Change From Baseline in Glycosylated Haemoglobin (HbA1c) W36	0.03 Percent HbA1c Standard Deviation 0.417
Change From Baseline in Glycosylated Haemoglobin (HbA1c) W52	0.09 Percent HbA1c Standard Deviation 0.377
Change From Baseline in Glycosylated Haemoglobin (HbA1c) W76	0.08 Percent HbA1c Standard Deviation 0.369

Adverse Events

RSG XR 8 mg

Serious events: 8 serious events

Other events: 42 other events

Deaths: 3 deaths

Serious adverse events

Serious adverse events
Measure	RSG XR 8 mg n=331 participants at risk Participants received RSG XR 4mg tablet once daily, orally for the first 4 weeks of the study followed by RSG XR 8mg tablet once daily, orally up to 52 weeks. If a participant and caregiver chose to extend treatment beyond the first 52 weeks, following re-consent, participants were allowed to continue the treatment and attended visits at the following time points every year: 12, 24, 36 and 52 weeks.
Cardiac disorders Atrioventricular block complete	0.30% 1/331 • On-treatment SAEs and non-SAEs were collected during the treatment period (up to 82 weeks) On-treatment SAEs and non-serious AEs were reported for the All subject population consisted of all participants who received at least one dose of study drug.
Cardiac disorders Coronary artery disease	0.30% 1/331 • On-treatment SAEs and non-SAEs were collected during the treatment period (up to 82 weeks) On-treatment SAEs and non-serious AEs were reported for the All subject population consisted of all participants who received at least one dose of study drug.
Gastrointestinal disorders Constipation	0.30% 1/331 • On-treatment SAEs and non-SAEs were collected during the treatment period (up to 82 weeks) On-treatment SAEs and non-serious AEs were reported for the All subject population consisted of all participants who received at least one dose of study drug.
Infections and infestations Urinary tract infection	0.30% 1/331 • On-treatment SAEs and non-SAEs were collected during the treatment period (up to 82 weeks) On-treatment SAEs and non-serious AEs were reported for the All subject population consisted of all participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Fracture	0.30% 1/331 • On-treatment SAEs and non-SAEs were collected during the treatment period (up to 82 weeks) On-treatment SAEs and non-serious AEs were reported for the All subject population consisted of all participants who received at least one dose of study drug.
Investigations Blood pressure increased	0.30% 1/331 • On-treatment SAEs and non-SAEs were collected during the treatment period (up to 82 weeks) On-treatment SAEs and non-serious AEs were reported for the All subject population consisted of all participants who received at least one dose of study drug.
Metabolism and nutrition disorders Dehydration	0.30% 1/331 • On-treatment SAEs and non-SAEs were collected during the treatment period (up to 82 weeks) On-treatment SAEs and non-serious AEs were reported for the All subject population consisted of all participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypoglycaemia	0.30% 1/331 • On-treatment SAEs and non-SAEs were collected during the treatment period (up to 82 weeks) On-treatment SAEs and non-serious AEs were reported for the All subject population consisted of all participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Pathological fracture	0.30% 1/331 • On-treatment SAEs and non-SAEs were collected during the treatment period (up to 82 weeks) On-treatment SAEs and non-serious AEs were reported for the All subject population consisted of all participants who received at least one dose of study drug.
Nervous system disorders Facial palsy	0.30% 1/331 • On-treatment SAEs and non-SAEs were collected during the treatment period (up to 82 weeks) On-treatment SAEs and non-serious AEs were reported for the All subject population consisted of all participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.30% 1/331 • On-treatment SAEs and non-SAEs were collected during the treatment period (up to 82 weeks) On-treatment SAEs and non-serious AEs were reported for the All subject population consisted of all participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Carbon monoxide poisoning	0.30% 1/331 • On-treatment SAEs and non-SAEs were collected during the treatment period (up to 82 weeks) On-treatment SAEs and non-serious AEs were reported for the All subject population consisted of all participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Subdural haematoma	0.30% 1/331 • On-treatment SAEs and non-SAEs were collected during the treatment period (up to 82 weeks) On-treatment SAEs and non-serious AEs were reported for the All subject population consisted of all participants who received at least one dose of study drug.
Cardiac disorders Atrial fibrillation	0.30% 1/331 • On-treatment SAEs and non-SAEs were collected during the treatment period (up to 82 weeks) On-treatment SAEs and non-serious AEs were reported for the All subject population consisted of all participants who received at least one dose of study drug.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.30% 1/331 • On-treatment SAEs and non-SAEs were collected during the treatment period (up to 82 weeks) On-treatment SAEs and non-serious AEs were reported for the All subject population consisted of all participants who received at least one dose of study drug.
General disorders Death	0.30% 1/331 • On-treatment SAEs and non-SAEs were collected during the treatment period (up to 82 weeks) On-treatment SAEs and non-serious AEs were reported for the All subject population consisted of all participants who received at least one dose of study drug.
Nervous system disorders Mental impairment	0.30% 1/331 • On-treatment SAEs and non-SAEs were collected during the treatment period (up to 82 weeks) On-treatment SAEs and non-serious AEs were reported for the All subject population consisted of all participants who received at least one dose of study drug.
Renal and urinary disorders Crush syndrome	0.30% 1/331 • On-treatment SAEs and non-SAEs were collected during the treatment period (up to 82 weeks) On-treatment SAEs and non-serious AEs were reported for the All subject population consisted of all participants who received at least one dose of study drug.
Vascular disorders Circulatory collapse	0.30% 1/331 • On-treatment SAEs and non-SAEs were collected during the treatment period (up to 82 weeks) On-treatment SAEs and non-serious AEs were reported for the All subject population consisted of all participants who received at least one dose of study drug.

Other adverse events

Other adverse events
Measure	RSG XR 8 mg n=331 participants at risk Participants received RSG XR 4mg tablet once daily, orally for the first 4 weeks of the study followed by RSG XR 8mg tablet once daily, orally up to 52 weeks. If a participant and caregiver chose to extend treatment beyond the first 52 weeks, following re-consent, participants were allowed to continue the treatment and attended visits at the following time points every year: 12, 24, 36 and 52 weeks.
General disorders Oedema peripheral	12.7% 42/331 • On-treatment SAEs and non-SAEs were collected during the treatment period (up to 82 weeks) On-treatment SAEs and non-serious AEs were reported for the All subject population consisted of all participants who received at least one dose of study drug.

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER