Open-Label Extension Assessing Long-Term Safety Of Rosiglitazone In Subjects With Mild To Moderate Alzheimer's Disease

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00381238
• Collaborator: (none)
• Enrollment: 33
• Locations: 7
• Arm: 1
• Duration (Months): 31.5
• Patients Per Site: 4.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is an open-label extension to study 49653/461, to assess the long-term safety of rosiglitazone (extended release tablets) in subjects with mild to moderate Alzheimer's Disease.

Condition or Disease	Intervention/Treatment	Phase
Alzheimer's Disease	Drug: rosiglitazone	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 33 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label Extension to Study 49653/461, to Assess the Long-term Safety of Rosiglitazone (Extended Release Tablets) in Subjects With Mild to Moderate Alzheimer's Disease
• Study Start Date: Jun 20, 2006
• Actual Primary Completion Date: Feb 1, 2009
• Actual Study Completion Date: Feb 3, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: rosiglitazone Extended Release Tablets	Drug: rosiglitazone; Extended Release Tablets

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Adverse Events (AE's) [From start of study medication (Wk 0) to Wk 50]

   An AE was defined as any untoward medical occurrence or clinical investigation in a participant, temporally associated with the use of a medicinal product, whether or not, considered related to the medicinal product. For marketed medicinal products, this also included failure to produce expected benefits (i.e. lack of efficacy), abuse or misuse. The number of participants with all AEs, drug related AEs, serious adverse events (SAEs), AE leading to permanent (prm) discontinuation (disc) of study drug or withdrawal were reported.

Secondary Outcome Measures

1. Mean Change From Baseline in Mini Mental State Examination (MMSE) Total Score [From baseline to Wk 48]

   The MMSE, is a score scale which consists of 11 tests of orientation (to time and place), memory (recent and immediate), concentration, language and praxis. The scoring ranged from 0 to 30, with lower scores indicative of greater cognitive impairment (more severe disease) and higher scores indicative less cognitive impairment (less severe disease). The total score was calculated by summing the scores from each of the tests. The investigator questioned the participants individually with set of questions and scored the participant, based on his performance. The baseline was defined as Wk 0. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values.

2. Number of Participants With SAEs [From start of study medication (Wk 0) to Wk 50]

   An SAE, is any untoward medical occurrence, that at any dose may result in death, is life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability or incapacity, is congenital anomaly or birth defect, and medically important events. The number of participants with any SAE, were reported.

3. Number of Participants With AE of Peripheral Edema by Grade [Up to Wk 50]

   Participants with AE of peripheral edema were evaluated. The test was performed by firmly pressing the thumb anterior to the participants ankle until further pressure produced no greater indentation. The depth of the pit was estimated and it was graded using below 5 point scale; where estimated depth of indentation corresponded to a particular grade (G). G 0 as depth of <1 millimeter (mm); G1 as depth of 1-2 mm; G2 as depth of 3-5 mm; G3 as depth of 6-10 mm; and G4 as depth of > 10 mm. The data for only the participants who had peripheral edema on more than one visit, then their most severe G were presented.

4. Mean Change From Baseline in Vital Signs- Systolic and Diastolic Blood Pressure [Baseline (Wk 0) to Wk 50]

   Participants systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured in mm of mercury (mmHg). These were collected after the participant sat quietly for at least five minutes. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values.

5. Mean Change From Baseline in Vital Signs-heart Rate (HR) [Baseline (Wk 0) to Wk 50]

   The HR for the participant's, were collected after the participant sat quietly for at least five minutes. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. The HR was measured in beats per minute (bpm).

6. Number of Participants With Vital Signs of Clinical Concern. [Up to Wk 50]

   The data for number of participants with vital sign data, outside the range of potential clinical concern for SBP, DBP, HR and body weight were reported. The values as of potential clinical concern were 'both' outside of reference range or met a change from baseline criterion. The RR, for SBP was 90-140 mmHg for which the increase from baseline was reported to be >= 40 mmHg and decrease from baseline reported as >=30 mmHg; the RR for DBP was 50-90 mmHg for which the increase from baseline was reported to be >= 30 mmHg and decrease from baseline reported as >=20 mmHg; and the RR, for HR was 50-100 bpm for which the increase from baseline was reported to be >= 30 bpm and the decrease from baseline reported as >=30 bpm. The data of number of participants with > clinical concern range (CCR) or < CCR were reported.

7. Mean Change From Baseline in Vital Signs- Weight [Baseline (Wk 0) to Wk 50]

   The weight for the participant, was measured without wearing shoes and with light clothing. There was no particular RR, reported for weight; however, the increase from baseline was reported to be >=7 % and the decrease also reported as >=7 %. The values as of potential clinical concern were 'both' outside of RR, or met a change from baseline criterion.

8. Number of Participants With Clinical Chemistry Parameters of Clinical Concern [Up to Wk 50]

   The data for participants for clinical parameters, with values only of potential clinical concern (PCI) were reported for creatine, creatinine kinase(CK), urea and glucose. Creatinine(unit: micromoles per litre) : low concern and high concern values were considered as 22 absolute value (AB) (<50% lower limit of RR ) and 155 (AB) (>125% upper limit of RR) respectively. CK (unit: international unit per litre ): low concern value and high concern values was none and 1.25 respectively. Glucose (unit: millimole per litre): low concern and high concern values were considered as 3.6 (AB) and 7.8 (AB) respectively.

9. Number of Participants With Clinical Chemistry Parameters of Clinical Concern-lipids [Up to Wk 50]

   Participant data for clinical concern lipid parameters for Total cholesterol, high density lipoprotein, low density lipoprotein, triglycerides was to be collected. However this data was not collected.

10. Number of Participant's With Hematology Parameters of Clinical Concern [Up to Wk 50]

    Participant data for clinical concern hematology parameters, were reported for hematocrit (Hct) (unit:1): low concern (LC) and high concern (HC) values as 0.8 and 1.2 respectively, hemoglobin (Hb) (unit: gram per deciliter): LC and HC values as value for female (F) 10 (AB) , value for male (M) 11; and value for F 16.5 (AB), value for M 18 respectively; lymphocytes absolute(LA) (unit: giga cells per litre [GI/L]) : LC and HC value as 0.75 and 1.5 respectively; monocytes absolute (MA) (unit: GI/L) LC and HC value as 0.75 and 2 respectively, platelet count (PC) (unit: x103/mm3): LC and HC value as 100 (AB) and 500(AB) respectively, red blood cell count (RBC) (unit: x106 micro litre): LC and HC value as 0.8 and 1.2 respectively, segmented neutrophils absolute (SNA) (unit: GI/L) LC and HC value as 0.75 and 1.3 respectively, total neutrophils absolute (TNA) (unit : GI/L) LC and HC value as 0.75 and 1.5 respectively; White blood cell (WBC) (unit: GI/L) LC and HC value as 3 and 15.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria:

• Male or female subject who has successfully completed the 12 Month Visit of 49653/461 (12 months of treatment) without tolerability issues, where in the opinion of the subject and of the investigator, it will be beneficial to continue treatment with RSG XR.

• Female subjects must be post-menopausal (i.e. >6 months without menstrual period), surgically sterile, or if of child-bearing potential, using effective contraceptive measures (oral contraceptives, Norplant, Depo-Provera, an intra-uterine device (IUD) a diaphragm with spermicide or a condom with spermicide). Women of childbearing potential must use effective contraceptive measures throughout the study and for 30 days after discontinuing study medication. The subject and their caregiver must ensure that the subject will continuously use contraceptive measures throughout the duration of the study.

• Subject is willing to participate in the extension study and has provided full written informed consent prior to the performance of any protocol-specified procedure; or if unable to provide informed consent due to cognitive status, full written informed consent on behalf of the subject has been provided by a legally acceptable representative[1].[1] Where this is in accordance with local laws, regulations and ethics committee policy.

• Caregiver has provided full written informed consent on his or her own behalf prior to the performance of any protocol-specified procedure.

Exclusion criteria:

• Subject had a serious adverse experience (SAE) or clinically significant laboratory abnormality during 49653/461, which in the opinion of the investigator could have been attributable to study medication, and which is ongoing at the end of 49653/461.

• The subject is felt by the investigator to be unsuitable (on the basis of health, compliance, caregiver availability, or for any other reason) for inclusion in the study based on the entry criteria for the primary study, 49653/461 (exclusive of the age criteria which may not be applicable to some of the subjects).

• The subject experienced a significant cardiovascular event during 49653/461 (e.g. intervention, percutaneous coronary intervention, vascular surgery, acute coronary syndrome [non Q-wave myocardial infarction, Q-wave myocardial infarction, unstable angina] or significant arrhythmia), unless a thorough cardiovascular evaluation has been performed which confirms that the subject does not have congestive heart failure, and is clinically stable.

• Treatment with a cholinesterase inhibitor, selegiline, memantine or any other treatment for cognitive symptoms/AD is initiated at the end of 49653/461.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Litchfield Park	Arizona	United States	85340
2	GSK Investigational Site	Phoenix	Arizona	United States	85006
3	GSK Investigational Site	Sun City	Arizona	United States	85351
4	GSK Investigational Site	Belmont	Massachusetts	United States	02478
5	GSK Investigational Site	Ann Arbor	Michigan	United States	48109
6	GSK Investigational Site	Durham	North Carolina	United States	27705
7	GSK Investigational Site	Montreal	Quebec	Canada	H4H 1R3

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Publications

• This study has not been published in the scientific literature.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT00381238
• Other Study ID Numbers: AVA104617
• First Posted: Sep 27, 2006
• Last Update Posted: May 23, 2017
• Last Verified: Feb 1, 2017

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by GlaxoSmithKline: Alzheimer's Disease; Rosiglitazone
• Additional relevant MeSH terms: Alzheimer Disease; Rosiglitazone

Study Results

Participant Flow

Recruitment Details	The study was conducted from 20 June 2006 to 03 February 2009, at seven centers in Canada and United States. This was an extension study, with a total of 33 participants with mild to moderate Alzheimer's disease, recruited in the study, who had completed 12-months of treatment in 49653/461 study.

Arm/Group Title	RSG XR, 8 mg
Arm/Group Description	The study duration was of 50-week (Wk), which comprised of a 48-Wk open-label treatment phase and a 2-Wk follow-up phase. During the treatment phase (48-Wk) the eligible participants received Rosiglitazone (RSG) extended release (XR), 4 milligram (mg) tablets once daily (od), orally in the morning for the first 4 Wks, which was followed by 8 mg od, orally in the morning for further 44 Wks of treatment.
Period Title: Overall Study
STARTED	33
COMPLETED	21
NOT COMPLETED	12

Baseline Characteristics

Arm/Group Title	RSG XR, 8 mg
Arm/Group Description	The study duration was of 50-Wk, which comprised of a 48-Wk open-label treatment phase and a 2-Wk follow-up phase. During the treatment phase (48-Wk) the eligible participants received RSG XR, 4 mg tablets od, orally in the morning for the first 4 Wks, which was followed by 8 mg od, orally in the morning for further 44 Wks of treatment.
Overall Participants	33
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	71.9 (9.75)
Sex: Female, Male (Count of Participants)
Female	15 45.5%
Male	18 54.5%
Race/Ethnicity, Customized (participants) [Number]
African American/African Heritage	1 3%
White - White/Caucasian/European Heritage	31 93.9%
Mixed Race	1 3%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Adverse Events (AE's)
Description	An AE was defined as any untoward medical occurrence or clinical investigation in a participant, temporally associated with the use of a medicinal product, whether or not, considered related to the medicinal product. For marketed medicinal products, this also included failure to produce expected benefits (i.e. lack of efficacy), abuse or misuse. The number of participants with all AEs, drug related AEs, serious adverse events (SAEs), AE leading to permanent (prm) discontinuation (disc) of study drug or withdrawal were reported.
Time Frame	From start of study medication (Wk 0) to Wk 50

Outcome Measure Data

Analysis Population Description

All subject population, is defined as all the participants who received at least one dose of study drug.

Arm/Group Title	RSG XR, 8 mg
Arm/Group Description	The study duration was of 50-Wk, which comprised of a 48-Wk open-label treatment phase and a 2-Wk follow-up phase. During the treatment phase (48-Wk) the eligible participants received RSG XR, 4 mg tablets od, orally in the morning for the first 4 Wks, which was followed by 8 mg od, orally in the morning for further 44 Wks of treatment.
Measure Participants	33
All AEs	25 75.8%
SAEs	2 6.1%
Drug related AEs	8 24.2%
AE leading to prm disc of study drug or withdrawal	3 9.1%

2. Secondary Outcome

Title	Mean Change From Baseline in Mini Mental State Examination (MMSE) Total Score
Description	The MMSE, is a score scale which consists of 11 tests of orientation (to time and place), memory (recent and immediate), concentration, language and praxis. The scoring ranged from 0 to 30, with lower scores indicative of greater cognitive impairment (more severe disease) and higher scores indicative less cognitive impairment (less severe disease). The total score was calculated by summing the scores from each of the tests. The investigator questioned the participants individually with set of questions and scored the participant, based on his performance. The baseline was defined as Wk 0. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values.
Time Frame	From baseline to Wk 48

Outcome Measure Data

Analysis Population Description

Intent to treat (ITT). The ITT population consisted of all participants in the safety population who also had at least one post-dose efficacy assessment within this study.

Arm/Group Title	RSG XR, 8 mg
Arm/Group Description	The study duration was of 50-Wk, which comprised of a 48-Wk open-label treatment phase and a 2-Wk follow-up phase. During the treatment phase (48-Wk) the eligible participants received RSG XR, 4 mg tablets od, orally in the morning for the first 4 Wks, which was followed by 8 mg od, orally in the morning for further 44 Wks of treatment.
Measure Participants	21
Mean (Standard Deviation) [score on scale]	-4.5 (4.07)

3. Secondary Outcome

Title	Number of Participants With SAEs
Description	An SAE, is any untoward medical occurrence, that at any dose may result in death, is life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability or incapacity, is congenital anomaly or birth defect, and medically important events. The number of participants with any SAE, were reported.
Time Frame	From start of study medication (Wk 0) to Wk 50

Outcome Measure Data

Analysis Population Description

All subject population

Arm/Group Title	RSG XR, 8 mg
Arm/Group Description	The study duration was of 50-Wk, which comprised of a 48-Wk open-label treatment phase and a 2-Wk follow-up phase. During the treatment phase (48-Wk) the eligible participants received RSG XR, 4 mg tablets od, orally in the morning for the first 4 Wks, which was followed by 8 mg od, orally in the morning for further 44 Wks of treatment.
Measure Participants	33
Number [participants]	2 6.1%

4. Secondary Outcome

Title	Number of Participants With AE of Peripheral Edema by Grade
Description	Participants with AE of peripheral edema were evaluated. The test was performed by firmly pressing the thumb anterior to the participants ankle until further pressure produced no greater indentation. The depth of the pit was estimated and it was graded using below 5 point scale; where estimated depth of indentation corresponded to a particular grade (G). G 0 as depth of <1 millimeter (mm); G1 as depth of 1-2 mm; G2 as depth of 3-5 mm; G3 as depth of 6-10 mm; and G4 as depth of > 10 mm. The data for only the participants who had peripheral edema on more than one visit, then their most severe G were presented.
Time Frame	Up to Wk 50

Outcome Measure Data

Analysis Population Description

All subject population

Arm/Group Title	RSG XR, 8 mg
Arm/Group Description	The study duration was of 50-Wk, which comprised of a 48-Wk open-label treatment phase and a 2-Wk follow-up phase. During the treatment phase (48-Wk) the eligible participants received RSG XR, 4 mg tablets od, orally in the morning for the first 4 Wks, which was followed by 8 mg od, orally in the morning for further 44 Wks of treatment.
Measure Participants	33
Participants with G0 peripheral edema	28 84.8%
Participants with G1 peripheral edema	3 9.1%
Participants with G2 peripheral edema	2 6.1%

5. Secondary Outcome

Title	Mean Change From Baseline in Vital Signs- Systolic and Diastolic Blood Pressure
Description	Participants systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured in mm of mercury (mmHg). These were collected after the participant sat quietly for at least five minutes. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values.
Time Frame	Baseline (Wk 0) to Wk 50

Outcome Measure Data

Analysis Population Description

All subject population. 'n' is participants available at the particular time of assessment which were included in analysis.

Arm/Group Title	RSG XR, 8 mg
Arm/Group Description	The study duration was of 50-Wk, which comprised of a 48-Wk open-label treatment phase and a 2-Wk follow-up phase. During the treatment phase (48-Wk) the eligible participants received RSG XR, 4 mg tablets od, orally in the morning for the first 4 Wks, which was followed by 8 mg od, orally in the morning for further 44 Wks of treatment.
Measure Participants	33
DBP, Wk 2	-1.1 (8.31)
SBP, Wk 2	1.7 (14.56)
DBP, Wk 4	-1.8 (9.25)
SBP, Wk 4	-1.3 (12.91)
DBP, Wk 8	0.3 (8.19)
SBP, Wk 8	3.2 (12.96)
DBP, Wk 16	-2.0 (9.69)
SBP, Wk 16	-1.4 (13.94)
DBP, Wk 24	-2.6 (10.22)
SBP, Wk 24	3.2 (17.96)
DBP, Wk 32	-0.9 (7.96)
SBP, Wk 32	4.7 (12.59)
DBP, Wk 40	-2.7 (10.10)
SBP, Wk 40	1.6 (13.96)
DBP, Wk 48	-3.7 (10.13)
SBP, Wk 48	1.0 (13.72)

6. Secondary Outcome

Title	Mean Change From Baseline in Vital Signs-heart Rate (HR)
Description	The HR for the participant's, were collected after the participant sat quietly for at least five minutes. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. The HR was measured in beats per minute (bpm).
Time Frame	Baseline (Wk 0) to Wk 50

Outcome Measure Data

Analysis Population Description

All subject population. 'n' is participants available at the particular time of assessment which were included in analysis.

Arm/Group Title	RSG XR, 8 mg
Arm/Group Description	The study duration was of 50-Wk, which comprised of a 48-Wk open-label treatment phase and a 2-Wk follow-up phase. During the treatment phase (48-Wk) the eligible participants received RSG XR, 4 mg tablets od, orally in the morning for the first 4 Wks, which was followed by 8 mg od, orally in the morning for further 44 Wks of treatment.
Measure Participants	33
HR, Wk 2	1.8 (5.70)
HR, Wk 4	1.2 (10.20)
HR, Wk 8	1.0 (12.72)
HR, Wk 16	0.3 (12.53)
HR, Wk 24	1.5 (13.24)
HR, Wk 32	-0.2 (12.34)
HR, Wk 40	1.9 (15.29)
HR, Wk 48	0.1 (7.57)

7. Secondary Outcome

Title	Number of Participants With Vital Signs of Clinical Concern.
Description	The data for number of participants with vital sign data, outside the range of potential clinical concern for SBP, DBP, HR and body weight were reported. The values as of potential clinical concern were 'both' outside of reference range or met a change from baseline criterion. The RR, for SBP was 90-140 mmHg for which the increase from baseline was reported to be >= 40 mmHg and decrease from baseline reported as >=30 mmHg; the RR for DBP was 50-90 mmHg for which the increase from baseline was reported to be >= 30 mmHg and decrease from baseline reported as >=20 mmHg; and the RR, for HR was 50-100 bpm for which the increase from baseline was reported to be >= 30 bpm and the decrease from baseline reported as >=30 bpm. The data of number of participants with > clinical concern range (CCR) or < CCR were reported.
Time Frame	Up to Wk 50

Outcome Measure Data

Analysis Population Description

All subject population. 'n' is participants available at the particular time of assessment which were included in analysis.

Arm/Group Title	RSG XR, 8 mg
Arm/Group Description	The study duration was of 50-Wk, which comprised of a 48-Wk open-label treatment phase and a 2-Wk follow-up phase. During the treatment phase (48-Wk) the eligible participants received RSG XR, 4 mg tablets od, orally in the morning for the first 4 Wks, which was followed by 8 mg od, orally in the morning for further 44 Wks of treatment.
Measure Participants	33
DBP >CCR, Wk 0	1 3%
DBP <CCR, Wk 4	1 3%
DBP >CCR, Wk 24	1 3%
DBP <CCR, Wk 48	1 3%
SBP >CCR, Wk 0	4 12.1%
SBP <CCR, Wk 0	1 3%
SBP >CCR, Wk 2	5 15.2%
SBP >CCR, Wk 4	4 12.1%
SBP <CCR, Wk 4	1 3%
SBP >CCR, Wk 8	5 15.2%
SBP >CCR, Wk 16	1 3%
SBP >CCR, Wk 24	3 9.1%
SBP >CCR, Wk 32	5 15.2%
SBP >CCR, Wk 40	7 21.2%
SBP >CCR, Wk 48	1 3%
HR >CCR, Wk 0	1 3%
HR <CCR, Wk 4	1 3%
HR <CCR, Wk 8	1 3%
HR <CCR, Wk 16	1 3%
HR >CCR, Wk 40	1 3%
HR <CCR, Wk 40	1 3%

8. Secondary Outcome

Title	Mean Change From Baseline in Vital Signs- Weight
Description	The weight for the participant, was measured without wearing shoes and with light clothing. There was no particular RR, reported for weight; however, the increase from baseline was reported to be >=7 % and the decrease also reported as >=7 %. The values as of potential clinical concern were 'both' outside of RR, or met a change from baseline criterion.
Time Frame	Baseline (Wk 0) to Wk 50

Outcome Measure Data

Analysis Population Description

All subject population. 'n' is participants available at the particular time of assessment which were included in analysis.

Arm/Group Title	RSG XR, 8 mg
Arm/Group Description	The study duration was of 50-Wk, which comprised of a 48-Wk open-label treatment phase and a 2-Wk follow-up phase. During the treatment phase (48-Wk) the eligible participants received RSG XR, 4 mg tablets od, orally in the morning for the first 4 Wks, which was followed by 8 mg od, orally in the morning for further 44 Wks of treatment.
Measure Participants	33
Weight, Wk 2	-0.4 (1.42)
Weight, Wk 4	-0.0 (1.93)
Weight, Wk 8	0.3 (2.12)
Weight, Wk 16	0.2 (3.18)
Weight, Wk 24	0.3 (3.21)
Weight, Wk 32	0.3 (3.97)
Weight, Wk 40	0.4 (3.25)
Weight, Wk 48	0.0 (2.91)

9. Secondary Outcome

Title	Number of Participants With Clinical Chemistry Parameters of Clinical Concern
Description	The data for participants for clinical parameters, with values only of potential clinical concern (PCI) were reported for creatine, creatinine kinase(CK), urea and glucose. Creatinine(unit: micromoles per litre) : low concern and high concern values were considered as 22 absolute value (AB) (<50% lower limit of RR ) and 155 (AB) (>125% upper limit of RR) respectively. CK (unit: international unit per litre ): low concern value and high concern values was none and 1.25 respectively. Glucose (unit: millimole per litre): low concern and high concern values were considered as 3.6 (AB) and 7.8 (AB) respectively.
Time Frame	Up to Wk 50

Outcome Measure Data

Analysis Population Description

All subjects population. 'n' is participants available at the particular time of assessment which were included in analysis.

Arm/Group Title	RSG XR, 8 mg
Arm/Group Description	The study duration was of 50-Wk, which comprised of a 48-Wk open-label treatment phase and a 2-Wk follow-up phase. During the treatment phase (48-Wk) the eligible participants received RSG XR, 4 mg tablets od, orally in the morning for the first 4 Wks, which was followed by 8 mg od, orally in the morning for further 44 Wks of treatment.
Measure Participants	33
CK, Wk 8, normal	0 0%
CK, Wk 8, high	1 3%
CK, Wk 16, normal	0 0%
CK, Wk 16, high	1 3%
CK, Wk 24, normal	0 0%
CK, Wk 24, high	1 3%
CK, Wk 32, normal	0 0%
CK, Wk 32, high	1 3%
CK, Wk 40, normal	0 0%
CK, Wk 40, high	2 6.1%
Creatinine, Wk 8, normal	0 0%
Creatinine, Wk 8, high	1 3%
Creatinine, Wk 8, low	0 0%
Creatinine, Wk 16, normal	0 0%
Creatinine, Wk 16, high	2 6.1%
Creatinine, Wk 16, low	0 0%
Creatinine, Wk 24, normal	0 0%
Creatinine,Wk 24, high	1 3%
Creatinine, Wk 24, low	0 0%
Creatinine, Wk 32, normal	0 0%
Creatinine,Wk 32, high	1 3%
Creatinine, Wk 32, low	0 0%
Glucose, Wk 0, normal	0 0%
Glucose, Wk 0, high	1 3%
Glucose, Wk 0, low	0 0%
Urea, Wk 0, normal	0 0%
Urea, Wk 0, high	1 3%

10. Secondary Outcome

Title	Number of Participants With Clinical Chemistry Parameters of Clinical Concern-lipids
Description	Participant data for clinical concern lipid parameters for Total cholesterol, high density lipoprotein, low density lipoprotein, triglycerides was to be collected. However this data was not collected.
Time Frame	Up to Wk 50

Outcome Measure Data

Analysis Population Description

All subject population. The data for 'The number of participants with clinical chemistry parameters of clinical concern- Lipids' was not collected.

Arm/Group Title	RSG XR, 8 mg
Arm/Group Description	The study duration was of 50-Wk, which comprised of a 48-Wk open-label treatment phase and a 2-Wk follow-up phase. During the treatment phase (48-Wk) the eligible participants received RSG XR, 4 mg tablets od, orally in the morning for the first 4 Wks, which was followed by 8 mg od, orally in the morning for further 44 Wks of treatment.
Measure Participants	0

11. Secondary Outcome

Title	Number of Participant's With Hematology Parameters of Clinical Concern
Description	Participant data for clinical concern hematology parameters, were reported for hematocrit (Hct) (unit:1): low concern (LC) and high concern (HC) values as 0.8 and 1.2 respectively, hemoglobin (Hb) (unit: gram per deciliter): LC and HC values as value for female (F) 10 (AB) , value for male (M) 11; and value for F 16.5 (AB), value for M 18 respectively; lymphocytes absolute(LA) (unit: giga cells per litre [GI/L]) : LC and HC value as 0.75 and 1.5 respectively; monocytes absolute (MA) (unit: GI/L) LC and HC value as 0.75 and 2 respectively, platelet count (PC) (unit: x103/mm3): LC and HC value as 100 (AB) and 500(AB) respectively, red blood cell count (RBC) (unit: x106 micro litre): LC and HC value as 0.8 and 1.2 respectively, segmented neutrophils absolute (SNA) (unit: GI/L) LC and HC value as 0.75 and 1.3 respectively, total neutrophils absolute (TNA) (unit : GI/L) LC and HC value as 0.75 and 1.5 respectively; White blood cell (WBC) (unit: GI/L) LC and HC value as 3 and 15.
Time Frame	Up to Wk 50

Outcome Measure Data

Analysis Population Description

All subjects population. 'n' is participants available at the particular time of assessment which were included in analysis.

Arm/Group Title	RSG XR, 8 mg
Arm/Group Description	The study duration was of 50-Wk, which comprised of a 48-Wk open-label treatment phase and a 2-Wk follow-up phase. During the treatment phase (48-Wk) the eligible participants received RSG XR, 4 mg tablets od, orally in the morning for the first 4 Wks, which was followed by 8 mg od, orally in the morning for further 44 Wks of treatment.
Measure Participants	33
Hct, Wk 32, normal	0
Hct, Wk 32, high	0
Hct, Wk 32, low	1
Hb, Wk 8, normal	0
Hb, Wk 8, high	0
Hb, Wk 8, low	1
Hb, Wk 24, normal	0
Hb, Wk 24, high	0
Hb, Wk 24, low	1
Hb, Wk 32, normal	0
Hb, Wk 32, high	0
Hb, Wk 32, low	1
Hb, Wk 40, normal	0
Hb, Wk 40, high	0
Hb, Wk 40, low	1
Hb,Wk 48, normal	0
Hb, Wk 48, high	0
Hb,Wk 48, low	1
LA, Wk 8, normal	0
LA, Wk 8, high	0
LA, Wk 8, low	1
LA, Wk 24, normal	0
LA, Wk 24, high	0
LA, Wk 24, low	1
MA, Wk 0, normal,	0
MA, Wk 0, high	0
MA, Wk 0, low	1
MA, Wk 24, normal	0
MA, Wk 24, high	0
MA, Wk 24, low	2
MA, Wk 40, normal	0
MA, Wk 40, high	0
MA, Wk 40, low	2
PC, Wk 8, normal	0
PC, Wk 8, high	0
PC, Wk 8, low	2
PC, Wk 32, normal	0
PC, Wk 32, high	0
PC, Wk 32, low	1
PC, Wk 40, normal	0
PC, Wk 40, high	0
PC, Wk 40, low	1
PC, Wk 48, normal	0
PC, Wk 48, high	0
PC, Wk 48, low	1
RBC, Wk 32, normal	0
RBC, Wk 32, high	0
RBC, Wk 32, low	1
SNP, Wk 8, normal	0
SNP, Wk 8, high	0
SNP, Wk 8, low	1
SNP, Wk 24, normal	0
SNP, Wk 24, high	0
SNP, Wk 24, low	1
TNA, Wk 8, normal	0
TNA, Wk 8, high	0
TNA, Wk 8, low	1
TNA, Wk 24, normal	0
TNA, Wk 24, high	0
TNA, Wk 24, low	1
WBC, Wk 8, normal	0
WBC, Wk 8, high	0
WBC, Wk 8, low	2
WBC, Wk 16, normal	0
WBC, Wk 16, high	0
WBC, Wk 16, low	2

Adverse Events

Time Frame	From start of study medication (Wk 0) to Wk 50
Adverse Event Reporting Description	All subject population was used
Arm/Group Title	RSG XR, 8 MG
Arm/Group Description	The study duration was of 50-Wk, which comprised of a 48-Wk open-label treatment phase and a 2-Wk follow-up phase. During the treatment phase (48-Wk) the eligible participants received RSG XR, 4 mg tablets od, orally in the morning for the first 4 Wks, which was followed by 8 mg od, orally in the morning for further 44 Wks of treatment.
All Cause Mortality
	RSG XR, 8 MG
	Affected / at Risk (%)	# Events
Total	0/33 (0%)
Serious Adverse Events
	RSG XR, 8 MG
	Affected / at Risk (%)	# Events
Total	2/33 (6.1%)
Injury, poisoning and procedural complications
Fall	1/33 (3%)
Pelvic fracture	1/33 (3%)
Nervous system disorders
Convulsion	1/33 (3%)
Other (Not Including Serious) Adverse Events
	RSG XR, 8 MG
	Affected / at Risk (%)	# Events
Total	10/33 (30.3%)
Gastrointestinal disorders
Vomiting	2/33 (6.1%)
General disorders
Oedema peripheral	3/33 (9.1%)
Injury, poisoning and procedural complications
Fall	2/33 (6.1%)
Musculoskeletal and connective tissue disorders
Bursitis	2/33 (6.1%)
Vascular disorders
Haematoma	2/33 (6.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.