Back to resultsOpen-Label Extension Assessing Long-Term Safety Of Rosiglitazone In Subjects With Mild To Moderate Alzheimer's Disease
Primary Purpose
Alzheimer's Disease
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
rosiglitazone
Sponsored by
About this trial
This is an interventional treatment trial for Alzheimer's Disease focused on measuring Alzheimer's Disease, Rosiglitazone
Eligibility Criteria
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.
Sites / Locations
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
rosiglitazone
Arm Description
Extended Release Tablets
Outcomes
Primary Outcome Measures
Number of Participants With Adverse Events (AE's)
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
Mean Change From Baseline in Mini Mental State Examination (MMSE) Total Score
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.
Number of Participants With SAEs
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.
Number of Participants With AE of Peripheral Edema by Grade
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.
Mean Change From Baseline in Vital Signs- Systolic and Diastolic Blood Pressure
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.
Mean Change From Baseline in Vital Signs-heart Rate (HR)
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).
Number of Participants With Vital Signs of Clinical Concern.
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.
Mean Change From Baseline in Vital Signs- Weight
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.
Number of Participants With Clinical Chemistry Parameters of Clinical Concern
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.
Number of Participants With Clinical Chemistry Parameters of Clinical Concern-lipids
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.
Number of Participant's With Hematology Parameters of Clinical Concern
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00381238
Brief Title
Open-Label Extension Assessing Long-Term Safety Of Rosiglitazone In Subjects With Mild To Moderate Alzheimer's Disease
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 Type
Interventional
2. Study Status
Record Verification Date
February 2017
Overall Recruitment Status
Completed
Study Start Date
June 20, 2006 (undefined)
Primary Completion Date
February 1, 2009 (Actual)
Study Completion Date
February 3, 2009 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline
4. Oversight
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer's Disease
Keywords
Alzheimer's Disease, Rosiglitazone
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
33 (Actual)
8. Arms, Groups, and Interventions
Arm Title
rosiglitazone
Arm Type
Experimental
Arm Description
Extended Release Tablets
Intervention Type
Drug
Intervention Name(s)
rosiglitazone
Intervention Description
Extended Release Tablets
Primary Outcome Measure Information:
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
Secondary Outcome Measure Information:
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
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
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
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
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
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
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
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
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
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
Litchfield Park
State/Province
Arizona
ZIP/Postal Code
85340
Country
United States
Facility Name
GSK Investigational Site
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85006
Country
United States
Facility Name
GSK Investigational Site
City
Sun City
State/Province
Arizona
ZIP/Postal Code
85351
Country
United States
Facility Name
GSK Investigational Site
City
Belmont
State/Province
Massachusetts
ZIP/Postal Code
02478
Country
United States
Facility Name
GSK Investigational Site
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
GSK Investigational Site
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27705
Country
United States
Facility Name
GSK Investigational Site
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H4H 1R3
Country
Canada
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
Citations:
Citation
This study has not been published in the scientific literature.
Results Reference
background
Links:
URL
https://www.clinicalstudydatarequest.com
Description
Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.
Available IPD and Supporting Information:
Available IPD/Information Type
Individual Participant Data Set
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
AVA104617
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Statistical Analysis Plan
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
AVA104617
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Dataset Specification
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
AVA104617
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Informed Consent Form
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
AVA104617
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Study Protocol
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
AVA104617
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Clinical Study Report
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
AVA104617
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Annotated Case Report Form
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
AVA104617
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Learn more about this trial
Open-Label Extension Assessing Long-Term Safety Of Rosiglitazone In Subjects With Mild To Moderate Alzheimer's Disease
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