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

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

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.

Study Overview

• Status: Completed
• Conditions: Alzheimer's Disease
• Intervention / Treatment: Drug: rosiglitazone

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H4H 1R3
      • GSK Investigational Site
• United States
  • Arizona
    • Litchfield Park, Arizona, United States, 85340
      • GSK Investigational Site
    • Phoenix, Arizona, United States, 85006
      • GSK Investigational Site
    • Sun City, Arizona, United States, 85351
      • GSK Investigational Site
  • Massachusetts
    • Belmont, Massachusetts, United States, 02478
      • GSK Investigational Site
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • GSK Investigational Site
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: rosiglitazone; Extended Release Tablets	Drug: rosiglitazone; Extended Release Tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	From start of study medication (Wk 0) to Wk 50

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	From baseline to Wk 48
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.	From start of study medication (Wk 0) to Wk 50
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.	Up to Wk 50
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.	Baseline (Wk 0) to Wk 50
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).	Baseline (Wk 0) to Wk 50
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.	Up to Wk 50
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.	Baseline (Wk 0) to Wk 50
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.	Up to Wk 50
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.	Up to Wk 50
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.	Up to Wk 50

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

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

Helpful Links

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

Study record dates

Study Major Dates

• Study Start: June 20, 2006
• Primary Completion (ACTUAL): February 1, 2009
• Study Completion (ACTUAL): February 3, 2009

Study Registration Dates

• First Submitted: September 26, 2006
• First Submitted That Met QC Criteria: September 26, 2006
• First Posted (ESTIMATE): September 27, 2006

Study Record Updates

• Last Update Posted (ACTUAL): May 23, 2017
• Last Update Submitted That Met QC Criteria: April 18, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: Alzheimer's Disease; Rosiglitazone
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease; Hypoglycemic Agents; Physiological Effects of Drugs; Rosiglitazone
• Other Study ID Numbers: AVA104617

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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.

Study Data/Documents

1. Individual Participant Data Set
   Information identifier: AVA104617
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Statistical Analysis Plan
   Information identifier: AVA104617
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Dataset Specification
   Information identifier: AVA104617
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Informed Consent Form
   Information identifier: AVA104617
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Study Protocol
   Information identifier: AVA104617
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Clinical Study Report
   Information identifier: AVA104617
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Annotated Case Report Form
   Information identifier: AVA104617
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register