Phase 3
N=579
Rosiglitazone (Extended Release Tablets) As Monotherapy In Subjects With Mild To Moderate Alzheimer's Disease
Alzheimer's Disease
Bottom Line
View on ClinicalTrials.gov: NCT00428090 ↗Enrolled (actual)
579
Serious AEs
5.4%
Results posted
May 2017
Primary outcome: Primary: Change From Baseline (W0) in Mean ADAS-Cog Total Score at W24 as a Function of APOE e4 Status in Apolipoprotein epsilon4 (APOE e4) Negative Cohort — 1.6; -0.2; 0.6; 0.9 Score on a scale — p=0.074
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Rosiglitazone (Drug)
- Age
- Adult, Older Adult · 50+ yrs
- Sex
- All
- Sponsor
- GlaxoSmithKline
- Primary completion
- Sep 2008
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline (W0) in Mean ADAS-Cog Total Score at W24 as a Function of APOE e4 Status in Apolipoprotein epsilon4 (APOE e4) Negative Cohort |
1.6; -0.2; 0.6; 0.9 | 0.074 |
| PRIMARY Change From Baseline (W0) in Mean ADAS-Cog Total Score at W24 as a Function of APOE e4 Status in All Except e4/e4's Cohort |
1.5; 0.3; 0.7; -0.1 | 0.131 |
| PRIMARY Change From Baseline (W0) in Mean ADAS-Cog Total Score at W24 as a Function of APOE e4 Status in Full Population Cohort |
2.0; 1.2; 1.2; 0.6 | 0.272 |
| PRIMARY Change From Baseline (W0) in Mean CIBIC+ Global Functioning Total Score at W24 as a Function of APOE e4 Status in APOE4 Negative Cohort |
4.2; 4.2; 4.1; 3.9 | 0.663 |
| PRIMARY Change From Baseline (W0) in Mean CIBIC+ Global Functioning Total Score at W24 as a Function of APOE e4 Status in All Except e4/e4's Cohort |
4.3; 4.3; 4.1; 3.8 | 0.913 |
| PRIMARY Change From Baseline (W0) in Mean CIBIC+ Global Functioning Total Score at W24 as a Function of APOE e4 Status in Full Population Cohort |
4.3; 4.3; 4.2; 3.8 | 0.939 |
| SECONDARY Change From Baseline (W0) in Mean ADAS-Cog Total Score at W8, W16, W24 |
0.4; -0.5; 0.5; -0.3; 0.5; 0.6 | 0.116 |
| SECONDARY Change From Baseline (W0) in Mean CIBIC+ Global Functioning Total Score at W8, W16, W24 |
4.1; 3.9; 4.1; 3.9; 4.2; 4.0 | 0.133 |
| SECONDARY Change From Baseline (W0) in Mean Neuropsychiatric Inventory (NPI) Total Score at W8, W16, W24 |
0.2; 0.1; 0.5; -0.1; -0.1; -0.0 | 0.957 |
| SECONDARY Change From Baseline (W0) in Mean Disability Assessment for Dementia (DAD) Scale Total Score at W8, W16, W24 |
-0.8; -0.6; -0.3; 0.5; -2.6; -1.7 | 0.919 |
| SECONDARY Change From Baseline (W0) in Mean Short Term Memory Assessment Total Score (ADAS-Cog Q1 Plus Q7) at W8, W16, W24 |
0.1; -0.1; 0.5; -0.4; 0.1; 0.6 | 0.635 |
| SECONDARY Change From Baseline (W0) in Mean European Quality of Life -5 Dimensions Proxy Version (EQ-5D Proxy) Total Score at W12, W24 Assessed by Utility |
-0.02; 0.00; 0.01; 0.01; -0.02; 0.02 | 0.199 |
| SECONDARY Change From Baseline (W0) in Mean European Quality of Life -5 Dimensions Proxy Version (EQ-5D Proxy) Total Score at W12, W24 Assessed by Thermometer (Visual Analog Scale [VAS]) |
1.4; 0.3; 1.7; -2.6; 1.9; -0.7 | 0.493 |
| SECONDARY Time Spent Caring for Basic and Instrumental Activities Resource Utilization in Dementia (RUD) Scale at W12 and W24 |
2.3; 4.5; -9.8; -5.7; 19.4; -0.6 | — |
| SECONDARY Change From Baseline (W0) in Alzheimer's Carer's Quality of Life Instrument (ACQLI) Score at W12 and W24. |
0.5; -0.6; -0.1; 0.5; 0.6; -0.2 | 0.027 sig |
| SECONDARY Change From Baseline (W0) in Mini Mental State Examination (MMSE) Total Score at W24. |
-0.5; -0.6; -0.7; 0.4 | 0.886 |
| SECONDARY Change From Baseline (W0) in Glycosylated Hemoglobin (HbA1c) at W24. |
0.1; 0.2; 0.1; 0.1 | 0.139 |
| SECONDARY Number of Participants With Adverse Events Defined by Severity |
62; 60; 69; 42; 32; 35 | — |
| SECONDARY Number of Participants With Systolic and Diastolic Blood Pressure (SBP and DBP), Heart Rate (HR) and Weight Values of Potential Clinical Concern (PCC) Any Time on Treatment (ATOT). |
52; 61; 41; 24; 1; 3 | — |
| SECONDARY Change From Baseline (W0) in 12-lead Electrocardiogram (ECG) |
2.2; 6.9; 6.0; -5.5; 1.1; 0.7 | — |
| SECONDARY Change From Baseline (W0) in Heart Rate (HR) Measured From 12-lead Electrocardiogram (ECG) |
2.1; -2.8; -0.3; -4.7 | — |
| SECONDARY Change From Baseline (W0) in Body Weight |
0.1; 0.4; 0.3; -0.1; -0.0; 0.5 | — |
| SECONDARY Change From Baseline (W0) in Hemoglobin |
0.1; -2.8; -3.9; -0.4; -0.2; -4.5 | — |
| SECONDARY Change From Baseline (W0) in Hematocrit |
-0.0011; -0.0088; -0.0125; -0.0024; -0.0007; -0.0152 | — |
| SECONDARY Change From Baseline (W0) in Periodic HbA1c Assessment |
-0.1; 0.2; 0.1; -0.2; 0.1; 0.2 | — |
| SECONDARY Number of Par. With Hematology Data of Potential Clinical Concern Any Time on Treatment |
2; 0; 1; 0; 0; 1 | — |
| SECONDARY Number of Par. With Clinical Chemistry Values of Potential Clinical Concern Any Time on Treatment |
2; 0; 0; 0; 2; 0 | — |
Summary
Rosiglitazone (RSG) has been tested and is approved as a treatment for type II diabetes mellitus, a disease that occurs when the body ineffectively uses glucose. RSG XR, the investigational drug, is an extended-release form of RSG. This study tests whether RSG XR safely provides benefit to people with mild to moderate Alzheimer's disease (AD). RSG XR is a new approach to AD therapy and this study tests whether one's genes alter the effectiveness of RSG XR. Glucose is used by cells to make energy that they need to live. Changes in the ability of cells to use of glucose can lead to diseases like diabetes. Glucose levels may be lower in the brains of AD patients, and their brain cells may also use glucose less well than in unaffected people. The proper function of brain cells may be critical to memory and thought. If brain cells use glucose poorly, this might impact AD. Drugs that help brain cells properly use glucose may help a person maintain normal memory and thinking. Data suggesting that RSG may help AD patients was first seen in a small study at the Univ. of Washington and then from a larger international GSK study. In the first study, those receiving RSG once daily for 6 months scored better on 3 tests of memory and thought than those who did not receive RSG. In the GSK study, those that benefited most from therapy with RSG XR had a specific genetic pattern. They lacked the gene that caused them to produce apolipoprotein E e4 (APOE e4). Subjects who have the APOE e4 gene may have two copies, one from each parent, or they may have only one APOE e4 gene meaning that they inherited either the APOE e2 or APOE e3 version of the gene from one parent. Subjects with one copy of the APOE e4 gene remained fairly stable while those with two copies of APOE e4 continued to worsen during the 6-month treatment. This study will directly test the effect of RSG XR on people who either have or lack the APOE e4 gene.
Eligibility Criteria
Inclusion criteria
- Clinical diagnosis of probable Alzheimer's Disease (AD).
- MMSE score 10 to 23
- Has not taken an approved AD therapy in last 30 days.
- No previous hypersensitivity/intolerance to AChEIs
- Have a regular caregiver.
Exclusion criteria
- Diagnosis of vascular dementia.
- Type I or secondary diabetes mellitus.
- Type II diabetes mellitus treated with insulin, sulfonylurea or glipizide.
- History or evidence of congestive heart failure, clinically significant peripheral edema or anemia.
- History of significant psychiatric illness, major depressive disorder or current depression needing initiation of treatment.
Data sourced from ClinicalTrials.gov (NCT00428090). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.