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Rosiglitazone (Extended Release Tablets) As Monotherapy In Subjects With Mild To Moderate Alzheimer's Disease

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00428090
First received: January 25, 2007
Last updated: February 13, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Alzheimer's Disease
Drug: Rosiglitazone
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A 24-week, Double-blind, Double-dummy, Randomized, Parallel-group Study to Investigate the Effects of Rosiglitazone (Extended Release Tablets), Donepezil, and Placebo as Monotherapy on Cognition and Overall Clinical Response in APOE ε4-stratified Subjects With Mild to Moderate Alzheimer's Disease. (REFLECT-1)

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Change from baseline in ADAS-Cog total score and CIBIC+ score at Week 24, as a function of APOE e4 status.

Secondary Outcome Measures:
  • Visits Week 4 to 24:changes in behavior, activities of daily living, healthcare resource utilization, subject/ caregiver quality of life, pharmacokinetics, exploratory pharmacogenetics, proteomics/transcriptomics. [ Time Frame: 24 Weeks ]
  • The following endpoints will be analyzed according to a prioritized hierarchy to preserve the type I error rate :
  • Change from baseline in ADAS-Cog total score for observed cases at Weeks 8, 16 and 24.
  • Change from baseline in CIBIC+ score for observed cases at Weeks 8, 16 and 24.
  • Change from baseline in Neuropsychiatric Inventory (NPI; [Cummings, 1994]) total score.
  • Change from baseline in Disability Assessment for Dementia scale (DAD; [Gelinas, 1999]) total score.
  • Combined analysis of Items 1 and 7 of ADAS-Cog to yield Short Term Memory Assessment
  • Change from baseline in European Quality of Life -5 Dimensions Proxy (EQ-5D Proxy) scale [The EuroQol Group, 1990] total score.
  • Domains of the Resource Utilization in Dementia scale (RUD; [Wimo, 1998]).
  • Change from baseline in Alzheimer's Carer's Quality of Life Instrument (ACQLI, [Doward, 1997]) score.
  • Change from baseline in Mini Mental State Examination (MMSE) [Folstein, 1975] total score.
  • Change from baseline in HbA1c at Week 24.

Enrollment: 862
Study Start Date: February 2007
Study Completion Date: September 2008
Primary Completion Date: September 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Rosiglitazone
XR (extended release) oral tablets
Drug: Rosiglitazone
XR (extended release) oral tablets
Placebo
Placebo (Double-Dummy to Match)
Drug: Rosiglitazone
XR (extended release) oral tablets

Detailed Description:

A 24-week, double-blind, double-dummy, randomized, parallel-group study to investigate the effects of rosiglitazone (extended release tablets), donepezil, and placebo as monotherapy on cognition and overall clinical response in APOE e4-stratified subjects with mild to moderate Alzheimer's disease. (REFLECT-1)

  Eligibility

Ages Eligible for Study:   50 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00428090

  Show 138 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided by GlaxoSmithKline

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00428090     History of Changes
Other Study ID Numbers: 105640
Study First Received: January 25, 2007
Last Updated: February 13, 2014
Health Authority: United States: Food and Drug Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by GlaxoSmithKline:
apolipoprotein E
monotherapy
cognition
mild
rosiglitazone
Alzheimer's disease
moderate

Additional relevant MeSH terms:
Alzheimer Disease
Rosiglitazone
Brain Diseases
Central Nervous System Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Dementia
Mental Disorders
Nervous System Diseases
Neurodegenerative Diseases
Tauopathies
Hypoglycemic Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 25, 2014