Home
Search
Study Topics
Glossary
|
|
|
|
|
|
Sponsored by: |
GlaxoSmithKline |
---|---|
Information provided by: | GlaxoSmithKline |
ClinicalTrials.gov Identifier: | NCT00348140 |
Rosiglitazone (RSG) has been tested in clinical studies and is approved by the FDA as a treatment for type II diabetes mellitus, a disease that occurs when the body is unable to effectively use glucose. RSG XR, the investigational drug used in this study, is an extended-release form of RSG.
This study tests whether RSG XR safely provides clinical benefit to people with mild to moderate Alzheimer's disease (AD) when combined with one of the currently approved AD medications, Aricept®, Razadyne® or Exelon®. RSG XR is a new approach to AD therapy and this study tests a new way to treat AD by testing whether one's genetic makeup affects the response to the study drug. Clinical data suggesting that RSG may benefit AD patients was first seen in a small study performed at the University of Washington and then from a larger GSK study conducted in Europe and New Zealand. In the first study, subjects receiving RSG once daily for 6 months scored significantly better on 3 tests of memory and thought than those who did not receive RSG. In the GSK study, those that appeared to benefit most from treatment with RSG XR had a specific genetic pattern. They did not have the gene that caused them to produce the protein 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, instead of APOE e4, from one of their parents. Subjects with one copy of the APOE e4 gene remained at their same level of thinking ability while those with two copies of the APOE e4 gene, continued to worsen during the 6-month treatment. The current study will more directly test the effectiveness or RSG XR on people who either have or lack the APOE e4 gene.
Condition | Intervention | Phase |
---|---|---|
Alzheimer's Disease |
Drug: Rosiglitazone XR (extended release) oral tablets |
Phase III |
Study Type: | Interventional |
Study Design: | Treatment, Randomized, Double-Blind, Parallel Assignment, Efficacy Study |
Official Title: | See Detailed Description |
Estimated Enrollment: | 1450 |
Study Start Date: | July 2006 |
Estimated Study Completion Date: | July 2009 |
Estimated Primary Completion Date: | July 2009 (Final data collection date for primary outcome measure) |
A 54-week, double-blind, randomized, placebo-controlled, parallel-group study to investigate the effects of rosiglitazone (extended release tablets) as adjunctive therapy to acetylcholinesterase inhibitors on cognition and overall clinical response in APOE e4-stratified subjects with mild to moderate Alzheimer's disease (REFLECT-3)
Ages Eligible for Study: | 50 Years to 90 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
A subject will be eligible for inclusion in this study only if all of the following criteria apply:
Male or female subject with a clinical diagnosis of probable Alzheimer's disease in accordance with NINCDS-ADRDA criteria (Appendix 2).
(Note: National Institute of Neurological and Communicative Disorders and Stroke (NINCDS) and Alzheimer's Disease and Related Disorders Association (ADRDA).)
Brain CT or MRI scan performed within the past 12 months or at Screening, showing no evidence of any other potential cause of dementia other than Alzheimer's disease.
(Note: Questionable CT or MRI scans should be discussed with the medical monitor, using central imaging guidelines.)
Subject lives with (or has substantial periods of contact with) a regular caregiver who is willing to attend all visits, oversee the subject's compliance with protocol-specified procedures and study medication, and report on subject's status.
(Note: A non-cohabiting caregiver must spend sufficient time with the subject so that, in the opinion of the Investigator, the caregiver can reliably assess cognitive function, activities and behavior, and report on the subject's compliance and health. As caregiver time spent with a potential subject is anticipated to be highly variable across countries and cultures, GSK will consider a variety of different measures by which this stipulation may be met, and GSK should be consulted if adequacy of a caregiver situation is in doubt. However, as guidance, the ability for a caregiver to meet his/her expected responsibilities for this study would normally be possible when the caregiver spends no less than 10 hours per week with the subject, divided over multiple days.)
Subject 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.
(Note: Consent by legally acceptable representative is allowed where this is in accordance with local laws, regulations and ethics committee policy.)
(Note: For the purposes of these criteria, QTc B is defined as (QT interval [msec]) / (square root of RR interval [seconds]); and QTc F is defined as (QT interval [msec]) / (cube root of RR interval [seconds]).)
Exclusion Criteria:
A subject will not be eligible for inclusion in this study if any of the following criteria apply:
Diagnosis of possible, probable, or definite vascular dementia in accordance with NINDS-AIREN criteria (Appendix 5).
(Note: National Institute of Neurological Disorders and Stroke (NINDS) and Association Internationale pour la Recherche et l'Enseignement en Neurosciences (AIREN).)
Evidence of the following disorders: current vitamin B12 deficiency, positive syphilis serology, or active thyroid dysfunction (particularly that suggestive of hypothyroidism), including abnormally high or low serum levels of thyroid stimulating hormone (TSH), that are clinically significant in the opinion of the investigator.
(Note: Testing is required for each parameter only when no result is available from previous 12 months.)
History of significant psychiatric illness such as schizophrenia or bipolar affective disorder that in the opinion of the Investigator would interfere with participation in the study, major depressive disorder (according to DSM-IV) in the past year, or current active depression requiring initiation of treatment.
(Note: If not currently treated, but active depression is suspected, the Cornell Scale for Depression in Dementia (CSDD, Appendix 7) can be used by the Investigator as a guide for deciding whether a prospective subject requires treatment. If the subject has a CSDD score >7, the Investigator should decide if the subject has depression in need of prescribed medication, and a CSDD >12 is considered a strong indicator that treatment is needed. Subjects will be allowed to re-screen after their depression has been adequately managed for >3 months.)
ALT, AST, or alkaline phosphatase values >2.5 times the ULN, total bilirubin values >1.5 times the ULN, or history of severe hepatobiliary disease (e.g. hepatitis B or C, or cirrhosis, Child-Pugh Class B/C).
(Note: For subjects with a diagnosis of Gilberts Syndrome and an isolated increase in total bilirubin >1.5 ULN, fractionation should be performed. If all of the following conditions are met, the patient may enter or remain in the study, even if total bilirubin >1.5 ULN: •an elevated unconjugated (indirect) bilirubin;
This amendment is country-specific and applies only to sites in Canada. The change was not incorporated into the body of the current amendment.
(1) Change in Exclusion criterion #16 regarding ALT cutoff in order to meet regulatory requirements.
This amendment will apply to:
5.2.2 Exclusion Criteria (p.31)
a.Original Verbatim Text:
1.ALT, AST, or alkaline phosphatase values >2.5 times the ULN, total bilirubin values >1.5 times the ULN, or history of severe hepatobiliary disease (e.g. hepatitis B or C, or cirrhosis, Child-Pugh Class B/C).
b.Amended Text: 2.ALT, AST, or alkaline phosphatase values >2.0 times the ULN, total bilirubin values >1.5 times the ULN, or history of severe hepatobiliary disease (e.g. hepatitis B or C, or cirrhosis, Child-Pugh Class B/C).
Study Director: | GSK Clinical Trials, MD | GlaxoSmithKline |
Responsible Party: | GSK ( Study Director ) |
Study ID Numbers: | AVA102670 |
Study First Received: | June 30, 2006 |
Last Updated: | January 8, 2009 |
ClinicalTrials.gov Identifier: | NCT00348140 |
Health Authority: | United States: Food and Drug Administration; United States: Food and Drug Administration |
mild moderate rosiglitazone Alzheimer's disease |
cognition apolipoprotein E adjunctive therapy |
Delirium, Dementia, Amnestic, Cognitive Disorders Mental Disorders Alzheimer Disease Central Nervous System Diseases Neurodegenerative Diseases |
Brain Diseases Dementia Rosiglitazone Cognition Disorders Delirium |
Hypoglycemic Agents Physiological Effects of Drugs Nervous System Diseases Tauopathies Pharmacologic Actions |