Home
Clinical Trials
NCT00348309

Rosiglitazone (Extended Release Tablets) As Adjunctive Therapy For Subjects With Mild To Moderate Alzheimer's Disease

Last Updated: 2017-11-28

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

Total Enrollment

1496 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-07-06

Study Completion Date

2009-01-28

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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 the currently approved AD medication, Aricept (donepezil). 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 their 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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

A 54-week, double-blind, randomized, placebo-controlled, parallel-group study to investigate the effects of rosiglitazone (extended release tablets) as adjunctive therapy to donepezil on cognition and overall clinical response in APOE e4-stratified subjects with mild to moderate Alzheimer's disease (REFLECT-2)

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Alzheimer's Disease

Keywords

Explore important study keywords that can help with search, categorization, and topic discovery.

apolipoprotein E Alzheimer's disease cognition rosiglitazone adjunctive therapy

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Arm 1

Rosiglitazone Extended Release 2mg OD

Group Type EXPERIMENTAL

Rosiglitazone Extended Release 2mg

Intervention Type DRUG

Rosiglitazone Extended Release 2mg OD

Donepezil

Intervention Type OTHER

Donepezil (At least 6 months of ongoing donepezil therapy for Alzheimer's disease, with stable dosing for at least the last 2 months (and with no intent to change for the duration of the study).

Arm 2

Rosiglitazone Extended Release 8mg OD

Group Type EXPERIMENTAL

Rosiglitazone Extended Release 8mg

Intervention Type DRUG

Rosiglitazone Extended Release 8mg OD

Donepezil

Intervention Type OTHER

Donepezil (At least 6 months of ongoing donepezil therapy for Alzheimer's disease, with stable dosing for at least the last 2 months (and with no intent to change for the duration of the study).

Arm 3

Placebo

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

Placebo

Donepezil

Intervention Type OTHER

Donepezil (At least 6 months of ongoing donepezil therapy for Alzheimer's disease, with stable dosing for at least the last 2 months (and with no intent to change for the duration of the study).

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Rosiglitazone Extended Release 2mg

Rosiglitazone Extended Release 2mg OD

Intervention Type DRUG

Rosiglitazone Extended Release 8mg

Rosiglitazone Extended Release 8mg OD

Intervention Type DRUG

Placebo

Intervention Type OTHER

Donepezil

Donepezil (At least 6 months of ongoing donepezil therapy for Alzheimer's disease, with stable dosing for at least the last 2 months (and with no intent to change for the duration of the study).

Intervention Type OTHER

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Aricept

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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.

(Note: National Institute of Neurological and Communicative Disorders and Stroke (NINCDS) and Alzheimer's Disease and Related Disorders Association (ADRDA).)

* Subject has mild to moderate Alzheimer's disease as defined by a MMSE score 10 to 26 inclusive at Screening.
* Hachinski Ischemia Score ≤ 4 at Screening.
* Age ≥50 and ≤90 years.
* At least 6 months of ongoing donepezil therapy for Alzheimer's disease, with stable dosing for at least the last 2 months (and with no intent to change for the duration of the study).
* Current use of medication is in accordance with the criteria listed in Table 2 (Permitted Medications,).
* Female subjects must be post-menopausal (i.e. \>1 year without menstrual period), surgically sterile, or agree to use adequate method of contraception for the duration of the study. Female subjects who are pre-menopausal or who have been post-menopausal for \<1 year must undertake pregnancy testing (urine test) at Visit 1, which must be negative.
* 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.)

* Neurological exam without focal changes (excluding changes attributable to AD or peripheral trauma).
* Subject has the ability to comply with procedures for cognitive and other testing.
* 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.)

* Caregiver has provided full written informed consent on his/her own behalf prior to the performance of any protocol-specified procedure.
* Subjects considered for enrolment must have a QTc (either QTc B (Bazett's correction) or QTc F (Fridericia's correction)) \<450msec at Visit 1, with the exception of subjects with bundle branch block (for whom either QTc B or QTc F must be \<480msec).
* (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.

(Note: National Institute of Neurological Disorders and Stroke (NINDS) and Association Internationale pour la Recherche et l'Enseignement en Neurosciences (AIREN).)

* History or evidence of any other CNS disorder that could be interpreted as a cause of dementia: e.g. cerebrovascular disease (stroke, hemorrhage), structural abnormality, epilepsy, infectious or inflammatory/demyelinating CNS conditions, Parkinson's disease.
* 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 Type 1 diabetes mellitus or secondary diabetes mellitus.
* Type 2 diabetes mellitus where the subject is being treated with insulin, a PPARγ agonist, or an insulin secretagogue (e.g. a sulfonylurea or glitinide).
* Any patient with an HbA1c ≥8.5%. (See Section 6.3.7.4 for Safety Measures for Enrolled Subjects with Type 2 Diabetes Mellitus.)
* History or clinical/investigational evidence of congestive heart failure defined by the New York Heart Association criteria (Class I to IV cardiac status;).
* History of cardiovascular event within the last 6 months (i.e. intervention, percutaneous coronary intervention, vascular surgery, acute coronary syndrome \[non Q-wave myocardial infarction, Q-wave myocardial infarction, unstable angina\] or significant arrhythmia; or major intervention (e.g. cardiac surgery or angiography plus stenting) scheduled).
* 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) 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.)

* History or presence of gastro-intestinal, hepatic, or renal disease or other condition known to interfere with the absorption, distribution, metabolism, or excretion of drugs, or any other clinically relevant abnormality, medical or psychiatric condition, which, in the opinion of the Investigator, makes the subject unsuitable for inclusion in the study.
* Clinically significant peripheral edema at the time of screening.
* Current or recent drug or alcohol abuse or dependence (defined by DSM-IV criteria for substance-related disorders), or recent or remote history of the same if that could be a contributing factor to the dementia.
* Systolic blood pressure \>165 or \<90 mmHg or diastolic blood pressure \>95 or \<60 mmHg at the time of screening.
* Clinically significant anemia (i.e. hemoglobin \<11 g/dL for males or \<10 g/dL for females) or presence of hemoglobinopathies which would prevent accurate assessment of HbA1c.
* Abnormal kidney function tests (\>1.5 the upper limit of normal (ULN)).
* 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;
* the percentage of direct bilirubin \<35%;
* ALT, AST, and alkaline phosphatase \<2.5 ULN if subject is in screening (\<2.0 ULN for Canadian subjects only), or ≤3 ULN if subject is already randomized into the study)
* History of a bone marrow transplant.
* Subject is unable (with assistance, if appropriate) to take study medication as prescribed throughout the study or is at risk of non-compliance with study medication or procedures.
* Subject is an immediate family member or employee of the participating Investigator, of any of the participating site staff, or of GSK.
* In France, a subject is neither affiliated with nor a beneficiary of a social security category.
* The French subject has participated in any study using an investigational drug during the previous 30 days or 5 half-lives (whichever is longer).
* Cognitive tasks prescribed for cognitive rehabilitation and performed under medical supervision are prohibited for 6 months prior to Screening, as well as for the duration of the study.

Minimum Eligible Age

50 Years

Maximum Eligible Age

90 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

GSK Investigational Site

Litchfield Park, Arizona, United States

Site Status

GSK Investigational Site

Phoenix, Arizona, United States

Site Status

GSK Investigational Site

Phoenix, Arizona, United States

Site Status

GSK Investigational Site

Phoenix, Arizona, United States

Site Status

GSK Investigational Site

Little Rock, Arkansas, United States

Site Status

GSK Investigational Site

Fresno, California, United States

Site Status

GSK Investigational Site

Rancho Mirage, California, United States

Site Status

GSK Investigational Site

Sacramento, California, United States

Site Status

GSK Investigational Site

Sherman Oaks, California, United States

Site Status

GSK Investigational Site

Denver, Colorado, United States

Site Status

GSK Investigational Site

New Haven, Connecticut, United States

Site Status

GSK Investigational Site

Delray Beach, Florida, United States

Site Status

GSK Investigational Site

Hallandale, Florida, United States

Site Status

GSK Investigational Site

Miami, Florida, United States

Site Status

GSK Investigational Site

Sarasota, Florida, United States

Site Status

GSK Investigational Site

St. Petersburg, Florida, United States

Site Status

GSK Investigational Site

West Palm Beach, Florida, United States

Site Status

GSK Investigational Site

Hoffman Estates, Illinois, United States

Site Status

GSK Investigational Site

Fort Wayne, Indiana, United States

Site Status

GSK Investigational Site

Indianapolis, Indiana, United States

Site Status

GSK Investigational Site

Baltimore, Maryland, United States

Site Status

GSK Investigational Site

Glen Burnie, Maryland, United States

Site Status

GSK Investigational Site

Rockville, Maryland, United States

Site Status

GSK Investigational Site

Saint Paul, Minnesota, United States

Site Status

GSK Investigational Site

Lebanon, New Hampshire, United States

Site Status

GSK Investigational Site

Morristown, New Jersey, United States

Site Status

GSK Investigational Site

Nutley, New Jersey, United States

Site Status

GSK Investigational Site

Princeton, New Jersey, United States

Site Status

GSK Investigational Site

Stratford, New Jersey, United States

Site Status

GSK Investigational Site

Albany, New York, United States

Site Status

GSK Investigational Site

Brooklyn, New York, United States

Site Status

GSK Investigational Site

New York, New York, United States

Site Status

GSK Investigational Site

Durham, North Carolina, United States

Site Status

GSK Investigational Site

Raleigh, North Carolina, United States

Site Status

GSK Investigational Site

Portland, Oregon, United States

Site Status

GSK Investigational Site

Providence, Rhode Island, United States

Site Status

GSK Investigational Site

Nashville, Tennessee, United States

Site Status

GSK Investigational Site

Austin, Texas, United States

Site Status

GSK Investigational Site

Houston, Texas, United States

Site Status

GSK Investigational Site

South Ogden, Utah, United States

Site Status

GSK Investigational Site

Bennington, Vermont, United States

Site Status

GSK Investigational Site

Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina

Site Status

GSK Investigational Site

Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina

Site Status

GSK Investigational Site

Ciudad de Buenos Aires, Buenos Aires, Argentina

Site Status

GSK Investigational Site

Córdoba, Córdoba Province, Argentina

Site Status

GSK Investigational Site

Córdoba, Córdoba Province, Argentina

Site Status

GSK Investigational Site

Córdoba, Córdoba Province, Argentina

Site Status

GSK Investigational Site

Godoy Cruz, Mendoza Province, Argentina

Site Status

GSK Investigational Site

Buenos Aires, , Argentina

Site Status

GSK Investigational Site

Mendoza, , Argentina

Site Status

GSK Investigational Site

Hall in Tirol, , Austria

Site Status

GSK Investigational Site

Innsbruck, , Austria

Site Status

GSK Investigational Site

Vienna, , Austria

Site Status

GSK Investigational Site

Vienna, , Austria

Site Status

GSK Investigational Site

Vienna, , Austria

Site Status

GSK Investigational Site

Vienna, , Austria

Site Status

GSK Investigational Site

Belo Horizonte, , Brazil

Site Status

GSK Investigational Site

Ribeirão Preto, , Brazil

Site Status

GSK Investigational Site

São Paulo, , Brazil

Site Status

GSK Investigational Site

Calgary, Alberta, Canada

Site Status

GSK Investigational Site

Medicine Hat, Alberta, Canada

Site Status

GSK Investigational Site

Victoria, British Columbia, Canada

Site Status

GSK Investigational Site

Moncton, New Brunswick, Canada

Site Status

GSK Investigational Site

Barrie, Ontario, Canada

Site Status

GSK Investigational Site

Kingston, Ontario, Canada

Site Status

GSK Investigational Site

Peterborough, Ontario, Canada

Site Status

GSK Investigational Site

Toronto, Ontario, Canada

Site Status

GSK Investigational Site

Toronto, Ontario, Canada

Site Status

GSK Investigational Site

Whitby, Ontario, Canada

Site Status

GSK Investigational Site

Charlottetown, Prince Edward Island, Canada

Site Status

GSK Investigational Site

Greenfield Park, Quebec, Canada

Site Status

GSK Investigational Site

Montreal, Quebec, Canada

Site Status

GSK Investigational Site

Montreal, Quebec, Canada

Site Status

GSK Investigational Site

Sherbrooke, Quebec, Canada

Site Status

GSK Investigational Site

Regina, Saskatchewan, Canada

Site Status

GSK Investigational Site

Québec, , Canada

Site Status

GSK Investigational Site

Viña del Mar, Región de Valparaíso, Chile

Site Status

GSK Investigational Site

Providencia / Santiago, Región Metro de Santiago, Chile

Site Status

GSK Investigational Site

Puente Alto - Santiago, Región Metro de Santiago, Chile

Site Status

GSK Investigational Site

Santiago, Región Metro de Santiago, Chile

Site Status

GSK Investigational Site

Ostrava, , Czechia

Site Status

GSK Investigational Site

Prague, , Czechia

Site Status

GSK Investigational Site

Prague, , Czechia

Site Status

GSK Investigational Site

Prague, , Czechia

Site Status

GSK Investigational Site

Prague, , Czechia

Site Status

GSK Investigational Site

Angoulême, , France

Site Status

GSK Investigational Site

Arcachon, , France

Site Status

GSK Investigational Site

Avignon, , France

Site Status

GSK Investigational Site

Bourg-en-Bresse, , France

Site Status

GSK Investigational Site

Caen, , France

Site Status

GSK Investigational Site

Dijon, , France

Site Status

GSK Investigational Site

Issy-les-Moulineaux, , France

Site Status

GSK Investigational Site

Ivry, , France

Site Status

GSK Investigational Site

Luynes, , France

Site Status

GSK Investigational Site

Lyon, , France

Site Status

GSK Investigational Site

Marseille, , France

Site Status

GSK Investigational Site

Marseille, , France

Site Status

GSK Investigational Site

Metz, , France

Site Status

GSK Investigational Site

Montpellier, , France

Site Status

GSK Investigational Site

Nantes, , France

Site Status

GSK Investigational Site

Nantes, , France

Site Status

GSK Investigational Site

Nantes, , France

Site Status

GSK Investigational Site

Nice, , France

Site Status

GSK Investigational Site

Paris, , France

Site Status

GSK Investigational Site

Paris, , France

Site Status

GSK Investigational Site

Paris, , France

Site Status

GSK Investigational Site

Pau, , France

Site Status

GSK Investigational Site

Pessac, , France

Site Status

GSK Investigational Site

Reims, , France

Site Status

GSK Investigational Site

Rennes, , France

Site Status

GSK Investigational Site

Rodez, , France

Site Status

GSK Investigational Site

Saint-Etienne, , France

Site Status

GSK Investigational Site

Saint-Jean-de-Luz, , France

Site Status

GSK Investigational Site

Saint-Nicolas-de-Port, , France

Site Status

GSK Investigational Site

Saint-Ouen-la-Rouërie, , France

Site Status

GSK Investigational Site

Tinténiac, , France

Site Status

GSK Investigational Site

Tours, , France

Site Status

GSK Investigational Site

Verny, , France

Site Status

GSK Investigational Site

Vichy, , France

Site Status

GSK Investigational Site

Böblingen, Baden-Wurttemberg, Germany

Site Status

GSK Investigational Site

Ostfildern, Baden-Wurttemberg, Germany

Site Status

GSK Investigational Site

Stuttgart, Baden-Wurttemberg, Germany

Site Status

GSK Investigational Site

Ulm, Baden-Wurttemberg, Germany

Site Status

GSK Investigational Site

Munich, Bavaria, Germany

Site Status

GSK Investigational Site

Munich, Bavaria, Germany

Site Status

GSK Investigational Site

Munich, Bavaria, Germany

Site Status

GSK Investigational Site

Munich, Bavaria, Germany

Site Status

GSK Investigational Site

Munich, Bavaria, Germany

Site Status

GSK Investigational Site

Neuburg an der Donau, Bavaria, Germany

Site Status

GSK Investigational Site

Nuremberg, Bavaria, Germany

Site Status

GSK Investigational Site

Nuremberg, Bavaria, Germany

Site Status

GSK Investigational Site

Regensburg, Bavaria, Germany

Site Status

GSK Investigational Site

Würzburg, Bavaria, Germany

Site Status

GSK Investigational Site

Hüttenberg, Hesse, Germany

Site Status

GSK Investigational Site

Achim, Lower Saxony, Germany

Site Status

GSK Investigational Site

Bockhorn, Lower Saxony, Germany

Site Status

GSK Investigational Site

Ganderkesee, Lower Saxony, Germany

Site Status

GSK Investigational Site

Göttingen, Lower Saxony, Germany

Site Status

GSK Investigational Site

Hanover, Lower Saxony, Germany

Site Status

GSK Investigational Site

Hildesheim, Lower Saxony, Germany

Site Status

GSK Investigational Site

Lüneburg, Lower Saxony, Germany

Site Status

GSK Investigational Site

Westerstede, Lower Saxony, Germany

Site Status

GSK Investigational Site

Schwerin, Mecklenburg-Vorpommern, Germany

Site Status

GSK Investigational Site

Schwerin, Mecklenburg-Vorpommern, Germany

Site Status

GSK Investigational Site

Bad Honnef, North Rhine-Westphalia, Germany

Site Status

GSK Investigational Site

Baesweiler, North Rhine-Westphalia, Germany

Site Status