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Rosiglitazone (Extended Release Tablets) As Adjunctive Therapy For Subjects With Mild To Moderate Alzheimer's Disease (REFLECT-2)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00348309
First received: June 30, 2006
Last updated: October 28, 2016
Last verified: October 2016
  Purpose

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.


Condition Intervention
Alzheimer's Disease
Drug: Rosiglitazone Extended Release 2mg
Drug: Rosiglitazone Extended Release 8mg
Other: Placebo
Other: Donepezil

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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 ε4-stratified Subjects With Mild to Moderate Alzheimer's Disease.

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Change from baseline in Alzheimer's Disease Assessment Scale - cognitive subscale (ADAS-Cog) total score at Week 48 for Apolipoprotein E gene (APOE) e4 [ Time Frame: Baseline (Week 0) and Week 48 ] [ Designated as safety issue: No ]
    ADAS is a performance-based test that measures specific cognitive and behavioral dysfunctions in patients with Alzheimer's Disease. The cognitive subscale of the ADAS (ADAS-Cog) comprises 11 items that are summed to a total score ranging from 0 to 70, with lower scores indicating less severe impairment. Change from baseline is calculated as Week 48 value minus the baseline value. APOE4 negative, All except E4/E4's: comprised of APOE4 negative and E4 heterozygote and full population was analyzed for this outcome measure.

  • Change from baseline in Clinical Dementia Rating scale - Sum of Boxes (CDR-SB) at Week 48 for APOE E4 [ Time Frame: Baseline (Week 0) and Week 48 ] [ Designated as safety issue: No ]
    CDR-SB is a semi-structured interview of participants and their caregivers. Participant's cognitive status is rated across 6 domains of functioning, including memory, orientation, judgment/problem solving, community affairs, home/hobbies, and personal care. Severity score assigned for each of 6 domains; Total score (SB) ranges from 0 to 18. Higher scores indicate greater disease severity. Change from baseline is calculated as Week 48 value minus the baseline value. APOE4 negative, All except E4/E4's: comprised of APOE4 negative and E4 heterozygote and full population was analyzed for this outcome measure.


Secondary Outcome Measures:
  • Change from baseline in Disability Assessment for Dementia Scale (DAD) total score [ Time Frame: Baseline (Week 0), Week 8, 16, 24 and 48 ] [ Designated as safety issue: No ]
    The DAD measures instrumental and basic activities of daily living in participants with Alzheimer's Disease (AD). This scale assesses a participants' ability to initiate, plan, and perform activities related to hygiene, dressing, continence, eating, meal preparation, telephoning, going on an outing, finance and correspondence, medications, leisure, and housework. Each item can be scored as 1 = yes, 0 = no, non applicable = NA. A total score is obtained by adding the rating for each question and converting this total score out of 100. Higher scores indicate better function; a positive change from baseline indicates an improvement. Change from baseline is calculated as endpoint value minus the baseline value.

  • Change from baseline in Neuropsychiatric Inventory (NPI) total score [ Time Frame: Baseline, Week 8, 16, 24 and 48 ] [ Designated as safety issue: No ]
    The NPI is a questionnaire that quantifies behavioral changes in dementia. For each of 12 behavioral domains there are 4 scores: Frequency (scale:1=occasionally to 4=very frequently), Severity (scale:1=Mild to 3=Severe), Total (frequency x severity), Caregiver distress (scale: 0=not at all distressing to 5=extremely distressing).The NPI Psychosis Subscale consists of the two domains of Delusions and Hallucinations, calculated by adding the Individual Item Scores, to yield a possible total score of 0 to 24. Lower score=less severity. Change from baseline is calculated as endpoint value minus the baseline value.

  • Change from screening in Mini Mental State Examination (MMSE) total score [ Time Frame: Screening (Week -4) and Week 48 ] [ Designated as safety issue: No ]
    The MMSE test consists of five sections (orientation, registration, attention-calculation, recall, and language) and results in a total possible score of 30, with higher scores indicating better function. The total MMSE score for participants at screening was between 10 and 26, inclusive, in order to be eligible to participate in the trial. Change from baseline is calculated as endpoint value minus the baseline value.

  • Change from baseline in the domains of the resource utilization in dementia scale (RUD) [ Time Frame: Baseline (Week 0), Week 12, 24, 36 and 48 ] [ Designated as safety issue: No ]
    RUD was used to assess amount of both formal and informal resources used by demented participants and primary caregiver. It was completed by caregivers and compiles data on following resources: use of social services, frequency and duration of hospitalizations, all contacts with health care professionals, participant living accommodations, amount of time the caregiver spends giving care and the impact of care giving on the caregiver's job. Overall cost of care was evaluated to quantify the resources utilized. Change from baseline is calculated as endpoint value minus the baseline value.

  • Change from baseline in European Quality of Life -5 Dimensions (EQ-5D) scale [ Time Frame: Baseline (Week 0), Week 12, 36 and 48 ] [ Designated as safety issue: No ]
    EQ-5D is a participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state ("confined to bed"). Total possible score is sum of individual items, ranged from 5 to 15; lower score indicated a better health state. Change from baseline is calculated as endpoint value minus the baseline value. Q1 corresponds to the number of hours during the last month the caregiver spent assisting the participants with toilet visits, eating, dressing, grooming, walking and bathing and Q2 corresponds to the number of hours during the last month the caregiver spent assisting the participants with shopping, food preparation, housekeeping, laundry, transportation, taking medication and managing financial matters.

  • Change from baseline in ADAS-Cog total score for observed cases at Week 48 [ Time Frame: Baseline (Week 0) and Week 48 ] [ Designated as safety issue: No ]
    ADAS is a performance-based test that measures specific cognitive and behavioral dysfunctions in patients with Alzheimer's Disease. The cognitive subscale of the ADAS (ADAS-Cog) comprises 11 items that are summed to a total score ranging from 0 to 70, with lower scores indicating less severe impairment. Change from baseline is calculated as endpoint value minus the baseline value.

  • Change from baseline in CDR-SB score for observed cases at Week 48 [ Time Frame: Baseline (Week 0) and Week 48 ] [ Designated as safety issue: No ]
    CDR-SB is a semi-structured interview of participants and their caregivers. Participant's cognitive status is rated across 6 domains of functioning, including memory, orientation, judgment/problem solving, community affairs, home/hobbies, and personal care. Severity score assigned for each of 6 domains; Total score (SB) ranges from 0 to 18. Higher scores indicate greater disease severity. Change from baseline is calculated as endpoint value minus the baseline value.

  • Change in ADAS-Cog total score for observed cases at Week 54 compared to Week 48 [ Time Frame: Week 48 and 54 ] [ Designated as safety issue: No ]
    ADAS is a performance-based test that measures specific cognitive and behavioral dysfunctions in patients with Alzheimer's Disease. The cognitive subscale of the ADAS (ADAS-Cog) comprises 11 items that are summed to a total score ranging from 0 to 70, with lower scores indicating less severe impairment. Change was calculated as endpoint value (Week 54) minus Week 48 value.

  • Change in CDR-SB total score at Week 54 compared to Week 48 [ Time Frame: Week 48 and 54 ] [ Designated as safety issue: No ]
    CDR-SB is a semi-structured interview of participants and their caregivers. Participant's cognitive status is rated across 6 domains of functioning, including memory, orientation, judgment/problem solving, community affairs, home/hobbies, and personal care. Severity score assigned for each of 6 domains; Total score (SB) ranges from 0 to 18. Higher scores indicate greater disease severity. Change was calculated as endpoint value (Week 54) minus Week 48 value.

  • Change from baseline in Glycosylated hemoglobin (HbA1c) at Week 48 [ Time Frame: Baseline (Week 0) and Week 48 ] [ Designated as safety issue: No ]
    Blood samples of participants were collected for HbA1c assessment. HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over a 2- to 3-month period. Change from Baseline in HbA1c was calculated as the value at Week 48 minus the value at Baseline.

  • Number of Participants with Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to Week 54 ] [ Designated as safety issue: No ]
    An adverse event (AE) was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started. An adverse event was therefore any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose results in death, are life threatening, requires hospitalization or prolongation of hospitalization or results in disability/incapacity, and congenital anomaly/birth defect. The data was reported for prospective period.

  • Mean Change From Baseline in Systolic and Diastolic Blood Pressure (BP) [ Time Frame: Baseline (Week 0), Week 4, 8, 12, 16, 24, 36, 48 and 56 ] [ Designated as safety issue: No ]
    The plethysmographic method was used to measure BP throughout the study. Change in Systolic and Diastolic BP was calculated as endpoint value minus the baseline value.

  • Mean Change From Baseline in Heart rate [ Time Frame: Baseline (Week 0), Week 4, 8, 12, 16, 24, 36, 48 and 56 ] [ Designated as safety issue: No ]
    Mean Change From Baseline in heart rate was calculated as endpoint value minus the baseline value.

  • Mean Change From Baseline in Weight [ Time Frame: Baseline (Week 0), Week 4, 8, 12, 16, 24, 36, 48 and 56 ] [ Designated as safety issue: No ]
    Body weight was measured at all visits, without shoes and wearing light clothing. Mean Change From Baseline in Weight was calculated as endpoint value minus the baseline value.

  • Change from baseline in Hemoglobin values [ Time Frame: Baseline (Week 0), Week 4, 16, 36 and 48 ] [ Designated as safety issue: No ]
    Blood samples of participants were collected for Hemoglobin. Change from baseline in Hemoglobin was calculated as endpoint value minus the baseline value.

  • Change from baseline in Hematocrit values [ Time Frame: Baseline (Week 0), Week 4, 8, 12, 16, 24, 36, 48 and 56 ] [ Designated as safety issue: No ]
    Blood samples of participants were collected for Hematocrit . Change from baseline in Hematocrit was calculated as endpoint value minus the baseline value.

  • Mean change from Baseline in Short Term Memory Assessment [ Time Frame: Baseline (Week 0), Week 8, 16, 24, 36, 48 and 56 ] [ Designated as safety issue: No ]
    Question 1 (Word Recall) and Question 7 (Word Recognition) of the ADAS-Cog questionnaire were summed to get a short term memory assessment. Mean change from Baseline in Short Term Memory Assessment was calculated as endpoint value minus the baseline value.

  • Change from baseline in HbA1c at Week 12, Week 24 and Week 36 [ Time Frame: Percent of total hemoglobin ] [ Designated as safety issue: No ]
    Blood samples of participants were collected for HbA1c assessment. HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over a 2- to 3-month period. Change from Baseline in HbA1c was calculated as the value at time point minus the value at Baseline.

  • Number of participants with laboratory Potential Clinical Concern (PCC) values [ Time Frame: Baseline (Week 0), Week 4, 8, 12, 16, 24, 36, 48 and 56 ] [ Designated as safety issue: No ]
    Only those parameters for which at least one value of clinical concern (CC) was reported are summarized. Pre-defined limits of potential clinical concern (CC Low [relative to the lower limit of normal], CC High [relative to the upper limit of normal]) are: Hematocrit 0.8, 1.2; hemoglobin 10-11, 16.5-18; Red blood corpuscles(RBC) 0.8, 1.2; mean corpuscular volume (MCV) 0.8, 1.2; mean corpuscular hemoglobin (MCH) 0.8, 1.2; White blood corpuscles (WBC) 3- absolute value, 15-absolute value, Red Cell Distribution Width (RDW) 0.8, 1.2; Lymphocytes 0.75, 1.5; Monocytes NA, 2; Eosinophil NA, 2; and platelet count 100-absolute, 500-absoulte.

  • Change from baseline in Alzheimer's Carer Quality of Life Instrument (ACQLI) score [ Time Frame: Baseline (Week 0), Week 12, 36 and 48 ] [ Designated as safety issue: No ]
    ACQLI had30 questions exploring various aspects of carer's quality of life. Each of the questions has a two point response, and the 30 questions were summed to provide a total score. The ACQLI took approximately 15 minutes for the caregiver to complete. Change from baseline is calculated as endpoint value minus the baseline value


Enrollment: 1496
Study Start Date: July 2006
Study Completion Date: January 2009
Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1
Rosiglitazone Extended Release 2mg OD
Drug: Rosiglitazone Extended Release 2mg
Rosiglitazone Extended Release 2mg OD
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).
Other Name: Aricept
Experimental: Arm 2
Rosiglitazone Extended Release 8mg OD
Drug: Rosiglitazone Extended Release 8mg
Rosiglitazone Extended Release 8mg OD
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).
Other Name: Aricept
Placebo Comparator: Arm 3
Placebo
Other: Placebo
Placebo
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).
Other Name: Aricept

Detailed Description:
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)
  Eligibility

Ages Eligible for Study:   50 Years to 90 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  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: NCT00348309

  Hide Study Locations
Locations
United States, Arizona
GSK Investigational Site
Litchfield Park, Arizona, United States, 85340
GSK Investigational Site
Phoenix, Arizona, United States, 85004
GSK Investigational Site
Phoenix, Arizona, United States, 85006
GSK Investigational Site
Phoenix, Arizona, United States, 85050
United States, Arkansas
GSK Investigational Site
Little Rock, Arkansas, United States, 72205
United States, California
GSK Investigational Site
Fresno, California, United States, 93720
GSK Investigational Site
Rancho Mirage, California, United States, 92270
GSK Investigational Site
Sacramento, California, United States, 95816
GSK Investigational Site
Sherman Oaks, California, United States, 91403
United States, Colorado
GSK Investigational Site
Denver, Colorado, United States, 80212
United States, Connecticut
GSK Investigational Site
New Haven, Connecticut, United States, 06510
United States, Florida
GSK Investigational Site
Delray Beach, Florida, United States, 33445
GSK Investigational Site
Hallandale Beach, Florida, United States, 33009
GSK Investigational Site
Miami, Florida, United States, 33143
GSK Investigational Site
Sarasota, Florida, United States, 34233
GSK Investigational Site
St. Petersburg, Florida, United States, 33701
GSK Investigational Site
West Palm Beach, Florida, United States, 33407
United States, Illinois
GSK Investigational Site
Hoffman Estates, Illinois, United States, 60194
United States, Indiana
GSK Investigational Site
Fort Wayne, Indiana, United States, 46805
GSK Investigational Site
Indianapolis, Indiana, United States, 46202
United States, Maryland
GSK Investigational Site
Baltimore, Maryland, United States, 21224
GSK Investigational Site
Glen Burnie, Maryland, United States, 21061
GSK Investigational Site
Rockville, Maryland, United States, 20852
United States, Minnesota
GSK Investigational Site
St. Paul, Minnesota, United States, 55101
United States, New Hampshire
GSK Investigational Site
Lebanon, New Hampshire, United States, 03756
United States, New Jersey
GSK Investigational Site
Morristown, New Jersey, United States, 07960
GSK Investigational Site
Nutley, New Jersey, United States, 07110
GSK Investigational Site
Princeton, New Jersey, United States, 08540
GSK Investigational Site
Stratford, New Jersey, United States, 08084
United States, New York
GSK Investigational Site
Albany, New York, United States, 12205
GSK Investigational Site
Brooklyn, New York, United States, 11235
GSK Investigational Site
New York, New York, United States, 10021
United States, North Carolina
GSK Investigational Site
Durham, North Carolina, United States, 27705
GSK Investigational Site
Raleigh, North Carolina, United States, 27607
United States, Oregon
GSK Investigational Site
Portland, Oregon, United States, 97239
United States, Rhode Island
GSK Investigational Site
Providence, Rhode Island, United States, 02906
United States, Tennessee
GSK Investigational Site
Nashville, Tennessee, United States, 37203
United States, Texas
GSK Investigational Site
Austin, Texas, United States, 78757
GSK Investigational Site
Houston, Texas, United States, 77030
United States, Utah
GSK Investigational Site
South Ogden, Utah, United States, 84403
United States, Vermont
GSK Investigational Site
Bennington, Vermont, United States, 05201
Argentina
GSK Investigational Site
Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina, C1192AAW
GSK Investigational Site
Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina, C1419HDN
GSK Investigational Site
Ciudad de Buenos Aires, Buenos Aires, Argentina, C1431FWO
GSK Investigational Site
Cordoba, Córdova, Argentina, 5000
GSK Investigational Site
Córdoba, Córdova, Argentina, X5004AOA
GSK Investigational Site
Córdoba, Córdova, Argentina, x5009bin
GSK Investigational Site
Godoy Cruz, Mendoza, Argentina, M5504FMI
GSK Investigational Site
Ciudad Autonoma de Buenos Aires, Argentina, C1425CDC
GSK Investigational Site
Mendoza, Argentina, CPM5500HIF
Austria
GSK Investigational Site
Hall in Tirol, Austria, A-6060
GSK Investigational Site
Innsbruck, Austria, A-6020
GSK Investigational Site
Vienna, Austria, 1010
GSK Investigational Site
Vienna, Austria, 1030
GSK Investigational Site
Vienna, Austria, A-1130
GSK Investigational Site
Vienna, Austria, A-1220
Brazil
GSK Investigational Site
Belo Horizonte, Brazil, 30130-110
GSK Investigational Site
Ribeirão Preto, Brazil, 14048-900
GSK Investigational Site
São Paulo, Brazil, 040023-900
Canada, Alberta
GSK Investigational Site
Calgary, Alberta, Canada, T2N 4N1
GSK Investigational Site
Medicine Hat, Alberta, Canada, T1A 4C2
Canada, British Columbia
GSK Investigational Site
Victoria, British Columbia, Canada, V8T 5G1
Canada, New Brunswick
GSK Investigational Site
Moncton, New Brunswick, Canada, E1C 4B7
Canada, Ontario
GSK Investigational Site
Barrie, Ontario, Canada, L4M 4S5
GSK Investigational Site
Kingston, Ontario, Canada, K7L 4X3
GSK Investigational Site
Peterborough, Ontario, Canada, K9H 2P4
GSK Investigational Site
Toronto, Ontario, Canada, M5T 2S8
GSK Investigational Site
Toronto, Ontario, Canada, M6M 3Z5
GSK Investigational Site
Whitby, Ontario, Canada, L1N 5S9
Canada, Prince Edward Island
GSK Investigational Site
Charlottetown, Prince Edward Island, Canada, C1A 5Y8
Canada, Quebec
GSK Investigational Site
Greenfield Park, Quebec, Canada, J4V 2J2
GSK Investigational Site
Montreal, Quebec, Canada, H1T 2M4
GSK Investigational Site
Montreal, Quebec, Canada, H4H 1R3
GSK Investigational Site
Québec, Quebec, Canada, G1R 3X5
GSK Investigational Site
Sherbrooke, Quebec, Canada, J1H 1Z1
Canada, Saskatchewan
GSK Investigational Site
Regina, Saskatchewan, Canada, S4T 1A5
Chile
GSK Investigational Site
Providencia / Santiago, Región Metro De Santiago, Chile, 7500710
GSK Investigational Site
Puente Alto - Santiago, Región Metro De Santiago, Chile, 8207257
GSK Investigational Site
Santiago, Región Metro De Santiago, Chile, 7560356
GSK Investigational Site
Viña del Mar, Valparaíso, Chile, 252-0997
Czech Republic
GSK Investigational Site
Ostrava, Czech Republic, 702 00
GSK Investigational Site
Praha 10, Czech Republic, 10000
GSK Investigational Site
Praha 2, Czech Republic, 120 00
GSK Investigational Site
Praha 5, Czech Republic, 150 18
GSK Investigational Site
Praha 7, Czech Republic, 170 00
France
GSK Investigational Site
Angoulême, France, 16000
GSK Investigational Site
Arcachon, France, 33120
GSK Investigational Site
Avignon, France, 84000
GSK Investigational Site
Bourg en Bresse, France, 01012
GSK Investigational Site
Caen, France, 14033
GSK Investigational Site
Dijon, France, 21000
GSK Investigational Site
Issy Les Moulineaux, France, 92130
GSK Investigational Site
Ivry, France, 94206
GSK Investigational Site
Luynes, France, 37230
GSK Investigational Site
Lyon, France, 69006
GSK Investigational Site
Marseille, France, 13008
GSK Investigational Site
Marseille, France, 13009
GSK Investigational Site
Metz, France, 57038
GSK Investigational Site
Montpellier, France, 34080
GSK Investigational Site
Nantes, France, 44000
GSK Investigational Site
Nantes, France, 44093
GSK Investigational Site
Nantes, France, 44200
GSK Investigational Site
Nice, France, 06002
GSK Investigational Site
Paris, France, 75012
GSK Investigational Site
Paris, France, 75013
GSK Investigational Site
Paris, France, 75018
GSK Investigational Site
Pau, France, 64000
GSK Investigational Site
Pessac, France, 33604
GSK Investigational Site
Reims, France, 51100
GSK Investigational Site
Rennes, France, 35000
GSK Investigational Site
Rodez, France, 12000
GSK Investigational Site
Saint Jean de Luz, France, 64500
GSK Investigational Site
Saint Ouen la Rouerie, France, 35460
GSK Investigational Site
Saint-Etienne, France, 42100
GSK Investigational Site
Saint-Nicolas de Port, France, 54210
GSK Investigational Site
Tinteniac, France, 35190
GSK Investigational Site
Tours, France, 37100
GSK Investigational Site
Verny, France, 57420
GSK Investigational Site
Vichy, France, 03200
Germany
GSK Investigational Site
Boeblingen, Baden-Wuerttemberg, Germany, 71034
GSK Investigational Site
Ostfildern, Baden-Wuerttemberg, Germany, 73760
GSK Investigational Site
Stuttgart, Baden-Wuerttemberg, Germany, 70178
GSK Investigational Site
Ulm, Baden-Wuerttemberg, Germany, 89073
GSK Investigational Site
Muenchen, Bayern, Germany, 80331
GSK Investigational Site
Muenchen, Bayern, Germany, 80333
GSK Investigational Site
Muenchen, Bayern, Germany, 80336
GSK Investigational Site
Muenchen, Bayern, Germany, 81377
GSK Investigational Site
Muenchen, Bayern, Germany, 81667
GSK Investigational Site
Neuburg / Donau, Bayern, Germany, 86633
GSK Investigational Site
Nuernberg, Bayern, Germany, 90402
GSK Investigational Site
Nuernberg, Bayern, Germany, 90403
GSK Investigational Site
Regensburg, Bayern, Germany, 93053
GSK Investigational Site
Wuerzburg, Bayern, Germany, 97070
GSK Investigational Site
Huettenberg, Hessen, Germany, 35625
GSK Investigational Site
Schwerin, Mecklenburg-Vorpommern, Germany, 19053
GSK Investigational Site
Schwerin, Mecklenburg-Vorpommern, Germany, 19055
GSK Investigational Site
Achim, Niedersachsen, Germany, 28832
GSK Investigational Site
Bockhorn, Niedersachsen, Germany, 26345
GSK Investigational Site
Ganderkesee, Niedersachsen, Germany, 27777
GSK Investigational Site
Goettingen, Niedersachsen, Germany, 37075
GSK Investigational Site
Hannover, Niedersachsen, Germany, 30559
GSK Investigational Site
Hildesheim, Niedersachsen, Germany, 31134
GSK Investigational Site
Lueneburg, Niedersachsen, Germany, 21335
GSK Investigational Site
Westerstede, Niedersachsen, Germany, 26655
GSK Investigational Site
Bad Honnef, Nordrhein-Westfalen, Germany, 53604
GSK Investigational Site
Baesweiler, Nordrhein-Westfalen, Germany, 52499
GSK Investigational Site
Bergisch Gladbach, Nordrhein-Westfalen, Germany, 51465
GSK Investigational Site
Bochum, Nordrhein-Westfalen, Germany, 44791
GSK Investigational Site
Bochum, Nordrhein-Westfalen, Germany, 44805
GSK Investigational Site
Bochum, Nordrhein-Westfalen, Germany, 44809
GSK Investigational Site
Bochum, Nordrhein-Westfalen, Germany, 44869
GSK Investigational Site
Bochum, Nordrhein-Westfalen, Germany, 44892
GSK Investigational Site
Dueren, Nordrhein-Westfalen, Germany, 52349
GSK Investigational Site
Duisburg, Nordrhein-Westfalen, Germany, 47051
GSK Investigational Site
Essen, Nordrhein-Westfalen, Germany, 45138
GSK Investigational Site
Hattingen, Nordrhein-Westfalen, Germany, 45525
GSK Investigational Site
Juelich, Nordrhein-Westfalen, Germany, 52428
GSK Investigational Site
Koeln, Nordrhein-Westfalen, Germany, 50767
GSK Investigational Site
Koeln, Nordrhein-Westfalen, Germany, 51069
GSK Investigational Site
Krefeld, Nordrhein-Westfalen, Germany, 47800
GSK Investigational Site
Remscheid, Nordrhein-Westfalen, Germany, 42853
GSK Investigational Site
Siegen, Nordrhein-Westfalen, Germany, 57072
GSK Investigational Site
Hamburg, Germany, 20249
GSK Investigational Site
Hamburg, Germany, 21149
GSK Investigational Site
Hamburg, Germany, 22083
GSK Investigational Site
Hamburg, Germany, 22143
Greece
GSK Investigational Site
Athens, Greece, 115 21
GSK Investigational Site
Athens, Greece, 151 23
GSK Investigational Site
Melissia, Greece, 151 27
GSK Investigational Site
Thessaloniki, Greece, 57010
Hungary
GSK Investigational Site
Debrecen, Hungary, 4043
GSK Investigational Site
Győr, Hungary, 9024
GSK Investigational Site
Szeged, Hungary, 6725
India
GSK Investigational Site
Bangalore, India, 560 054
GSK Investigational Site
Bangalore, India, 560034
GSK Investigational Site
Hyderabad, India, 500 034
GSK Investigational Site
Mumbai, India, 400010
GSK Investigational Site
Nagpur, India, 440010
GSK Investigational Site
New Delhi, India, 110002
GSK Investigational Site
Pune, India, 411004
GSK Investigational Site
Varanasi, India, 221005
Italy
GSK Investigational Site
Chieti Scalo, Abruzzo, Italy, 66013
GSK Investigational Site
Napoli, Campania, Italy, 80131
GSK Investigational Site
San Felice a Cancello Caserta, Campania, Italy, 81027
GSK Investigational Site
Bologna, Emilia-Romagna, Italy, 40138
GSK Investigational Site
Roma, Lazio, Italy, 00148
GSK Investigational Site
Roma, Lazio, Italy, 00163
GSK Investigational Site
Roma, Lazio, Italy, 00186
GSK Investigational Site
Brescia, Lombardia, Italy, 25123
GSK Investigational Site
Brescia, Lombardia, Italy, 25125
GSK Investigational Site
Milano, Lombardia, Italy, 20122
GSK Investigational Site
Milano, Lombardia, Italy, 20127
GSK Investigational Site
Pavia, Lombardia, Italy, 27100
GSK Investigational Site
Rho, Lombardia, Italy, 20017
GSK Investigational Site
Ancona, Marche, Italy, 60020
GSK Investigational Site
Bari, Puglia, Italy, 70124
GSK Investigational Site
Arezzo, Toscana, Italy, 52100
GSK Investigational Site
Firenze, Toscana, Italy, 50134
GSK Investigational Site
Pisa, Toscana, Italy, 56126
GSK Investigational Site
Verona, Veneto, Italy, 37100
Japan
GSK Investigational Site
Aichi, Japan, 451-0052
GSK Investigational Site
Aichi, Japan, 455-8530
GSK Investigational Site
Fukuoka, Japan, 813-8588
GSK Investigational Site
Fukuoka, Japan, 819-0165
GSK Investigational Site
Gunma, Japan, 375-0017
GSK Investigational Site
Hiroshima, Japan, 733-0864
GSK Investigational Site
Hokkaido, Japan, 005-0853
GSK Investigational Site
Hokkaido, Japan, 080-2470
GSK Investigational Site
Hyogo, Japan, 672-8043
GSK Investigational Site
Ibaraki, Japan, 300-0053
GSK Investigational Site
Kagawa, Japan, 761-8024
GSK Investigational Site
Kanagawa, Japan, 231-0023
GSK Investigational Site
Kanagawa, Japan, 238-0042
GSK Investigational Site
Kochi, Japan, 780-0842
GSK Investigational Site
Kumamoto, Japan, 861-8002
GSK Investigational Site
Kyoto, Japan, 607-8062
GSK Investigational Site
Nagano, Japan, 399-8695
GSK Investigational Site
Osaka, Japan, 567-0011
GSK Investigational Site
Osaka, Japan, 569-1041
GSK Investigational Site
Tokyo, Japan, 193-0998
Mexico
GSK Investigational Site
Saltillo, Coahuila, Mexico, 25000
GSK Investigational Site
Monterrey, Nuevo León, Mexico, 64660
GSK Investigational Site
Monterrey, Nuevo León, Mexico, 64710
GSK Investigational Site
Mexico, Mexico, 14000
Poland
GSK Investigational Site
Bydgoszcz, Poland, 85-096
GSK Investigational Site
Katowice, Poland, 40-752
GSK Investigational Site
Lodz, Poland, 91-348
GSK Investigational Site
Mosina, Poland, 62-050
GSK Investigational Site
Poznan, Poland, 61-298
GSK Investigational Site
Sopot, Poland, 81-824
GSK Investigational Site
Warszawa, Poland, 02-507
Portugal
GSK Investigational Site
Coimbra, Portugal, 3000-548
GSK Investigational Site
Lisboa, Portugal, 1649-035
Spain
GSK Investigational Site
Burgos, Spain, 09006
GSK Investigational Site
Castellón, Spain, 12004
GSK Investigational Site
Elche (Alicante), Spain, 03202
GSK Investigational Site
Galdakano, Spain, 48960
GSK Investigational Site
Gerona, Spain, 17190
GSK Investigational Site
Granada, Spain, 18013
GSK Investigational Site
La Coruña, Spain, 15006
GSK Investigational Site
Madrid, Spain, 28006
GSK Investigational Site
Madrid, Spain, 28040
GSK Investigational Site
Madrid, Spain, 28046
GSK Investigational Site
Murcia, Spain, 30120
GSK Investigational Site
Málaga, Spain, 29071
GSK Investigational Site
Pamplona, Spain, 31008
GSK Investigational Site
San Sebastián, Spain, 20014
GSK Investigational Site
Valencia, Spain, 46010
Switzerland
GSK Investigational Site
Zuerich, Switzerland, 8032
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Additional Information:
Publications:
Study Data/Documents: Clinical Study Report  This link exits the ClinicalTrials.gov site
Identifier: AVA102672
For additional information about this study please refer to the GSK Clinical Study Register
Dataset Specification  This link exits the ClinicalTrials.gov site
Identifier: AVA102672
For additional information about this study please refer to the GSK Clinical Study Register
Study Protocol  This link exits the ClinicalTrials.gov site
Identifier: AVA102672
For additional information about this study please refer to the GSK Clinical Study Register
Annotated Case Report Form  This link exits the ClinicalTrials.gov site
Identifier: AVA102672
For additional information about this study please refer to the GSK Clinical Study Register
Statistical Analysis Plan  This link exits the ClinicalTrials.gov site
Identifier: AVA102672
For additional information about this study please refer to the GSK Clinical Study Register
Informed Consent Form  This link exits the ClinicalTrials.gov site
Identifier: AVA102672
For additional information about this study please refer to the GSK Clinical Study Register
Individual Participant Data Set  This link exits the ClinicalTrials.gov site
Identifier: AVA102672
For additional information about this study please refer to the GSK Clinical Study Register

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00348309     History of Changes
Other Study ID Numbers: AVA102672 
Study First Received: June 30, 2006
Last Updated: October 28, 2016
Health Authority: Japan: Ministry of Health, Labor and Welfare
United States: Food and Drug Administration
Europe: European Medicines Agency
Individual Participant Data  
Plan to Share IPD: Yes
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.

Keywords provided by GlaxoSmithKline:
apolipoprotein E
Alzheimer's disease
cognition
rosiglitazone
adjunctive therapy

Additional relevant MeSH terms:
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Donepezil
Rosiglitazone
Cholinesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Cholinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Nootropic Agents
Hypoglycemic Agents

ClinicalTrials.gov processed this record on December 08, 2016