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)

Conditions: MedDRA version: 8.1Level: LLTClassification code 10001896Term: Alzheimer's disease
Mild to Moderate Alzheimer's Disease

Registration Number: EUCTR2006-002038-39-EE

Lead Sponsor: GlaxoSmithKline R&D Ltd

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 686

Inclusion Criteria

A subject will be eligible for inclusion in this study only if all of the following criteria apply:
A subject will be eligible for inclusion in this study only if all of the following criteria apply:
1.Male or female subject with a clinical diagnosis of probable Alzheimer's disease in accordance with NINCDS-ADRDA criteria for at least 3 months (Appendix 3)
(Note: National Institute of Neurological and Communicative Disorders and Stroke (NINCDS) and Alzheimer's Disease and Related Disorders Association (ADRDA).)
2.Subject has mild to moderate Alzheimer's disease as defined by a MMSE score 10 to 23 inclusive at Screening.
3.Hachinski Ischemia Score = 4 at Screening (See Appendix 4).
4.Age =50 and =90 years.
5.Subject has not taken an approved Alzheimer’s therapy in the last 30 days.
6.Subject has not had a previous history of hypersensitivity or intolerance to AChEIs.
7.Current use of medication is in accordance with the criteria listed in Table 2 (Permitted Medications, Section 8.1).
8.Female subjects must be post-menopausal (i.e. > 1 year without menstrual period), surgically sterile, or agree to use adequate method of contraception (Appendix 5) 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.
9.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.)
10.Neurological exam without focal changes (excluding changes attributable to AD or peripheral trauma).
11.Subject has the ability to comply with procedures for cognitive and other testing
Please refer to the protocol for full ist of inclusion criteria
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

A subject will not be eligible for inclusion in this study if any of the following criteria apply:
1.Diagnosis of possible, probable, or definite vascular dementia in accordance with NINDS-AIREN criteria (Appendix 6).
(Note: National Institute of Neurological Disorders and Stroke (NINDS) and Association Internationale pour la Recherche et l'Enseignement en Neurosciences (AIREN).)
2.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.
3.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.)
4.History of Type 1 diabetes mellitus or secondary diabetes mellitus.
5.Type 2 diabetes mellitus where the subject is being treated with insulin, a PPAR? agonist, or an insulin secretagogue (e.g. a sulfonylurea or glitinide).
6.Any patient with an HbA1c =8.5% (See Section 6.3.8.4 for Safety Measures for Enrolled Subjects with Type 2 Diabetes Mellitus).
7.History or clinical/laboratory evidence congestive heart failure defined by the New York Heart Association criteria (Class I to IV cardiac status; Appendix7).
8.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).
9.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 8) 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.)
10.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.
11.Clinically significant peripheral edema at the time of screening.
12.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.
13.Systolic blood pressure >165 or <90 mm