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

Registration Number: EUCTR2006-002038-39-HU

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:
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 2)
2.Subject has mild to moderate Alzheimer's disease as defined by a MMSE score 10 to 26 inclusive at Screening.
3.Hachinski Ischemia Score = 4 at Screening (See Appendix 3).
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. >24 weeks 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 < 2 years 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.
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.
12.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.
13.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 .
14.Caregiver has provided full written informed consent on his/her own behalf prior to the performance of any protocol-specified procedure.
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 4).
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 is clinically significant in the opinion of the investigator.
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; Appendix 5).
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 .
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 mmHg or diastolic blood pressure >95 or <60 mmHg at the time of screening.
14.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.
15.Abnormal kidney function tests (more than 1.5 ULN).
16.ALT, AST, or alkaline phosphatase values >2.5 times the upper limit of normal, total bilirubin values >1.5 times the upper limit of normal, or history of severe hepatobiliary disease (e.g. hepatitis B or C, or cirrhosis, Child-Pugh Class B/C).
17.History of a bone marrow transplant.
18.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.
19.Subject is an immediate family member