Mild to Moderate Alzheimer's Disease MedDRA version: 8.1 Level: LLT Classification code 10001896 Term: Alzheimer's disease
Conditions
Interventions
Product Name: Rosiglitazone XR
Pharmaceutical Form: Tablet
INN or Proposed INN: Rosiglitazone Maleate
CAS Number: 155141290
Current Spon
Sponsors
GlaxoSmithKline R&D Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
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 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 =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
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 screen
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: •To investigate the effects of daily dosing for 24 weeks with RSG XR versus placebo on cognitive function in subjects with mild to moderate Alzheimer’s disease as a function of APOE e4 status. •To investigate the effects of daily dosing for 24 weeks with RSG XR versus placebo on overall clinical response in subjects with mild to moderate Alzheimer’s disease as a function of APOE e4. •To estimate the effects of donepezil on cognitive function and overall clinical response in the total population ; Secondary Objective: 1.To assess the safety and tolerability of RSG XR versus placebo in subjects with mild to moderate AD and to monitor the safety and tolerability of donepezil. 2.To examine the time course of any cognitive effects of RSG XR. 3.To investigate the effects of RSG XR on measures of behavior and activities of daily living. 4.To investigate the effects of RSG XR on subject- and caregiver-reported health outcomes measures, including resource utilization, subject quality of life, and caregiver quality of life. 5.To investigate the effects of RSG XR on short term memory. 6.To evaluate RSG XR for cognitive efficacy in relation to potential disease modification effects. 7.To evaluate the pharmacokinetics of RSG XR in mild to moderate Alzheimer’s disease subject. 8.To explore the relationship between systemic RSG XR exposure and clinical efficacy. *Please refer to protocol for additional secondary objectives ; Primary end point(s): Change from baseline in Alzheimer's Disease Assessment Scale – cognitive subscale (ADAS-Cog; [Rosen, 1984]) total score at Week 24, as a function of APOE e4 status. Change from baseline in Clinician’s Interview-Based Impression of Change – plus (CIBIC) [Schneider, 1997]) score at Week 24, as | — |
Countries
Austria, Bulgaria, Estonia, Germany, Greece, Hungary, United Kingdom
Outcome results
None listed