| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Mild-Moderate Alzheimer disease |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10012271 |
| E.1.2 | Term | Dementia Alzheimer's type |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To investigate the add-on effects of daily dosing for 48 weeks with RSG XR versus placebo on cognitive function in donepezil-treated subjects with mild to moderate Alzheimer s disease, as a function of APOE 949;4 status. To investigate the add-on effects of daily dosing for 48 weeks with RSG XR versus placebo on overall clinical response in donepezil-treated subjects with mild to moderate Alzheimer s disease, as a function of APOE 949;4 status. |
|
| E.2.2 | Secondary objectives of the trial |
| 1. To assess the safety and tolerability of RSG XR versus placebo in donepezil-treated subjects with mild to moderate AD. 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 patient- and caregiver-reported health outcomes measures, including resource utilization, patient 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 seek post-hoc correlation of any effects of RSG XR with a measure of glycemic control. |
|
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
| 1. Male or female subject with a clinical diagnosis of probable Alzheimer s disease in accordance with NINCDS-ADRDA criteria 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 8804; 4 at Screening. See Appendix 3. 4. Age 8805;50 and 8804;90 years. 5. 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 . 6. Current use of medication is in accordance with the criteria listed in Table 2 Permitted Medications, Section 8.1 . 7. 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. 8. 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. 9. Neurological exam without focal changes excluding changes attributable to AD or peripheral trauma . 10. Subject has the ability to comply with procedures for cognitive and other testing. 11. 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. 12. 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 . 13. Caregiver has provided full written informed consent on his/her own behalf prior to the performance of any protocol-specified procedure. |
|
| E.4 | Principal exclusion criteria |
| 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 947; agonist, or an insulin secretagogue e.g. a sulfonylurea or glitinide . 6. Any patient with an HbA1c 8805;8.5 . See Section 6.3.7.4 for Safety Measures for Enrolled Subjects with Type 2 Diabetes Mellitus. 7. History or clinical/investigational evidence of 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 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 1.5 the upper limit of normal ULN . 16. 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 . 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 or employee of the participating Investigator, of any of the participating site staff, or of GSK. 20. In France, a subject is neither affiliated with nor a beneficiary of a social security category. 21. The French subject has participated in any study using an investigational drug during the previous 30 days or 5 half-lives whichever is longer . |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Change from baseline in Alzheimer s Disease Assessment Scale cognitive subscale ADAS-Cog Rosen, 1984 total score at Week 48, as a function of APOE 949;4 status. Change from baseline in Clinical Dementia Rating scale - Sum of Boxes CDR-SB Morris, 1993 at Week 48, as a function of APOE 949;4 status. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | Information not present in EudraCT |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Information not present in EudraCT |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 11 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 1 |
Print
