Enfermedad de Alzheimer leve a moderada Mild to moderate Alzheimer's Disease MedDRA version: 9.1 Level: LLT Classification code 10001896 Term: Alzheimer's disease
Conditions
Interventions
Product Name: nicotinic alpha 7
Product Code: RO5313534/F02 (MEM3454)
Pharmaceutical Form: Capsule*
INN or Proposed INN: n/a
CAS Number: 667305-02-1
Current Sponsor code: RO5313534-001
Other descripti
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Probable AD, based on the NINCDS/ADRDA and DSM-IV criteria. 2. Males or females of non-childbearing potential (more than two years after the cessation of menses or surgically sterile by means of hysterectomy, bilateral oopherectomy or tubal ligation). Additional blood tests will be done if required by the local regulations/guidelines/EC/IRB for further confirmation of non-childbearing potential. 3. Age range: 50-85 years of age at the time of screening visit. 4. Non smokers and not using nicotine-containing products for at least 3 months prior to baseline. 5. Have a MMSE score at screening between 13 and 22 inclusive. 6. Have a Modified Hachinski Ischemia Scale score of ? 4 (see Appendix 5) 7. Are under stable donepezil treatment given at a fixed dose either 5 or 10 mg daily for at least 4 months prior to baseline. 8. Adequate vision & hearing (physical ability to perform all the study assessments). 9. Not requiring nursing home care. 10. Have a caregiver or some other identified responsible person (e.g., family member, social worker, caseworker or nurse) who is considered reliable by the Investigator to provide support to the patient to ensure compliance with study treatment, accompany patient to study visits and help with protocol procedures, and who is also able and willing to provide input for completing the caregiver scales and sign the caregiver consent form. 11. Are cooperative, willing and able to complete all aspects of the study, and capable of doing so either alone or with the help of a responsible caregiver. 12. Signed a written consent for participation in the study (co-signed by the patient?s next of kin or caregiver, if required by the local regulations/guidelines/EC/IRB). 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
Exclusion criteria: CNS 1. Dementia due to condition other than AD 2. Other significant neurological disorder, including seizures, stroke, a history of head traumatism (resulting in hospitalization), Parkinson?s disease (as a primary diagnosis) 3. Background of mental retardation 4. Untreated / non stabilized Major Depressive Disorder (DSM-IV) 5. Bipolar disorder, schizophrenia or any serious psychiatric condition (Axis I Disorder, DSM-IV-TR) 6. At risk of suicide in the opinion of the investigator 7. Uncontrolled behavioral symptoms incompatible with compliance or evaluability: e.g. severe agitation, lack of impulse control, violence, severe dysphoria 8. Alcohol and/or substance abuse or dependence (DSM ?IV) in the past 2 years Cardiovascular 9. Unstable or poorly controlled hypertension 10. Unstable or clinically significant cardiovascular disease that could be expected to progress, recur or change during study period to such an extent that it could bias the assessment of the clinical or mental status of the patient. 11. Patients with a screening QTcF > 450 msec (males) or > 470 msec (females), based on the average interval on triplicate ECGs obtained after five minutes rest in a supine position using a digital ECG machine algorithm. Hepatic 12. Screening AST, ALT or total bilirubin ? 2 times the upper limit of normal (ULN) which is still ? 2 times ULN when retested. Renal 13. Screening creatinine clearance 36 at screening. Other 20. History of cancer with survival expected to be less than 3 years or within the next 3 years may require systemic treatment. Except for localized, non recurrent treated skin cancer and stabilized prostate adenocarcinoma, i.e.: patients stable without treatment or under hormone therapy for at least 6 months, these patients must be individually approved by the Study science leader. 21. Any other medical condition not previously mentioned that could be expected to progress, recur, or change to such an extent that it could bias the assessment of the clinical or mental status of the patient to a significant degree or put the patient at special risk 22. Clinically significant abnormal blood or urine safety tests which do not improve when retested. 23. Positive result for either drug of abuse, alcohol breath test or cotinine test at screening. 24. Recent (within 60 days of screening) intake of investigational drug or prior intake of MEM 3454 (RO5313534) 25. Does not make an effortful attempt to perform the cognition batteries (at screening) Treatment History 26. Treatment for Alzheimer?s disease other than donepezil, i.e. ? Rivastigmine, galantamine, memantine ? Nutritional supplements used at doses higher than Recommended Daily Intake as assessed by the investigator, Ginkgo, lecithin within 2 weeks
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): The primary efficacy variable is the ADAS-Cog score change from baseline at week 24;Main Objective: The primary objective is to evaluate efficacy of 24 weeks treatment of 3 - 4 fixed doses of RO5313534 (1, 5, 15 mg/day with an option of 30 mg/day) added to donepezil (5 or 10 mg/day) on cognitive endpoint (measured with the ADAS-Cog) as compared to placebo added to donepezil.;Secondary Objective: 1. To evaluate the tolerability and safety 2. To evaluate efficacy on behavioral, global and functional endpoints 3. To evaluate on cognitive endpoints measured with the cognitive battery CANTAB (The Cambridge Neuropsychological Test Automated Battery) 4. To evaluate maintenance of efficacy (primary and secondary variables) 4 weeks after discontinuation of treatment 5. To investigate by a population PK analysis approach the pharmacokinetics of RO5313534 in the target population, including the influence of covariates such as age, gender, body-weight and renal function. 6. To explore the relationship between PK exposure and response using population PK-PD methods. 7. To evaluate whether the genetic markers of APOE?4, Nicotinic alpha7 and duplicated alpha 7 are predictive of response to RO5313534 treatment. | — |
Countries
France, Germany, Italy, Slovakia, Spain, United Kingdom
Outcome results
None listed