A dose ranging, randomized, double blind, parallel-group placebo-controlled multi-center study of RO5313534 used as add-on to donepezil treatment in patients with mild to moderate symptoms of Alzheimer’s Disease

Phase 1

Conditions: MedDRA version: 9.1Level: LLTClassification code 10001896Term: Alzheimer's disease
Mild to moderate Alzheimer’s Disease

Registration Number: EUCTR2008-004012-13-FR

Lead Sponsor: F. Hoffmann-La Roche Ltd

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 420

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

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 < 30 mL/min as calculated by the central lab using the Cockcroft-Gault formula, which remains < 30 mL/min when retested.
Infections/Immune Disorders
14. History of HIV infection, history of Hepatitis B infection within the past year, or history of Hepatitis C infection.
15. Hepatitis B surface Antigen and/or Hepatitis C core antibodies positivity at screening
Metabolic/Endocrine
16. Screening thyroid function tests (TSH, T3, T4) that are clinically significantly abnormal (taking into account prior results and treatments) .
17. Screening folic acid or B12 levels that are clinically significantly abnormal (taking into account prior results and treatments).
18. Poorly controlled diabetes (Hb1Ac= 9% at screening)
19. BMI > 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 b

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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