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

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

• Registration Number: EUCTR2008-004012-13-DE
• Lead Sponsor: F. Hoffmann-La Roche Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-05-12
• Last Update Posted: 24 April 2012

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, 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

1. Dementia due to condition other than AD
2. Other significant neurological disorder, including seizures, stroke (patients found with clinically silent lacunar stroke at MRI or CT may be allowed if the lesion is unique, =1 cm in max. diameter and not located in any of the following regions: hippocampus of either hemisphere, head of the left caudate, dorsomedial region of the left thalamus) 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 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 yrs
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 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 5 minutes rest in a supine position using a digital ECG machine algorithm.
12. Screening AST, ALT or total bilirubin =2 times the upper limit of normal (ULN) which is still =2 times ULN when retested.
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.
14. History of HIV infection, history of Hep B infection within the past year, or history of Hep C infection.
15. Hep B surface Antigen and/or Hep C core antibodies positivity at screening
16. Screening thyroid function tests (TSH, free T3, free 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.
20. History of cancer with survival expected to be less than 3 yrs or within the next 3 yrs may require systemic treatment. Except for localized, non recurrent treated skin cancer and stabilized prostate adenocarcinoma, i.e.: patients stable w/o treatment or under hormone therapy for at least 6 mo., 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 continine test at screening.
24. Recent (within 60 days of screening) intake of investigational drug or prior intake of (RO5313534)
25. Does not make an effortful attempt to perform the cognition batteries (at screening)
26. Treatment for Alzheimer’s disease other than donepezil, i.e.
•Rivastigmine, galantamine or memantine within 6 mo. before baseline are not pe

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified