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 DiseaseMedDRA version: 9.1Level: LLTClassification code 10001896Term: Alzheimer's disease
- Registration Number
- EUCTR2008-004012-13-GB
- Lead Sponsor
- F. Hoffmann-La Roche Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 360
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: A minimum of 50 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. Patients who make an effortful attempt to perform CANTAB at screening but are unable to complete all aspects may be considered eligible if other eligibility criteria are met.
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
1.Dementia due to condition other than AD
2.Other significant neurological disorder, including current diagnosis of epilepsy, stroke, history of brain injury, Parkinson’s disease
3.Background of mental retardation
4.Untreated/non stabilized Major Depressive Disorder
5.Bipolar disorder, schizophrenia or any serious psychiatric condition 6.At risk of suicide in the opinion of the investigator
7.Uncontrolled behavioral symptoms incompatible with compliance or evaluability
8.Alcohol and/or substance abuse or dependence 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
11.Patients with a screening QTcF >450 msec (males) or >470 msec (females), Patients who have a pacemaker rhythm with non-evaluable QTc are to be excluded as well. Note: pacemaker patients who have an evaluable QTc are eligible if screening QTcF is < 450 msec (males) or < 470 msec (females) (e.g. patients with atrial pacemaker or demand pacemaker).
12.Screening AST, ALT or total bilirubin =2 times the upper limit of normal (ULN)
13.Screening creatinine clearance <30 mL/min14.History of HIV ,Hep B, or Hep C infection
15.Hep B surface Antigen and/or Hep C core antibodies positivity
16.Screening thyroid function tests that are clinically significantly abnormal 17.Screening folic acid or B12 levels that are clinically significantly abnormal)
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
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
23.Positive result for either drug of abuse, alcohol breath test or continine test
24.Recent (within 60 days of screening) intake of investigational drug 25.Does not make an effortful attempt to perform CANTAB and ADAS-Cog 26.Treatment for Alzheimer’s disease other than donepezilare not permitted
•Nutritional supplements used at doses higher than Recommended Daily Intake, Ginkgo, huperizine, lecithin
within 2 wks before baseline are not permitted.
•Nutritional supplements are permitted, if not taken in high doses
and the patient is on a stable dose at least 3 months prior to screening. Huperizine within 2 weeks before baseline is not permitted.
•Estrogen hormone replacement, NSAIDs within 2 wks before baseline are not permitted (unless treat conditions other than AD)
27.Psychotropic medication
•Antidepressants use within 2 wks before screening are not permitted, except
antidepressant medication with minimal or no anticholinergic effects, Trazodone treatment for depression is permitted.
•Anti-psychotic use within 4 wks before screening are not permitted except haloperidol, risperidone or quetiapine at given max dose
•Anxiolytics/Hypnotics use within 2 wks before screening are not permitted except for
•Benzodiazepines of short half life for anxiety/sleeping disorders
•Zolpidem, zopiclone for insomnia
•Anticonvulsive therapy (note: neuropathic pain and tremor therapy with anticonvulsants is allowed
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