Alzheimer's Disease MedDRA version: 17.0 Level: LLT Classification code 10001896 Term: Alzheimer's disease System Organ Class: 100000004852
Conditions
Interventions
Product Name: MAO-B Inhibitor
Product Code: Ro 460-2522/F02
Pharmaceutical Form: Tablet
CAS Number: 676479-06-4
Current Sponsor code: RO4602522
Other descriptive name: MAO-B inhibitor
Concentration un
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Probable AD, based on the National Institute of Neurological and Communicative Disorders and Stroke (NINCDS)/Alzheimer’s Disease and Related Disorders Association (ADRDA) and DSM-IV-TR criteria. 2. 50-90 years of age 3. MMSE score at screening between 13 and 20, inclusive 4. MRI supports a diagnosis of AD, with no evidence of other disease likely to account for the subject’s dementia. 5. Body mass index (BMI) between 18 and 36. 6. Modified Hachinski Ischemia Score of =4. 7. Patients with CSDD scores =13. 8. Receiving treatment with donepezil, rivastigmine, galantamine or any of these AChEIs in combination with memantine for at least 4 months, with their dose and formulation stabilized for at least 3 months prior to screening. All formulation and dosages are allowed except donezepil 23 mg (alone or in combination). 9. Generally healthy and ambulatory or ambulatory-aided (i.e., walker or cane). 10. Have a caregiver who has frequent contact with the patient, who is considered reliable, who can 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. Females of childbearing potential must have a negative pregnancy test and must agree to use effective contraception 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 124 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 371
Exclusion criteria
Exclusion criteria: 1. Any neurological or psychiatric condition that may currently or during the course of the study impair cognition or functioning that is not associated with Alzheimer's disease 2. Background of mental retardation 3. At risk of suicide 4. Uncontrolled behavioral symptoms 5. Alcohol and/or substance abuse or dependence in the past 2 years, except nicotine use 6. Preexisting neuropathy 7. Unstable or poorly controlled hypertension and/or cardiovascular disease 8. Clinically relevant ECG abnormality 9. Bradycardia 10. Aspartate aminotransferase, alanine aminotransferase or total bilirubin =1.5 times the upper limit of normal 11. HIV positive, history of Hepatitis B infection within the past year, or history of Hepatitis C infection 12. Hepatitis B virus surface Antigen (HBsAg) and/or Hepatitis C antibodies (HepCAb) positive 13. Abnormal thyroid function tests 14. Poorly controlled diabetes 15. Severe renal impairment 16. Requiring nursing home care. Patients living in assisted living facilities are allowed if a reliable caregiver is available (see inclusion criteria) 17. History of cancer except if considered likely to be cured as documented by an oncologist / surgeon or in the case of non-melanoma skin cancers and prostate adenocarcinoma if there has been no significant progression over the last 2 years 18. Involvement in any other investigational trial in the last 3 months 19. Current treatment for AD other than those listed in inclusion criteria 20. Participation at any time in an active AD vaccine study 21. Participation in a passive AD immunization study less than 1 year before screening, with exceptions as per protocol 22. Recent (= 12 weeks) use of MAO inhibitors 23. Antidepressant treatment recently initiated (= 6 weeks). 24. Psychotropic medication as defined by protocol 25. Unwilling/ Unable to avoid ingesting food with high tyramine content (yeast concentrate, soy sauce, aged overripe cheese or very salty food)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To evaluate the efficacy of a 12-month treatment of RO4602522 versus placebo added to AChEI alone or in combination with memantine in patients with moderate severity AD (MMSE 13-20 inclusive), based on mean change in ADAS-Cog-11 scores (cognitive endpoint) from baseline over time.;Secondary Objective: • Effect on cognition assessed with the ADAS-Cog-11 scale • Effect on functioning assessed with the ADCS-ADL scale • Effect on behavioral symptoms • Effect on the global measures assessed with the ADCS-CGIC scale and the Global Deterioration Scale (GDS). • Assessment of safety and tolerability • Estimating population-PK parameters and investigating the influence of various covariates on these parameters. ;Primary end point(s): The change from baseline in ADAS-Cog-11 over 12 months.;Timepoint(s) of evaluation of this end point: following 12-month treatment (compared to baseline) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Mean ADCS-CGIC score, the mean change from baseline over time in ADCS-ADL, BEHAVE-AD-FW, AES and GDS scores, and the proportion of patients worsening over time in BEHAVE-AD-FW and ADCS-CGIC scores.;Timepoint(s) of evaluation of this end point: following 12-month treatment (compared to baseline) | — |
Countries
Australia, Canada, Czech Republic, Germany, Italy, Poland, Sweden, United Kingdom, United States
Contacts
Public ContactTrial Information Support Line-TISL
F.Hoffmann-La Roche Ltd
Outcome results
None listed