A GLOBAL CLINICAL STUDY TO INVESTIGATE THE EFFECTIVENESS AND SAFETY OF RO4602522 WHEN TAKEN IN ADDITION TO ALZHEIMER'S DISEASE THERAPY IN PATIENTS WITH MODERATE ALZHEIMER'S DISEASE

• Conditions: Alzheimer's Disease; Therapeutic area: Psychiatry and Psychology [F] - Mental Disorders [F03]; MedDRA version: 18.0Level: LLTClassification code 10001896Term: Alzheimer's diseaseSystem Organ Class: 100000004852

• Registration Number: EUCTR2012-000943-29-PL
• Lead Sponsor: F. Hoffmann-La Roche Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2012-10-22
• Last Update Posted: 28 September 2015

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 495

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 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

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)

Study & Design

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

Primary Outcome Measures

Name	Time	Method
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<br>• Effect on functioning assessed with the ADCS-ADL scale<br>• Effect on behavioral symptoms <br>• Effect on the global measures assessed with the ADCS-CGIC scale and the Global Deterioration Scale (GDS). <br>• Assessment of safety and tolerability<br>• Estimating population-PK parameters and investigating the influence of various covariates on these parameters.<br>;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 Outcome Measures

Name	Time	Method
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<br>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)