Patients with probable Alzheimer's Disease (AD) diagnosis according to NINCDS-ADRDA and DSM–IV criteria, who suffer from mild to moderate dementia with a Mini Mental State Examination (MMSE) of 15-26 MedDRA version: 7.0 Level: HLT Classification code 10001897
Conditions
Interventions
Product Name: Ladostigil Tablets 20 mg
Pharmaceutical Form: Tablet
INN or Proposed INN: Ladostigil
CAS Number: 209394-46-7
Current Sponsor code: TV-3326
Other descriptive name: Ladostigil Tartrate
Con
Sponsors
Teva Pharmaceutical Industries Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subjects of 60 years of age and older. 2. Gender distribution: men and women. 3. Diagnosis of probable Alzheimer’s disease according to DSM-IV (290.00 or 290.10) and NINCDS-ADRDA criteria. 4. Degree of dementia: MMSE score of =15 and =26 at Screening 5. Ambulatory or ambulatory-aided outpatients (i.e., walker or cane). 6. Corrected vision and corrected hearing sufficient for compliance with testing procedures. 7. Subjects must have a caregiver with whom they have daily contact (e.g., an average of 10 or more hours per week), and can observe possible adverse events, can assist the patient in study medication administration and can accompany the patient to all visits. 8. Subjects must be able to read, write and speak the local language. 9. Subjects and caregiver must be willing and able to give written informed consent prior to entering the study. 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
Exclusion criteria: 1. Subjects taking acetylcholine esterase inhibitors within 8 weeks prior to screening. 2. Subjects taking memantine within 4 weeks prior to screening. 3. Subjects taking MAO inhibitors within 3 months prior to screening. 4. Neurological disorders affecting cognition other than Alzheimer’s Disease. 5. Neurological disorders, other than Alzheimer’s Disease that may be accounted for the dementia as verified by brain imaging (CT or MRI) obtained within 12 months prior to screening. 6. History of Schizophrenia or bipolar affective disorder. 7. Dementia complicated by delirium (DSM 290.30 or 290.11). 8. Any behavioral impairment within the last month prior to screening which in the discretion of the investigator could effect the subject’s ability to comply with study protocol (such as severe agitation). 9. Drug or alcohol abuse or dependence during the previous 5 years by DSM-IV criteria. 10. Abnormal laboratory values which are considered by the investigator to be of clinical significance. 11. Non-treated vitamin B12 deficiency. 12. Uncontrolled hypothyroidism. 13. Any acute or chronic clinically significant conditions affecting absorption, distribution, or metabolism of the study medication. 14. Significant or unstable medical or surgical condition which would preclude safe and complete study participation. 15. Uncontrolled hypertension (sitting systolic BP=160 mmHg and/or diastolic =90 mmHg) regardless of whether or not the patient is taking antihypertensive medications. 16. Two or more abnormal blood pressure readings according to exclusion criterion number 15 during home blood pressure recording at screening period. 17. Uncontrolled Insulin or Non Insulin Dependant Diabetes Mellitus. 18. A current diagnosis of bradycardia (Heart rate<50 BPM), sick sinus syndrome or specific conduction deficits (sino-atrial block, second or third degree atrio-ventricular block, LBBB). 19. Donation of blood or blood products during 30 days prior to screening or plans to donate blood while participating in the study or planned donation within 30 days after completion of the study. 20. Patients and/or caregivers who are unwilling or unable to fulfill the requirements of the study. 21. Known hypersensitivity to cholinesterase inhibitors or MAO or MAO-B inhibitors. 22. Use of any experimental medication within 3 months prior to screening or as concomitant medications.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Assessment of tolerability, safety and MTD of different dose ranges of ladostigil in AD patients Pharmacokinetic assessment of ladostigil and its metabolites. Pharmacodynamic assessment of Ladostigil (in a study subpopulation ): (a) Inhibition of plasma and erythrocyte cholinesterase (ChE) (b) Inhibition of MAO-B in platelets (c) DHPG levels in plasma;Secondary Objective: psychometric assessment ;Primary end point(s): Outcome Measures: • Safety of and tolerability of ladostigil will be monitored and evaluated by: o Safety: ? Adverse events ? Vital signs ? ECG ? Clinical laboratory parameters o Tolerability: ? Number of subjects who terminated the study early. ? Number of subjects who terminated the study early due to AE. • Pharmacokinetic evaluation of ladostigil and its metabolites in plasma. • Pharmacodynamic evaluation of ChE inhibition in serum and erythrocytes and evaluation of MAO-B inhibition in platelets. Additional Assessments: Psychometric evaluation: • ADAS-cog • NPI • CSDD • CGIC | — |
Countries
Italy, Spain
Outcome results
None listed