The purpose of this study is to evaluate the safety, tolerability, and efficacy of two dose levels of rasagiline mesylate versus placebo in patients with mild-to-moderate Alzheimer's Disease who are taking Aricept.

Condition	Treatment or Intervention	Phase
Dementia, Alzheimer Type	Drug: rasagiline mesylate	Phase II

Further Study Details: 

Primary Outcomes: Cognitive Function
Secondary Outcomes: Other Cognitive Assessments; Activities of Daily Living (ADLs); Functional Assessments; Safety; Tolerability
Expected Total Enrollment:  345

Ages Eligible for Study:  45 Years   -   90 Years,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

1) Age range: Adult patients, 45 to 90 years of age inclusive.

2) Gender distribution: men and women. Women of child-bearing potential (< 1 year post-menopausal) must be practicing effective contraception and have a negative serum b-hCG at Screening.

3) Diagnosis: diagnostic evidence of probable Alzheimer’s Disease consistent with DSM-IV 290.00 or 290.10 and NINCDS ADRDA criteria. This evidence may be compiled during Screening but must be fully documented in the patient’s study file before the Baseline visit.

4) Stable Aricept® dose of 10 mg daily for >= 8 weeks.

5) Head image (CT or MRI): no evidence of focal disease to account for dementia on any head image (CT or MRI) obtained within 12 months prior to Baseline. If no such head image has been obtained prior to Screening, a head MRI will be obtained as part of the Screening evaluation; this MRI will also be used for Baseline volumetric analysis. The Baseline MRI obtained for volumetric analysis must also not show any evidence of focal disease to account for dementia.

6) Degree of dementia: MMSE score of >= 15 and <= 26 at Screening and Baseline.

7) Race and ethnicity: any race and ethnic group.

8) Health: generally healthy and ambulatory or ambulatory-aided (i.e., walker or cane). Corrected vision and hearing sufficient for compliance with testing procedures.

9) Clinical laboratory values must be within normal limits or, if abnormal, must be judged clinically insignificant by the Investigator.

10) Patients with vitamin B12 deficiency who are on a stable dose of medication for at least 12 weeks prior to Screening and who have normal serum vitamin B12 levels at Screening will be eligible. This stable dose of vitamin B12 must be maintained throughout the study. Subjects who might otherwise have been eligible can be re-screened for Vitamin B12 before Baseline.

11) Patients with hypothyroidism who are on a stable dose of medication for at least 12 weeks prior to Screening, have normal TSH and free T4 at screening, and are considered euthyroid will be eligible. This stable dose must be maintained throughout the study.

12) Patients must have a caregiver who has daily contact with the patient (e.g., an average of 10 or more hours per week), can observe for possible adverse events, and can accompany the patient to all visits.

13) Patients must be sufficiently fluent in English to be capable of reliably completing all study assessments.

Exclusion Criteria:

1) Patients taking (a) Aricept® doses other than 10 mg daily (or 10 mg for < 8 weeks); (b) other medications for Alzheimer’s disease except for stable, prescribed doses of 20 mg daily memantine for at least 4 weeks (preceded by titration to 20 mg daily).

2) No reliable caregiver.

3) Neurological disorders affecting cognition or the ability to assess it that are not associated with Alzheimer’s disease, such as Parkinson’s disease, multi-infarct dementia, dementia due to cerebrovascular disease, Huntington’s disease, Pick’s disease, Creutzfeld-Jacob disease, Lewy Body disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, or multiple sclerosis, as well as patients with human immunodeficiency virus (HIV) disease, neurosyphilis, or a history of significant head trauma followed by persistent neurological deficits or known structural brain abnormalities.

4) Psychiatric disorders affecting the ability to assess cognition such as schizophrenia, bipolar or unipolar depression, and sleep disorders.

5) Dementia complicated by other organic disease or Alzheimer’s disease with delusions (DSM 290.20 or 290.12), delirium (DSM 290.30 or 290.11), or depression (DSM 290.21 or 290.13).

6) Drug or alcohol abuse or dependence in <= 5 years by DSM IV criteria.

7) Any active or clinically significant conditions affecting absorption, distribution, or metabolism of the study medication (e.g., inflammatory bowel disease, gastric or duodenal ulcers, hepatic disease, or severe lactose intolerance).

8) Uncontrolled hypertension (sitting systolic >= 160 mmHg and/or diastolic >= 95 mmHg) as assessed by the Investigator regardless of whether or not the patient is taking antihypertensive medications.

9) Insulin-dependent diabetes or diabetes not stabilized by diet and/or oral hypoglycemic agents as demonstrated by an Hb A1c of > 8.0% or a random serum glucose value of > 170 mg/dL.

10) Evidence of clinically significant, active gastrointestinal, renal, hepatic, respiratory, endocrine, or cardiovascular system disease. Patients with right bundle branch block (complete or partial) may be included in the study, but patients with left bundle branch block are excluded.

11) History of malignant neoplasms (does not include basal or squamous cell carcinoma of the skin) treated within 5 years prior to study entry, current evidence of malignant neoplasm, recurrent, metastatic disease, or major risk factors for malignant melanoma (xeroderma pigmentosum, personal history of melanoma, more than 100 moles, and puva or other radiotherapy.

12) Donation of blood or blood products during 30 days prior to Screening or plans to donate blood while participating in the study or within 30 days after completion of the study.

13) Women who are pregnant or breast-feeding.

14) Patients and/or caregivers who are unwilling or unable to fulfill the requirements of the study.

15) Known hypersensitivity to cholinesterase inhibitors or MAO or MAO-B inhibitors.

16) Use of any unapproved prior or concomitant medications, including:

• Recent (<= 12 weeks) or concomitant use of other MAO inhibitors.
• Recent (<= 6 weeks) or concomitant use of SSRIs. (SSRIs and tricyclic and tetracyclic antidepressants in low doses are permissible, as follows: citalopram <= 20 mg daily, escitalopram <= 10 mg daily, and sertraline 25-100 mg daily).
• Recent (<= 1 week) or concomitant use of sympathomimetics (including ephedra supplements).
• Recent (<= 1 week) or concomitant use of meperidine.
• Recent (<= 1 week) or concomitant use of dextromethorphan.
• Recent (<= 1 week) or concomitant use of gentamicin.

17) Any condition that would make the patient or the caregiver, in the opinion of the Investigator, unsuitable for the study.

18) Involvement in any other investigational trial in the preceding 3 months or likely involvement in any other investigational trial during the course of this study.

19) Contraindications to MRI scanning, including CNS aneurysm clips, implanted neural stimulators, implanted cardiac pacemakers or defibrillators, cochlear implants, metallic ocular foreign body, insulin pump, or metal shrapnel or bullet.

Eisai Medical Services      1-888-422-4743 

Alabama
      Huntsville,  Alabama,  United States; Recruiting
Arkansas
      Little Rock,  Arkansas,  United States; Recruiting
California
      San Francisco,  California,  United States; Recruiting
      Fresno,  California,  United States; Recruiting
      Santa Monica,  California,  United States; Recruiting
      Garden Grove,  California,  United States; Recruiting
      Berkeley,  California,  United States; Recruiting
      Laguna Woods,  California,  United States; Recruiting
      Oceanside,  California,  United States; Recruiting
Colorado
      Denver,  Colorado,  United States; Recruiting
Connecticut
      Danbury,  Connecticut,  United States; Recruiting
Florida
      West Palm Beach,  Florida,  United States; Recruiting
      Punta Gorda,  Florida,  United States; Recruiting
      Pompano Beach,  Florida,  United States; Recruiting
      Ocala,  Florida,  United States; Recruiting
Georgia
      Atlanta,  Georgia,  United States; Recruiting
      Decatur,  Georgia,  United States; Recruiting
Illinois
      Chicago,  Illinois,  United States; Recruiting
Indiana
      Fort Wayne,  Indiana,  United States; Recruiting
      Elkhart,  Indiana,  United States; Recruiting
Kansas
      Lenexa,  Kansas,  United States; Recruiting
Kentucky
      Paducah,  Kentucky,  United States; Recruiting
      Louisville,  Kentucky,  United States; Recruiting
Louisiana
      New Orleans,  Louisiana,  United States; Recruiting
Maryland
      Baltimore,  Maryland,  United States; Recruiting
Massachusetts
      Boston,  Massachusetts,  United States; Recruiting
Michigan
      Traverse City,  Michigan,  United States; Recruiting
New Jersey
      Piscataway,  New Jersey,  United States; Recruiting
New York
      New York,  New York,  United States; Recruiting
      Albany,  New York,  United States; Recruiting
      Brooklyn,  New York,  United States; Recruiting
North Dakota
      Fargo,  North Dakota,  United States; Recruiting
Ohio
      Columbus,  Ohio,  United States; Recruiting
      Toledo,  Ohio,  United States; Recruiting
      Dayton,  Ohio,  United States; Recruiting
Oklahoma
      Oklahoma City,  Oklahoma,  United States; Recruiting
South Carolina
      North Charleston,  South Carolina,  United States; Recruiting
Texas
      Houston,  Texas,  United States; Recruiting
Vermont
      Bennington,  Vermont,  United States; Recruiting
Canada, Alberta
      Edmonton,  Alberta,  Canada; Recruiting
Canada, British Columbia
      Victoria,  British Columbia,  Canada; Recruiting
Canada, Manitoba
      Winnipeg,  Manitoba,  Canada; Recruiting
Canada, Ontario
      Peterborough,  Ontario,  Canada; Recruiting
      Toronto,  Ontario,  Canada; Recruiting
      London,  Ontario,  Canada; Not yet recruiting
South Africa
      Bellville,  South Africa; Recruiting
      Johannesberg,  South Africa; Not yet recruiting
      Richard's Bay,  South Africa; Not yet recruiting
      Durban,  South Africa; Not yet recruiting
      PARKTOWN,  South Africa; Not yet recruiting
      Pretoria,  South Africa; Not yet recruiting
      Plumstead,  South Africa; Not yet recruiting
      Panorama,  South Africa; Not yet recruiting
      Pinetown,  South Africa; Not yet recruiting
      Westdene, Boemfontein,  South Africa; Not yet recruiting

Study ID Numbers:  TVP-1012-A001-201
Record last reviewed:  February 2005
Last Updated:  February 25, 2005
Record first received:  February 24, 2005
ClinicalTrials.gov Identifier:  NCT00104273
Health Authority: United States: Food and Drug Administration; Canada: Health Canada (Awaiting confirmation); South Africa: Medicines Control Council (Awaiting confirmation)
ClinicalTrials.gov processed this record on 2005-04-08