Rasagiline 1 mg and 2 mg Added to Aricept 10 mg Daily in Patients With Mild to Moderate Alzheimer's Disease (AD)

NCT ID: NCT00104273

Last Updated: 2009-07-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 376 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-08-31

Brief Summary

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.

Conditions

Dementia; Alzheimer's Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Interventions

Rasagiline

Intervention Type: DRUG

Eligibility 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.

• Minimum Eligible Age: 45 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eisai Inc.

INDUSTRY

Sponsor Role: collaborator

Teva Branded Pharmaceutical Products R&D, Inc.

INDUSTRY

Sponsor Role: lead

Principal Investigators

Timothy Hsu

Role: STUDY_DIRECTOR

Eisai Inc.

Locations

Collaborative Neuroscience Network

Huntsville, Alabama, United States

North Alabama Neuroscience Research

Huntsville, Alabama, United States

Northwest Neurospecialists, PLLC

Tucson, Arizona, United States

Clinical Study Centers, LLC

Little Rock, Arkansas, United States

East Bay Region Associates in Neurology

Berkeley, California, United States

Margolin Brain Institute

Fresno, California, United States

Collaborative Neuroscience Network

Garden Grove, California, United States

San Francisco Clinical Research Center

San Francisco, California, United States

Neurological Research Institute

Santa Monica, California, United States

University of Colorado Health Sciences Center

Denver, Colorado, United States

Premiere Research Institute

West Palm Beach, Florida, United States

North Broward Medical Center/Memory Disorder Center

West Palm Beach, Florida, United States

Emory University Wesley Woods Health Center

Altanta, Georgia, United States

Dekalb Neurology Associates, LLC

Decatur, Georgia, United States

Radiant Research

Chicago, Illinois, United States

Fort Wayne Neurological Center

Fort Wayne, Indiana, United States

Mid America Neuroscience Institute

Lenexa, Kansas, United States

Four Rivers Clinical Research

Paducah, Kentucky, United States

Tulane University Health Sciences Center, Dept of Psychiatry and Neurology

New Orleans, Louisiana, United States

Department of Neurology - Brigham and Women's Hospital

Boston, Massachusetts, United States

Northern Michigan Neurology

Traverse City, Michigan, United States

University Behavioral Healthcare Centre Department of Psychiatry

Piscataway, New Jersey, United States

Odyssey Research

Fargo, North Dakota, United States

Ohio State University, Department of Neurology

Columbus, Ohio, United States

Pahl Brain Associates

Oklahoma City, Oklahoma, United States

Medical University of South Carolina Alzheimer's Research and Clinical Programs

North Charleston, South Carolina, United States

Department of Neurology Baylor College of Medicine

Houston, Texas, United States

Premiere Research Institute

Houston, Texas, United States

University of Texas Mental Sciences Institute

Houston, Texas, United States

Peninsula Internal Medicine Associates

Gig Harbor, Washington, United States

Internal Medicine Northwest

Tacoma, Washington, United States

Ballarat Health Service - Queen Elizabeth Center

Ballarat, , Australia

Aged Mental Health Research Unit - Kingston Centre

Cheltenham, , Australia

Prince Charles Hospital - Dept. of Geriatrics

Chermside, , Australia

Central Coast Neuroscience Research

East Gosford, , Australia

Heidelberg Repatriation Hospital

Heidelberg West, , Australia

Hornsby Kur-ing-gai Hospital, Rehabilitation and Aged Care Service

Hornsby, , Australia

St. George's Hospital

Kew, , Australia

McCusker Foundation for Alzheimer's Disease Research

Nedlands, , Australia

The Queen Elizabeth Hospital

Woodville, , Australia

Glenrose Rehabilitation Hospital

Edmonton, Alberta, Canada

Memory Disorder Clinic/Winnipeg Clinic

Winnipeg, Manitoba, Canada

Dept. of Clinical Neurological Sciences - University of Western Ontario

London, Ontario, Canada

155974 Ont. Inc.

Peterborough, Ontario, Canada

Neurology Research Inc.

Toronto, Ontario, Canada

Bloemfontein Medi Clinic

Westdene, Bloemfontein, South Africa

Westdene Research Centre

Westdene, Bloemfontein, South Africa

Suite C, Black C

Sandton, Gauteng, South Africa

St. Augustine's Medical Mews.

Durban, , South Africa

The Memory Centre

Johannesburg, , South Africa

Dr. Felix Potocnik

Oakdale, , South Africa

Panorama Medical Centre

Panorama, , South Africa

Milpark Hospital

Parktown, , South Africa

Crompton Medical Centre West

Pinetown, , South Africa

Constantiaberg Medi Clinic

Plumstead, , South Africa

Willows Medical Center

Pretoria, , South Africa

Little Company of Mary Hospital

Pretoria, , South Africa

Richard's Bay Trial Centre

Richard's Bay, , South Africa

Countries

United States; Australia; Canada; South Africa

Other Identifiers

TVP-1012-A001-201

Identifier Type: -

Identifier Source: org_study_id