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

Dementia Clinical Trial

Official title:

A 1-Year, Double-Blind, Randomized, Placebo-Controlled, Study of Rasagiline 1 mg and 2 mg Added to Aricept 10 mg Daily in Patients With Mild to Moderate Dementia of the Alzheimer's Type

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00104273
• Other study ID #: TVP-1012-A001-201
• Status: Completed
• Phase: Phase 2
• First received: February 24, 2005
• Last updated: July 14, 2009
• Start date: August 2004

Study information

• Verified date: April 2008
• Source: Teva Pharmaceutical Industries
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 376
• Est. primary completion date: March 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 45 Years to 90 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease
• Dementia

Intervention

Drug:
• Rasagiline

Locations

Country	Name	City	State
Australia	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
Canada	Glenrose Rehabilitation Hospital	Edmonton	Alberta
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	Memory Disorder Clinic/Winnipeg Clinic	Winnipeg	Manitoba
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	Little Company of Mary Hospital	Pretoria
South Africa	Willows Medical Center	Pretoria
South Africa	Richard's Bay Trial Centre	Richard's Bay
South Africa	Suite C, Black C	Sandton	Gauteng
South Africa	Bloemfontein Medi Clinic	Westdene	Bloemfontein
South Africa	Westdene Research Centre	Westdene	Bloemfontein
United States	Emory University Wesley Woods Health Center	Altanta	Georgia
United States	East Bay Region Associates in Neurology	Berkeley	California
United States	Department of Neurology - Brigham and Women's Hospital	Boston	Massachusetts
United States	Radiant Research	Chicago	Illinois
United States	Ohio State University, Department of Neurology	Columbus	Ohio
United States	Dekalb Neurology Associates, LLC	Decatur	Georgia
United States	University of Colorado Health Sciences Center	Denver	Colorado
United States	Odyssey Research	Fargo	North Dakota
United States	Fort Wayne Neurological Center	Fort Wayne	Indiana
United States	Margolin Brain Institute	Fresno	California
United States	Collaborative Neuroscience Network	Garden Grove	California
United States	Peninsula Internal Medicine Associates	Gig Harbor	Washington
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	Collaborative Neuroscience Network	Huntsville	Alabama
United States	North Alabama Neuroscience Research	Huntsville	Alabama
United States	Mid America Neuroscience Institute	Lenexa	Kansas
United States	Clinical Study Centers, LLC	Little Rock	Arkansas
United States	Tulane University Health Sciences Center, Dept of Psychiatry and Neurology	New Orleans	Louisiana
United States	Medical University of South Carolina Alzheimer's Research and Clinical Programs	North Charleston	South Carolina
United States	Pahl Brain Associates	Oklahoma City	Oklahoma
United States	Four Rivers Clinical Research	Paducah	Kentucky
United States	University Behavioral Healthcare Centre Department of Psychiatry	Piscataway	New Jersey
United States	San Francisco Clinical Research Center	San Francisco	California
United States	Neurological Research Institute	Santa Monica	California
United States	Internal Medicine Northwest	Tacoma	Washington
United States	Northern Michigan Neurology	Traverse City	Michigan
United States	Northwest Neurospecialists, PLLC	Tucson	Arizona
United States	North Broward Medical Center/Memory Disorder Center	West Palm Beach	Florida
United States	Premiere Research Institute	West Palm Beach	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Teva Pharmaceutical Industries	Eisai Inc.

Countries where clinical trial is conducted

United States,  Australia,  Canada,  South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cognitive Function
Secondary	Other Cognitive Assessments; Activities of Daily Living (ADLs); Functional Assessments; Safety; Tolerability.