Clinical trial NCT00104273: Rasagiline 1 mg and 2 mg Added to Aricept 10 mg Daily in Patients With Mild to Moderate Alzheimer's Disease (AD)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Dementia
Alzheimer's Disease
Keywords: Dementia, Alzheimer's Disease
Lead sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Eisai Inc.
First posted: 2005-02-25
Enrollment: 376
Sex: ALL
Minimum age (years): 45
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Cognitive Function
Secondary outcomes:
measure: Other Cognitive Assessments; Activities of Daily Living (ADLs); Functional Assessments; Safety; Tolerability.
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Collaborative Neuroscience Network
state: Alabama
city: Huntsville
country: United States
facility: North Alabama Neuroscience Research
state: Alabama
city: Tucson
country: United States
facility: Northwest Neurospecialists, PLLC
state: Arizona
city: Little Rock
country: United States
facility: Clinical Study Centers, LLC
state: Arkansas
city: Berkeley
country: United States
facility: East Bay Region Associates in Neurology
state: California
city: Fresno
country: United States
facility: Margolin Brain Institute
state: California
city: Garden Grove
country: United States
facility: Collaborative Neuroscience Network
state: California
city: San Francisco
country: United States
facility: San Francisco Clinical Research Center
state: California
city: Santa Monica
country: United States
facility: Neurological Research Institute
state: California
city: Denver
country: United States
facility: University of Colorado Health Sciences Center
state: Colorado
city: West Palm Beach
country: United States
facility: Premiere Research Institute
state: Florida
city: West Palm Beach
country: United States
facility: North Broward Medical Center/Memory Disorder Center
state: Florida
city: Altanta
country: United States
facility: Emory University Wesley Woods Health Center
state: Georgia
city: Decatur
country: United States
facility: Dekalb Neurology Associates, LLC
state: Georgia
city: Chicago
country: United States
facility: Radiant Research
state: Illinois
city: Fort Wayne
country: United States
facility: Fort Wayne Neurological Center
state: Indiana
city: Lenexa
country: United States
facility: Mid America Neuroscience Institute
state: Kansas
city: Paducah
country: United States
facility: Four Rivers Clinical Research
state: Kentucky
city: New Orleans
country: United States
facility: Tulane University Health Sciences Center, Dept of Psychiatry and Neurology
state: Louisiana
city: Boston
country: United States
facility: Department of Neurology - Brigham and Women's Hospital
state: Massachusetts
city: Traverse City
country: United States
facility: Northern Michigan Neurology
state: Michigan
city: Piscataway
country: United States
facility: University Behavioral Healthcare Centre Department of Psychiatry
state: New Jersey
city: Fargo
country: United States
facility: Odyssey Research
state: North Dakota
city: Columbus
country: United States
facility: Ohio State University, Department of Neurology
state: Ohio
city: Oklahoma City
country: United States
facility: Pahl Brain Associates
state: Oklahoma
city: North Charleston
country: United States
facility: Medical University of South Carolina Alzheimer's Research and Clinical Programs
state: South Carolina
city: Houston
country: United States
facility: Department of Neurology Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: Premiere Research Institute
state: Texas
city: Houston
country: United States
facility: University of Texas Mental Sciences Institute
state: Texas
city: Gig Harbor
country: United States
facility: Peninsula Internal Medicine Associates
state: Washington
city: Tacoma
country: United States
facility: Internal Medicine Northwest
state: Washington
city: Ballarat
country: Australia
facility: Ballarat Health Service - Queen Elizabeth Center
city: Cheltenham
country: Australia
facility: Aged Mental Health Research Unit - Kingston Centre
city: Chermside
country: Australia
facility: Prince Charles Hospital - Dept. of Geriatrics
city: East Gosford
country: Australia
facility: Central Coast Neuroscience Research
city: Heidelberg West
country: Australia
facility: Heidelberg Repatriation Hospital
city: Hornsby
country: Australia
facility: Hornsby Kur-ing-gai Hospital, Rehabilitation and Aged Care Service
city: Kew
country: Australia
facility: St. George's Hospital
city: Nedlands
country: Australia
facility: McCusker Foundation for Alzheimer's Disease Research
city: Woodville
country: Australia
facility: The Queen Elizabeth Hospital
city: Edmonton
country: Canada
facility: Glenrose Rehabilitation Hospital
state: Alberta
city: Winnipeg
country: Canada
facility: Memory Disorder Clinic/Winnipeg Clinic
state: Manitoba
city: London
country: Canada
facility: Dept. of Clinical Neurological Sciences - University of Western Ontario
state: Ontario
city: Peterborough
country: Canada
facility: 155974 Ont. Inc.
state: Ontario
city: Toronto
country: Canada
facility: Neurology Research Inc.
state: Ontario
city: Westdene
country: South Africa
facility: Bloemfontein Medi Clinic
state: Bloemfontein
city: Westdene
country: South Africa
facility: Westdene Research Centre
state: Bloemfontein
city: Sandton
country: South Africa
facility: Suite C, Black C
state: Gauteng
city: Durban
country: South Africa
facility: St. Augustine's Medical Mews.
city: Johannesburg
country: South Africa
facility: The Memory Centre
city: Oakdale
country: South Africa
facility: Dr. Felix Potocnik
city: Panorama
country: South Africa
facility: Panorama Medical Centre
city: Parktown
country: South Africa
facility: Milpark Hospital
city: Pinetown
country: South Africa
facility: Crompton Medical Centre West
city: Plumstead
country: South Africa
facility: Constantiaberg Medi Clinic
city: Pretoria
country: South Africa
facility: Willows Medical Center
city: Pretoria
country: South Africa
facility: Little Company of Mary Hospital
city: Richard's Bay
country: South Africa
facility: Richard's Bay Trial Centre
Study officials:
affiliation: Eisai Inc.
name: Timothy Hsu
role: STUDY_DIRECTOR
References: