Clinical trial NCT00153010: An Evaluation of Three Doses of NS 2330 in Patients With Mild to Moderate Dementia of the Alzheimer's Type
Official title: A Phase II Double-Blind, Randomized, Dose-Ranging, Placebo-Controlled, Multicenter, Safety and Efficacy Evaluation of Three Doses of NS 2330 in Patients With Mild to Moderate Dementia of the Alzheimer's Type
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Alzheimer Disease
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2005-09-12
Enrollment: 430
Sex: ALL
Minimum age (years): 40
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Objectives: The objective of this study will be to determine the safety, tolerability, drug blood levels, and efficacy of each of three doses of NS 2330 (Tesofensine) given once daily compared with placebo in patients with mild to moderate Dementia of the Alzheimer's Type.


Eligibility criteria: INCLUSION CRITERIA

Patients may be included in this study if they meet all of the following criteria:

1. Male, and female without child bearing potential between 40 and 85 years of age, inclusive. Women who have been postmenopausal for less than 2 years must have a negative pregnancy test at screening.
2. Diagnosis of probable mild to moderate Dementia of the Alzheimer's Type as defined by National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS ADRDA) guidelines.9
3. Mini-Mental State Examination (MMSE) score of 10-24 and Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) score greater than 12 at screening.
4. Modified Hachinski Scale10 score no greater than 4.
5. Central nervous system imaging (CT or MRI scan of brain) compatible with Dementia of the Alzheimer's Type within the past year (also see exclusion criteria).
6. Exhibits reliability and physiologic capability sufficient to comply with all protocol procedures. Patient must be familiar with and fluent in English (i.e., sufficient to complete all study assessments from the language perspective).
7. Patients and/or a legal representative and their caregivers must have given informed consent. The legal representative and caregiver may be the same person.
8. Patient must have a reliable caregiver that is in frequent or daily contact with the patient, who will accompany the patient to the office and who will monitor the administration of prescribed medications. The caregiver will be able to communicate in English and be willing to comply with protocol requirements.

EXCLUSION CRITERIA

Patients must be excluded from this study if they meet any of the following criteria:

1. Secondary disorders inducing dementia such as neurosyphilis, craniocerebral trauma (CT/MRI), hyperthyroidism, or folic acid deficiency.
2. History of malignancy within 3 years, except for basal cell carcinoma.
3. History or diagnosis of symptomatic and/or unstable/uncontrolled:

   * Cardiovascular illnesses such as chronic congestive heart failure (with or without edema), arrhythmias, labile hypertension, ischemic heart disease, myocardial infarction (with residual angina), orthopnea, conduction defects (ECG), or other heart disease classified NYHA III or IV.
   * Liver disease such as cirrhosis, hepatitis B, hepatitis C, or primary or metastatic neoplasm.
   * Gastrointestinal disorder such as GI bleeding, malabsorption syndromes, post-gastrectomy, or active peptic ulcer disease.
   * Renal disease (primary or secondary) such as chronic renal failure (CLCR \< 30 mL/min).
   * Endocrine disease such as diabetes mellitus or hypothyroidism.
   * Neurological disease (other than Dementia of the Alzheimer's Type such as Huntington's disease, Parkinson's disease, encephalitis, epilepsy, stroke, or multiple sclerosis) and psychiatric disorders such as schizophrenia, major depression, or mental retardation.
   * Significant pulmonary disease predisposing to hypoxia.
   * Immunological disorder such as clinically significant allergies, Lupus erythematosis, or scleroderma.
   * Hematological disease (regardless of cause) such as refractory anemia or refractory myelosuppression.
   * Organ system diseases which, in the opinion of the investigator, would impact on the primary and secondary endpoints of the trial such as dehydration (hematocrit \>48%) or hypothyroidism.
4. Significant history of drug dependence or abuse (including alcohol, as defined in DSM IV or in the opinion of the investigator) within two years, or a positive urine drug screen for cocaine, heroin, or marijuana.
5. HIV positive.
6. Presence of Hepatitis C antibody.
7. Planned elective surgery requiring general anesthesia or hospitalization for more than 1 day during the study period.
8. Previous participation in any NS 2330 study.
9. Use of any investigational drug or procedure within 30 days before randomization.
10. Use of any drug within 14 days prior to randomization unless:

    * the dose of the drug and the condition being treated have been stable for at least 30 days and are expected to remain stable during the study
    * neither the drug nor the condition being treated is expected to interfere with the study endpoints.
11. Treatment with donepezil, galantamine, rivastigmine, or tacrine, is prohibited within 6 weeks before randomization.
12. Treatment with drugs that inhibit CYP 450 3A4 (see Appendix II for a list of relevant drugs.) If they are needed under emergency conditions, the patient should discontinue the trial.
13. Treatment with antipsychotics/neuroleptics is prohibited for 8 weeks prior to randomisation (see listing Appendix II).
14. Treatment with monoamine oxidase inhibitors is prohibited for 8 weeks prior to randomization.
15. Treatment with selective serotonin reuptake inhibitors is prohibited for 6 weeks prior to randomization.
16. Tricyclic antidepressants and antihistamines are prohibited for 4 weeks prior to randomization.

Primary outcomes:
measure: Changes in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog)
timeFrame: week 0, 4, 9, 14 and 20
Secondary outcomes:
measure: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change
timeFrame: weeks 0 and 14
measure: Alzheimer's Disease Cooperative Study-Activities of Daily Living
timeFrame: weeks 0, 4, and 14
measure: Neuropsychiatric Inventory
timeFrame: weeks 0, 4, and 14
measure: Mini-Mental State Examination
timeFrame: weeks 0 and 14
measure: ADAS-Cog Extension
timeFrame: weeks 0, 4, 9, 14 and 20
measure: ADAS-Cog total score including Extension
timeFrame: weeks 0, 4, and 14
measure: types and frequencies of adverse events
timeFrame: 20 weeks
measure: proportion of patients discontinued from the trial because of adverse events
timeFrame: 20 weeks
measure: changes from baseline in vital signs
timeFrame: 20 weeks
measure: changes from baseline in laboratory measurements
timeFrame: 20 weeks
measure: changes from baseline in ECG readings
timeFrame: 20 weeks
measure: comparison of study groups for drug plasma concentrations
timeFrame: weeks 0, 4, 9, 14 and 20
measure: population PK parameters
timeFrame: Weeks 0, 4, 9, 14 and 20
Other outcomes:
Locations:
city: Mesa
country: United States
facility: Pivotal Research Center
state: Arizona
city: Peoria
country: United States
facility: Pivotal Research Center
state: Arizona
city: Phoenix
country: United States
facility: Xenoscience
state: Arizona
city: Berkeley
country: United States
facility: Boehringer Ingelheim Investigational Site
state: California
city: Culver City
country: United States
facility: California Clinical Trials Medical Group
state: California
city: Fresno
country: United States
facility: Margolin Brain Institute
state: California
city: Granada Hills
country: United States
facility: Care@ Granada Hills Community Hospital
state: California
city: LaMesa
country: United States
facility: Optimum Health Services
state: California
city: Oceanside
country: United States
facility: Optimum Health Services
state: California
city: Rancho Mirage
country: United States
facility: Southwest Institute for Clinical Research
state: California
city: San Diego
country: United States
facility: Health Quest Clinical Trials
state: California
city: San Francisco
country: United States
facility: Institute on Aging Research Center
state: California
city: Torrance
country: United States
facility: Torrance Clinical Research
state: California
city: Danbury
country: United States
facility: Associated Neurologists PC - Danbury
state: Connecticut
city: Hamden
country: United States
facility: Center for Geriatric & Adult Psychiatry
state: Connecticut
city: Wilmington
country: United States
facility: Neurology Associates PA
state: Delaware
city: Boca Raton
country: United States
facility: Baumel-Eisner Neuromedical Institute
state: Florida
city: Fort Lauderdale
country: United States
facility: Baumel-Eisner Neuromedical Institute
state: Florida
city: Fort Lauderdale
country: United States
facility: Neurologic Consulting/PA
state: Florida
city: Fort Meyers
country: United States
facility: Clinical Physiology Associates Study Center
state: Florida
city: Hialeah
country: United States
facility: Berma Research Group
state: Florida
city: Hollywood
country: United States
facility: Sunrise Clinical Research
state: Florida
city: Miami
country: United States
facility: Baumel-Eisner Neuromedical Institute
state: Florida
city: Miami
country: United States
facility: Miami Jewish Home and Hospital for the Aged
state: Florida
city: N. Miami
country: United States
facility: Segal Institute for Clinical Research
state: Florida
city: Ocala
country: United States
facility: Magnolia Research Group
state: Florida
city: Pompano Beach
country: United States
facility: Memory Disorder Clinic
state: Florida
city: Tampa
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Florida
city: Tampa
country: United States
facility: USF Suncoast Gerontology Center
state: Florida
city: W. Palm Beach
country: United States
facility: Palm Beach Neurology/Premier Research Institute
state: Florida
city: Atlanta
country: United States
facility: Atlanta Center for Medical Research
state: Georgia
city: Chicago
country: United States
facility: Peryam and Kroll Healthcare Research
state: Illinois
city: LaGrange
country: United States
facility: LaGrange Hospital
state: Illinois
city: Indianapolis
country: United States
facility: Agewell, Ltd.
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa College of Medicine
state: Iowa
city: Florence
country: United States
facility: Hartford Research Group
state: Kentucky
city: Lexington
country: United States
facility: Associates in Neurology-Research
state: Kentucky
city: New Orleans
country: United States
facility: Louisiana State University Medical Center
state: Louisiana
city: Sharon
country: United States
facility: Attn: M. Lannom, RN, MS
state: Massachusetts
city: Springfield
country: United States
facility: Future Care Studies
state: Massachusetts
city: Saginaw
country: United States
facility: Saginaw Cooperative Hosp. Inc./ Internal medicine
state: Michigan
city: Traverse City
country: United States
facility: North Michigan Neurology
state: Michigan
city: Columbia
country: United States
facility: University of Missouri
state: Missouri
city: St. Louis
country: United States
facility: St. Louis University
state: Missouri
city: Las Vegas
country: United States
facility: University of Nevada School of Medicine
state: Nevada
city: Tom's River
country: United States
facility: Atlantic Coast Research
state: New Jersey
city: Albuquerque
country: United States
facility: Albuquerque Neuroscience
state: New Mexico
city: Albany
country: United States
facility: Neurological Associates of Albany
state: New York
city: Albany
country: United States
facility: Upstate Clinical Research
state: New York
city: Amherst
country: United States
facility: Dent Neurologic Institute
state: New York
city: New York
country: United States
facility: Eastside Comprehensive Medical Services
state: New York
city: New York
country: United States
facility: Social Psychiatry Research Institute
state: New York
city: New York
country: United States
facility: The Jewish Home and Hospital
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Lexington Road
country: United States
facility: Triangle Medical Research
state: North Carolina
city: Winston-Salem
country: United States
facility: Boehringer Ingelheim Investigational Site
state: North Carolina
city: Beachwood
country: United States
facility: North Coast Clinical Trials, Inc.
state: Ohio
city: Cincinnati
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Ohio
city: Dayton
country: United States
facility: Midwest Clinical Research Center
state: Ohio
city: Toledo
country: United States
facility: Neurology Center of Ohio
state: Ohio
city: Oklahoma City
country: United States
facility: Linden Research Consultants
state: Oklahoma
city: Oklahoma City
country: United States
facility: Pahl Brain Associates
state: Oklahoma
city: Eugene
country: United States
facility: Oregon Center for Clinical Investigators, Inc.
state: Oregon
city: Eugene
country: United States
facility: PRO Research
state: Oregon
city: Portland
country: United States
facility: Attn: Valerie MacDonald
state: Oregon
city: Jenkintown
country: United States
facility: The Clinical Trial Center, LLC
state: Pennsylvania
city: Moon Township
country: United States
facility: Crosswords Counseling and Consulting Associates
state: Pennsylvania
city: Norristown
country: United States
facility: Pearl Clinical Research, Inc.
state: Pennsylvania
city: E. Providence
country: United States
facility: Rhode Island Mood and Memory Research Institute
state: Rhode Island
city: Providence
country: United States
facility: Butler Hospital Dept. of Neurology
state: Rhode Island
city: N Charleston.
country: United States
facility: Medical Univ. of South Carolina, Alzheimer's Research
state: South Carolina
city: Nashville
country: United States
facility: Psychiatric Consultants
state: Tennessee
city: Houston
country: United States
facility: Baylor College of Medicine VA Medical Center
state: Texas
city: Houston
country: United States
facility: University of Texas Medical Science Institute
state: Texas
city: Lubbock
country: United States
facility: Caprock Clinical Trials Center
state: Texas
city: San Antonio
country: United States
facility: Integra Clinical Research
state: Texas
city: Wichita Falls
country: United States
facility: Grayline Clinical Drug Trials
state: Texas
city: Bennington
country: United States
facility: The Memory Clinic/Southwestern Vermont Medical Center
state: Vermont
city: Charlottesville
country: United States
facility: UVA Dept. of Neurology
state: Virginia
city: Waukesha
country: United States
facility: Independent Psychiatric Consultants
state: Wisconsin
city: Vancouver
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: British Columbia
city: Winnipeg
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Manitoba
city: Moncton
country: Canada
facility: Infectious Disease
state: New Brunswick
city: London
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Ontario
city: Beaconsfield
country: Canada
facility: Clinical Research Consultant Group
state: Quebec
city: Greenfield Park
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Quebec
city: Regina
country: Canada
facility: Pasqua Hospital
state: Saskatchewan
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim Study Coordinator
role: STUDY_CHAIR
References: