An Evaluation of Three Doses of NS 2330 in Patients With Mild to Moderate Dementia of the Alzheimer's Type

Alzheimer Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00153010
• Other study ID #: 1198.52
• Status: Completed
• Phase: Phase 2
• First received: September 9, 2005
• Last updated: October 28, 2013
• Start date: February 2003

Study information

• Verified date: October 2013
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Other known NCT identifiers

• NCT00055406

Recruitment information / eligibility

• Status: Completed
• Enrollment: 430
• Est. primary completion date: March 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years to 85 Years

Eligibility

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.

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Alzheimer Disease

Intervention

Drug:
• NS 2330 (Tesofensine)

Locations

Country	Name	City	State
Canada	Clinical Research Consultant Group	Beaconsfield	Quebec
Canada	Boehringer Ingelheim Investigational Site	Greenfield Park	Quebec
Canada	Boehringer Ingelheim Investigational Site	London	Ontario
Canada	Infectious Disease	Moncton	New Brunswick
Canada	Pasqua Hospital	Regina	Saskatchewan
Canada	Boehringer Ingelheim Investigational Site	Vancouver	British Columbia
Canada	Boehringer Ingelheim Investigational Site	Winnipeg	Manitoba
United States	Neurological Associates of Albany	Albany	New York
United States	Upstate Clinical Research	Albany	New York
United States	Albuquerque Neuroscience	Albuquerque	New Mexico
United States	Dent Neurologic Institute	Amherst	New York
United States	Atlanta Center for Medical Research	Atlanta	Georgia
United States	North Coast Clinical Trials, Inc.	Beachwood	Ohio
United States	The Memory Clinic/Southwestern Vermont Medical Center	Bennington	Vermont
United States	Boehringer Ingelheim Investigational Site	Berkeley	California
United States	Baumel-Eisner Neuromedical Institute	Boca Raton	Florida
United States	UVA Dept. of Neurology	Charlottesville	Virginia
United States	Peryam and Kroll Healthcare Research	Chicago	Illinois
United States	Boehringer Ingelheim Investigational Site	Cincinnati	Ohio
United States	University of Missouri	Columbia	Missouri
United States	California Clinical Trials Medical Group	Culver City	California
United States	Associated Neurologists PC - Danbury	Danbury	Connecticut
United States	Midwest Clinical Research Center	Dayton	Ohio
United States	Duke University Medical Center	Durham	North Carolina
United States	Rhode Island Mood and Memory Research Institute	E. Providence	Rhode Island
United States	Oregon Center for Clinical Investigators, Inc.	Eugene	Oregon
United States	PRO Research	Eugene	Oregon
United States	Hartford Research Group	Florence	Kentucky
United States	Baumel-Eisner Neuromedical Institute	Fort Lauderdale	Florida
United States	Neurologic Consulting/PA	Fort Lauderdale	Florida
United States	Clinical Physiology Associates Study Center	Fort Meyers	Florida
United States	Margolin Brain Institute	Fresno	California
United States	Care@ Granada Hills Community Hospital	Granada Hills	California
United States	Center for Geriatric & Adult Psychiatry	Hamden	Connecticut
United States	Berma Research Group	Hialeah	Florida
United States	Sunrise Clinical Research	Hollywood	Florida
United States	Baylor College of Medicine VA Medical Center	Houston	Texas
United States	University of Texas Medical Science Institute	Houston	Texas
United States	Agewell, Ltd.	Indianapolis	Indiana
United States	University of Iowa College of Medicine	Iowa City	Iowa
United States	The Clinical Trial Center, LLC	Jenkintown	Pennsylvania
United States	LaGrange Hospital	LaGrange	Illinois
United States	Optimum Health Services	LaMesa	California
United States	University of Nevada School of Medicine	Las Vegas	Nevada
United States	Associates in Neurology-Research	Lexington	Kentucky
United States	Triangle Medical Research	Lexington Road	North Carolina
United States	Caprock Clinical Trials Center	Lubbock	Texas
United States	Pivotal Research Center	Mesa	Arizona
United States	Baumel-Eisner Neuromedical Institute	Miami	Florida
United States	Miami Jewish Home and Hospital for the Aged	Miami	Florida
United States	Crosswords Counseling and Consulting Associates	Moon Township	Pennsylvania
United States	Medical Univ. of South Carolina, Alzheimer's Research	N Charleston.	South Carolina
United States	Segal Institute for Clinical Research	N. Miami	Florida
United States	Psychiatric Consultants	Nashville	Tennessee
United States	Louisiana State University Medical Center	New Orleans	Louisiana
United States	Eastside Comprehensive Medical Services	New York	New York
United States	Social Psychiatry Research Institute	New York	New York
United States	The Jewish Home and Hospital	New York	New York
United States	Pearl Clinical Research, Inc.	Norristown	Pennsylvania
United States	Magnolia Research Group	Ocala	Florida
United States	Optimum Health Services	Oceanside	California
United States	Linden Research Consultants	Oklahoma City	Oklahoma
United States	Pahl Brain Associates	Oklahoma City	Oklahoma
United States	Pivotal Research Center	Peoria	Arizona
United States	Xenoscience	Phoenix	Arizona
United States	Memory Disorder Clinic	Pompano Beach	Florida
United States	Attn: Valerie MacDonald	Portland	Oregon
United States	Butler Hospital Dept. of Neurology	Providence	Rhode Island
United States	Southwest Institute for Clinical Research	Rancho Mirage	California
United States	Saginaw Cooperative Hosp. Inc./ Internal medicine	Saginaw	Michigan
United States	Integra Clinical Research	San Antonio	Texas
United States	Health Quest Clinical Trials	San Diego	California
United States	Institute on Aging Research Center	San Francisco	California
United States	Attn: M. Lannom, RN, MS	Sharon	Massachusetts
United States	Future Care Studies	Springfield	Massachusetts
United States	St. Louis University	St. Louis	Missouri
United States	Boehringer Ingelheim Investigational Site	Tampa	Florida
United States	USF Suncoast Gerontology Center	Tampa	Florida
United States	Neurology Center of Ohio	Toledo	Ohio
United States	Atlantic Coast Research	Tom's River	New Jersey
United States	Torrance Clinical Research	Torrance	California
United States	North Michigan Neurology	Traverse City	Michigan
United States	Palm Beach Neurology/Premier Research Institute	W. Palm Beach	Florida
United States	Independent Psychiatric Consultants	Waukesha	Wisconsin
United States	Grayline Clinical Drug Trials	Wichita Falls	Texas
United States	Neurology Associates PA	Wilmington	Delaware
United States	Boehringer Ingelheim Investigational Site	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog)		week 0, 4, 9, 14 and 20	No
Secondary	Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change		weeks 0 and 14	No
Secondary	Alzheimer's Disease Cooperative Study-Activities of Daily Living		weeks 0, 4, and 14	No
Secondary	Neuropsychiatric Inventory		weeks 0, 4, and 14	No
Secondary	Mini-Mental State Examination		weeks 0 and 14	No
Secondary	ADAS-Cog Extension		weeks 0, 4, 9, 14 and 20	No
Secondary	ADAS-Cog total score including Extension		weeks 0, 4, and 14	No
Secondary	types and frequencies of adverse events		20 weeks	No
Secondary	proportion of patients discontinued from the trial because of adverse events		20 weeks	No
Secondary	changes from baseline in vital signs		20 weeks	No
Secondary	changes from baseline in laboratory measurements		20 weeks	No
Secondary	changes from baseline in ECG readings		20 weeks	No
Secondary	comparison of study groups for drug plasma concentrations		weeks 0, 4, 9, 14 and 20	No
Secondary	population PK parameters		Weeks 0, 4, 9, 14 and 20	No