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

This study has been completed.
Sponsor:
Information provided by:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00153010
First received: September 9, 2005
Last updated: October 28, 2013
Last verified: October 2013
  Purpose

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.


Condition Intervention Phase
Alzheimer Disease
Drug: NS 2330 (Tesofensine)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Changes in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) [ Time Frame: week 0, 4, 9, 14 and 20 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change [ Time Frame: weeks 0 and 14 ] [ Designated as safety issue: No ]
  • Alzheimer's Disease Cooperative Study-Activities of Daily Living [ Time Frame: weeks 0, 4, and 14 ] [ Designated as safety issue: No ]
  • Neuropsychiatric Inventory [ Time Frame: weeks 0, 4, and 14 ] [ Designated as safety issue: No ]
  • Mini-Mental State Examination [ Time Frame: weeks 0 and 14 ] [ Designated as safety issue: No ]
  • ADAS-Cog Extension [ Time Frame: weeks 0, 4, 9, 14 and 20 ] [ Designated as safety issue: No ]
  • ADAS-Cog total score including Extension [ Time Frame: weeks 0, 4, and 14 ] [ Designated as safety issue: No ]
  • types and frequencies of adverse events [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]
  • proportion of patients discontinued from the trial because of adverse events [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]
  • changes from baseline in vital signs [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]
  • changes from baseline in laboratory measurements [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]
  • changes from baseline in ECG readings [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]
  • comparison of study groups for drug plasma concentrations [ Time Frame: weeks 0, 4, 9, 14 and 20 ] [ Designated as safety issue: No ]
  • population PK parameters [ Time Frame: Weeks 0, 4, 9, 14 and 20 ] [ Designated as safety issue: No ]

Enrollment: 430
Study Start Date: February 2003
Primary Completion Date: March 2005 (Final data collection date for primary outcome measure)
  Eligibility

Ages Eligible for Study:   40 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00153010

  Show 87 Study Locations
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Study Coordinator Boehringer Ingelheim
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00153010     History of Changes
Obsolete Identifiers: NCT00055406
Other Study ID Numbers: 1198.52
Study First Received: September 9, 2005
Last Updated: October 28, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Alzheimer Disease
Brain Diseases
Central Nervous System Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Dementia
Mental Disorders
Nervous System Diseases
Neurodegenerative Diseases
Tauopathies

ClinicalTrials.gov processed this record on November 27, 2014