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The Safety & Efficacy of Combination BMS-201038 (AEGR-733) & Ezetimibe vs. Monotherapy in Moderate Hypercholesterolemia
This study has been completed.
First Received: November 28, 2006   No Changes Posted
Sponsors and Collaborators: University of Pennsylvania
Aegerion Pharmaceuticals, Inc.
Information provided by: University of Pennsylvania
ClinicalTrials.gov Identifier: NCT00405067
  Purpose

The main objectives of this study are to evaluate the efficacy and safety of combination therapy BMS-201038 (AEGR-733) plus ezetimibe vs. each agent given alone on LDL cholesterol and other lipoproteins over 12 weeks of therapy.


Condition Intervention Phase
Hypercholesterolemia
Drug: BMS-201038 (AEGR-733)
Drug: Ezetimibe
Phase II

Study Type: Interventional
Study Design: Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title: A Randomized, Double-Blind, Active Controlled, Parallel-Group Study to Evaluate the Safety and Efficacy of the Combination BMS-201038 (AEGR-733) and Ezetimibe vs. Monotherapy in Subjects With Moderate Hypercholesterolemia

Resource links provided by NLM:


Further study details as provided by University of Pennsylvania:

Primary Outcome Measures:
  • % LDL-C at 12 weeks therapy compared to baseline between treatments

Secondary Outcome Measures:
  • % changes at 12 weeks therapy compared to baseline between treatments for the following parameters:
  • other baseline serum lipoproteins (TC, non-HDL, VLDL, TG, HDL-C, Lp (a), apolipoproteins AI and B)
  • high sensitivity C-reactive protein
  • body weight
  • markers of safety and overall safety and tolerability.
  • Additional objectives are to characterize the safety and tolerability of BMS-201038 (AEGR-733) alone and in combination with ezetimibe.

Estimated Enrollment: 60
Study Start Date: May 2006
Estimated Study Completion Date: January 2007
Detailed Description:

Subjects will participate in this study for approximately 14-17 weeks. This study has 2 periods: 1) a 1-2-week screening period with 2 visits where baseline cholesterol and other characteristics will be evaluated to determine study eligibility. This period also includes a 4-week washout for patients on prior lipid-lowering therapies; and 2) a 12-week treatment period with interim visits at weeks 4 and 8.

Approximately 60 subjects will be randomized into one of 3 treatment arms with equal probability. In treatment arm 1, subjects will receive BMS-201038 (AEGR-733) 5 mg plus ezetimibe placebo. In treatment arm 2, subjects will receive BMS-201038 (AEGR-733) placebo plus 10 mg of ezetimibe. In treatment arm 3, subjects will receive BMS-201038 (AEGR-733) 5 mg plus ezetimibe 10 mg. After 4 weeks of treatment, subjects in arms 1 and 3 will be force-titrated to BMS-201038 (AEGR-733) 7.5 mg. After another 4 weeks of treatment, subjects in arms 1 and 3 will then be force-titrated to BMS-201038 (AEGR-733) 10 mg for 4 more additional weeks of treatment. Subjects in arm 2 will continue to receive BMS-201038 (AEGR-733) matching placebo for the entire 12 weeks of treatment.

Subjects randomized to ezetimibe 10 mg in arms 2 and 3 and ezetimibe placebo in arm 1 will remain on these doses for the entire 12-week treatment period.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Men and women between the ages of 18 and 70 years .
  2. For subjects with 0 to 1 risk factor (cigarette smoking, hypertension (BP > 140/90 or on antihypertensive medication), low HDL (<40mg/dl), family history of premature CHD (CHD in male first degree relative <55 years; CHD in female first degree relative <65 years), age (men> 45 years; women > 55 years): Baseline mean LDL-C must be >160 and <250 mg/dl as determined by the arithmetic mean of measures taken at visit 1 and 2. Fasting mean TGs should be <400 mg/dl.
  3. For subjects with 2 or more risk factors (cigarette smoking, hypertension (BP > 140/90 or on antihypertensive medication), low HDL (<40mg/dl), family history of premature CHD (CHD in male first degree relative <55 years; CHD in female first degree relative <65 years), age (men> 45 years; women > 55 years) or prior stable CHD: Baseline mean LDL-C must be >130 and <250 mg/dl as determined by the arithmetic mean of measures taken at visit 1 and 2. Fasting mean TGs should be <400 mg/dl.
  4. Able to understand and willing to comply with all study requirements, particularly the study drug regimen.
  5. Able to understand and willing to sign the Informed Consent Form.

Exclusion Criteria:

  1. Women who are pregnant or lactating or who are planning to become pregnant or women of child bearing potential who have not successfully been using acceptable contraceptive methods over the previous 3 months (e.g. intrauterine device and barrier method plus spermicide).
  2. Uncontrolled hypertension defined as: systolic blood pressure > 180 mmHg, diastolic blood pressure > 95 mmHg
  3. History of chronic renal insufficiency (serum creatinine >2.5 mg/dL)
  4. History of liver disease or transaminases above 1.5 X ULN at screening
  5. Any major surgical procedure occurring less than 3 months prior to the screening visit
  6. Cardiac insufficiency defined by the NYHA classification as functional Class II-Class IV
  7. History of a malignancy (other than basal cell or squamous cell carcinoma of the skin that has been removed) within the previous 5 years
  8. Participation in an investigational drug study within 6 weeks prior to the screening visit.
  9. Serious or unstable medical or psychological conditions that, in the opinion of the investigator, would compromise the subject’s safety or successful participation in the study.
  10. Regular alcohol use > 1 drink per day
  11. Regular consumers of grapefruit juice, or currently taking medications known to be metabolized by CYP 3A4 (cyclosporine, itraconazole, ketoconazole, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors, and nefazodone)
  12. Other lipid-lowering medications (washouts will be permitted)
  13. Acute CVD (CVD event within the previous 6 months)
  14. Diabetes Mellitus
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00405067

Locations
United States, New Jersey
Pharmanet, Inc
Princeton, New Jersey, United States, 08540-6242
Sponsors and Collaborators
University of Pennsylvania
Aegerion Pharmaceuticals, Inc.
Investigators
Principal Investigator: Michael Davidson, MD Radiant Research
Principal Investigator: Jackson Downey, MD Jacksonville Center for Clinical Research
Principal Investigator: Paul Grena, MD Cardiology Consultants of Philadelphia
Principal Investigator: Barry Lubin, MD Hampton Roads Center for Clinical Research
Principal Investigator: James McKenney, Pharm D National Clinical Research
Principal Investigator: Eli Roth, MD Sterling Research Group, LTD
  More Information

No publications provided

Study ID Numbers: AEGR-733-001
Study First Received: November 28, 2006
Last Updated: November 28, 2006
ClinicalTrials.gov Identifier: NCT00405067     History of Changes
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Pennsylvania:
Cholesterol

Study placed in the following topic categories:
Antimetabolites
Metabolic Diseases
Hyperlipidemias
Antilipemic Agents
Ezetimibe
Anticholesteremic Agents
Metabolic Disorder
Hypercholesterolemia
Dyslipidemias
Lipid Metabolism Disorders

Additional relevant MeSH terms:
Antimetabolites
Metabolic Diseases
Hyperlipidemias
Molecular Mechanisms of Pharmacological Action
Therapeutic Uses
Antilipemic Agents
Ezetimibe
Anticholesteremic Agents
Hypercholesterolemia
Pharmacologic Actions
Dyslipidemias
Lipid Metabolism Disorders

ClinicalTrials.gov processed this record on September 03, 2009