Effects of Ezetimibe on the Absorption of Oxidized Cholesterol

This study has been completed.
Sponsor:
Collaborator:
Merck Schering-Plough
Information provided by:
Children's Hospital & Research Center Oakland
ClinicalTrials.gov Identifier:
NCT00794677
First received: November 19, 2008
Last updated: July 31, 2009
Last verified: July 2009
  Purpose

The purpose of this study is to test the effects of Zetia™ (ezetimibe) 10 milligrams (mg) on the absorption of oxysterol into the blood following a meal containing oxysterol.


Condition Intervention Phase
Hypercholesterolemia
Drug: ezetimibe
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Basic Science
Official Title: A Randomized, Double-Blind, Placebo-Controlled, 2-Period, Crossover Study to Evaluate the Effects of Ezetimibe on the Plasma Appearance of 7-Ketocholesterol After an Oral Bolus in Patients With Primary Hypercholesterolemia

Resource links provided by NLM:


Further study details as provided by Children's Hospital & Research Center Oakland:

Primary Outcome Measures:
  • Log[Area-under-the-plasma-concentration-curve(AUC) 0-8 Hours 7-ketocholesterol] After an Oral Bolus [ Time Frame: Over 8 hours after 6 weeks of treatment with ezetimibe or placebo ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Log(Maximal Plasma Concentration (Cmax) of 7-ketocholesterol) After an Oral Bolus [ Time Frame: Over 8 hours after 6 weeks of treatment with ezetimibe or placebo ] [ Designated as safety issue: No ]

Enrollment: 26
Study Start Date: June 2006
Study Completion Date: September 2008
Primary Completion Date: February 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Sugar Pill
Placebo medication will be taken orally once daily in the morning on rising either during the first intervention period or the second intervention period. Single-blind ezetimibe placebo will be taken during the Run-In Period. Patients will be issued one bottle containing either active drug or placebo for each treatment period.
Drug: ezetimibe
Blinded study medication (ezetimibe 10 mg or matching placebo in tablet form) will be taken orally once daily in the morning on rising. Single-blind ezetimibe placebo will be taken during the Run-In Period. Patients will be issued one bottle containing either active drug or placebo for each treatment period.
Other Name: Zetia
Experimental: ezetimibe
10 mg medication will be taken orally once daily in the morning on rising either during the first intervention period or the second intervention period. Single-blind ezetimibe placebo will be taken during the Run-In Period. Patients will be issued one bottle containing either active drug or placebo for each treatment period.
Drug: ezetimibe
Blinded study medication (ezetimibe 10 mg or matching placebo in tablet form) will be taken orally once daily in the morning on rising. Single-blind ezetimibe placebo will be taken during the Run-In Period. Patients will be issued one bottle containing either active drug or placebo for each treatment period.
Other Name: Zetia

Detailed Description:

There are a number of cholesterol-lowering drugs available that can lower blood cholesterol to a healthier level. Zetia™ (ezetimibe) 10 mg is available by prescription for the treatment of high cholesterol. While Zetia has been shown to inhibit the absorption of dietary cholesterol into the bloodstream, its effects on oxysterol absorption from the diet have not been completely evaluated.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Not currently pregnant or lactating and is highly unlikely to conceive
  • Body Mass Index (BMI) between 20-30 kilograms per meter squared (kg/m2) inclusive.
  • Body weight, as reported by patient, stable (±2 kg) for >6 weeks
  • Plasma low density lipoprotein cholesterol (LDL-C) between 130 and 180 milligrams per deciliter (mg/dL) inclusive. Note: One retest allowed.
  • Triglyceride (TG) concentrations ≤150 mg/dL. Note: One retest allowed.
  • Fasting blood glucose <110 mg/dL and hemoglobin A1c (HbA1C) ≤ 6 percent at Visit 1. Note: One retest allowed.
  • Liver transaminases (ALT, AST) ≤1.5 x upper limit of normal (ULN) and no active liver disease. Note: One retest allowed.
  • Creatine Phosphokinase (CPK) ≤2x ULN. Note: One retest allowed.
  • Willingness to maintain a stable diet for the duration of the study.
  • Can understand and comply with study procedures and signs a written informed consent.
  • Patient is ≥80 precent compliant with dosing during Placebo Run-In Period or, in the opinion of the investigator, is able to maintain ≥80 percent therapy compliance during the active treatment period of the study.

Exclusion Criteria:

  • Lipid-lowering therapy and replacement of this therapy with study medication is considered inappropriate by the investigator.
  • Consumes an average of more than 2 alcoholic drinks per day.
  • Smokes.
  • Currently engages in a vigorous exercise regimen or intensive exercise bouts >4x per month.
  • Treated with any other investigational drug within 30 days of Visit 1.
  • Hypersensitivity or intolerance to ezetimibe or any component of this medication.
  • Any condition or situation which poses a risk to the patient or interfere with participation in the study.
  • Congestive heart failure.
  • Uncontrolled cardiac arrhythmias.
  • History of myocardial infarction, stroke, or any other clinical manifestation of coronary, cerebral, or peripheral vascular disease.
  • Uncontrolled hypertension
  • Impaired renal function, nephrotic syndrome or other clinically significant renal disease at Visit 1.
  • Active or chronic hepatobiliary or hepatic disease.
  • History of irritable bowel syndrome, ileal bypass, gastric bypass or any gastrointestinal disorder/condition associated with malabsorption.
  • Uncontrolled endocrine or metabolic disease known to influence serum lipids or lipoproteins.
  • Type I or Type II diabetes mellitus.
  • Disorders of the hematologic, digestive, or central nervous systems including cerebrovascular disease and degenerative disease that would limit study evaluation or participation.
  • Human Immunodeficiency Virus (HIV) positive.
  • History of cancer within the past 5 years (except for successfully treated basal and squamous cell carcinomas).
  • History of uncontrolled psychiatric illness or drug/alcohol abuse within the past 5 years. Individuals with psychiatric illness adequately controlled and stable on pharmacotherapy may be enrolled at the discretion of the investigator.
  • Lipid-lowering agents taken within 6 weeks and fibrates taken within 8 weeks prior to visit 3.
  • Cardiovascular medications are acceptable provided the patient has been on a stable regimen for at least 6 weeks prior to Visit 3 and indicates a willingness to continue the stable regimen for the duration of the study.
  • Supplementation with antioxidants beyond a standard multivitamin for the duration of the study.
  • Psyllium, other fiber-based laxatives, and/or over the counter (OTC) therapies known to affect serum lipid levels taken within 6 weeks of Visit 3.
  • Female patients receiving hormone replacement therapy, any estrogen antagonist/agonist or hormonal contraceptives.
  • Treatment with cyclosporine except for ophthalmic indication
  • Anti-obesity medications such as orlistat or sibutramine taken within 3 months prior to Visit 1.
  • Therapeutic doses of systemic corticosteroids except inhaled steroid therapy (for example, Pulmicort®) maintained on a stable dosing regimen for at least 6 weeks prior to randomization (Visit 3) and throughout the duration of the study
  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: NCT00794677

Locations
United States, California
Cholesterol Research Center
Berkeley, California, United States, 94705
Sponsors and Collaborators
Children's Hospital & Research Center Oakland
Merck Schering-Plough
Investigators
Principal Investigator: Ronald M Krauss, M.D. Children's Hospital & Research Center Oakland
  More Information

No publications provided

Responsible Party: Ronald Krauss, M.D., Children's Hospital Oakland Research Institute
ClinicalTrials.gov Identifier: NCT00794677     History of Changes
Other Study ID Numbers: MM6997
Study First Received: November 19, 2008
Results First Received: January 30, 2009
Last Updated: July 31, 2009
Health Authority: United States: Institutional Review Board

Keywords provided by Children's Hospital & Research Center Oakland:
Hypercholesterolemia
Oxysterol
Ezetimibe
Zetia

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

ClinicalTrials.gov processed this record on July 22, 2014