Effects of Ezetimibe on the Absorption of Oxidized Cholesterol

NCT00794677 | Completed Phase 4 Results

• 1 other identifier: MM6997
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hypercholesterolemia

Keywords

Hypercholesterolemia; Oxysterol; Ezetimibe; Zetia

Outcome Measures

Primary Outcomes (1)

• Log[Area-under-the-plasma-concentration-curve(AUC) 0-8 Hours 7-ketocholesterol] After an Oral Bolus

  Log of Area-under-the-plasma-concentration curve (AUC 0-8hrs) of 7-ketocholesterol after an oral bolus in patients with primary hypercholesterolemia after treatment with ezetimibe versus placebo

  6 weeks

Secondary Outcomes (1)

• Log(Maximal Plasma Concentration (Cmax) of 7-ketocholesterol) After an Oral Bolus

  6 weeks

Other Outcomes (7)

• Log(Fasting Plasma Levels of Diet-derived Oxysterols (7-ketocholesterol))

  6 weeks

• Log (AUC of Plasma Total Cholesterol) After an Oral Bolus

  6 weeks

• Log (AUC of Plasma Triglyceride) After an Oral Bolus

  6 weeks

Study Arms (2)

Sugar Pill

PLACEBO COMPARATOR

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: placebo

ezetimibe

EXPERIMENTAL

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

Interventions

ezetimibe DRUG

Blinded study medication (ezetimibe 10 mg 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.

Also known as: Zetia

ezetimibe

placebo DRUG

Blinded study medication (matched placebo) 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.

Also known as: Sugar Pill

Sugar Pill

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• UCSF Benioff Children's Hospital Oakland: lead
• Merck Schering-Plough: collaborator

Study Sites (1)

Cholesterol Research Center

Berkeley, California, 94705, United States

Location

MeSH Terms

Conditions

Hypercholesterolemia

Interventions

Ezetimibe; Sugars

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Azetidines; Azetines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Carbohydrates

Results Point of Contact

• Title: Ronald M Krauss
• Organization: Children's Hospital Oakland Research Institute

rkrauss@chori.org

510.450.7912

Study Officials

• Ronald M Krauss, M.D.

  UCSF Benioff Children's Hospital Oakland

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2008
• First Posted: November 20, 2008
• Study Start: June 1, 2006
• Primary Completion: February 1, 2008
• Study Completion: September 1, 2008
• Last Updated: March 9, 2021
• Results First Posted: September 4, 2009

Record last verified: 2021-02

Locations

US (1)