A Long-term Safety and Tolerability Study of Ezetimibe Plus Atorvastatin in Participants With Coronary Heart Disease, Multiple Risk Factors, or Hypercholesterolemia Not Controlled by Atorvastatin (P01418/MK-0653-032)

Long-Term, Open-Label, Safety and Tolerability Study of Ezetimibe (SCH 58235) in Addition to Atorvastatin in Subjects With Coronary Heart Disease or Multiple Risk Factors and With Primary Hypercholesterolemia Not Controlled by a Starting Dose (10 mg) of Atorvastatin

The purpose of this study was to evaluate the long-term safety and tolerability of ezetimibe 10 mg once daily co-administered with atorvastatin 10 to 80 mg daily for up to 12 consecutive months in participants with heterozygous familial hypercholesterolemia (HeFH) or in participants with coronary heart disease (CHD) or multiple cardiovascular risk factors and primary hypercholesterolemia not controlled by a starting dose (10 mg daily) of atorvastatin.

Study Overview

• Status: Completed
• Conditions: Hypercholesterolemia
• Intervention / Treatment: Drug: Ezetimibe; Drug: Atorvastatin

Detailed Description

Adult participants with a diagnosis of HeFH or CHD or multiple risk factors (≥2) and with primary hypercholesterolemia who had successfully completed the 14-week, double-blind efficacy and safety study of ezetimibe co-administered with atorvastatin (Protocol No. P00693/MK-0653-030; NCT03867318) were eligible for enrollment in this long-term extension study.

• Study Type: Interventional
• Enrollment (Actual): 432
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Participants who have successfully completed the 14-week double-blind, efficacy and safety study of SCH 58235 in addition to atorvastatin in participants with CHD or multiple risk factors or HeFH, (Protocol P00693/MK-0653-030; NCT03867318). Entry into this protocol must occur at the time of completion of Protocol P00693/MK-0653-030; NCT03867318
• All women must have a negative pregnancy test prior to study entry. Women of child bearing potential must agree to practice an effective barrier method of birth control for the duration of the study. In addition, participants must agree to practice an effective barrier method of birth control for 30 days following the last dose of atorvastatin administered
• Postmenopausal women who are receiving postmenopausal hormonal therapy or raloxifene must be maintained on a stable estrogen (ERT), estrogen/progestin (HRT) or raloxifene regimen during study period

Exclusion Criteria:

• Participants who discontinued from the Protocol P00693 due to adverse events or poor compliance
• Pregnant or lactating women
• Participants who are known to be HIV positive

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Ezetimibe 10 mg + Atorvastatin; Ezetimibe 10 mg plus atorvastatin 10 to 80 mg daily for up to 12 months

Drug: Ezetimibe; Ezetimibe 10 mg daily in the morning; Other Names: MK-0653; SCH 058235; Zetia®; Drug: Atorvastatin; Atorvastatin 10 mg daily in the morning. Atorvastatin dose could be titrated up (by doubling the dose up to a maximum of 80 mg daily) to achieve the target low-density-lipoprotein cholesterol (LDL-C) level of 100 mg/dL (2.59 mmol/L) after a minimum of 4 weeks of treatment.; Other Names: Lipitor®; SCH 412387; MK-9396

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of participants who experienced an adverse event	Up to 12 months
Number of participants who discontinued study drug due to an adverse event	Up to 12 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Percentage of participants achieving target LDL-C level (≤100 mg/dL)	Up to 12 months
Change from baseline in LDL-C levels	Up to 12 months
Change from baseline in HDL-C levels	Up to 12 months
Change from baseline in triglyceride levels	Up to 12 months

Collaborators and Investigators

• Sponsor: Organon and Co

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 6, 2000
• Primary Completion (ACTUAL): February 4, 2003
• Study Completion (ACTUAL): February 4, 2003

Study Registration Dates

• First Submitted: March 19, 2019
• First Submitted That Met QC Criteria: March 19, 2019
• First Posted (ACTUAL): March 20, 2019

Study Record Updates

• Last Update Posted (ACTUAL): February 17, 2022
• Last Update Submitted That Met QC Criteria: February 7, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Heart Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Hypercholesterolemia; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin; Ezetimibe
• Other Study ID Numbers: P01418 (OTHER: Merck); MK-0653-032 (OTHER: Merck)