Long-Term Safety and Tolerability of Ezetimibe (SCH 58235, MK-0653) With Atovastatin (P02154, MK-0653-017)

Long-Term, Safety and Tolerability Study of SCH 58235 or Placebo in Addition to Atorvastatin in Subjects With Primary Hypercholesterolemia

The purpose of this study is to examine the long-term safety and tolerability of ezetimibe (SCH 58235) 10 mg once daily or placebo in combination with atorvastatin (10 to 80 mg/day) for up to 12 consecutive months in participants with primary hypercholesterolemia.

Study Overview

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

Detailed Description

This study is a long-term extension study of the protocol P00692 parent study.

• Study Type: Interventional
• Enrollment (Anticipated): 400
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 86 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Has successfully completed the 12-week double-blind, efficacy and safety parent study (P00692).
• If female, has a negative pregnancy test prior to study entry and, if of childbearing potential, agrees to practice an effective barrier method of birth control for the duration of the study and for 30 days after the last statin dose.
• If postmenopausal female receiving hormone therapy, a stable estrogen (ERT), estrogen/progestin (HRT) or raloxifene regimen must be maintained during the study period.
• Is willing to continue to follow their prescribed National Cholesterol Education Program (NCEP) Step 1 diet for the duration of the study.

Exclusion Criteria:

• Has discontinued from the parent study (P00692) prior to study completion.
• Is in a situation, or has any condition which, in the opinion of the investigator may interfere with optimal participation.
• Is a pregnant or lactating female.
• Is human immunodeficiency virus (HIV) positive.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo + Atorvastatin; Participants who received placebo in the parent study (P00692) receive placebo (blinded) + atorvastatin (10 mg/day; open-label) in this study.	Drug: Atovastatin; Atorvastatin 10, 20, and 40 mg tablets at a daily dose of 10 to 80 mg; Drug: Placebo; Placebo tablets matched to ezetimibe
EXPERIMENTAL: Ezetimibe + Atorvastatin; Participants who received ezetimibe + atorvastatin, or atorvastatin alone, in the parent study (P00692) receive ezetimibe (blinded) + atorvastatin (10 mg/day; open-label) in this study.	Drug: Atovastatin; Atorvastatin 10, 20, and 40 mg tablets at a daily dose of 10 to 80 mg; Drug: Ezetimibe; Ezetimibe 10 mg tablets; Other Names: SCH 58235

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of Participants Experiencing ≥1 Adverse Event (AE)	Up to 12 months
Percentage of Participants Discontinuing from Study Treatment due to an Adverse Event (AE)	Up to 12 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Mean Percent Change from Baseline in Low-Density Lipoprotein Cholesterol (LDL-C)	Baseline and 1.5, 3, 6, 9, and 12 months
Mean Percent Change from Baseline in High-Density Lipoprotein Cholesterol (HDL-C)	Baseline and 1.5, 3, 6, 9, and 12 months
Mean Percent Change from Baseline in Triglyceride Levels	Baseline and 1.5, 3, 6, 9, and 12 months
Mean Percent Change from Baseline in Total Cholesterol (TC)	Baseline and 1.5, 3, 6, 9, and 12 months
Mean Percent Change from Baseline in Calculated Low-Density Lipoprotein Cholesterol (LDL-C)	Baseline and 1.5, 3, 6, 9, and 12 months

Collaborators and Investigators

• Sponsor: Organon and Co

Publications and helpful links

General Publications

• Ballantyne CM, Lipka LJ, Sager PT, Strony J, Alizadeh J, Suresh R, Veltri EP. Long-term safety and tolerability profile of ezetimibe and atorvastatin coadministration therapy in patients with primary hypercholesterolaemia. Int J Clin Pract. 2004 Jul;58(7):653-8. doi: 10.1111/j.1368-5031.2004.00278.x.

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 2, 2001
• Primary Completion (ACTUAL): August 8, 2002
• Study Completion (ACTUAL): August 8, 2002

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: Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Hypercholesterolemia; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Ezetimibe
• Other Study ID Numbers: P02154 (OTHER: Schering-Plough Protocol Number); MK-0653-017 (OTHER: Merck Protocol Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No