Evaluation of Ezetimibe and Atorvastatin Coadministration Versus Atorvastatin or Rosuvastatin Monotherapy in Japanese Patients With Hypercholesterolemia (Study P06027)(COMPLETED)

Ezetimibe Phase IV Clinical Study in Patients With Hypercholesterolemia

The purpose of this study is to evaluate the efficacy and safety of atorvastatin 10 mg and ezetimibe 10 mg coadministration in Japanese participants with hypercholesterolemia whose low-density lipoprotein (LDL)-cholesterol levels have not reached the lipid management target value with atorvastatin 10 mg alone, versus increasing the dose of atorvastatin to 20 mg or changing to rosuvastatin 2.5 mg.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 125
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• atorvastatin 10 mg monotherapy for 4 weeks or longer before the start of the 4-week washout and low density lipoprotein-cholesterol (LDL-C) levels that had not reached the following lipid management target values during treatment: Category I (low-risk group) with no other risk factors - LDL-C <160 mg/dL; Category II (mid-risk group) with 1-2 risk factors other than LDL-C levels - LDL-C <140 mg/dL; Category III (high-risk group) with 3 or more other risk factors - LDL-C <120 mg/dL; and for participants with history of coronary artery disease - LDL-C <100 mg/dL.
• outpatient men or women, age 20 years and older

Exclusion Criteria:

• fasted triglyceride level at the start of washout or treatment period exceeding 400 mg/dL.
• homozygous familial hypercholesterolemia.
• creatine phosphokinase (CPK) >2 times the upper limit of normal (X ULN) at start of washout or treatment period.
• glycosylated hemoglobin (HbA1c) >=8％ at start of washout or treatment period.
• severe hepatic function disorder, or aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2X ULN at start of washout or treatment period.
• hypersensitivity to ezetimibe, atorvastatin, or rosuvastatin tablets.
• pregnant or lactating
• discontinued use of atorvastatin 10 mg for less than 4 weeks at start of treatment period (however, if participant had taken atorvastatin 10 mg before the test conducted at the start of the observation period, a period of discontinuation of 27 days is allowed.)
• cyclosporine treatment
• hyperlipidemia associated with hypothyroidism, obstructive gall bladder or biliary disease, chronic renal failure, and/or pancreatitis.
• hyperlipidemia associated with drug administration that causes adverse serum lipid effects.
• participation in a clinical study within 4 weeks of washout
• cancer or cancer history within previous 5 years, except for successfully treated basal cell carcinoma of the skin.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ezetimibe + Atorvastatin; Participants with hypercholesterolemia receiving atorvastatin 10 mg and ezetimibe 10 mg for 12 weeks after a 4-week washout and 4 weeks of daily atorvastatin 10 mg	Drug: Ezetimibe; 1 tablet of 10 mg daily for 12 weeks (Weeks 5-16); Other Names: SCH 058235; Drug: Atorvastatin; 1 tablet of 10 mg daily for 12 weeks (Weeks 5-16); Drug: Atorvastatin; 2 tablets of 10 mg daily for 12 weeks (Weeks 5-16)
Active Comparator: Atorvastatin; Participants with hypercholesterolemia receiving atorvastatin 20 mg for 12 weeks after a 4-week washout and 4 weeks of daily atorvastatin 10 mg	Drug: Atorvastatin; 1 tablet of 10 mg daily for 12 weeks (Weeks 5-16); Drug: Atorvastatin; 2 tablets of 10 mg daily for 12 weeks (Weeks 5-16)
Active Comparator: Rosuvastatin; Participants with hypercholesterolemia receiving rosuvastatin 2.5 mg for 12 weeks after a 4-week washout and 4 weeks of daily atorvastatin 10 mg	Drug: Rosuvastatin; 1 tablet of 2.5 mg daily for 12 weeks (Weeks 5-16)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change in Low-Density Lipoprotein - Cholesterol (LDL-C) Values	LDL-C was measured before group study drug administration (Week 4, end of atorvastatin single therapy) and at the end of study drug administration (after 12 weeks of study drug treatment, or at discontinuation).	End of Week 4 to Week 16 or discontinuation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change in LDL-C	LDL-C was measured at the start of the atorvastatin 10 mg treatment period (end of the washout period) and at the end of administration of the study drug (Week 16 or discontinuation).	End of washout period to Week 16 or discontinuation
Number of Participants Whose LDL-C Levels Reached the Lipid Management Target Values	LDL-C was measured at the end of administration of the study drug (Week 16 or discontinuation). Target values: For participants with history of coronary artery disease: <100 mg/dL; for participants with at least 3 cardiovascular (CV) risk factors: <120 mg/dL; for participants with 1-2 CV risk factors: <140 mg/dL; for participants with no CV risk factors: <160 mg/dL.	Week 16 or discontinuation
Percent Change in Total Lipids and High Sensitivity C-reactive Protein (Hs-CRP)	Total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), non-HDL-C, and hs-CRP were measured at 4 weeks after the start of the treatment period (after completion of administration of atorvastatin 10 mg alone) and at Week 16 or at discontinuation.	End of Week 4 to Week 16 or discontinuation
Percent Change in Total Lipids and Hs-CRP	Total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), non-HDL-C, and hs-CRP were measured at the start of the treatment period (at start of administration of atorvastatin 10 mg alone) and at the end of study drug (Week 16 or discontinuation).	End of washout to Week 16 or discontinuation

Collaborators and Investigators

• Sponsor: Organon and Co

Publications and helpful links

General Publications

• Teramoto T, Sawada T, Iwamoto K, Daida H. Clinical Efficacy and Tolerability of Ezetimibe in Combination With Atorvastatin in Japanese Patients With Hypercholesterolemia-Ezetimibe Phase IV Randomized Controlled Trial in Patients With Hypercholesterolemia. Curr Ther Res Clin Exp. 2012 Feb;73(1-2):16-40. doi: 10.1016/j.curtheres.2012.02.002.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2009
• Primary Completion (Actual): May 1, 2010
• Study Completion (Actual): May 1, 2010

Study Registration Dates

• First Submitted: March 26, 2009
• First Submitted That Met QC Criteria: March 27, 2009
• First Posted (Estimate): March 30, 2009

Study Record Updates

• Last Update Posted (Actual): February 22, 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; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin; Rosuvastatin Calcium; Ezetimibe
• Other Study ID Numbers: P06027

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf

http://engagezone.msd.com/ds_documentation.php