Ezetimibe (SCH 58235) Taken With Either Atorvastatin or Simvastatin in Participants With Familial Hypercholesterolemia (MK-0653-018)

• ClinicalTrials.gov Identifier: NCT03884452
• Recruitment Status: Completed
• First Posted: March 21, 2019
• Last Update Posted: June 13, 2019
• Sponsor: Merck Sharp & Dohme Corp.
• Information provided by (Responsible Party): Merck Sharp & Dohme Corp.

Study Description

Brief Summary:

The primary objective of this study is to evaluate the efficacy and the safety of ezetimibe (SCH 58235) co-administered with either atorvastatin or simvastatin in participants with homozygous familial hypercholesterolemia (FH).

Condition or disease	Intervention/treatment	Phase
Familial Hypercholesterolemia	Drug: Atorvastatin; Drug: Simvastatin; Drug: Ezetimibe; Drug: Placebo for Ezetimibe	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 50 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase III Efficacy And Safety Study of Ezetimibe (SCH58235) 10 mg in Addition to Atorvastatin or Simvastatin in the Therapy of Homozygous Familial Hypercholesterolemia
• Actual Study Start Date: May 3, 2000
• Actual Primary Completion Date: May 24, 2001
• Actual Study Completion Date: May 24, 2001

Arms and Interventions

Arm	Intervention/treatment
Experimental: Atorvastatin 80 mg; 80 mg atorvastatin taken orally, once daily for 12 weeks	Drug: Atorvastatin; Tablets taken orally once daily in the morning; Drug: Placebo for Ezetimibe; Tablets taken orally once daily in the morning or evening
Experimental: Ezetimibe + Atorvastatin 40 mg; 10 mg ezetimibe and 40 mg atorvastatin taken orally, once daily for 12 weeks	Drug: Atorvastatin; Tablets taken orally once daily in the morning; Drug: Ezetimibe; Tablet taken orally once daily in the morning or evening
Experimental: Ezetimibe + Atorvastatin 80 mg; 10 mg ezetimibe and 80 mg atorvastatin taken orally, once daily for 12 weeks	Drug: Atorvastatin; Tablets taken orally once daily in the morning; Drug: Ezetimibe; Tablet taken orally once daily in the morning or evening
Experimental: Simvastatin 80 mg; 80 mg simvastatin taken orally, once daily for 12 weeks	Drug: Simvastatin; Tablets taken orally once daily in the morning or evening; Drug: Placebo for Ezetimibe; Tablets taken orally once daily in the morning or evening
Experimental: Ezetimibe + Simvastatin 40 mg; 10 mg ezetimibe and 40 mg simvastatin taken orally, once daily for 12 weeks	Drug: Simvastatin; Tablets taken orally once daily in the morning or evening; Drug: Ezetimibe; Tablet taken orally once daily in the morning or evening
Experimental: Ezetimibe + Simvastatin 80 mg; 10 mg ezetimibe and 80 mg simvastatin taken orally, once daily for 12 weeks	Drug: Simvastatin; Tablets taken orally once daily in the morning or evening; Drug: Ezetimibe; Tablet taken orally once daily in the morning or evening

Outcome Measures

Primary Outcome Measures :

1. Percent change from baseline in Low Density Lipoprotein Cholesterol (LDL-C) measured directly [ Time Frame: Baseline and Up to Week 12 ]
2. Percentage of participants with an Adverse Event (AE) [ Time Frame: Up to Week 12 ]

Secondary Outcome Measures :

1. Percent change from baseline in calculated LDL-C [ Time Frame: Baseline and Up to Week 12 ]
2. Percent change from baseline in Total Cholesterol (TC) [ Time Frame: Baseline and Up to Week 12 ]
3. Percent change from baseline in Triglycerides (TG) [ Time Frame: Baseline and Up to Week 12 ]
4. Percent change from baseline in High-density-lipoprotein cholesterol (HDL-C) [ Time Frame: Baseline and Up to Week 12 ]
5. Percent change from baseline in High-density-lipoprotein 2 cholesterol (HDL2-C) [ Time Frame: Baseline and Up to Week 12 ]
6. Percent change from baseline in High-density-lipoprotein 3 cholesterol (HDL3-C) [ Time Frame: Baseline and Up to Week 12 ]
7. Percent change from baseline in Apolipoprotein A-I (Apo A-I) [ Time Frame: Baseline and Up to Week 12 ]
8. Percent change from baseline in Apolipoprotein B (Apo B) [ Time Frame: Baseline and Up to Week 12 ]
9. Percent change from baseline in Lipoprotein(a) [Lp(a)] [ Time Frame: Baseline and Up to Week 12 ]

Eligibility Criteria

• Ages Eligible for Study: 12 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• With a diagnosis of homozygous familial hypercholesterolemia
• All females 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, until one month after treatment.
• 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 the study period. ERT, HRT or raloxifene cannot be changed during study period.
• Must follow prescribed or stricter diet, and demonstrate completion of Diet Diaries

Exclusion Criteria:

• A history of mental instability, drug or alcohol abuse; or have been treated or are being treated for severe psychiatric illness which, in the opinion of the Investigator, may interfere with optimal participation in the study.
• With underlying disease likely to limit life span to less than 1 year.
• Have previously been randomized in any studies examining ezetimibe
• Pregnant or lactating women.
• With known hypersensitivity or any contraindication to statin therapy.

Contacts and Locations

Sponsors and Collaborators

Merck Sharp & Dohme Corp.

Investigators

• Study Director: Medical Director; Merck Sharp & Dohme Corp.

More Information

Publications of Results:

Gagné C, Gaudet D, Bruckert E; Ezetimibe Study Group. Efficacy and safety of ezetimibe coadministered with atorvastatin or simvastatin in patients with homozygous familial hypercholesterolemia. Circulation. 2002 May 28;105(21):2469-75.

• Responsible Party: Merck Sharp & Dohme Corp.
• ClinicalTrials.gov Identifier: NCT03884452
• Other Study ID Numbers: P01030; P01030 ( Other Identifier: Schering-Plough Protocol Number ); MK-0653-018 ( Other Identifier: Merck Protocol Number )
• First Posted: March 21, 2019
• Last Update Posted: June 13, 2019
• Last Verified: June 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
• URL: http://engagezone.msd.com/ds_documentation.php

Additional relevant MeSH terms:

Hyperlipoproteinemia Type II; Hypercholesterolemia; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Hyperlipoproteinemias; Atorvastatin; Simvastatin; Ezetimibe; Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Enzyme Inhibitors