MK0653C in High Cardiovascular Risk Patients With High Cholesterol (Switch Study)(MK-0653C-162)

NCT01154036 | Completed Phase 3 Results

• 2 other identifiers: 0653C-1622010_517
• Study Type: interventional
• Target: 1,547
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study will compare the lipid-altering efficacy and safety of switching to co-administration of ezetimibe and atorvastatin versus treatment with atorvastatin or rosuvastatin in high cardiovascular risk patients with hypercholesterolemia who have not achieved specified low-density lipoprotein cholesterol (LDL-C) levels. The primary hypothesis is that the co-administration of ezetimibe 10 mg and atorvastatin 10 mg will be superior to both atorvastatin 20 mg and rosuvastatin 10 mg with respect to the percentage reduction in low-density lipoprotein-cholesterol (LDL-C) after 6 weeks of treatment.

Conditions

Hypercholesterolemia

Outcome Measures

Primary Outcomes (1)

• Percent Change From Baseline in Low-Density Lipoprotein-Cholesterol (LDL-C) (Phase I)

  LDL-C levels measured at Baseline and after 6 weeks of treatment (Week 6; end of Phase I). Baseline was defined as the average value of the measurements taken at Visits 3 and 4. LDL-C was calculated using the Friedewald method when triglyceride (TG)\<350 mg/dL (3.95 mmol/L) and beta quantification ultracentrifugation when TG≥350 mg/dL (3.95 mmol/L).

  Baseline and Week 6 (end of Phase I )

Secondary Outcomes (27)

• Percent Change From Baseline in Low-Density Lipoprotein-Cholesterol (LDL-C) (Phase II).

  Baseline (Week 6) and Week 12

• Percentage of Participants That Reach Target LDL-C Level of < 100 mg/dL (Phase I)

  Week 6 (End of Phase I)

• Percentage of Participants That Reach Target LDL-C Level of < 100 mg/dL (Phase II)

  Week 12 (End of Phase II)

• Percentage of Participants That Reach Target LDL-C Level of < 70 mg/dL (Phase I)

  Week 6 (End of Phase I)

• Percentage of Participants That Reach Target LDL-C Level of < 70 mg/dL (Phase II)

  Week 12 (end of Phase II)

Study Arms (8)

Phase I: ezetimibe (EZ) 10 mg + atorvastatin (Atorva) 10 mg

EXPERIMENTAL

Co-administration of EZ 10 mg tablet + Atorva 10 mg tablet; once daily for 6 weeks

Drug: ezetimibe 10 mg; Drug: atorvastatin

Phase I: Atorvastatin 20 mg

ACTIVE COMPARATOR

Atorvastatin 20 mg tablet once daily for 6 weeks

Drug: atorvastatin

Phase I: Rosuvastatin 10 mg

ACTIVE COMPARATOR

Rosuvastatin 10 mg tablet once daily for 6 weeks

Drug: Comparator: rosuvastatin

Phase II: EZ 10mg+Atorva 10mg

EXPERIMENTAL

Participants who had previously received EZ 10 mg + Atorva 10 mg in Phase I and continued on EZ 10 mg + Atorva 10 mg once daily for 6 weeks during Phase II regardless of whether or not LDL-C goals were achieved in Phase I

Drug: ezetimibe 10 mg; Drug: atorvastatin

Phase II: EZ 10mg + Atorva 20mg [A]

EXPERIMENTAL

Participants who had previously received Atorva 20 mg in Phase I and did not reach LDL-C goal and were switched to EZ 10 mg + Atorva 20 mg once daily for 6 weeks in Phase II

Drug: ezetimibe 10 mg; Drug: atorvastatin

Phase II: Atorva 40mg

ACTIVE COMPARATOR

Participants who had previously received Atorva 20 mg in Phase I and did not reach LDL-C goal and were switched Atorva 40 mg once daily for 6 weeks in Phase II

Drug: atorvastatin

Phase II: EZ 10mg + Atorva 20mg [R]

EXPERIMENTAL

Participants who had previously received Rosuvastatin 10 mg in Phase I and did not reach LDL-C goal and received EZ 10 mg + Atorva 20 mg once daily for 6 weeks in Phase II

Drug: ezetimibe 10 mg; Drug: atorvastatin

Phase II: Rosuvastatin 20mg

ACTIVE COMPARATOR

Participants who had previously received Rosuvastatin 10 mg in Phase I and did not reach LDL-C goal and were switched to Rosuvastatin 20 mg once daily for 6 weeks in Phase

Drug: Comparator: rosuvastatin

Interventions

ezetimibe 10 mg DRUG

Phase I: ezetimibe (EZ) 10 mg + atorvastatin (Atorva) 10 mg; Phase II: EZ 10mg + Atorva 20mg [A]; Phase II: EZ 10mg + Atorva 20mg [R]; Phase II: EZ 10mg+Atorva 10mg

atorvastatin DRUG

Phase I: Atorvastatin 20 mg; Phase I: ezetimibe (EZ) 10 mg + atorvastatin (Atorva) 10 mg; Phase II: Atorva 40mg; Phase II: EZ 10mg + Atorva 20mg [A]; Phase II: EZ 10mg + Atorva 20mg [R]; Phase II: EZ 10mg+Atorva 10mg

Comparator: rosuvastatin DRUG

Phase I: Rosuvastatin 10 mg; Phase II: Rosuvastatin 20mg

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient is at high cardiovascular risk and meets one of the following conditions: has never taken lipid-lowering therapy or has been off such therapy for at least 6 weeks; or, is currently taking a stable dose of certain lipid-lowering agents
• Patient is willing to maintain a cholesterol lowering diet during the study
• Female patients receiving non-cyclical hormone therapy have maintained a stable dose and regimen for at least 8 weeks and are willing to continue the same regimen during the study

You may not qualify if:

• Patient is Asian
• Patient routinely has more than 2 alcoholic drinks per day
• Female patient is pregnant or breastfeeding
• Patient has congestive heart failure
• Patient has had a myocardial infarction, coronary bypass surgery, angioplasty, or acute coronary syndrome within 3 months of screening
• Patient has uncontrolled cardiac arrhythmias
• Patient has had a partial ileal or gastric bypass or other significant intestinal malabsorption
• Patient has uncontrolled high blood pressure
• Patient has kidney disease
• Patient has any disease known to influence blood lipid levels
• Patient has any disorders of the blood, digestive system, or nervous system including stroke and degenerative disease that would limit study participation
• Patient has poorly controlled or newly diagnosed diabetes
• Patient is known to be HIV positive
• Patient has a history of cancer in the last 5 years, except certain skin and cervical cancers

Sponsors & Collaborators

• Organon and Co: lead

Related Publications (2)

• Krempf M, Simpson RJ Jr, Ramey DR, Brudi P, Giezek H, Tomassini JE, Lee R, Farnier M. Patient and physician factors influence decision-making in hypercholesterolemia: a questionnaire-based survey. Lipids Health Dis. 2015 May 19;14:45. doi: 10.1186/s12944-015-0037-y.

  PMID: 25985907 DERIVED

• Bays HE, Averna M, Majul C, Muller-Wieland D, De Pellegrin A, Giezek H, Lee R, Lowe RS, Brudi P, Triscari J, Farnier M. Efficacy and safety of ezetimibe added to atorvastatin versus atorvastatin uptitration or switching to rosuvastatin in patients with primary hypercholesterolemia. Am J Cardiol. 2013 Dec 15;112(12):1885-95. doi: 10.1016/j.amjcard.2013.08.031. Epub 2013 Sep 21.

  PMID: 24063830 DERIVED

MeSH Terms

Conditions

Hypercholesterolemia

Interventions

Ezetimibe; Atorvastatin

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; Pyrroles; Azoles; Heptanoic Acids; Fatty Acids; Lipids

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Monitor

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 29, 2010
• First Posted: June 30, 2010
• Study Start: July 1, 2010
• Primary Completion: September 1, 2012
• Study Completion: October 1, 2012
• Last Updated: February 9, 2022
• Results First Posted: February 12, 2014

Record last verified: 2022-02