CLINICAL TRIALS PROFILE FOR VYTORIN

All Clinical Trials for VYTORIN

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00166504 ↗	Ezetimibe Plus (+) Simvastatin Versus Atorvastatin Comparative Study (0653A-092)(COMPLETED)	Completed	Merck Sharp & Dohme Corp.	Phase 4	2005-10-01	This is an efficacy and safety study of Vytorin (ezetimibe (+) simvastatin) compared to atorvastatin (ezetimibe/simvastatin) at week 6 in primary hypercholesterolemia patients in Korea. The primary hypothesis being tested is that daily administration of Vytorin will result in a greater reduction of low density lipoprotein cholesterol (LDL-C) concentration from baseline after 6 weeks treatment compared to atorvastatin.
NCT00202878 ↗	IMPROVE-IT: Examining Outcomes in Subjects With Acute Coronary Syndrome: Vytorin (Ezetimibe/Simvastatin) vs Simvastatin (P04103)	Completed	Merck Sharp & Dohme Corp.	Phase 3	2005-10-17	This is a randomized, active-control, double-blind study of subjects with stabilized high-risk acute coronary syndrome (ACS). The primary objective is to evaluate the clinical benefit of Ezetimibe/Simvastatin Combination 10/40 (single tablet, under the brand VYTORIN in the United States) compared with Simvastatin 40 mg. As per the original protocol, if low-density lipoprotein cholesterol (LDL-C) response was inadequate, the dose of simvastatin in the VYTORIN arm or simvastatin arm, could be increased to 80 mg (Note: per June 2011 protocol amendment, criteria for continued use of 80 mg simvastatin were modified and new increases of simvastatin dose to 80 mg were stopped). Clinical benefit will be defined as the reduction in the risk of the occurrence of the composite endpoint of cardiovascular (CV) death, major coronary events, and stroke.
NCT00395603 ↗	Vytorin Treating Uncontrolled Lipids (VyTUL) Study (0653A-122)	Terminated	Merck Sharp & Dohme Corp.	Phase 3	2006-09-01	To compare the effectiveness of ezetimibe/simvastatin 10/40 daily to atorvastatin 80 daily in reducing the concentration of ldl-c at endpoint after 6 weeks of treatment.
NCT00413972 ↗	Effects of Vytorin Versus Placebo in Subjects With Primary Hypercholesterolemia (Study P04420)	Completed	Schering-Plough	Phase 3	2006-04-01	This is a multicenter, randomized, double-blind, placebo-controlled, parallel-group Phase 3 study of Vytorin 10/10 (ezetimibe 10 mg with simvastatin 10 mg), Vytorin 10/20 (ezetimibe 10 mg with simvastatin 20 mg), and Vytorin 10/40 (ezetimibe 10 mg with simvastatin 40 mg) compared to placebo administered daily for 8 consecutive weeks in subjects with primary hypercholesterolemia (LDL-C >3.64 mmol/L [140 mg/dL]). The efficacy of daily Vytorin versus placebo in reducing the concentration of LDL-C will be evaluated, and the efficacy of daily Vytorin versus placebo with respect to change in the concentrations of total cholesterol, triglycerides, and HDL-C will be compared. The safety of Vytorin versus placebo will also be assessed.
NCT00413972 ↗	Effects of Vytorin Versus Placebo in Subjects With Primary Hypercholesterolemia (Study P04420)	Completed	Merck Sharp & Dohme Corp.	Phase 3	2006-04-01	This is a multicenter, randomized, double-blind, placebo-controlled, parallel-group Phase 3 study of Vytorin 10/10 (ezetimibe 10 mg with simvastatin 10 mg), Vytorin 10/20 (ezetimibe 10 mg with simvastatin 20 mg), and Vytorin 10/40 (ezetimibe 10 mg with simvastatin 40 mg) compared to placebo administered daily for 8 consecutive weeks in subjects with primary hypercholesterolemia (LDL-C >3.64 mmol/L [140 mg/dL]). The efficacy of daily Vytorin versus placebo in reducing the concentration of LDL-C will be evaluated, and the efficacy of daily Vytorin versus placebo with respect to change in the concentrations of total cholesterol, triglycerides, and HDL-C will be compared. The safety of Vytorin versus placebo will also be assessed.
NCT00442897 ↗	Vytorin (10/20 Or 10/40) Compared to Atorvastatin (10 mg or 20 mg) in Patients With Coronary Artery Disease (0653A-126)(COMPLETED)	Completed	Merck Sharp & Dohme Corp.	Phase 4	2006-09-01	Evaluate the proportion of hyperlipaemic persons with known coronary heart disease achieving ldl-c goal as defined by the national cholesterol education program (NCEP) adult treatment panel (ATP) III guidelines
NCT00461630 ↗	Treatment of HDL to Reduce the Incidence of Vascular Events HPS2-THRIVE	Completed	Merck Sharp & Dohme Corp.	Phase 3	2007-01-01	The primary aim is to assess the effects of raising HDL cholesterol (the good type) with extended release niacin/laropiprant 2g (previously known as MK-0524A) versus matching placebo on the risk of heart attack or coronary death, stroke, or the need for arterial bypass procedures (revascularisation) in people with a history of circulatory problems. The secondary aim is to assess the effects of extended release niacin/laropiprant 2g daily on heart attack, coronary death, stroke, and revascularisation separately and to assess the effects on mortality both overall and in various categories of causes of death, and of the effects on major cardiovascular events in people with a history of different diseases at the beginning of the study.

Clinical Trial Conditions for VYTORIN

Condition Name

Condition Name for VYTORIN
Intervention	Trials
Hypercholesterolemia	15
Hyperlipidemia	4
Dyslipidemia	3
Atherosclerosis	3

Condition MeSH

Condition MeSH for VYTORIN
Intervention	Trials
Hypercholesterolemia	15
Dyslipidemias	6
Hyperlipidemias	5
Diabetes Mellitus	5

Clinical Trial Locations for VYTORIN

Trials by Country

Trials by Country for VYTORIN
Location	Trials
United States	10
Korea, Republic of	6
Brazil	5
United Kingdom	1
Taiwan	1

Trials by US State

Trials by US State for VYTORIN
Location	Trials
New York	3
Michigan	1
California	1
Florida	1
Texas	1

Clinical Trial Progress for VYTORIN

Clinical Trial Phase

Clinical Trial Phase for VYTORIN
Clinical Trial Phase	Trials
Phase 4	18
Phase 3	12
Phase 2/Phase 3	1

Clinical Trial Status

Clinical Trial Status for VYTORIN
Clinical Trial Phase	Trials
Completed	30
Unknown status	3
Not yet recruiting	2

Clinical Trial Sponsors for VYTORIN

Sponsor Name

Sponsor Name for VYTORIN
Sponsor	Trials
Merck Sharp & Dohme Corp.	22
Gachon University Gil Medical Center	2
Schering-Plough	1

Sponsor Type

Sponsor Type for VYTORIN
Sponsor	Trials
Other	26
Industry	25
NIH	3

VYTORIN Market Analysis and Financial Projection

Clinical Trials and Efficacy of VYTORIN

Introduction to VYTORIN

VYTORIN is a prescription medication that combines two active ingredients: ezetimibe and simvastatin. It is designed to reduce elevated levels of cholesterol, triglycerides, and other lipids in the blood, thereby lowering the risk of heart attacks and strokes[5].

The IMPROVE-IT Study

One of the most significant clinical trials for VYTORIN is the IMPROVE-IT (IMProved Reduction of Outcomes: VYTORIN Efficacy International Trial) study. This international, multi-center, randomized, double-blind active comparator trial involved over 18,000 patients presenting with acute coronary syndromes (ACS), including unstable angina, non-ST-segment elevation acute myocardial infarction (NSTEMI), and ST-segment elevation acute myocardial infarction (STEMI)[1][3][4].

Primary Endpoints

The study evaluated the incidence of major cardiovascular events, such as cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, re-hospitalization for unstable angina, or coronary revascularization occurring at least 30 days after randomization. The results showed that patients treated with VYTORIN experienced a 6.4% relative risk reduction in the primary composite endpoint compared to those treated with simvastatin alone. At seven years, 32.7% of patients taking VYTORIN experienced a first primary endpoint event, compared to 34.7% of patients taking simvastatin alone[1][3].

Recurrent Events

A pre-specified exploratory analysis of the IMPROVE-IT study also examined the impact of VYTORIN on recurrent cardiovascular events. This analysis revealed that VYTORIN reduced total cardiovascular events (both initial and recurrent) by 9% compared to simvastatin alone. Specifically, there was a 12% reduction in recurrent events among patients treated with VYTORIN[1].

Safety Profile

The IMPROVE-IT study found no significant differences between the VYTORIN and simvastatin groups in terms of adverse events of special interest, including myopathy, rhabdomyolysis, gallbladder adverse events, liver enzyme elevations, and cancer. This safety profile is consistent with previous studies on statins and ezetimibe[3].

FDA Labeling and Market Impact

Despite the statistically significant reductions in cardiovascular events observed in the IMPROVE-IT study, the FDA rejected Merck's proposal to update the labeling for VYTORIN and ZETIA (ezetimibe) to include claims of reducing the risk of heart attacks and strokes in patients with heart disease. The FDA panel determined that the benefits, although statistically significant, were not robust enough to warrant a label change[2].

This decision had implications for Merck's marketing strategy and potentially affected the broader cholesterol-lowering drug market, including newer PCSK9 inhibitors like Amgen's Repatha and Sanofi/Regeneron's Praluent[2].

Market Analysis

Current Market Position

VYTORIN, along with its component drugs ezetimibe and simvastatin, remains a significant player in the cholesterol-lowering market. However, the rejection of the label change request by the FDA has limited its potential for expanded market share based on cardiovascular risk reduction claims[2].

Competitive Landscape

The cholesterol-lowering drug market is highly competitive, with various statins, non-statin drugs like ezetimibe, and newer PCSK9 inhibitors. The inability to secure a label change for VYTORIN means it must compete based on its existing indications and efficacy profile, which, while strong, does not include the coveted cardiovascular risk reduction claim[2].

Future Projections

Given the existing data from the IMPROVE-IT study, VYTORIN is likely to remain a viable option for patients with high cholesterol, particularly those who have experienced acute coronary syndromes. However, its growth potential may be capped by the lack of an FDA-approved label for cardiovascular risk reduction. The market will continue to evolve with new drugs and therapies, and VYTORIN will need to compete based on its proven efficacy and safety profile[1][3].

Patient Demographics and Age Considerations

Age-Specific Benefits

A secondary analysis of the IMPROVE-IT study focused on outcomes by age among patients 50 years or older. This analysis suggested that elderly patients may benefit from the combination of simvastatin and ezetimibe compared to simvastatin alone, particularly in terms of higher-intensity lipid-lowering therapy after an acute coronary syndrome[4].

Pediatric Use

VYTORIN has been studied in children aged 10 years and older for the treatment of certain forms of high cholesterol. However, the specific age ranges and outcomes in pediatric populations are less detailed compared to adult studies[5].

Side Effects and Interactions

Common Side Effects

Common side effects of VYTORIN include muscle pain, dizziness, and gastrointestinal issues. Serious side effects can include myopathy, rhabdomyolysis, and liver enzyme elevations, although these are rare[5].

Drug Interactions

VYTORIN should not be taken with strong CYP3A4 inhibitors, such as certain antifungal medications, HIV protease inhibitors, and some antibiotics, due to the risk of increased simvastatin levels and associated adverse effects[1][3].

Conclusion

VYTORIN, combining ezetimibe and simvastatin, has demonstrated significant efficacy in reducing cardiovascular events in patients with acute coronary syndromes. Despite the FDA's decision not to update its labeling for cardiovascular risk reduction, VYTORIN remains an important treatment option for managing high cholesterol and reducing the risk of major cardiovascular events.

Key Takeaways

• Efficacy in Reducing Cardiovascular Events: VYTORIN has been shown to reduce total cardiovascular events by 9% compared to simvastatin alone in the IMPROVE-IT study.
• Safety Profile: The drug has a favorable safety profile with no significant differences in adverse events compared to simvastatin alone.
• Market Impact: The FDA's rejection of the label change request limits VYTORIN's potential for expanded market share.
• Competitive Landscape: VYTORIN competes in a crowded market with other statins and newer PCSK9 inhibitors.
• Patient Demographics: Elderly patients may particularly benefit from VYTORIN, and it has been studied in children aged 10 years and older.

FAQs

Q: What is VYTORIN used for? A: VYTORIN is used to reduce elevated levels of cholesterol, triglycerides, and other lipids in the blood, thereby lowering the risk of heart attacks and strokes.

Q: What were the key findings of the IMPROVE-IT study? A: The IMPROVE-IT study found that VYTORIN reduced total cardiovascular events by 9% compared to simvastatin alone and showed a 6.4% relative risk reduction in the primary composite endpoint.

Q: Why did the FDA reject the label change request for VYTORIN? A: The FDA determined that the benefits, although statistically significant, were not robust enough to warrant a label change for cardiovascular risk reduction.

Q: What are the common side effects of VYTORIN? A: Common side effects include muscle pain, dizziness, and gastrointestinal issues, with rare but serious side effects including myopathy and rhabdomyolysis.

Q: Can VYTORIN be used in children? A: Yes, VYTORIN has been studied and is approved for use in children aged 10 years and older for certain forms of high cholesterol.

Sources

1. Merck. "New Analysis from Investigational IMPROVE-IT Study Shows VYTORIN® (ezetimibe/simvastatin) Reduced Total (Initial and Recurrent) Cardiovascular Events More than Simvastatin Alone in Patients Presenting with Acute Coronary Syndromes." March 16, 2015.
2. FiercePharma. "Merck's cholesterol meds Zetia, Vytorin lose final appeal for bigger CV market." February 16, 2016.
3. Merck. "Results from Investigational IMPROVE-IT Study of VYTORIN® (ezetimibe and simvastatin) Published in the New England Journal of Medicine." June 3, 2015.
4. JAMA Network. "Effect of Simvastatin-Ezetimibe Compared With Simvastatin Alone on Cardiovascular Outcomes in Elderly Patients After Acute Coronary Syndrome." July 17, 2019.
5. Medical News Today. "Vytorin: Side effects, uses, dosage, interactions, and more."