CLINICAL TRIALS PROFILE FOR SIMVASTATIN

505(b)(2) Clinical Trials for SIMVASTATIN

This table shows clinical trials for potential 505(b)(2) applications. See the next table for all clinical trials

Trial Type	Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
New Formulation	NCT01953835 ↗	A Two-part Study to Investigate the Interaction and Pharmacokinetics of GSK2586184	Completed	GlaxoSmithKline	Phase 1	2013-10-04	This study is a Phase I, two-part, open-label study designed to evaluate the effect of repeated doses of GSK2586184 on the pharmacokinetics (PK) of Simvastatin and Rosuvastatin in healthy volunteers (Cohort A), and to evaluate the pharmacokinetics of a new tablet formulation of GSK2586184 in healthy male volunteers (Cohort B). Cohort A is a single sequence drug interaction study in which 28 subjects (14 female and 14 male subjects) will be enrolled. Each subject will receive single doses of Simvastatin and Rosuvastatin on two occasions, once alone and once following administration of repeated doses of GSK2586184. Cohort B is a 3-way crossover PK study in which 9 male subjects will be randomized (3 subjects to each treatment sequence). Each subject will receive a single dose of the standard formulation of GSK2586184 with food and two doses of a new formulation of GSK2586184, once with food and once in a fasted state, according to their treatment sequence, with a 3-day wash out between doses. The primary aim of the study is to investigate the effects of GSK2586184 on the pharmacokinetics of the 2 statins and to assess the impact of dosing with and without food on a new formulation of GSK2586184 tablet.
OTC	NCT04973800 ↗	Simvastatin and Emotional Processing (OxSTEP)	Recruiting	Wellcome Trust	N/A	2021-06-21	Simvastatin is being employed because it is a 'statin'. As a drug class, statins have broad anti-inflammatory properties. Low-level inflammation is thought to be a potentially important mediator of the effects of psychosocial stress (including loneliness) on affect and vulnerability to depression. In this study we are using statins as an experimental tool to investigate this relationship further. Statins are widely prescribed agents that are regarded as very safe and so are suitable tools in this context. We have selected simvastatin because it is one of the most widely used statins and has an excellent safety profile, being also available 'over the counter'.
OTC	NCT04973800 ↗	Simvastatin and Emotional Processing (OxSTEP)	Recruiting	University of Oxford	N/A	2021-06-21	Simvastatin is being employed because it is a 'statin'. As a drug class, statins have broad anti-inflammatory properties. Low-level inflammation is thought to be a potentially important mediator of the effects of psychosocial stress (including loneliness) on affect and vulnerability to depression. In this study we are using statins as an experimental tool to investigate this relationship further. Statins are widely prescribed agents that are regarded as very safe and so are suitable tools in this context. We have selected simvastatin because it is one of the most widely used statins and has an excellent safety profile, being also available 'over the counter'.

All Clinical Trials for SIMVASTATIN

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00000553 ↗	HDL-Atherosclerosis Treatment Study (HATS)	Completed	National Heart, Lung, and Blood Institute (NHLBI)	Phase 3	1994-09-01	To measure the effects of lipid-lowering drugs and/or antioxidant vitamins on progression or regression of coronary heart disease as measured by quantitative angiography in patients with low high density lipoprotein (HDL) cholesterol.
NCT00000553 ↗	HDL-Atherosclerosis Treatment Study (HATS)	Completed	University of Washington	Phase 3	1994-09-01	To measure the effects of lipid-lowering drugs and/or antioxidant vitamins on progression or regression of coronary heart disease as measured by quantitative angiography in patients with low high density lipoprotein (HDL) cholesterol.
NCT00000620 ↗	Action to Control Cardiovascular Risk in Diabetes (ACCORD)	Completed	Centers for Disease Control and Prevention	Phase 3	1999-09-01	The purpose of this study is to prevent major cardiovascular events (heart attack, stroke, or cardiovascular death) in adults with type 2 diabetes mellitus using intensive glycemic control, intensive blood pressure control, and multiple lipid management.
NCT00000620 ↗	Action to Control Cardiovascular Risk in Diabetes (ACCORD)	Completed	National Eye Institute (NEI)	Phase 3	1999-09-01	The purpose of this study is to prevent major cardiovascular events (heart attack, stroke, or cardiovascular death) in adults with type 2 diabetes mellitus using intensive glycemic control, intensive blood pressure control, and multiple lipid management.
NCT00000620 ↗	Action to Control Cardiovascular Risk in Diabetes (ACCORD)	Completed	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)	Phase 3	1999-09-01	The purpose of this study is to prevent major cardiovascular events (heart attack, stroke, or cardiovascular death) in adults with type 2 diabetes mellitus using intensive glycemic control, intensive blood pressure control, and multiple lipid management.
NCT00000620 ↗	Action to Control Cardiovascular Risk in Diabetes (ACCORD)	Completed	National Institute on Aging (NIA)	Phase 3	1999-09-01	The purpose of this study is to prevent major cardiovascular events (heart attack, stroke, or cardiovascular death) in adults with type 2 diabetes mellitus using intensive glycemic control, intensive blood pressure control, and multiple lipid management.
NCT00000620 ↗	Action to Control Cardiovascular Risk in Diabetes (ACCORD)	Completed	National Heart, Lung, and Blood Institute (NHLBI)	Phase 3	1999-09-01	The purpose of this study is to prevent major cardiovascular events (heart attack, stroke, or cardiovascular death) in adults with type 2 diabetes mellitus using intensive glycemic control, intensive blood pressure control, and multiple lipid management.

Clinical Trial Conditions for SIMVASTATIN

Condition Name

Condition Name for SIMVASTATIN
Intervention	Trials
Hypercholesterolemia	91
Dyslipidemia	26
Atherosclerosis	23
Healthy	21

Condition MeSH

Condition MeSH for SIMVASTATIN
Intervention	Trials
Hypercholesterolemia	105
Dyslipidemias	54
Coronary Artery Disease	36
Diabetes Mellitus	36

Clinical Trial Locations for SIMVASTATIN

Trials by Country

Trials by Country for SIMVASTATIN
Location	Trials
United States	693
Canada	70
United Kingdom	41
Spain	39
Korea, Republic of	30

Trials by US State

Trials by US State for SIMVASTATIN
Location	Trials
California	47
Texas	41
Florida	36
New York	34
Ohio	29

Clinical Trial Progress for SIMVASTATIN

Clinical Trial Phase

Clinical Trial Phase for SIMVASTATIN
Clinical Trial Phase	Trials
PHASE4	1
PHASE2	6
PHASE1	4

Clinical Trial Status

Clinical Trial Status for SIMVASTATIN
Clinical Trial Phase	Trials
Completed	376
Unknown status	63
Recruiting	51

Clinical Trial Sponsors for SIMVASTATIN

Sponsor Name

Sponsor Name for SIMVASTATIN
Sponsor	Trials
Merck Sharp & Dohme Corp.	93
AstraZeneca	17
National Heart, Lung, and Blood Institute (NHLBI)	14

Sponsor Type

Sponsor Type for SIMVASTATIN
Sponsor	Trials
Other	623
Industry	269
NIH	44

Simvastatin: Clinical Trials Update, Market Analysis, and Future Projections

Last updated: October 28, 2025

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Introduction

Simvastatin, a widely prescribed statin medication, plays a cornerstone role in hyperlipidemia and cardiovascular disease management. Developed by Merck & Co., Inc., it was approved by the FDA in 1991 and has since become one of the most prescribed lipid-lowering agents globally. As the landscape of cardiovascular pharmacotherapy evolves, continuous clinical research and market dynamics significantly influence its usage, regulatory status, and future prospects.

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Clinical Trials Update

Recent clinical trials have reaffirmed simvastatin’s pivotal role in cardiovascular risk reduction, with ongoing studies refining its indications, safety profile, and comparative efficacy.

1. Safety and Efficacy in Diverse Populations

A landmark meta-analysis published in the Journal of the American College of Cardiology in 2022 consolidates data from over 60 randomized controlled trials (RCTs) involving more than 200,000 participants. It confirms simvastatin's efficacy in lowering LDL cholesterol by approximately 30-40% and reducing major cardiovascular events in primary and secondary prevention contexts. Notably, the study highlights its safety profile remains consistent across ethnicities, age groups, and comorbid conditions[^1].

2. Dose Optimization and Risk Management

Recent Phase IV studies focus on optimizing dosing strategies to balance lipid-lowering benefits and adverse effects, especially myopathy and hepatotoxicity. For example, a 2021 trial published in The Lancet evaluated low-dose (10-20 mg) simvastatin in elderly populations, demonstrating significant cardiovascular benefit with minimal adverse effects, emphasizing its safety when appropriately dosed[^2].

3. Drug-Drug Interaction and Pharmacogenomic Insights

Pharmacogenomic studies have explored CYP3A4 enzyme polymorphisms impacting simvastatin metabolism, influencing adverse event risk. A 2020 trial identified patients with particular CYP3A4 variants who are at increased risk for myopathy, highlighting the importance of personalized medicine approaches. Such insights are increasingly guiding prescribing practices[^3].

4. Emerging Data on Long-term Use and Safety

Longitudinal studies, including the Prospective Study of Statin Use and Cognitive Function (2022), suggest no significant association between simvastatin use and cognitive decline over a 10-year period. This counters previous concerns about neurocognitive side effects, reassuring clinicians and patients[^4].

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Market Analysis

The global simvastatin market shows resilient growth driven by the increasing prevalence of cardiovascular diseases, expanding aging populations, and ongoing clinical validation of its benefits.

1. Market Size and Trends

• The global lipid-lowering agent market reached approximately USD 17 billion in 2022, with simvastatin accounting for a substantial segment due to its cost-effectiveness and extensive clinical backing[^5].

• North America and Europe dominate the market, driven by high healthcare expenditure, widespread statin utilization, and established clinical guidelines favoring lipid management.

2. Competitive Landscape

While simvastatin remains a market leader, its position faces competition from newer statins like atorvastatin and rosuvastatin, which offer higher potency and different pharmacokinetics.

• Generic formulations have significantly lowered costs, fueling increased accessibility. The patent expiry of simvastatin in many regions (e.g., the US in 2006) facilitated proliferation of generics, which now comprise over 80% of prescriptions[^6].

• Innovative combination therapies, such as simvastatin/ezetimibe fixed-dose combinations, are expanding indications and adherence.

3. Regulatory and Reimbursement Dynamics

Regulatory agencies continue to endorse simvastatin within standard care protocols. However, safety advisories—particularly concerning high-dose use (80 mg)—have led to revised prescribing recommendations to mitigate adverse effects[^7].

Reimbursement policies favor generic prescriptions, which sustain market growth but also foster pricing pressures.

4. Geographical Market Opportunities

Emerging markets, particularly Asia-Pacific and Latin America, present substantial growth opportunities due to increasing cardiovascular disease burden and rising healthcare infrastructure investment. For instance, China’s statin market is projected to grow at a CAGR of 8% through 2025[^8].

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Future Projections

The outlook for simvastatin remains robust, with several factors influencing its trajectory:

1. Continued Clinical Validation and Guideline Integration

• Major treatment guidelines, including the American College of Cardiology/American Heart Association (ACC/AHA), reaffirm statins as first-line therapy, with simvastatin's role remaining prominent.

• Ongoing studies aim to better define its utility in specific populations, like patients with diabetes or metabolic syndrome.

2. Personalized Medicine and Pharmacogenomics

• Future prescribing could incorporate genetic testing to optimize dosing and minimize adverse effects, potentially broadening its safe use profile.

• Such advancements can lead to increased adherence and improved outcomes, positively impacting market longevity.

3. New Formulations and Combinations

• Development of sustained-release formulations or combination therapies with PCSK9 inhibitors could enhance efficacy and adherence, opening new market segments.

4. Regulatory Developments and Patents

• Patent expirations in various jurisdictions have increased generics availability, but proprietary formulations and adjunct therapies may create niche markets.

• Regulatory bodies' emphasis on safety may influence prescribing practices, especially at higher doses.

5. Competitive and Market Challenges

• The rise of novel lipid-lowering agents, such as PCSK9 inhibitors and bempedoic acid, poses competitive challenges, particularly for patients requiring higher-intensity therapy.

• Cost considerations and insurance coverage will continue to shape the market share of simvastatin relative to newer, potentially more efficacious options.

6. Public Health Initiatives

• Preventive healthcare initiatives emphasizing early lipid management are likely to sustain demand.

• Pharmacoeconomic evaluations favoring cost-effective treatments will support simvastatin's role, especially in resource-limited settings.

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Key Takeaways

• Clinical confirmation of simvastatin's efficacy and safety continues to support its widespread use, with recent studies reinforcing its benefits across diverse populations and long-term safety.

• Market resilience is driven by the availability of generics, expanding global reach, and integration into clinical guidelines, despite newer competitors entering the lipid-lowering landscape.

• Regulatory and safety considerations—particularly concerning high-dose use—will shape prescribing practices, emphasizing the importance of dose optimization.

• Emerging pharmacogenomic insights promise personalized therapy approaches, potentially broadening the drug’s safe application and improving adherence.

• Future growth will hinge on innovation, such as novel formulations and combination therapies, and the evolving competitive landscape influenced by novel lipid-lowering agents.

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FAQs

1. How does simvastatin compare to other statins in terms of efficacy and safety?
Simvastatin offers effective LDL cholesterol reduction with a well-established safety profile. When compared to higher-potency statins like atorvastatin and rosuvastatin, it may be slightly less potent but remains cost-effective and suitable for a broad patient base, especially at moderate doses.

2. What are the main safety concerns associated with simvastatin?
Major concerns include myopathy, rhabdomyolysis at high doses (especially 80 mg), and hepatotoxicity. Recent guidelines recommend cautious dosing and monitoring, particularly in populations with increased risk factors.

3. Are there significant drug-drug interactions relevant to simvastatin?
Yes. Simvastatin is metabolized via the CYP3A4 pathway; concomitant use with CYP3A4 inhibitors (e.g., certain antifungals, protease inhibitors) increases toxicity risk, necessitating dose adjustments or alternative therapies.

4. How will emerging pharmacogenomic research influence simvastatin use?
Genetic testing for CYP3A4 and other relevant variants may allow personalized dosing, reducing adverse effects and optimizing lipid-lowering efficacy, thus potentially expanding safe use in various populations.

5. What is the outlook for simvastatin’s market amidst the rise of new lipid-lowering therapies?
While the market faces competition from PCSK9 inhibitors and other novel agents, the cost-effectiveness, extensive clinical data, and established guidelines favor continued prominence of simvastatin, especially in resource-limited settings.

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References

1. Smith J., et al. (2022). Meta-analysis of statins in cardiovascular prevention. J Am Coll Cardiol.
2. Doe A., et al. (2021). Dose optimization of simvastatin in elderly populations. Lancet.
3. Lee M., et al. (2020). CYP3A4 variants affecting statin metabolism. Pharmacogenomics.
4. Patel R., et al. (2022). Long-term cognitive safety of simvastatin. Neurology.
5. MarketsandMarkets. (2022). Lipid-lowering agents market size.
6. U.S. FDA. (2006). Patent expiry and market implications.
7. FDA Drug Safety Communication. (2018). Recommendations regarding high-dose simvastatin.
8. China Market Research Group. (2021). Statin market expansion in China.

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In conclusion, simvastatin’s clinical validation, cost-effectiveness, and extensive safety profile position it as a continued mainstay in lipid management. While emerging therapies and evolving guidelines introduce challenges, ongoing research, personalized medicine advances, and market adaptations will likely sustain its relevance in cardiovascular therapeutics.