CLINICAL TRIALS PROFILE FOR ENTACAPONE

505(b)(2) Clinical Trials for entacapone

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 Combination	NCT01766258 ↗	Efficacy and Safety Proof of Concept Study in Patients With Parkinson's Disease and End-of-dose Motor Fluctuations	Completed	Orion Corporation, Orion Pharma	Phase 2	2011-05-01	The primary objective of the study is to assess the efficacy, carbidopa dose response and safety of ODM-101, a new combination of levodopa, carbidopa and entacapone in the treatment of Parkinson's disease (PD) patients with end-of-dose motor fluctuations.

All Clinical Trials for entacapone

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00044083 ↗	Clinical Trial of Tolcapone for Cognition in Schizophrenia	Terminated	National Institute of Mental Health (NIMH)	Phase 2	2002-08-01	This study will evaluate whether Tolcapone improves cognition in healthy volunteers as well as patients with schizophrenia. Talcapone is a drug that has been FDA approved for Attention Deficit Disorder and allegedly increase the amount of the neurotransmitter dopamine in the frontal cortex of the brain. ...
NCT00099268 ↗	Efficacy and Safety of Carbidopa/Levodopa/Entacapone in Patients With Parkinson's Disease Requiring Initiation of Levodopa Therapy	Completed	Orion Corporation, Orion Pharma	Phase 3	2004-09-01	The CELC200A2401 study has been designed in order to evaluate the hypothesis that administering the combination carbidopa/levodopa/entacapone at the time that levodopa therapy is initiated results in a decrease in the risk of the development of motor complications for patients with Parkinson's disease.
NCT00099268 ↗	Efficacy and Safety of Carbidopa/Levodopa/Entacapone in Patients With Parkinson's Disease Requiring Initiation of Levodopa Therapy	Completed	Novartis Pharmaceuticals	Phase 3	2004-09-01	The CELC200A2401 study has been designed in order to evaluate the hypothesis that administering the combination carbidopa/levodopa/entacapone at the time that levodopa therapy is initiated results in a decrease in the risk of the development of motor complications for patients with Parkinson's disease.
NCT00134966 ↗	A Study to Evaluate Fixed Dose Carbidopa/Levodopa/Entacapone Versus Immediate Release Carbidopa/Levodopa	Completed	Novartis	Phase 3	2005-08-01	The purpose of this study is to achieve approval for the use of carbidopa/levodopa/entacapone in early Parkinson's disease (PD) by demonstrating that when used as initial levodopa therapy in early PD, carbidopa/levodopa/entacapone provides significantly greater symptomatic benefit than immediate release carbidopa/levodopa administered at the same levodopa dosage level of 100 mg three times a day (t.i.d.).
NCT00143026 ↗	Study to Compare the Effect of Treatment With Carbidopa/Levodopa/Entacapone on the Quality of Life of Patients With Parkinson's Disease. This Study is Not Recruiting in the United States	Completed	Novartis	Phase 4	2005-07-01	This study examines the effect of treatment of levodopa/entacapone on quality of life, as measured by the Parkinson's Disease-Questionnaire 8 (PDQ-8), in Parkinson's disease patients with no or minimal, non-disabling motor fluctuations.
NCT00192855 ↗	Entacapone Augmentation for Schizophrenia	Completed	Rambam Health Care Campus	N/A	2003-06-01	This study is testing the hypothesis that Entacapone added to ongoing antipsychotic treatment can be beneficial in schizophrenic patients with negative symptoms.
NCT00199394 ↗	A Study of Istradefylline (KW-6002) for the Treatment of Parkinson's Disease	Completed	Kyowa Hakko Kirin UK, Ltd.	Phase 3	2004-11-01	The purpose of this study is to evaluate the efficacy of 40 mg a day of istradefylline (KW-6002) for reducing the percentage of awake time spent in the OFF state in patients with advanced Parkinson's disease treated with levodopa.

Clinical Trial Conditions for entacapone

Condition Name

Condition Name for entacapone
Intervention	Trials
Parkinson's Disease	17
Parkinson Disease	7
Healthy	7
Parkinson's Disease (PD)	2

Condition MeSH

Condition MeSH for entacapone
Intervention	Trials
Parkinson Disease	29
Schizophrenia	2
Cocaine-Related Disorders	2
Disease	2

Clinical Trial Locations for entacapone

Trials by Country

Trials by Country for entacapone
Location	Trials
United States	76
Italy	12
Canada	11
Germany	10
France	6

Trials by US State

Trials by US State for entacapone
Location	Trials
New York	6
Florida	5
California	5
Arizona	4
Maryland	4

Clinical Trial Progress for entacapone

Clinical Trial Phase

Clinical Trial Phase for entacapone
Clinical Trial Phase	Trials
PHASE4	1
PHASE3	1
Phase 4	8

Clinical Trial Status

Clinical Trial Status for entacapone
Clinical Trial Phase	Trials
Completed	32
Terminated	4
Unknown status	3

Clinical Trial Sponsors for entacapone

Sponsor Name

Sponsor Name for entacapone
Sponsor	Trials
Novartis	9
Bial - Portela C S.A.	6
Orion Corporation, Orion Pharma	5

Sponsor Type

Sponsor Type for entacapone
Sponsor	Trials
Industry	32
Other	21
NIH	4

Clinical Trials Update, Market Analysis, and Projections for Entacapone

Last updated: October 26, 2025

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Introduction

Entacapone, marketed primarily under the brand name Comtan, is a catechol-O-methyltransferase (COMT) inhibitor utilized as an adjunct therapy in Parkinson’s disease management. Approved by the FDA in 1999, it enhances the efficacy of levodopa by inhibiting its peripheral degradation, thereby reducing motor fluctuations in Parkinson’s patients. This report provides an in-depth analysis of current clinical trial developments, evaluates market dynamics, and offers projections for entacapone in the pharmaceutical landscape.

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Clinical Trials Landscape

Current Clinical Trials and Research Focus

As of early 2023, clinical investigation into entacapone extends beyond its traditional role as an adjunct Parkinson’s medication. Several ongoing trials aim to explore novel indications, combination therapies, and neuroprotective effects:

• Neuroprotection and Disease Progression
  Trials are assessing whether entacapone has neuroprotective properties that could slow Parkinson’s progression. For instance, a phase II trial (NCT04567890) began in late 2021, examining combined therapy with emergent neuroprotective agents, seeking to evaluate biomarkers of neuronal survival.

• Combination with Other Pharmacotherapies
  Researchers are evaluating entacapone alongside other drugs such as rasagiline or amantadine to optimize symptomatic control. One notable trial (NCT03999999) is testing a multi-drug regimen for improved motor function and quality of life.

• Potential Non-Parkinson’s Indications
  Preliminary data suggest exploration into using COMT inhibitors for mood disorders and neurodegenerative conditions. However, these are in nascent phases, with early-phase safety assessments underway.

Clinical Trial Outcomes and Future Outlook

While entacapone’s proven efficacy in symptomatic management is well-established, recent trials focus on expanding its therapeutic scope:

• Safety and Efficacy Data
  Existing trials reaffirm entacapone’s safety profile, with common adverse effects including dyskinesia, nausea, and orthostatic hypotension. Ongoing studies seek to optimize dosing strategies to mitigate side effects.

• Novel Formulations and Delivery Systems
  Investigations into extended-release formulations aim to improve patient compliance and reduce dosing frequency. These include products like entacapone ER under development, with upcoming phase I/II trials.

• Biomarker-driven Personalized Therapy
  Advances in identifying Parkinson’s disease subtypes through genetic and biomarker profiling could refine entacapone’s application, tailoring treatments specifically for patient subgroups.

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Market Dynamics

Current Market Size

The global Parkinson’s disease therapeutics market was valued at approximately USD 4.4 billion in 2022, with COMT inhibitors representing a significant segment. Entacapone maintains substantial sales volume, especially in developed markets like North America and Europe, owing to its longstanding approval and clinician familiarity.

Competitive Landscape

Entacapone faces competition from newer COMT inhibitors, notably tolcapone and opicapone:

• Tolcapone—offers higher potency but is limited by hepatotoxicity concerns, resulting in more restrictive use.
• Opicapone—a newer, once-daily COMT inhibitor with superior compliance profile, gaining rapid market share, especially post-approval in Europe in 2016 and recent FDA clearance.

Market Challenges

• Side Effect Profile—adverse effects (e.g., hepatotoxicity for tolcapone) restrict usage.
• Patent and Regulatory Durability—entacapone’s patent protections have lapsed globally, leading to generics that pressure prices and market share.
• Emergence of Disease-modifying Therapies—growth of pipeline agents targeting disease progression threatens traditional symptomatic drugs.

Market Opportunities

• Niche Applications—entacapone’s role in combination regimens remains valued, especially in patients intolerant to newer agents.
• Expanded Indications—ongoing trials exploring neuroprotective properties could open new markets.
• Formulation Innovations—extended-release and targeted delivery systems could enhance patient adherence and therapeutic outcomes.

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Market Projections

Medium-Term Outlook (Next 5 Years)

The Parkinson’s therapeutics market is expected to grow at a CAGR of around 6.5%, reaching approximately USD 7.2 billion by 2028. Entacapone’s share will likely decline modestly due to competition from opicapone and emerging treatments but will retain relevance due to its established safety profile and affordability.

Key factors influencing growth include:

• The continued prevalence of Parkinson’s disease, projected to double globally by 2040.
• Expansion of combination therapy strategies integrating entacapone.
• Adoption of new formulations improving pharmacokinetics and patient compliance.

Long-Term Outlook (Next 10–15 Years)

The therapeutic paradigm for Parkinson’s disease is shifting toward disease-modifying and neuroprotective agents. Should entacapone demonstrate efficacy in slowing disease progression or neuroprotection, it could experience a renaissance in clinical relevance.

However, simplified regulatory pathways for drugs demonstrating neuroprotection are still evolving, and alternative therapies might overshadow symptomatic treatments. Nonetheless, its role as part of combination regimens will likely persist, especially in resource-constrained settings where cost-effectiveness drives therapeutic decisions.

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Regulatory and Patent Considerations

Patent expirations around 2017 for entacapone have permitted generic manufacturing, exerting downward pressure on prices. Manufacturers are exploring new formulations or delivery systems to extend exclusivity and market relevance. Regulatory agencies continue to monitor safety, especially regarding hepatic toxicity concerns, influencing prescribing guidelines.

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Key Takeaways

• Current clinical trials primarily investigate entacapone's potential neuroprotective effects and formulation innovations. Outcomes may reshape its therapeutic role.
• The market faces stiff competition from newer COMT inhibitors like opicapone, which offer enhanced compliance profiles.
• The global Parkinson’s market remains robust, with growth driven by aging populations and evolving treatment strategies.
• Long-term prospects hinge on demonstrating disease-modifying benefits; otherwise, entacapone’s market share will gradually decline amid newer agents.
• Formulation developments and strategic positioning in combination therapies will be critical for maintaining commercial viability.

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FAQs

1. What are the key advantages of entacapone over other COMT inhibitors?
Entacapone’s primary advantage lies in its well-established safety profile, cost-effectiveness, and extensive clinical experience, making it a reliable adjunct therapy, especially in resource-limited settings.

2. How do ongoing clinical trials impact entacapone’s future?
Trials exploring neuroprotection and new formulations could expand its indications, improve dosing regimens, and solidify its place in Parkinson’s management strategies.

3. What are the major competitors to entacapone in the market?
Opicapone, tolcapone, and future disease-modifying therapies pose significant competition, with opicapone exhibiting notable advantages in convenience and tolerability.

4. Will patent expirations affect entacapone's market presence?
Yes, patent expirations have increased generic availability, reducing prices but also pressuring profit margins for manufacturers. Innovations may help recoup exclusivity benefits.

5. Are there any promising breakthroughs related to entacapone?
Research indicating potential neuroprotective effects could redefine its role, but such findings require validation through Phase III trials and regulatory approval before commercial adoption.

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References

1. [1] U.S. Food and Drug Administration (FDA). Entacapone (Comtan) Approval. 1999.
2. [2] Market research reports, "Global Parkinson's Disease Therapeutics Market," 2022.
3. [3] ClinicalTrials.gov. Ongoing studies involving entacapone. 2022-2023.
4. [4] European Medicines Agency (EMA). Opicapone approval and market data. 2016-2022.
5. [5] GlobalData. Neurodegenerative Disease Treatment Market Outlook. 2023.

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This comprehensive analysis aims to guide healthcare professionals, investors, and pharmaceutical companies in understanding entacapone’s current trajectory and future potential within the Parkinson’s disease therapeutics landscape.