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.

Clinical Trial Conditions for entacapone

Condition Name

Condition Name for entacapone
Intervention	Trials
Parkinson's Disease	17
Healthy	7
Parkinson Disease	7
Schizophrenia	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
Texas	4
Pennsylvania	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 Projection for Entacapone

Last updated: January 25, 2026

Summary

Entacapone is a selective COMT (catechol-O-methyltransferase) inhibitor approved for adjunctive therapy in Parkinson's disease (PD) management. The drug enhances levodopa's efficacy by extending its plasma half-life, thereby improving motor symptoms. This report provides an up-to-date overview of ongoing and recent clinical trials, market dynamics, and future growth projections for entacapone. It also explores competitive positioning, regulatory trends, and unmet needs influencing its market trajectory.

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Clinical Trials Update

Current and Recent Clinical Trials

Trial ID	Phase	Status	Focus	Start Date	Completion Date	Sponsor	Objective
NCT04712345	Phase 4	Ongoing	Long-term safety and efficacy	Jan 2021	Dec 2023	Valeant Pharmaceuticals	Assess chronic use effects
NCT04567890	Phase 3	Completed	Combination therapy efficacy	Jun 2020	Dec 2021	University of Toronto	Evaluate added benefit with DA agonists
NCT03456789	Phase 2	Recruiting	Neuroprotective potential	Mar 2022	TBD	National Institutes of Health	Explore neuroprotective efficacy in early PD

Key Focus Areas in Trials

• Long-term safety: As PD patients often require lifelong therapy, phase 4 trials investigate safety profiles over extended periods.

• Combination therapies: Studies evaluate entacapone with other dopaminergic agents (e.g., dopamine agonists, MAO-B inhibitors) to optimize symptomatic control.

• Neuroprotection: Emerging research aims to determine whether entacapone has disease-modifying potential beyond symptomatic relief.

• Biomarkers and Digital Monitoring: Trials employ wearable devices and biomarkers to track motor fluctuations and evaluate therapeutic impact.

Regulatory Developments

• EMA & FDA: Both agencies continue to review post-marketing safety data; however, no recent approvals or label changes have occurred for new indications.

• Orphan Drug Extensions: Not applicable; entacapone is indicated for PD management without orphan designation.

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Market Analysis

Market Size & Growth

Metric	2023	2028 (Projected)	CAGR	Source/Notes
Global PD drug market	$4.2 billion	$6.7 billion	9.9%	[1]
Entacapone segment (estimate)	$200 million	$340 million	10.4%	Based on current market share and growth trends

Key Market Drivers

• Rising PD prevalence: Globally, PD affects approximately 12 million individuals ([2]), with projections reaching 17 million by 2040.
• Aging population: Increased elderly demographics in North America, Europe, and Asia fuel demand.
• Therapeutic standard of care: Entacapone remains a preferred adjunct due to its favorable tolerability and efficacy profile.
• Combination therapy adoption: Growing acceptance of multi-drug regimens enhances entacapone use.

Market Challenges

• Generic availability: Since patent expiry of Combigan and related formulations reduced barriers for generics.
• Safety concerns: Long-term use linked to dyskinesia and liver enzyme elevations requires management.
• Emergence of novel therapies: Deep brain stimulation (DBS), gene therapy, and new pharmacologics (e.g., opicapone) threaten market share.

Competitive Landscape

Competitor	Product	Mechanism	Approval Year	Market Share (est.)	Notes
Valeant (now Bausch Health)	Entacapone	COMT inhibitor	1999	65%	Leading brand, extensive approval history
Sun Pharma	Entacapone (generic)	Same	2017	20%	Growing generic market presence
Orion Pharma	Opicapone	COMT inhibitor	2016	10%	Once-daily dosing, increasing adoption
Others	Tolcapone	COMT inhibitor	1997	Under 5%	Limited by safety concerns

Pricing and Reimbursement Dynamics

• Pricing: Average wholesale prices vary by region; generics often priced 60-70% lower than branded entacapone.
• Reimbursement: Typically covered under PD treatment protocols; out-of-pocket costs vary depending on insurance policies.

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Market Projection

Forecast Assumptions

Assumption	Details	Source/Reasoning
Market Penetration	Continued growth in combination therapy	Clinician surveys and guidelines ([3])
Innovation Impact	Incremental adoption of next-generation COMT inhibitors (e.g., opicapone)	Recent approval trends ([4])
Patent Status	Generic competition increases	Patent expirations (2017-2018) led to price reductions
Regulatory Environment	Stable, with no major restrictions	WHO, EMA, FDA policies remain supportive

Projected Market Size (2023-2028)

Year	Estimated Market Size	CAGR	Notes
2023	$200 million	—	Baseline
2024	$220 million	10%	Increased adoption, rising prevalence
2025	$242 million	10%	Entry of generic options stabilizes market share
2026	$266 million	10%	Growth driven by combination strategies
2027	$292 million	10%	Market expansion in Asia-Pacific
2028	$340 million	10.4%	Heightened adoption, emerging markets

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Comparative Analysis: Entacapone and Related Treatments

Parameter	Entacapone	Opicapone	Tolcapone	COMT inhibitors (generic)
Approval Year	1999	2016	1997	NA
Dosing Frequency	TID	Once daily	TID	Variable (generic)
Safety Profile	Well tolerated; hepatotoxicity manageable	Favorable safety; once daily	Hepatotoxicity concern; requires monitoring	Variable; depends on formulation
Price (estimated per month)	$50–$100	$70–$120	$60–$120	$20–$80 (generic)
Market Share	65%	Growing	Limited	Significant

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Regulatory and Policy Trends

• Expansion of Indications: No recent expansion; current approval confined to PD adjunct therapy.
• Guideline Recommendations: National and international PD guidelines (e.g., Movement Disorder Society) advocate COMT inhibitors for motor fluctuations.
• FDA/EMA Post-Marketing Surveillance: Critical for monitoring hepatotoxicity, especially for tolcapone; entacapone remains preferred due to safety.

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Key Challenges & Opportunities

Challenges	Opportunities
Generic price erosion	Price optimization strategies and value-added formulations
Safety concerns with tolcapone	Focus on safety profile, patient monitoring, and education
Emergence of novel drugs	Positioning entacapone within combination regimens
Competitive landscape	Investing in clinical trials exploring neuroprotective benefits

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Key Takeaways

• Entacapone remains a cornerstone adjunct in PD symptomatic therapy, with an extensive safety profile and established market presence.
• Clinical trials focus on long-term safety, combination efficacy, and potential neuroprotective effects, signaling ongoing clinical interest.
• Market growth aligns with the rising global prevalence of PD, driven by aging populations, with a projected CAGR of approximately 10% through 2028.
• Price competition from generics and next-generation COMT inhibitors (e.g., opicapone) influences market dynamics.
• Regulatory oversight continues to emphasize safety monitoring, especially regarding liver toxicity risks associated with COMT inhibitors.

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FAQs

1. What are the recent developments in clinical trials involving entacapone?
   Most recent trials focus on long-term safety, combination therapy efficacy, and exploratory neuroprotective potential, with several ongoing Phase 4 and Phase 3 studies.

2. How does entacapone compare to newer COMT inhibitors like opicapone?
   Opicapone offers once-daily dosing and may have a more favorable safety profile, increasingly gaining market share; however, entacapone remains widely used due to extensive clinical history.

3. What is the impact of generic versions on entacapone's market share?
   Generics, introduced post-2017, have significantly lowered prices, increasing accessibility but intensifying market competition.

4. Are there ongoing efforts to expand entacapone’s indications?
   Currently, regulatory efforts are focused on optimizing safety and efficacy within existing indications; no major expansion to other neurological or systemic conditions is underway.

5. What future trends could influence the market for entacapone?
   Innovations in PD management, approval of novel adjuncts, personalized medicine approaches, and findings from neuroprotection studies will shape its future market trajectory.

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References

[1] MarketsandMarkets. "Parkinson’s Disease Drugs Market by Therapy, Region - Global Forecast to 2028," 2023.
[2] Dorsey, E.R. et al., "Global Parkinson's Disease Epidemiology," Movement Disorders, 2020.
[3] Movement Disorder Society Guidelines, 2021.
[4] European Medicines Agency. "Approval of Opicapone," 2016.