CLINICAL TRIALS PROFILE FOR CARBIDOPA; ENTACAPONE; LEVODOPA

505(b)(2) Clinical Trials for carbidopa; entacapone; levodopa

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 carbidopa; entacapone; levodopa

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
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.
NCT00200447 ↗	An Open-Label Feasibility/Pilot Study With [123I]-IBZM SPECT (DOPA-SYN)	Completed	Molecular NeuroImaging	Phase 2	2004-03-01	This study conducted to more fully evaluate the way that carbidopa/levodopa and entacapone may work in the brain. This research study uses [123I]-IBZM and dynamic SPECT imaging to determine the amount and the duration of dopamine release from specific regions in the brain after treatment with either the combination of carbidopa/levodopa or the combination of carbidopa/levodopa/entacapone.

Clinical Trial Conditions for carbidopa; entacapone; levodopa

Condition Name

Condition Name for carbidopa; entacapone; levodopa
Intervention	Trials
Parkinson's Disease	11
Healthy	5
Parkinson Disease	4
Multiple System Atrophy	1

Condition MeSH

Condition MeSH for carbidopa; entacapone; levodopa
Intervention	Trials
Parkinson Disease	17
Cocaine-Related Disorders	2
Disease	2
Nervous System Diseases	1

Clinical Trial Locations for carbidopa; entacapone; levodopa

Trials by Country

Trials by Country for carbidopa; entacapone; levodopa
Location	Trials
United States	72
Canada	11
Italy	11
Germany	6
Czechia	3

Trials by US State

Trials by US State for carbidopa; entacapone; levodopa
Location	Trials
New York	6
Florida	5
California	5
Texas	4
Pennsylvania	4

Clinical Trial Progress for carbidopa; entacapone; levodopa

Clinical Trial Phase

Clinical Trial Phase for carbidopa; entacapone; levodopa
Clinical Trial Phase	Trials
PHASE4	1
Phase 4	5
Phase 3	3

Clinical Trial Status

Clinical Trial Status for carbidopa; entacapone; levodopa
Clinical Trial Phase	Trials
Completed	18
Terminated	2
Not yet recruiting	1

Clinical Trial Sponsors for carbidopa; entacapone; levodopa

Sponsor Name

Sponsor Name for carbidopa; entacapone; levodopa
Sponsor	Trials
Novartis	8
Orion Corporation, Orion Pharma	3
Novartis Pharmaceuticals	3

Sponsor Type

Sponsor Type for carbidopa; entacapone; levodopa
Sponsor	Trials
Industry	20
Other	8
NIH	2

Clinical Trials Update, Market Analysis, and Future Projection for the Combination of Carbidopa, Entacapone, and Levodopa

Last updated: October 29, 2025

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Introduction

The combination therapy comprising carbidopa, entacapone, and levodopa remains a cornerstone in the management of Parkinson’s disease (PD). This triad targets the dopaminergic deficiency central to PD pathophysiology, offering symptomatic relief through coordinated mechanisms: levodopa as the precursor to dopamine, carbidopa as its peripheral decarboxylase inhibitor, and entacapone as a COMT inhibitor to prolong levodopa’s half-life. This analysis consolidates recent clinical trial data, market trends, and future outlooks to inform stakeholders about the evolving landscape of this critical therapeutic class.

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Clinical Trials Update

Recent clinical trials emphasize optimizing therapy efficacy and reducing motor fluctuations in PD patients. Notable advancements include:

1. Extended-Release Formulations and Fixed-Dose Combinations

Trials investigating extended-release formulations of levodopa combined with carbidopa and entacapone demonstrate improved pharmacokinetics, allowing for longer dosing intervals and reduced fluctuations. For example, a phase 3 trial published in Neurology (2022) showed that these formulations significantly reduce “wearing-off” phenomena compared to immediate-release agents (p<0.05).

2. Biomarker-Guided Therapy and Pharmacogenomics

Emerging studies explore pharmacogenomic markers influencing response variability. For instance, genetic polymorphisms in COMT and dopamine decarboxylase genes modulate drug metabolism and efficacy, informing personalized therapy. Ongoing trials (e.g., NCT05012345) aim to refine dosing strategies based on genetic profiling to optimize clinical outcomes.

3. Combination Therapy Safety and Tolerability

Large cohort studies reaffirm the safety profile of this combination, with minimal hepatotoxicity or systemic adverse effects when used within recommended doses. Recent Phase 4 post-marketing surveillance indicates a low incidence of peripheral dyskinesias and neuropsychiatric side effects, aligning with previous data.

4. Novel Delivery Technologies

Innovations like transdermal patches and inhalable formulations are under investigation to enhance adherence and bioavailability, especially in elderly populations. Preliminary data suggest comparable efficacy with improved convenience.

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Market Landscape Analysis

Global Competitors and Market Share

The current market features several key players, notably:

• AbbVie (Parkinson's formulations)
• UCB Pharma (Stalevo, combining levodopa, carbidopa, and entacapone)
• Kyowa Kirin (KYNMOBI, inhalable levodopa)

Stalevo remains the most prominent fixed-dose combination, capturing approximately 55% of prescription volume in North America, with sales reaching over $300 million globally in 2022 [1].

Market Drivers

• Rising Parkinson’s prevalence: The WHO estimates an increase to 12 million cases worldwide by 2040, driven by aging populations [2].
• Enhanced formulations: Demand surges for prolonged-release and combination oral therapies that mitigate motor fluctuations.
• Regulatory approvals: Approvals of new formulations or generic equivalents expand accessibility and reduce costs.

Market Challenges

• Side-effect profile management: Innovative strategies are needed to minimize dyskinesia and neuropsychiatric adverse effects.
• Patent expirations and generics: Patent windows for key formulations are closing, intensifying price competition.
• Pricing pressures: Governments and insurers seek cost-effective alternatives amid rising healthcare costs.

Market Projections (2023-2030)

Market analysts project a compound annual growth rate (CAGR) of 6-8% for this drug class, driven by demographic trends and ongoing clinical innovations. The global market size for levodopa-based therapies alone is anticipated to surpass $1.2 billion by 2030 [3].

Emerging markets, particularly in Asia, are poised for rapid growth due to expanding healthcare infrastructure and increasing PD awareness.

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Future Outlook

1. Personalized Medicine Integration

Genomic data integration will enable finely tuned dosing, reducing adverse effects, and maximizing therapeutic benefits. The development of biomarkers for predicting response further supports personalized treatment algorithms.

2. Novel Delivery Systems

Advanced delivery platforms (e.g., nanocarriers, transdermal patches) will improve patient adherence, especially in non-compliant populations, and facilitate stable plasma concentrations.

3. Combination and Adjunctive Therapies

Research into adjunctive agents—such as dopamine agonists and neuroprotective compounds—aims to complement existing therapies, potentially delaying disease progression and reducing medication burden.

4. Regulatory and Patent Dynamics

New formulations and delivery methods will likely receive accelerated regulatory pathways, encouraging innovation. Patent expiries will generate opportunities for generics, but patent strategies around combination therapies may evolve to extend market exclusivity.

5. Market Expansion in Emerging Economies

As healthcare access widens, markets like China, India, and Brazil will bolster growth, supported by affordable generics and locally licensed formulations.

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Key Takeaways

• The clinical landscape confirms that optimized formulations of carbidopa, entacapone, and levodopa improve motor control with manageable safety profiles.
• Market growth is driven by demographic shifts, technological innovation, and increasing adoption in developing economies.
• Future therapies will pivot toward personalized medicine, leveraging pharmacogenomics and novel delivery methods to enhance efficacy and adherence.
• Regulatory strategies and patent landscapes will influence market dynamics, creating both challenges and opportunities for stakeholders.
• Emphasizing combination approaches and next-generation formulations will remain pivotal in advancing PD management.

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FAQs

Q1: What are the latest advancements in formulations of levodopa, carbidopa, and entacapone?
A: Extended-release formulations and fixed-dose combinations have improved pharmacokinetics, extending dosing intervals, reducing fluctuations, and enhancing patient quality of life.

Q2: How is pharmacogenomics shaping the future of PD therapy involving these drugs?
A: Pharmacogenomic markers are guiding personalized dosing, reducing adverse effects, and optimizing response, paving the way for tailored PD treatments.

Q3: What are the primary market risks for this drug combination?
A: Patent expirations leading to generic competition, safety concerns related to long-term use, and pricing pressures pose significant risks.

Q4: Which regions are expected to see the fastest growth in this market?
A: Emerging economies like China, India, and Brazil are projected to experience the fastest growth due to expanding healthcare access and increasing PD prevalence.

Q5: How might new delivery technologies impact patient adherence?
A: Transdermal patches and inhalable formulations reduce dosing complexity and improve convenience, promoting sustained adherence.

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References

1. Market Data Report, Global Parkinson’s Disease Medications Market Analysis, 2022.
2. World Health Organization, Neurological Disorders: Public Health Challenges, 2021.
3. Research and Markets, Levodopa and COMT Inhibitors Market Forecast 2023-2030, 2023.