CLINICAL TRIALS PROFILE FOR CARBIDOPA, LEVODOPA AND ENTACAPONE

505(b)(2) Clinical Trials for Carbidopa, Levodopa And 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 Carbidopa, Levodopa And Entacapone

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.
NCT00219284 ↗	Effects of Carbidopa/Levodopa/Entacapone on Motor Function and Quality of Life in Patients With Parkinson's Disease	Completed	Novartis Pharmaceuticals	Phase 4	2005-01-01	To assess motor function and quality of life (QoL) in Parkinson's disease (PD) subjects with end-of-dose wearing off, comparing immediate and delayed switch to carbidopa/levodopa and entacapone.
NCT00391898 ↗	Efficacy of Levodopa/Carbidopa/Entacapone vs Levodopa/Carbidopa in Parkinson's Disease Patients With Early Wearing-off	Completed	Novartis	Phase 4	2006-10-01	The study evaluated the efficacy of levodopa/carbidopa/entacapone vs levodopa/carbidopa in patients with Parkinson's disease and early wearing-off with levodopa

Clinical Trial Conditions for Carbidopa, Levodopa And Entacapone

Condition Name

Condition Name for Carbidopa, Levodopa And Entacapone
Intervention	Trials
Parkinson's Disease	11
Healthy	5
Parkinson Disease	3
Parkinson's Disease With End of Dose "Wearing Off"	1

Condition MeSH

Condition MeSH for Carbidopa, Levodopa And Entacapone
Intervention	Trials
Parkinson Disease	16
Disease	2
Cocaine-Related Disorders	2
Shy-Drager Syndrome	1

Clinical Trial Locations for Carbidopa, Levodopa And Entacapone

Trials by Country

Trials by Country for Carbidopa, Levodopa And Entacapone
Location	Trials
United States	72
Canada	11
Italy	11
Germany	6
Turkey	3

Trials by US State

Trials by US State for Carbidopa, Levodopa And Entacapone
Location	Trials
New York	6
Florida	5
California	5
Arizona	4
Texas	4

Clinical Trial Progress for Carbidopa, Levodopa And Entacapone

Clinical Trial Phase

Clinical Trial Phase for Carbidopa, Levodopa And Entacapone
Clinical Trial Phase	Trials
Phase 4	5
Phase 3	3
Phase 2/Phase 3	1

Clinical Trial Status

Clinical Trial Status for Carbidopa, Levodopa And Entacapone
Clinical Trial Phase	Trials
Completed	18
Terminated	2
Unknown status	1

Clinical Trial Sponsors for Carbidopa, Levodopa And Entacapone

Sponsor Name

Sponsor Name for Carbidopa, Levodopa And Entacapone
Sponsor	Trials
Novartis	8
Orion Corporation, Orion Pharma	3
Novartis Pharmaceuticals	3

Sponsor Type

Sponsor Type for Carbidopa, Levodopa And Entacapone
Sponsor	Trials
Industry	20
Other	7
NIH	2

Carbidopa, Levodopa, and Entacapone: Clinical Trials, Market Analysis, and Projections

Introduction

Carbidopa, levodopa, and entacapone are key components in the treatment of Parkinson's disease (PD), a progressive brain disorder characterized by shaking, slow movement, and muscle stiffness. This combination therapy has been extensively studied and is widely used to manage the motor symptoms of PD.

Clinical Trials and Efficacy

End-of-Dose Wearing Off

Clinical trials have consistently shown that the addition of entacapone to levodopa/carbidopa therapy significantly benefits patients experiencing end-of-dose wearing off. These studies have demonstrated increased "on" time, decreased "off" time, and enhanced motor function in patients with PD[1][5].

Quality of Life and Motor Function

A prospective, double-blind, placebo-controlled trial found that entacapone treatment was associated with significant benefits in quality-of-life measures, including improved scores in the PDQ-39 total score, activities of daily living (ADL), mobility domain subscores, and physical functioning and vitality domains of the SF-36. Additionally, patients on entacapone required levodopa rescue less frequently than those on placebo[1].

Dyskinesia and Motor Complications

However, initiating levodopa therapy with the combination of levodopa/carbidopa/entacapone (LCE) did not delay the onset or reduce the frequency of dyskinesia compared to levodopa/carbidopa (LC) alone. In fact, LCE was associated with a shorter time to onset and increased frequency of dyskinesia, possibly due to higher levodopa dose equivalents in the LCE group[4].

Market Analysis

Global Market Growth

The global entacapone market is anticipated to grow at a significant Compound Annual Growth Rate (CAGR) during the forecast period of 2021-2027. This growth is driven by the increasing prevalence of Parkinson's disease, with approximately 10 million people worldwide living with PD and an expected rise in the US from 1 million to 1.2 million by 2030[2].

Market Segmentation

The market is segmented by product purity, application, and region. Key products include tablets and capsules with varying purities, and the market spans across North America, Europe, Asia-Pacific, and the rest of the world. Major players such as Novartis International AG, Teva Pharmaceutical Industries Ltd., and Sun Pharmaceutical Industries Ltd. are driving market growth through strategies like mergers, acquisitions, and new product launches[2].

Regional Insights

North America and Europe are significant markets due to the high prevalence of PD and advanced healthcare infrastructure. The Asia-Pacific region is also expected to show rapid growth due to increasing awareness and improving healthcare facilities. The launch of new formulations, such as the Lecigon triple-combination of levodopa, carbidopa, and entacapone, further supports market expansion[2].

Market Projections

Growth Drivers

The primary drivers of market growth include the increasing incidence of Parkinson's disease, especially among the aging population, and the need for more effective and convenient treatment options. The combination of levodopa, carbidopa, and entacapone in a single tablet, such as Levodopa/Carbidopa/Entacapone Orion, enhances patient compliance and reduces the number of tablets patients need to take[2][5].

Challenges

Despite the growth potential, the market faces challenges such as the high cost of treatment, which can be a barrier for many patients. Additionally, side effects associated with entacapone, such as dyskinesia, muscle pain, and gastrointestinal issues, need to be carefully managed[5].

Key Players and Strategies

Major Players

Companies like Novartis International AG, Teva Pharmaceutical Industries Ltd., and Sun Pharmaceutical Industries Ltd. are key players in the entacapone market. These companies are adopting various strategies to stay competitive, including geographical expansion, partnerships, and the launch of new products[2].

Recent Developments

For instance, STADA's European launch of the Lecigon triple-combination in 2021 highlights the ongoing innovation in this market. Such launches not only expand treatment options but also contribute to market growth by offering more convenient and effective therapies[2].

Side Effects and Safety Profile

Common Side Effects

The most common side effects associated with Levodopa/Carbidopa/Entacapone Orion include dyskinesia, muscle pain, diarrhea, nausea, and harmless urine discoloration. Serious but less common side effects include gastrointestinal hemorrhage and angioedema[5].

Risk Benefit Assessment

The overall risk-benefit ratio of this combination therapy is therapeutically acceptable, with the benefits of extended levodopa availability and improved motor function outweighing the risks of side effects. However, careful monitoring and management of side effects are essential[3].

Bioequivalence and Formulations

Bioequivalence Studies

Studies have shown that Levodopa/Carbidopa/Entacapone Orion is bioequivalent to separate tablets containing entacapone and the combination of levodopa and carbidopa. This ensures that patients receive the same therapeutic benefits from a single tablet as they would from multiple tablets[5].

Available Formulations

Various formulations are available, including immediate release and extended release versions of carbidopa/levodopa, and the triple combination with entacapone. These formulations cater to different patient needs and help in managing the motor symptoms of PD effectively[3].

Conclusion

The combination of carbidopa, levodopa, and entacapone is a cornerstone in the treatment of Parkinson's disease, particularly for managing end-of-dose wearing off and improving motor function. Clinical trials have demonstrated its efficacy, and market projections indicate significant growth driven by increasing prevalence and innovative product launches.

Key Takeaways

• Efficacy in Motor Symptoms: The combination therapy significantly improves motor function and reduces end-of-dose wearing off.
• Quality of Life: Entacapone enhances quality-of-life measures, including ADL and physical functioning.
• Market Growth: The global entacapone market is expected to grow significantly due to the increasing prevalence of PD.
• Side Effects: Common side effects include dyskinesia and gastrointestinal issues, which need careful management.
• Bioequivalence: The triple combination is bioequivalent to separate tablets, ensuring therapeutic equivalence.

FAQs

Q: What is the primary use of carbidopa, levodopa, and entacapone in Parkinson's disease?

A: The primary use is to manage end-of-dose wearing off and improve motor function in patients with PD.

Q: How does entacapone enhance levodopa therapy?

A: Entacapone blocks the enzyme catechol-O-methyltransferase (COMT), extending the elimination half-life of levodopa and keeping it active for longer.

Q: What are the common side effects associated with Levodopa/Carbidopa/Entacapone Orion?

A: Common side effects include dyskinesia, muscle pain, diarrhea, nausea, and harmless urine discoloration.

Q: Which regions are expected to show the fastest growth in the entacapone market?

A: The Asia-Pacific region is expected to show rapid growth due to increasing awareness and improving healthcare facilities.

Q: What strategies are key players adopting to stay competitive in the market?

A: Key players are adopting strategies such as mergers, acquisitions, geographical expansion, partnerships, and new product launches.

Sources

1. JAMA Network: Double-blind, Placebo-Controlled Study of Entacapone in Levodopa ...
2. OMR Global: Global Entacapone Market Size, Share and Trends Analysis Report ...
3. FDA: 203312Orig1s000 - accessdata.fda.gov
4. PubMed: Initiating levodopa/carbidopa therapy with and without entacapone ...
5. EMA: Levodopa/Carbidopa/Entacapone Orion

Last updated: 2025-01-02