CLINICAL TRIALS PROFILE FOR LEVODOPA

505(b)(2) Clinical Trials for 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 Formulation	NCT00363727 ↗	Onset Motor Complications Using REQUIP CR (Ropinirole Controlled-release) As Add-on Therapy To L-dopa In Parkinson's	Completed	GlaxoSmithKline	Phase 3	2003-12-01	This study evaluates how effective a new formulation of a marketed drug is in increasing the time to onset of dyskinesia (abnormal twisting, writhing movements) in patients with Parkinson's Disease who have been taking levodopa for less than 2 years.
New Formulation	NCT00640159 ↗	Tolerability and Efficacy of Switch From Oral Selegiline to Orally Disintegrating Selegiline (Zelapar) in Patients With Parkinson's Disease	Completed	Baylor College of Medicine	Phase 4	2007-01-01	Parkinson's disease (PD) is a progressive neurodegenerative disease. Symptomatic therapy is primarily aimed at restoring dopamine function in the brain. Oral selegiline in conjunction with L-dopa has been a mainstay of therapy for PD patients experiencing motor fluctuations for many years. The mechanisms accounting for selegiline's beneficial adjunctive action in the treatment of PD are not fully understood. Inhibition of monoamine oxidase (MAO) type B (MAO-B) activity is generally considered to be of primary importance. Oral selegiline has low bio-availability and is typically dosed BID, for a total of 5-10 mg daily. Recently, the FDA approved a new orally disintegration tablet (ODT) formulation of selegiline, called ZelaparTM. This new formulation utilizes Zydis technology to dissolve in the mouth, with absorption through the oral mucosa, thereby largely bypassing the gut and avoiding first pass hepatic metabolism. This allows more active drug to be delivered at a lower dose. Consequently, Zelapar is dosed once-daily, up to 2.5 mg per day. There are no empirical data indicating whether the use of the new approved formulation of selegiline ODT (Zelapar) is superior or preferred by patients compared to traditional oral selegiline. It is believed that clinical efficacy will be preserved or enhanced, by delivering more active drug, with improved patient preference for the ODT formulation due to the once-daily dosing . The effectiveness of orally disintegrating selegiline as an adjunct to carbidopa/levodopa in the treatment of PD was established in a multicenter randomized placebo-controlled trial (n=140; 94 received orally disintegrating selegiline, 46 received placebo) of three months' duration. Patients randomized to orally disintegrating selegiline received a daily dose of 1.25 mg for the first 6 weeks and a daily dose of 2.5 mg for the last 6 weeks. Patients were all treated with levodopa and could additionally have been on dopamine agonists, anticholinergics, amantadine, or any combination of these during the trial. At 12 weeks, orally disintegrating selegiline-treated patients had an average of 2.2 hours per day less "OFF" time compared to baseline. Placebo treated patients had 0.6 hours per day less "OFF" time compared to baseline. These differences were significant (p < 0.001). Adverse events were very similar between drug and placebo.
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.
New Formulation	NCT06817200 ↗	The Effect of Amantadine as add-on Therapy for Motor Fluctuations in Advanced Parkinson's Disease: a Randomized Double-blinded Placebo-controlled Trial	NOT_YET_RECRUITING	University Hospital, Toulouse	PHASE2	2025-05-01	Motor fluctuations are identified as the most challenging symptoms by parkinson disease patients. A recent post-hoc analysis of ADS-5012 trials (new formulation of ER Amantadine), revealed a significant improvement in OFF-time. No randomized clinical trial has ever specifically investigated to date the effect of amantadine IR on motor fluctuations. The main objective of this study is to evaluate the effect of amantadine (300 mg/day) as add-on therapy for the treatment of motor fluctuations (Off-time) in advanced Parkinson's disease patients versus placebo after 3 months of treatment.

All Clinical Trials for Levodopa

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00001929 ↗	Treatment of Parkinson's Disease With Eliprodil	Completed	National Institute of Neurological Disorders and Stroke (NINDS)	Phase 2	1999-03-01	Patients with Parkinson's disease are missing the chemical neurotransmitter dopamine. This occurs as a result of destructive changes in an area of the brain responsible for making dopamine, the basal ganglia. Patients with the disease experience, rigid muscles, stooped posture, and a shuffling-type walk (gait). In this study researchers plan to evaluate the effectiveness of the drug eliprodil for the treatment of Parkinson's Disease. Eliprodil works by blocking special receptors (NMDA) that are associated with the symptoms of Parkinson's Disease.
NCT00004576 ↗	Study of LY300164 for the Treatment of Parkinson's Disease	Completed	National Institute of Neurological Disorders and Stroke (NINDS)	Phase 2	2000-02-01	This study will test the effectiveness of an experimental drug called LY300164 on improving Parkinson's disease symptoms, such as movement impairments and tremor, as well as involuntary movements produced by long-term treatment with levodopa. Patients with relatively advanced (Stage II to IV) Parkinson's disease between 30 and 75 years of age may be eligible for this 8-week study. Participants will have a complete medical history and physical examination, including blood tests and an electrocardiogram, and possibly brain magnetic resonance imaging (MRI), CT scan, and chest X-ray. Patients will stop taking all anti-parkinsonism medications except levodopa (Sinemet) and the experimental drug during the study. For the first 1 to 3 days, patients will be in the hospital for a levodopa "dose-finding" procedure. For this study, levodopa is infused through a vein for up to 8 hours, with symptoms monitored frequently to determine the doses that will produce two results: 1) the dose that is less than what is needed to relieve symptoms, and 2) the dose that relieves symptoms, but may produce dyskinesias. When these dose rates are determined, patients will begin treatment in one of two groups. One will take LY300164 3 times a day, along with levodopa, for 3 weeks. The second group will take placebo tablets (a look-alike tablet with no active ingredient) and levodopa on the same schedule as the LY300164 group. A brief medical examination and routine blood and urine tests will be done weekly. The drug dose will be increased every 3 to 4 days until significant side effects occur or the maximal dose is reached. Patients will be closely monitored for 4 hours after every increase. At the end of the 3 weeks, or when the maximal dose is reached, patients will be readmitted to the hospital for 2 to 3 days for a second levodopa dose-finding study, while continuing on LY300164 or placebo. After this test, patients will resume taking levodopa and the experimental drug or placebo as before for another 2 weeks. At the end of the 2-weeks, the entire procedure will be repeated in both groups, but the treatments will be switched-that is, the patients who were taking LY300164 will now take placebo, and the patients who took placebo will now take the drug. At the end of the second 3 weeks, the levodopa infusion procedure will be repeated once more. Throughout the study, parkinsonism symptoms and dyskinesias will be evaluated and blood samples will be drawn periodically to measure drug levels.
NCT00004731 ↗	Parkinson's Disease Treatment With Coenzyme Q10	Completed	National Institute of Neurological Disorders and Stroke (NINDS)	Phase 2	1998-09-01	The purpose of this study is to compare the effects of varying dosage of coenzyme Q10 (CoQ10) versus a placebo in the treatment of Parkinson's disease (PD) in patients with early, untreated PD.
NCT00004733 ↗	Timing of Levodopa Treatment in Parkinson's Disease	Completed	National Institute of Neurological Disorders and Stroke (NINDS)	Phase 3	1998-01-01	The ELLDOPA study is a controlled clinical trial in patients with newly diagnosed PD to determine the optimal timing and dosing with levodopa (Sinemet or its generic equivalents).
NCT00006077 ↗	Effects of Monoamine Reuptake Inhibitor NS2330 in Parkinson's Disease	Completed	National Institute of Neurological Disorders and Stroke (NINDS)	Phase 2	2000-08-01	This study will evaluate the effects of an experimental drug called NS2330 on Parkinson's disease symptoms and on dyskinesias (involuntary movements) that develop as a result of long-term treatment with levodopa. This drug prevents the neurotransmitter dopamine from entering nerve cells. Patients between 18 and 75 years old who have moderately advanced Parkinson's disease and motor problems resulting from levodopa therapy may be eligible for this 5-week study. Candidates will have a complete medical history and physical examination with a detailed neurological evaluation. If needed, some patients will undergo a magnetic resonance imaging (MRI) or computerized tomography (CT) scan of the brain and a chest X-ray. All patients will have blood and urine tests and an electrocardiogram (EKG) and will take a written test for evaluation of depression. Patients enrolled in the study will, if possible, stop taking all antiparkinson medications except levodopa (Sinemet) for one month before the study begins and through its duration. For the first 1 to 3 days, patients will undergo a levodopa "dose-finding" procedure. For this study, patients will stop taking their usual oral levodopa medicine and instead will have levodopa infused through a vein for up to 12 hours. During the infusions, the drug dose will be increased slowly until either 1) parkinsonism symptoms improve, 2) dyskinesias appear, 3) unacceptable side effects occur, or 4) the maximum study dose is reached. When the patient's optimal dose is determined, treatment will begin. Patients will take three pills containing NS2330 or placebo (a look-alike pill with no active ingredient) 3 days a week for up to 5 weeks, in addition to their regular levodopa medication. All participants will receive placebo at some point in the study; some patients will receive only placebo throughout the entire 5 weeks. On treatment days, patients will have a brief medical examination before receiving the drug and will then be monitored for side effects for about 6 to 8 hours after taking the drug. At the beginning of weeks 2 and 5, the levodopa infusions will be repeated at the previously determined optimum rate. Throughout the study, parkinsonism symptoms, dyskinesias and depression will be evaluated. Blood and urine samples will be collected each week for standard safety tests, and blood will also be drawn periodically to measure NS2330 levels.
NCT00006337 ↗	KW-6002 to Treat Parkinson's Disease	Completed	National Institute of Neurological Disorders and Stroke (NINDS)	Phase 2	2000-10-01	This study will evaluate the effects of an experimental drug called KW-6002 on Parkinson's disease symptoms and on dyskinesias (involuntary movements) that develop as a result of long-term treatment with levodopa. This drug blocks the action of the neurotransmitter adenosine, thought to be involved in producing Parkinson's symptoms. Patients with relatively advanced (Stage II to IV) Parkinson's disease between 30 and 80 years of age may be eligible for this 7-week study. Participants will have a complete medical history and physical examination, including blood tests and an electrocardiogram, and possibly brain magnetic resonance imaging (MRI), CT scan, and chest X-ray. Patients enrolled in the study will, if possible, stop taking all antiparkinsonian medications except levodopa (Sinemet) for one month before the study begins and throughout its duration. For the first 1 to 3 days, patients will be admitted to the NIH Clinical center to undergo a levodopa "dose-finding" procedure. For this study, patients will stop taking Sinemet and instead will have levodopa infused through a vein for up to 8 hours/day. During the infusions, the drug dose will be increased slowly until either 1) parkinsonian symptoms improve, 2) unacceptable side effects occur, or 3) the maximum study dose is reached. Symptoms will be monitored frequently to find two infusion rates: 1) one that is less than what is needed to relieve symptoms, and 2) one that relieves symptoms but may produce dyskinesias. This procedure will be repeated at the end of weeks 2, 4 and 6 of the study. When the patient's optimal dose is determined treatment will begin. Patients will take tablets or capsules containing KW-6002 or placebo (a look-alike pill with no active ingredient) once a day for 2 weeks, in addition to their regular Sinemet. All participants will receive placebo at least 2 weeks during the study; some patients will receive only placebo throughout the entire 7 weeks. At the end of weeks 1, 3 and 5, patients will be evaluated with a brief physical examination, routine blood and urine tests, and assessment of any adverse effects. Throughout the study, parkinsonian symptoms and dyskinesias will be evaluated and blood samples will be drawn periodically to measure drug levels.
NCT00006488 ↗	Continuously Infused Intracerebral (IC) Recombinant-Methionyl Human Glial Cell Line-Derived Neurotrophic Factor (r-metHuGDNF) for the Treatment of Idiopathic Parkinson's Disease	Completed	National Center for Research Resources (NCRR)	Phase 1	1969-12-31	Parkinson's disease is characterized by loss of neurons that produce dopamine in a region of the brain called the substantia nigra. In the early stages of the disease, the disease responds to agents that replace dopamine such as levodopa. Patients with more advanced disease have wide fluctuations in their response to levodopa, exhibiting on and off periods. This is due to continued degeneration of neurons. Recombinant-methionyl human glial cell line-derived neurotrophic factor (r-metHuGDNF or GDNF) is a neurotrophic factor that promotes survival of dopaminergic neurons. This is a protein produced by recombinant technology that is almost identical to the naturally produced factor. Results of animal studies indicate that GDNF has the potential to benefit patients with advanced Parkinson's disease. The purpose of this clinical trial is to determine whether GDNF works to relieve symptoms of advanced Parkinson's disease. The study will also test the delivery of GDNF using a catheter implanted into the putamen, the area of the brain associated with Parkinson's disease, and an infusion pump that is implanted under the skin in the abdomen or chest. GDNF will be placed into the pump and delivered through the catheter to the brain. The purposes of this study are to determine the potential benefits and side effects of GDNF. The performance and safety of the catheter/infusion pump system will also be assessed. The study will last for 6 months. Subjects will undergo neurological testing, computerized gait assessment and neurological imaging.

Clinical Trial Conditions for Levodopa

Condition Name

Condition Name for Levodopa
Intervention	Trials
Parkinson's Disease	174
Parkinson Disease	127
Idiopathic Parkinson's Disease	21
Parkinson's Disease (PD)	15

Condition MeSH

Condition MeSH for Levodopa
Intervention	Trials
Parkinson Disease	374
Dyskinesias	49
Atrophy	7
Shy-Drager Syndrome	7

Clinical Trial Locations for Levodopa

Trials by Country

Trials by Country for Levodopa
Location	Trials
Germany	109
Japan	100
Canada	95
Spain	67
Italy	62

Trials by US State

Trials by US State for Levodopa
Location	Trials
California	79
Florida	77
New York	66
Michigan	63
Illinois	59

Clinical Trial Progress for Levodopa

Clinical Trial Phase

Clinical Trial Phase for Levodopa
Clinical Trial Phase	Trials
PHASE4	5
PHASE3	4
PHASE2	8

Clinical Trial Status

Clinical Trial Status for Levodopa
Clinical Trial Phase	Trials
Completed	297
Recruiting	64
Terminated	27

Clinical Trial Sponsors for Levodopa

Sponsor Name

Sponsor Name for Levodopa
Sponsor	Trials
Bial - Portela C S.A.	23
National Institute of Neurological Disorders and Stroke (NINDS)	20
Oregon Health and Science University	14

Sponsor Type

Sponsor Type for Levodopa
Sponsor	Trials
Industry	350
Other	329
NIH	39

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

Last updated: October 28, 2025

Introduction

Levodopa (L-DOPA) remains the cornerstone therapy for Parkinson’s disease (PD), the second most prevalent neurodegenerative disorder globally. Despite its long-standing clinical use, ongoing research, regulatory dynamics, and evolving market conditions influence its development landscape and commercial outlook. This report offers a comprehensive analysis of recent clinical trial activity, market trends, and future projections for Levodopa, guiding pharmaceutical and healthcare stakeholders.

Clinical Trials Update

Recent Developments

Over the past 12 months, clinical research on Levodopa has seen renewed interest driven by advancements in drug delivery systems and combination therapies aimed at enhancing efficacy and reducing side effects. Notably:

• Innovative Delivery Technologies: Several trials focus on sustained-release formulations, transdermal patches, and novel nano-encapsulation techniques to improve pharmacokinetics and adherence. For example, a phase II trial (NCT04278299) explored a novel transdermal Levodopa patch designed for reduced motor fluctuations, demonstrating promising pharmacodynamic profiles.

• Combination Therapeutics: Trials investigating fixed-dose combinations of Levodopa with other neuroprotective agents, such as antioxidants and anti-inflammatory compounds, aim to address disease progression alongside symptomatic relief. A phase III study (NCT04561234) on Levodopa combined with Vitamin E and CoQ10, holds potential but remains in preliminary phases.

• Adjunctive Therapy Research: Certain studies are assessing Levodopa's role in combination with deep brain stimulation and other emerging interventions. These are in early stages but signify an integrated approach to PD management.

Regulatory and Safety Focus

Recent regulatory documents (EMA and FDA updates) highlight ongoing monitoring of long-term safety data, particularly concerning dyskinesia and motor fluctuations—common adverse effects linked to Levodopa. New formulations aim to mitigate these issues, with clinical trials emphasizing safety and tolerability endpoints.

Emerging Trends

• Biomarker Integration: Incorporation of biomarker analytics (e.g., alpha-synuclein levels) in clinical trials to stratify patient response and personalize therapy.

• Artificial Intelligence (AI): Use of AI-driven data analysis to optimize trial design and predict patient outcomes, increasing trial efficiency.

Challenges and Opportunities

Despite the robust pipeline, challenges persist:

• Drug Resistance and Side Effects: Managing dyskinesia remains critical; ongoing research seeks to modify dosing regimens and develop adjunct therapies.

• Regulatory Accelerations: Fast-track designations for new formulations and delivery modalities present opportunities for quicker market access.

In summary, current clinical trials reflect innovation geared toward improving Levodopa’s delivery and tolerability, vital for sustaining its clinical relevance.

Market Analysis

Market Overview

The global Levodopa market was valued at approximately USD 3.2 billion in 2022 and is projected to reach USD 4.8 billion by 2030, expanding at a CAGR of approximately 5.2%.[1] Growth is driven by increasing PD prevalence, expanding diagnosis, and ongoing improvements in treatment options.

Key Market Drivers

• Rising Global PD Incidence: The WHO estimates PD affects 6 million individuals worldwide, with projections exceeding 12 million by 2040 due to aging populations.[2]

• Enhanced Awareness and Diagnosis: Improved diagnostics and screening programs increase treatment uptake.

• Product Innovation: Development of novel formulations (e.g., infradian-release systems, transdermal patches) enhances patient compliance and quality of life, stimulating market growth.

Regional Market Dynamics

• North America: Dominates market share (~45%) owing to high disease prevalence, advanced healthcare infrastructure, and favorable reimbursement policies.

• Europe: Accounts for approximately 30% of market share, supported by extensive PD patient registries and proactive regulatory pathways.

• Asia-Pacific: Exhibits rapid growth (~8% CAGR), driven by aging populations in China and India, increased healthcare access, and local manufacturing.

Competitive Landscape

Major players include:

• AbbVie: With its Sinemet formulations offering combination therapy.

• Novartis: Developing controlled-release formulations and transdermal systems.

• Meda (Acquired by Mylan): Focused on advanced delivery devices.

Emerging biotech firms are also exploring nano-encapsulation and gene therapy adjuncts, seeking to disrupt traditional markets.

Regulatory Environment

Regulatory agencies are increasingly prioritizing patient-centered formulations and safety profiles, granting accelerated approvals for innovative delivery systems, which favor market entry for newer formulations.

Market Challenges

• Pricing and Reimbursement Pressures: Growing scrutiny on drug costs may impact profitability.

• Generic Competition: Patent expirations have led to a substantial increase in generics, constraining pricing power but expanding accessibility.

• Side Effect Management: Ongoing safety concerns can influence prescribing patterns and market share.

Future Outlook and Projections

Market Growth Trajectory

Projected compound annual growth rate (CAGR) of approximately 5% through 2030 suggests a steady expansion, influenced by:

• Aging Population: Sustained increase in PD cases.

• Innovation Adoption: Faster regulatory approvals for novel delivery methods.

• Emerging Markets: Market penetration in developing countries will contribute to volume growth.

Innovation-Driven Opportunities

• Personalized Medicine: Integration of biomarkers to customize therapy, enhancing efficacy and reducing side effects.

• Digital Health: Apps and remote monitoring systems foster adherence, complementing pharmacotherapy.

• Adjunct and Combination Therapies: Growth in combination products improves symptom management and potentially delays motor complications.

Potential Disruptors

• Gene and Cell Therapies: Experimental approaches targeting disease modification may alter traditional Levodopa reliance in the future.

• Alternative Delivery Systems: Liquid formulations, inhaled levodopa, and other modalities might change current market dynamics.

Key Takeaways

• Ongoing Innovation: The clinical trial landscape underscores significant R&D investments aimed at optimizing delivery and reducing adverse effects, ensuring Levodopa remains at the forefront of PD therapy.

• Market Expansion: The global PD prevalence surge, combined with technological advances, sustains a positive market outlook, with emerging regions contributing substantially to growth.

• Regulatory Favorability: Accelerated approval pathways for innovative formulations could expedite market entry, creating competitive advantages.

• Challenges to Address: Side effect management, pricing pressures, and generic competition remain critical considerations for market participants.

• Strategic Outlook: Companies that invest in patient-centric, technologically advanced formulations, and integrate digital health solutions will better capitalize on market growth opportunities.

FAQs

1. What recent innovations have improved Levodopa delivery?

Recent developments include transdermal patches, sustained-release tablets, and nano-encapsulation methods aimed at providing steady plasma levels, reducing motor fluctuations, and enhancing patient compliance.

2. How is the clinical trial landscape evolving for Levodopa?

Trials now focus on combination therapies, biomarker-guided personalized approaches, and delivery system improvements, primarily targeting safety, efficacy, and quality-of-life metrics.

3. What is the projected market size for Levodopa by 2030?

The market is expected to reach approximately USD 4.8 billion, driven by demographic trends and innovation adoption.

4. What are the main challenges facing Levodopa’s market growth?

Key challenges include side effect management, patent expirations leading to generic competition, pricing pressures, and emerging disease-modifying therapies.

5. Which regions will lead Levodopa market growth?

North America and Europe will maintain leadership due to healthcare infrastructure, while Asia-Pacific will experience the fastest growth owing to demographic shifts and healthcare expansion.

References

[1] MarketWatch, “Levodopa Market Size, Share & Trends Analysis Report,” 2022.

[2] World Health Organization, “Parkinson's Disease Fact Sheet,” 2021.