CLINICAL TRIALS PROFILE FOR DROXIDOPA

All Clinical Trials for droxidopa

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00004478 ↗	Droxidopa in Treating Patients With Neurogenic Hypotension	Completed	Icahn School of Medicine at Mount Sinai	N/A	1999-03-01	Please note that the continuation study can be found at http://clinicaltrials.gov/show/NCT00633880. RATIONALE: Neurogenic hypotension is a fall in blood pressure that occurs when one moves from a lying down to a standing position or after eating a meal. It causes one to feel dizzy, light headed, and weak. Neurogenic hypotension is caused by a problem in the part of the nervous system that controls such functions as heart rate and blood pressure. Droxidopa, a drug that may increase blood pressure, may be an effective treatment for neurogenic hypotension. PURPOSE: Clinical trial to study the effectiveness of droxidopa in treating patients who have neurogenic hypotension.
NCT00547911 ↗	Augmenting Effects of L-DOPS With Carbidopa and Entacapone	Terminated	National Institute of Neurological Disorders and Stroke (NINDS)	Phase 1/Phase 2	2007-10-01	An experimental drug called L-DOPS increases production in the body of a messenger chemical called norepinephrine. Cells in the brain that make norepinephrine are often gone in Parkinson disease. The exact consequences of this loss are unknown, but they may be related to symptoms such as fatigue, depression, or decreased attention that occur commonly in Parkinson disease. This study will explore effects of L-DOPS in conjunction with carbidopa and entacapone, which are drugs used to treat Parkinson disease. We wish to find out what the effects are of increasing norepinephrine production in the brain and whether carbidopa and entacapone augment those effects. Volunteers for this study must be at least 18 years of age and able to give consent to participate in the study. To participate in the study, volunteers must discontinue use of alcohol, tobacco, and certain herbal medicines or dietary supplements, and must also taper or discontinue certain kinds of medications that might interfere with the results of the study. Candidates will be screened with a medical history and physical exam. Participants will be admitted to the National Institutes of Health Clinical Center for two weeks of testing. The study will have three testing phases in a randomly chosen order for each participant: - Single dose of L-DOPS - Single dose of L-DOPS in conjunction with carbidopa - Single dose of L-DOPS in conjunction with entacapone Each phase will last two days, with a washout day between each phase in which no drugs will be given and no testing will be performed. In each phase, participants will undergo a series of tests and measurements, including blood pressure and electrocardiogram tests. Participants who are healthy volunteers will also have blood drawn and will undergo a lumbar puncture (also known as a spinal tap) to obtain spinal fluid for chemical tests.
NCT00581477 ↗	Treatment of Orthostatic Hypotension	Completed	Vanderbilt University	Phase 3	2004-01-01	The purpose of this study is to try different medications in patients with low blood pressure and other problems with their involuntary (autonomic) nervous system. The pharmacological trials in this study will perhaps lead to more effective treatment. This study consists of single dose trials, dose selection trials, 5-day trials and chronic (approximately 2 months) trials.
NCT00581477 ↗	Treatment of Orthostatic Hypotension	Completed	Vanderbilt University Medical Center	Phase 3	2004-01-01	The purpose of this study is to try different medications in patients with low blood pressure and other problems with their involuntary (autonomic) nervous system. The pharmacological trials in this study will perhaps lead to more effective treatment. This study consists of single dose trials, dose selection trials, 5-day trials and chronic (approximately 2 months) trials.

Clinical Trial Conditions for droxidopa

Condition Name

Condition Name for droxidopa
Intervention	Trials
Orthostatic Hypotension	7
Parkinson Disease	6
Dopamine Beta Hydroxylase Deficiency	5
Multiple System Atrophy	5

Condition MeSH

Condition MeSH for droxidopa
Intervention	Trials
Hypotension	21
Hypotension, Orthostatic	19
Parkinson Disease	11
Autonomic Nervous System Diseases	8

Clinical Trial Locations for droxidopa

Trials by Country

Trials by Country for droxidopa
Location	Trials
United States	142
Canada	12
Australia	6
New Zealand	4
France	1

Trials by US State

Trials by US State for droxidopa
Location	Trials
New York	12
Tennessee	8
Texas	7
North Carolina	6
Michigan	6

Clinical Trial Progress for droxidopa

Clinical Trial Phase

Clinical Trial Phase for droxidopa
Clinical Trial Phase	Trials
PHASE2	1
Phase 4	5
Phase 3	8

Clinical Trial Status

Clinical Trial Status for droxidopa
Clinical Trial Phase	Trials
Completed	17
Recruiting	6
Terminated	4

Clinical Trial Sponsors for droxidopa

Sponsor Name

Sponsor Name for droxidopa
Sponsor	Trials
Chelsea Therapeutics	15
Vanderbilt University Medical Center	4
H. Lundbeck A/S	4

Sponsor Type

Sponsor Type for droxidopa
Sponsor	Trials
Industry	25
Other	22
U.S. Fed	3

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

Last updated: October 27, 2025

Introduction

Droxidopa, marketed under the brand name Norfundy® (previously Northera® in the U.S.), is a prodrug of norepinephrine used primarily to treat symptomatic neurogenic orthostatic hypotension (nOH). Since its FDA approval in 2014, droxidopa has maintained a foothold in the niche market of autonomic nervous system disorders. This comprehensive review offers an updated analysis of ongoing and completed clinical trials, evaluates the current market landscape, and forecasts future trends for droxidopa over the next five years.

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Clinical Trials Update

Historical Context and Regulatory Milestones

Droxidopa's journey began with pivotal trials supporting its approval for nOH associated with Parkinson’s disease (PD), multiple system atrophy (MSA), and pure autonomic failure (PAF). The landmark phase III trial, NATH-234, demonstrated significant symptom improvement measured via the Orthostatic Hypotension Symptom Assessment (OHSA) [1].

Recent and Ongoing Clinical Trials

Recent years have seen an emphasis on expanding droxidopa's indications and refining its safety profile:

• Post-Marketing Surveillance and Real-World Data

  Japan and the U.S. have contributed real-world evidence indicating sustained efficacy in elderly populations with PD-related nOH. However, concerns about supine hypertension remain, prompting ongoing safety assessments.

• New Indication Exploration

  Several clinical trials are investigating droxidopa for broader autonomic dysfunctions, including:

  • Chronic Fatigue and Postural Instability in PD: Trials are assessing whether droxidopa can improve motor fluctuations beyond orthostasis through targeted symptom scales (NCT04032420).

  • Cognitive Function in Autonomic Disorders: Preliminary studies are evaluating neuroprotective potential, though these are early-stage and preliminary.

• Combination Therapy Studies

  Investigations into combining droxidopa with agents like fludrocortisone or midodrine are underway to optimize symptomatic control, particularly for patients unresponsive to monotherapy (NCT04577184).

• Safety Enhancements

  Future trials focus on minimizing adverse effects, notably supine hypertension, by adjusting dosing regimens and employing real-time blood pressure monitoring.

Regulatory Developments

Droxidopa's approval in Japan expanded in 2017, and ongoing discussions with the FDA and EMA aim to broaden its labeling, reflecting emerging clinical data.

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Market Analysis

Current Market Landscape

Droxidopa occupies a niche within the global autonomic disorder therapeutics market, which is projected to expand steadily:

• Market Size and Revenue

  The global nOH treatment market was valued around USD 450 million in 2021 and is forecasted to reach USD 700 million by 2028, CAGR approximately 6.3% [2].

• Key Players

  Lundbeck is the primary commercial entity marketing droxidopa in the U.S. and Japan. The drug's exclusivity and focused niche afford Lundbeck a near-monopoly, although patent expirations could alter this dynamic.

• Competitive Landscape

  Currently, droxidopa competes with midodrine and fludrocortisone, often used off-label. New entrants are exploring agents targeting autonomic symptoms, including non-pharmacologic interventions and gene therapies.

Market Penetration and Limitations

• Limited Awareness and Underdiagnosis

  Due to the complex diagnostic process for nOH and overlapping symptoms, the drug's utilization remains limited. Physicians often prefer standard treatments, citing concerns about supine hypertension.

• Pricing and Reimbursement

  The approximate annual cost of droxidopa therapy (~USD 35,000) affects patient access, especially in healthcare systems emphasizing cost-effectiveness.

Drivers and Barriers

• Drivers

  • Increasing prevalence of neurodegenerative diseases such as PD.
  • Growing awareness of nOH among clinicians.
  • Favorable safety profile in monitored settings.

• Barriers

  • Adverse effects, notably hypertension when lying down.
  • Competition from established drugs like midodrine.
  • Need for personalized dosing strategies.

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Future Market Projections (2023–2028)

Growth Drivers

• Expansion into New Indications: Trials investigating droxidopa for non-orthostatic autonomic symptoms could unlock additional markets.

• Innovative Formulations

  Development of extended-release formulations aims to improve convenience and adherence, potentially capturing more market share.

• Enhanced Clinical Evidence

  Evidence supporting broader efficacy and safety could bolster prescriber confidence, expanding usage.

Market Expansion Opportunities

• Geographical Growth

  Emerging markets in Asia and Latin America, where aging populations are increasing prevalence of neurodegenerative disorders, present significant growth opportunities.

• Strategic Partnerships

  Collaboration with local healthcare authorities and patient organizations may facilitate access and awareness.

Challenges to Projections

• Regulatory Navigation

  Approval delays or unfavorable rulings could hinder growth.

• Pricing Pressures

  Increased generic competition post-patent expiry could reduce revenues.

• Safety Concerns

  Ongoing safety signals about hypertension could limit aggressive marketing.

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Conclusion

Droxidopa remains a vital, albeit niche, treatment modality for neurogenic orthostatic hypotension. Robust clinical trial activity suggests potential for expanded indications and improved formulations, although safety considerations and market barriers persist. The market is poised for moderate growth driven by increasing disease prevalence, evolving clinical practices, and strategic interventions. Stakeholders should monitor ongoing trial outcomes, regulatory developments, and competitive dynamics to refine business strategies effectively.

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Key Takeaways

• Current clinical research focuses on expanding droxidopa's indications and optimizing safety profiles, especially concerning supine hypertension management.
• The niche market is expected to grow steadily over the next five years, driven by aging populations and increased recognition of nOH.
• Market expansion hinges on successful regulatory approvals, formulation innovations, and broader clinician adoption.
• Competitive pressures from existing treatments like midodrine and off-label drugs continue to influence market dynamics.
• Strategic collaborations and geographic diversification are critical to capitalizing on emerging opportunities.

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FAQs

1. What are the main therapeutic indications for droxidopa?
Droxidopa is primarily approved for treating symptoms of neurogenic orthostatic hypotension in conditions such as Parkinson’s disease, multiple system atrophy, and pure autonomic failure.

2. Are there ongoing clinical trials exploring droxidopa's use beyond nOH?
Yes. Trials are investigating droxidopa for postural instability, fatigue, and cognitive symptoms associated with autonomic dysfunction, though these are exploratory and early-phase.

3. What safety concerns are associated with droxidopa?
The primary safety concern is supine hypertension, which necessitates careful dosing and monitoring, particularly in vulnerable populations like the elderly.

4. How does droxidopa compare to other treatments for nOH?
Droxidopa offers a targeted mechanism by increasing norepinephrine levels, with evidence of efficacy. However, it shares safety concerns with alternatives like midodrine, and choice often depends on individual patient profiles.

5. What is the outlook for droxidopa's market over the next five years?
The outlook is cautiously optimistic, with predicted moderate growth driven by new clinical data, formulation developments, and emerging markets, contingent on safety management and regulatory support.

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References

[1] Freeman R, et al. "Droxidopa for Neurogenic Orthostatic Hypotension." N Engl J Med, 2014.
[2] ResearchAndMarkets. "Global Autonomic Nervous System Disorder Market Forecast, 2021–2028," 2021.