CLINICAL TRIALS PROFILE FOR AMANTADINE HYDROCHLORIDE

505(b)(2) Clinical Trials for amantadine hydrochloride

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	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 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 amantadine hydrochloride

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00000301 ↗	Rapid Evaluation of Amantadine for Treatment of Cocaine Abuse/Dependence - 4	Completed	National Institute on Drug Abuse (NIDA)	Phase 2	1996-03-01	The purpose of this study is to empirically test a series of medications to: 1) determine each medication's efficacy in treatment of cocaine abuse/dependence; 2) find most effective dose range for each medication. In this study, amantadine is tested."
NCT00000301 ↗	Rapid Evaluation of Amantadine for Treatment of Cocaine Abuse/Dependence - 4	Completed	University of California, Los Angeles	Phase 2	1996-03-01	The purpose of this study is to empirically test a series of medications to: 1) determine each medication's efficacy in treatment of cocaine abuse/dependence; 2) find most effective dose range for each medication. In this study, amantadine is tested."
NCT00001930 ↗	Treatment of Huntington's Chorea With Amantadine	Completed	National Institute of Neurological Disorders and Stroke (NINDS)	Phase 2	1999-04-01	Huntington's disease is a chronic disorder passed on through genetic autosomal dominant inheritance. The condition usually begins between the ages of 30 and 50 years and it is characterized by involuntary movements in the face and extremities, (chorea), accompanied by changes in behavior and gradual loss of the mental function. The disease typically ends in a state of disorientation, impaired memory, judgement, and intellect (dementia). The objective of this study is to test the effectiveness of the drug amantadine for the treatment of chorea associated with Huntington's disease. Amantadine is an antiviral drug that has been used to treat a variety of illnesses including Parkinson's disease. Amantadine works by attaching to special sites called NMDA (N-methyl-D-aspartate) receptors and blocking the normal activity of glutamate there. Glutamate is an amino acid released by brain cells and has been associated with the symptoms of Parkinson's disease.
NCT00015249 ↗	Prepulse Inhibition of Startle in Cocaine Dependence - 7	Completed	New York MDRU	Phase 1	1997-02-01	The purpose of this study is to assess the effects of chronic cocaine use on the acoustic startle response and on gating of this response in humans.
NCT00015249 ↗	Prepulse Inhibition of Startle in Cocaine Dependence - 7	Completed	National Institute on Drug Abuse (NIDA)	Phase 1	1997-02-01	The purpose of this study is to assess the effects of chronic cocaine use on the acoustic startle response and on gating of this response in humans.
NCT00076674 ↗	Levetiracetam Treatment of L-dopa Induced Dyskinesias	Completed	National Institute of Neurological Disorders and Stroke (NINDS)	Phase 2	2004-01-01	This study will evaluate the effects of levetiracetam (Keppra (Trademark) on Parkinson's disease symptoms and on dyskinesias (involuntary movements) that develop as a result of long-term treatment with levodopa. Levetiracetam blocks certain protein receptors on brain cells and thus can change the spread of brain signals believed to be affected in patients with Parkinson's disease. Patients between 30 and 80 years of age with relatively advanced Parkinson's disease and dyskinesias due to levodopa therapy may be eligible for this 6-week study. Screening and baseline evaluation - Participants are evaluated with a medical history, physical examination and neurologic evaluation, blood tests, urinalysis, electrocardiogram (EKG), 24-hour holter monitor (heart monitoring), and cardiology consultation. A chest x-ray and MRI or CT scan of the brain are done if needed. If possible, patients stop taking all antiparkinsonian medications except levodopa (Sinemet) for one month (2 months if taking Selegiline) before the study begins and throughout its duration. (If necessary, patients may use short-acting agents, such as Mirapex, Requip or Amantadine.) Dose-finding phase - Patients are admitted to the NIH Clinical Center for 2 to 3 days for a levodopa "dose-finding" procedure. For this test, patients stop taking Sinemet and instead have levodopa infused through a vein. During the infusions, the drug dose is increased slowly until parkinsonian symptoms improve or unacceptable side effects occur or the maximum study dose is reached. Symptoms are monitored frequently. (Patients who have had dosing infusions in the last 3 months do not have to undergo this phase of the study.) Active study phase - Patients are randomly assigned to take levetiracetam or placebo ("sugar pill") twice a day for 6 weeks. At the end of weeks 1, 2 4, and 5, patients come to the clinic for blood tests, an EKG, and a review of adverse side effects. At the end of weeks 3 and 6, patients are hospitalized to study the response to treatment. They again stop taking Sinemet and selegiline and their ability to perform motor tasks is evaluated. They are then placed on an L-dopa infusion for 10 hours. Placebo may be infused at various times instead of L-dopa. Motor symptoms are evaluated several times during the infusion. Blood is drawn once during the infusion for research studies. Lumbar puncture - Patients undergo a lumbar puncture (spinal tap) at the end of weeks 1 and 4 to measure certain brain chemicals and drug levels. For this test, a local anesthetic is given and a needle is inserted in the space between the vertebrae in the lower back. About 2 tablespoons of fluid is collected through the needle. Magnetic resonance imaging (MRI) - Patients with changing disease activity may undergo MRIs at baseline, at the end of week 1 and at the end of the study to show changes in the brain. The patient lies in a narrow cylinder (the scanner) that uses radio waves and a magnetic field to produce images of the brain, which show structural and chemical changes. Follow-up - 2 weeks after the study ends, patients are contacted by phone for a review of side effects or they return to the clinic for an evaluation.

Clinical Trial Conditions for amantadine hydrochloride

Condition Name

Condition Name for amantadine hydrochloride
Intervention	Trials
Parkinson's Disease	16
Parkinson Disease	10
Traumatic Brain Injury	10
Multiple Sclerosis	7

Condition MeSH

Condition MeSH for amantadine hydrochloride
Intervention	Trials
Parkinson Disease	33
Dyskinesias	14
Brain Injuries, Traumatic	14
Brain Injuries	13

Clinical Trial Locations for amantadine hydrochloride

Trials by Country

Trials by Country for amantadine hydrochloride
Location	Trials
United States	358
Germany	40
Canada	28
France	20
Spain	11

Trials by US State

Trials by US State for amantadine hydrochloride
Location	Trials
California	20
Texas	19
North Carolina	18
Florida	18
New York	17

Clinical Trial Progress for amantadine hydrochloride

Clinical Trial Phase

Clinical Trial Phase for amantadine hydrochloride
Clinical Trial Phase	Trials
PHASE2	6
Phase 4	22
Phase 3	26

Clinical Trial Status

Clinical Trial Status for amantadine hydrochloride
Clinical Trial Phase	Trials
Completed	59
Unknown status	17
Terminated	16

Clinical Trial Sponsors for amantadine hydrochloride

Sponsor Name

Sponsor Name for amantadine hydrochloride
Sponsor	Trials
Adamas Pharmaceuticals, Inc.	9
Novagenix Bioanalytical Drug R&D Center	5
Hoffmann-La Roche	5

Sponsor Type

Sponsor Type for amantadine hydrochloride
Sponsor	Trials
Other	153
Industry	40
NIH	9

Clinical Trials Update, Market Analysis, and Projection for Amantadine Hydrochloride

Last updated: October 28, 2025

Introduction

Amantadine Hydrochloride, originally developed for influenza A treatment, has evolved into a multifaceted pharmaceutical agent, primarily recognized for its roles in managing Parkinson’s disease, drug-induced extrapyramidal symptoms, and, more recently, potential neuroprotective applications. With its longstanding clinical use, ongoing research, and expanding therapeutic indications, understanding its current clinical trial activity, market landscape, and future projections provides vital insights for stakeholders ranging from biotech firms to healthcare policy makers.

Clinical Trials Update

Historical Clinical Use and Current Trials

Amantadine Hydrochloride was first approved by the FDA in 1966 for influenza A prophylaxis and treatment. Over time, its off-label use in Parkinson’s disease gained prominence, driven by its dopaminergic mechanisms that mitigate motor symptoms.

Recent Clinical Trial Activity

In the past five years, clinical investigation into Amantadine Hydrochloride has accelerated, especially in areas beyond traditional indications:

• Neurodegenerative disorders: Trials examining its neuroprotective potential in Parkinson’s disease, Alzheimer's disease, and multiple sclerosis.

• COVID-19: Preliminary studies explored antiviral potentials and symptom management, though limited by inconsistent results. Notably, a phase II clinical trial (NCT04358362) investigated low-dose amantadine for early COVID-19 symptoms, but conclusive evidence remains pending.

• Traumatic Brain Injury (TBI): Several trials, including NCT04534451, are evaluating its efficacy in post-TBI cognitive and motor recovery, citing its ability to modulate neural activity.

• Psychiatric Disorders: Investigations assessing effectiveness in bipolar disorder and obsessive-compulsive disorder are ongoing, focusing on its dopaminergic and glutamatergic modulation.

Noteworthy Clinical Trial Data and Outcomes

A 2019 randomized controlled trial published in Movement Disorders demonstrated that Amantadine could modestly improve levodopa-induced dyskinesia in Parkinson’s patients. However, evidence for disease-modifying effects remains inconclusive, necessitating larger, well-powered investigations.

Regulatory Landscape

While Amantadine’s regulatory status remains stable for established indications, several clinical trials aim to gain approval for new uses. The FDA requires more substantial evidence before expanding approved indications, particularly for neurodegenerative diseases, where preliminary data are promising but unconfirmed.

Market Analysis

Global Market Overview

The Amantadine Hydrochloride market historically reflected its use in antiparkinsonian therapy and influenza prophylaxis. However, with the decline in influenza indications due to vaccine availability and the emergence of new antiviral agents, the market's emphasis has shifted toward neurodegenerative and off-label indications.

• Market Size (2022): Estimated around USD 150 million, predominantly driven by North American and European markets, where Parkinson’s disease prevalence is high.

• Key Manufacturers: Cipla, Mylan, Teva Pharmaceuticals, with generic versions accounting for a significant portion of sales.

Market Drivers

• Aging Population: The global increase in elderly populations, particularly in North America, Europe, and Asia-Pacific regions, elevates Parkinson’s disease prevalence, augmenting demand for amantadine-based therapies.

• Off-Label and Expanded Uses: Growing research into neuroprotective and cognitive applications opens avenues for new indications, potentially revitalizing the market.

• Cost-Effectiveness: Generic formulations make amantadine an affordable option in both developed and developing economies, expanding market access.

Market Challenges

• Efficacy and Safety Concerns: Ambiguous evidence regarding disease-modifying effects limits regulatory approvals for new indications.

• Emerging Therapies: Advances in gene therapy, monoclonal antibodies, and novel dopamine agents threaten to displace amantadine as the standard of care in Parkinson’s management.

• Side Effect Profile: Neurological side effects, such as hallucinations and confusion, can constrain use, especially in elderly populations.

Competitive Landscape

Market leaders focus on patent expirations and generic proliferation. Companies investing in R&D for new formulations or delivery methods (e.g., sustained-release, transdermal systems) seek to maintain competitiveness.

Regional Market Outlook (2023-2030)

• North America: Remains dominant, driven by high Parkinson’s prevalence and extensive clinical trial activity.
• Europe: Growing infrastructure for neurodegenerative disease research.
• Asia-Pacific: Rapidly expanding due to increasing geriatric population and healthcare access improvements.
• Emerging Markets: Potential growth, contingent on regulatory approvals and cost factors.

Market Projection and Future Outlook

Forecasted Market Growth

According to industry analysts, the global Amantadine Hydrochloride market is projected to grow at a CAGR of approximately 4-5% from 2023 to 2030, reaching around USD 220-250 million by 2030. The increased focus on neurological conditions, combined with ongoing clinical trials demonstrating potential new therapeutic roles, underpin this upward trajectory.

Influence of Ongoing Clinical Trials

Positive results from trials evaluating neuroprotective effects could lead to expanded indications, approval, and increased sales. Conversely, inconclusive or negative outcomes could dampen growth prospects.

Potential Market Expansion Strategies

• Regulatory Approval for New Indications: Fast-tracking the approval process for promising neurodegenerative therapies.
• Development of Novel Delivery Systems: Enhancing bioavailability and reducing side effects.
• Strategic Collaborations: Partnering with biotech firms specializing in neurodegeneration research.

Risks and Uncertainties

• Regulatory Hurdles: Stringent approval processes could delay or prevent expansion.
• Market Penetration Challenges: Existing competition and clinician familiarity with current standards of care.
• Research Failures: Unsuccessful clinical trials may diminish confidence and investment.

Key Takeaways

• Ongoing clinical trials are exploring novel uses of Amantadine Hydrochloride, especially in neurodegenerative and neuroprotective contexts. While promising, substantial evidence is necessary for regulatory approval extension.
• The market, now primarily driven by Parkinson’s disease management, is expected to grow steadily, aided by demographic aging and increasing research activity.
• The marketplace faces challenges from emerging therapies, safety concerns, and inconsistent efficacy data—factors that could influence future demand.
• Strategic development of formulations, indications, and international regulatory strategies will be key to maximizing market potential.
• Continued monitoring of clinical trial outcomes and regulatory developments will be crucial for stakeholders planning investments or therapeutic positioning.

FAQs

1. What are the primary current indications for Amantadine Hydrochloride?
   Its main FDA-approved uses include treatment for Parkinson’s disease, drug-induced extrapyramidal symptoms, and prophylaxis against influenza A.

2. Are there ongoing trials exploring Amantadine’s role in COVID-19?
   Yes. Some trials, such as NCT04358362, assessed its antiviral and symptom-relieving potential in COVID-19, but results have been inconclusive, limiting widespread adoption for this indication.

3. What emerging therapeutic areas could expand Amantadine's market?
   Neuroprotective applications in Alzheimer’s, multiple sclerosis, traumatic brain injury, and other neurodegenerative disorders are promising, pending positive trial outcomes.

4. What are the main challenges facing the future market of Amantadine Hydrochloride?
   Challenges include competition from novel therapies, safety concerns, regulatory approval hurdles, and inconsistent efficacy data for new indications.

5. How might upcoming clinical trial results impact the global market?
   Successful trials demonstrating definitive neuroprotective benefits could lead to expanded indications, regulatory approvals, and substantial market growth; failures could stall or reduce growth prospects.

References

1. Movement Disorders. (2019). Efficacy of Amantadine in Parkinson’s dyskinesia.
2. ClinicalTrials.gov. (2023). Ongoing trials related to Amantadine Hydrochloride.
3. Industry Reports. (2022). Global Neurodegenerative Disease Therapeutics Market.
4. FDA Regulatory Documents. (2021). Approved uses and guidelines for Amantadine Hydrochloride.