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.
NCT00108667 ↗	Talampanel to Treat Parkinson's Disease	Completed	National Institute of Neurological Disorders and Stroke (NINDS)	Phase 2	2005-04-01	This study will evaluate the effects of the experimental drug talampanel on dyskinesias (involuntary movements) that develop in patients with Parkinson's disease as a result of long-term treatment with levodopa (Sinemet). The drug will be tested alone and in combination with amantadine-a drug commonly used to alleviate dyskinesias. Patients between 21 and 80 years of age with Parkinson's disease and dyskinesias may be eligible for this study. Screening and baseline evaluation. Participants are evaluated with a medical history, physical and neurologic examinations, blood and urine tests, electrocardiogram (EKG) and pregnancy test, if applicable. A chest x-ray and MRI or CT scan of the brain are done if needed. Patients stop taking all antiparkinsonian medications for one month (2 months if taking Selegiline) before the study begins and throughout its duration, except for certain medicines allowed, including Sinemet, Mirapex and Requip. Amantadine can be taken up to 1 week before beginning the study. 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 it 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. At given times during the infusion, saline is given instead of Sinemet. The infusions usually begin in the early morning and continue until evening. Patients resume taking Sinemet between infusions. (Patients who have had dosing infusions in the last 3 months do not have to undergo this phase of the study.) After the dose-finding phase, patients are randomly assigned to take placebo (a "sugar pill") or talampanel. Those taking talampanel also receive amantadine at their usual dosages. At some point in the study, amantadine is replaced with placebo. Patients in the talampanel group also receive placebo for portions of the study. Active study phase. At study weeks 1, 5 and 7, patients are admitted to the Clinical Center overnight for a levodopa infusion with talampanel or placebo. The day before the infusion, patients have a brief physical examination, blood and urine tests, an EKG, and a review of symptoms or changes in their condition. The next day, they receive an infusion of levodopa at the dose determined in the dose-finding phase. Then they take a pill containing either talampanel or placebo. Their parkinsonian symptoms and dyskinesias are evaluated and videotaped every 30 minutes for about 6 hours. Blood is drawn and an EKG is obtained. At the end of the infusions and ratings, patients resume their regular Parkinson's medications and are given a new supply of study medications to take home. At weeks 2, 3, 4 and 6, patients come to the Clinical Center for a review of drug side effects. They have blood drawn and receive a new supply of study medications that last until the next visit. Follow-up. Two 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
Brain Injuries, Traumatic	14
Dyskinesias	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
Florida	18
North Carolina	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
Hoffmann-La Roche	5
Oregon Health and Science University	5

Sponsor Type

Sponsor Type for Amantadine Hydrochloride
Sponsor	Trials
Other	153
Industry	40
NIH	9

Amantadine Hydrochloride: Clinical Trial Landscape, Market Analysis, and Future Projections

Last updated: February 19, 2026

Amantadine hydrochloride demonstrates a persistent presence in clinical trials, primarily for neurological and psychiatric conditions. The current market, while mature for its established indications, shows potential for expansion driven by novel therapeutic applications and lifecycle management strategies. Projections indicate steady, albeit modest, growth, contingent on the successful navigation of ongoing clinical development and regulatory approvals.

What is the current status of amantadine hydrochloride's clinical development?

Amantadine hydrochloride continues to be evaluated across a spectrum of clinical trials, reflecting its established antiviral and dopaminergic properties. The majority of active studies focus on its utility in conditions beyond its original approved uses, with a notable concentration on Parkinson's disease (PD) and related motor fluctuations, as well as certain psychiatric disorders, particularly those associated with cognitive impairment or specific symptom clusters.

As of the latest available data, the distribution of amantadine hydrochloride clinical trials by indication is as follows:

• Parkinson's Disease (PD) and Motor Fluctuations: This remains the largest category of ongoing trials. Studies are investigating amantadine's efficacy in reducing L-DOPA induced dyskinesias, managing motor symptoms in early and advanced PD, and as an adjunct therapy. Trial phases range from Phase II to Phase IV.
• Cognitive Impairment Associated with Neurological Conditions: Trials are exploring amantadine's potential to improve cognitive function in conditions such as traumatic brain injury (TBI), stroke recovery, and certain forms of dementia. These studies often focus on executive function, attention, and memory.
• Psychiatric Disorders: A subset of trials examines amantadine for its effects on symptoms in conditions like schizophrenia, particularly for negative symptoms or cognitive deficits, and in some cases, for managing specific behavioral aspects of other psychiatric conditions.
• Other Neurological Conditions: Smaller cohorts of trials investigate amantadine's role in conditions such as multiple sclerosis (MS) for fatigue management and in post-herpetic neuralgia.
• COVID-19 and Post-Viral Syndromes: Following its antiviral history, amantadine has seen limited investigation in trials related to COVID-19 symptoms or post-viral fatigue, although this area represents a smaller portion of current research.

The progression of these trials indicates a continued interest in leveraging amantadine's mechanism of action, which includes NMDA receptor antagonism and dopaminergic effects, to address unmet needs in various neurological and psychiatric domains. Data from completed Phase III trials for novel indications, where available, inform the current trajectory of development. Regulatory submissions are anticipated for indications where robust efficacy and safety data emerge from late-stage trials.

What is the market landscape for amantadine hydrochloride?

The market for amantadine hydrochloride is characterized by its established presence in its approved indications, primarily Parkinson's disease (for dyskinesia) and influenza A. However, the market dynamics are influenced by several factors including generic competition, the development of extended-release formulations, and ongoing clinical research exploring new therapeutic avenues.

Market Size and Growth Drivers

The global amantadine hydrochloride market is estimated to be in the range of \$150 million to \$250 million annually. Growth in this segment is projected to be modest, with a compound annual growth rate (CAGR) of 2% to 4% over the next five years.

Key drivers for this market include:

• Aging Global Population: This demographic trend increases the prevalence of age-related neurological disorders like Parkinson's disease, thereby sustaining demand.
• Off-Label Use and Investigational Therapies: The ongoing clinical trials exploring amantadine for conditions such as TBI, cognitive impairment, and certain psychiatric symptoms contribute to market potential if these indications receive regulatory approval.
• Lifecycle Management: The introduction of extended-release formulations aims to improve patient compliance and potentially expand market share within existing indications by offering differentiated delivery profiles.
• Generic Availability: The presence of multiple generic manufacturers for immediate-release formulations exerts downward pressure on pricing but also ensures broad accessibility, contributing to overall volume.

Competitive Landscape

The competitive landscape is fragmented, with both branded and generic manufacturers participating.

• Major Generic Manufacturers: Companies such as Teva Pharmaceutical Industries Ltd., Mylan N.V. (now part of Viatris), and generics divisions of larger pharmaceutical firms are significant players, offering cost-effective amantadine hydrochloride products.
• Branded and Specialty Formulations: Companies that have developed or market specific extended-release formulations may hold a premium position for these differentiated products.

The market is characterized by price sensitivity, particularly for immediate-release generics. However, extended-release formulations can command higher price points. The primary competitive factors are price, product availability, and the perceived value proposition of differentiated formulations for patient adherence and efficacy.

Pricing and Reimbursement

Pricing for amantadine hydrochloride varies significantly based on formulation, manufacturer, and geographic region. Immediate-release generic versions are priced competitively, typically ranging from \$0.10 to \$0.50 per capsule/tablet. Extended-release formulations are priced higher, potentially ranging from \$2.00 to \$5.00 per capsule.

Reimbursement policies generally cover amantadine hydrochloride for its approved indications, particularly Parkinson's disease. However, coverage for off-label or investigational uses is dependent on specific payer policies and the availability of robust clinical evidence supporting efficacy and cost-effectiveness. Prior authorization may be required for certain uses or formulations.

What are the future projections and market opportunities for amantadine hydrochloride?

Future projections for amantadine hydrochloride indicate a stable market for its established indications, with potential for expansion contingent on the success of ongoing clinical research and strategic lifecycle management.

Potential Market Expansion through New Indications

The most significant opportunity for market growth lies in the potential approval of amantadine hydrochloride for new indications arising from current clinical trials.

• Cognitive Enhancement in Neurological Conditions: If trials demonstrate statistically significant and clinically meaningful improvements in cognitive function for patients with TBI, stroke, or specific forms of dementia, regulatory approval could open substantial new patient populations. This area is particularly attractive due to the significant unmet need and the growing prevalence of these conditions.
• Adjunct Therapy in Psychiatric Disorders: Success in trials for negative symptoms or cognitive deficits in schizophrenia, or for specific behavioral management in other psychiatric conditions, could lead to new market segments, albeit potentially smaller than neurological indications.
• Post-Viral Fatigue Syndromes: Should research definitively establish amantadine's efficacy in managing chronic fatigue associated with viral infections, including Long COVID, this could represent a significant, albeit speculative, growth area.

The timeline for these potential expansions is dependent on trial completion, data analysis, regulatory review periods, and market access strategies. Successful approvals could lead to an incremental increase in market size, with the CAGR potentially rising to the higher end of the projected 2%-4% range, or even exceeding it if multiple indications are approved.

Lifecycle Management and Product Differentiation

Manufacturers are likely to continue focusing on product differentiation to maintain and grow market share.

• Extended-Release Formulations: Further development and promotion of once-daily extended-release formulations will be a key strategy. These products offer improved convenience and potentially more consistent therapeutic levels, which can enhance patient adherence and physician preference, particularly in chronic disease management.
• Combination Therapies: Research into amantadine as part of combination therapy for established or novel indications could create new treatment paradigms and market opportunities.
• Targeted Delivery Systems: While speculative, future research could explore more targeted delivery systems to optimize efficacy and minimize side effects in specific patient populations.

Challenges and Risks

Several challenges could impact future market performance:

• Clinical Trial Failures: The failure of ongoing Phase II or III trials to meet primary endpoints would significantly diminish the prospects for new indication approvals and associated market growth.
• Intensified Generic Competition: Continued price erosion from generic competition could offset volume gains, particularly if new indications are not approved or if market penetration in these areas is slow.
• Emergence of Novel Therapies: The development of new, more effective, or safer treatments for amantadine's current and potential future indications could reduce its market share.
• Regulatory Hurdles: Navigating the rigorous regulatory approval processes for new indications, especially for complex neurological or psychiatric conditions, presents significant challenges.

Overall, the future of amantadine hydrochloride hinges on its ability to demonstrate continued efficacy and safety in ongoing clinical investigations and on the strategic execution of lifecycle management initiatives by manufacturers.

Key Takeaways

• Amantadine hydrochloride remains active in clinical trials, primarily for Parkinson's disease, cognitive impairment, and psychiatric disorders.
• The current market for amantadine hydrochloride is mature, with modest projected growth (2%-4% CAGR).
• Market expansion opportunities are tied to the potential approval of new indications derived from ongoing clinical research.
• Lifecycle management, particularly through extended-release formulations, is a key strategy for competitive differentiation.
• Clinical trial outcomes and the emergence of novel therapies represent significant risks to future market performance.

Frequently Asked Questions

1. What are the primary approved indications for amantadine hydrochloride? Amantadine hydrochloride is primarily approved for the treatment of dyskinesia associated with Parkinson's disease and for the prophylaxis and treatment of influenza A virus infections.
2. Which neurological conditions are currently the focus of amantadine hydrochloride clinical trials? Ongoing clinical trials are heavily focused on amantadine's potential in Parkinson's disease for motor symptom management, and for cognitive enhancement in conditions such as traumatic brain injury and stroke recovery.
3. What is the anticipated impact of generic competition on amantadine hydrochloride pricing? The widespread availability of generic versions of immediate-release amantadine hydrochloride exerts significant downward pressure on pricing for these formulations, making them highly cost-competitive.
4. Are there any emerging antiviral applications for amantadine hydrochloride being investigated? While amantadine has an antiviral history, current clinical investigations into its antiviral properties are limited, with some exploration in post-viral syndromes like Long COVID but representing a smaller segment of ongoing research.
5. What factors could lead to a significant increase in the projected market growth rate for amantadine hydrochloride? A substantial increase in the projected market growth rate would likely be driven by the successful regulatory approval and subsequent market adoption of amantadine hydrochloride for novel indications, particularly in the area of cognitive impairment or in managing the unmet needs of specific psychiatric disorders.

Citations

[1] U.S. National Library of Medicine. (n.d.). ClinicalTrials.gov. Retrieved from https://clinicaltrials.gov/ [2] Multiple Market Research Reports (Proprietary Data on Pharmaceutical Market Size and Growth Rates). Specific report titles and publishers vary and are typically licensed for internal business use. These reports analyze global pharmaceutical markets, including specific drug categories and therapeutic areas.