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.

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

Condition MeSH

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

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 Trials Update, Market Analysis, and Exclusivity-Driven Generic/Biosimilar Forecast

Last updated: May 21, 2026

Amantadine hydrochloride is an established small-molecule therapy with ongoing clinical activity that is concentrated in neurologic use cases (Parkinson’s disease and drug-induced/neurologic syndromes) and in investigational strategies such as combination regimens and dose/formulation optimization. Market exposure is driven by (1) continued use in Parkinson’s-related indications, (2) off-label prescribing patterns, and (3) the degree of generic penetration across multiple dosage forms, which typically compresses pricing and shifts revenues to low-cost supply chains. Patent exclusivity is generally not expected to function as a long-duration barrier because the ingredient is long off-patent; near-term competition is therefore governed primarily by generic supply continuity, formulation differentiation, and any remaining lifecycle patents in specific dosage forms.

What clinical trials are ongoing for amantadine hydrochloride, and what is their timeline?

Current trial activity for amantadine hydrochloride is best categorized by investigational intent rather than single “new blockbuster” development, with most studies aiming to refine efficacy/safety in neurologic syndromes or evaluate use in combination/setting-specific protocols. Trial formats commonly include randomized controlled comparisons against other symptomatic agents, open-label extension safety, and pragmatic studies designed to capture outcomes in routine care.

Which conditions are most frequently studied

Featured intent areas include:

• Parkinson’s disease symptom management and levodopa-related motor complications
• Drug-induced movement disorders (including antipsychotic-associated syndromes)
• Neurologic symptom clusters where amantadine is used for symptomatic effects
• Combination regimens in neurologic pathways, including exploratory dosing schedules

What endpoints dominate

Common endpoints in amantadine trials align with neurologic symptom quantification:

• Standardized motor scales in Parkinson’s populations
• Event-based safety endpoints such as cognitive effects, orthostatic hypotension, and neuropsychiatric adverse events
• Patient-reported outcomes and time-to-clinically-meaningful change in symptom control (in more recent protocol designs)

How to read the pipeline signal

For a long-established active ingredient, “ongoing trials” usually indicate:

• Lifecycle opportunities (formulation, dosing frequency, adherence, tolerability)
• Evidence generation for guideline inclusion or payer coverage expansion
• Evidence support for specific subpopulations (age, disease severity, comedication profiles)

What is the current FDA status of amantadine hydrochloride, and is it listed in the Orange Book?

Amantadine hydrochloride is marketed in the US as a conventional small-molecule drug product. The FDA regulatory footprint typically includes multiple generic products, meaning Orange Book listings are expected to be populated primarily with ANDA approvals and their associated expiration dates tied to older drug substance and product formulation patents, plus any remaining method-of-use or formulation patents for specific products.

Orange Book status: what matters commercially

For investors and litigators, the commercial question is not “is it listed,” but:

• Are any Orange Book patents still listed with future expiration dates for specific NDA/ANDA product codes?
• Do any patents cover a formulation, dosing regimen, or method-of-use that could affect launch timing for a specific applicant?

In practice, for long-established actives like amantadine hydrochloride, the most material exclusivity constraints are typically limited to:

• Remaining formulation patents for particular dosage strengths or release characteristics (if any exist)
• Use-based patents tied to narrow populations or dosing schedules, where ANDA design-arounds can be complex

What patents protect amantadine hydrochloride today, and how strong is the patent estate?

The ingredient amantadine hydrochloride is widely recognized as long beyond primary discovery-cycle exclusivity. Current competitive risk is usually less about “ingredient patent cliffs” and more about:

• Product-specific lifecycle claims (formulation, stability, bioavailability, manufacturing)
• Narrow method-of-use patents in neurologic indications
• Litigation history that shapes settlement-driven entry schedules

Where patent protection can still matter

Even when drug substance patents expire, protection can persist for:

• Specific formulations (e.g., particular salt form/process, excipient system, tablet/extended-release characteristics)
• Methods of treating a defined neurologic condition with a defined regimen
• Manufacturing methods that affect bioequivalence strategy

How strong is the estate in practical terms

For a commodity-like small molecule with extensive generic penetration, patent strength is usually evaluated at the level of:

• Specific Orange Book-listed patents per product/NDC
• Likelihood of design-around for generic applicants
• Litigation track record and whether settlements are triggered by Para IV risk

When does amantadine hydrochloride lose exclusivity, and what are the generic entry risks?

Exclusivity timeline overview

Because amantadine hydrochloride is a legacy molecule, the “exclusivity timeline” is typically already expired for most, if not all, relevant drug-substance and core formulation protections. Near-term entry risks are primarily:

• Patent-by-patent for any remaining Orange Book listings on specific reference/brand or long-lifecycle products
• Manufacturing approvals and quality system capacity
• ANDA timing constraints and paragraph IV outcomes tied to any still-listed patents

Generic entry risk profile

Expected risk profile is:

• Low risk for new generic entrants when there are no active Orange Book patents preventing bioequivalent substitution
• Moderate risk when an applicant must navigate active method-of-use or formulation patents tied to a specific NDC strength or dosing form

How does amantadine hydrochloride compare with other Parkinson’s symptom drugs on efficacy, safety, and market position?

Amantadine hydrochloride competes within symptomatic management segments rather than as a disease-modifying agent. In market terms, it overlaps with:

• Amantadine-class and dopaminergic symptomatic therapies (depending on indication and patient profile)
• Adjunctive Parkinson’s medication regimens

Competitive differentiators

Typical differentiation levers:

• Dosing convenience and tolerability
• Clinical positioning in guidelines and payer policies
• Local generic availability and pricing

Market position dynamics

Because amantadine is not a high-pricing specialty product, market share is sensitive to:

• Generic supply stability
• Pharmacy stocking patterns
• Formulary exclusions or preferred status decisions

What market segments drive revenue for amantadine hydrochloride, and what are the forecast assumptions?

Market demand is driven by real-world prescribing for:

• Parkinson’s-related symptoms
• Drug-induced movement disorders in neurologic or psychiatric contexts
• Off-label use where supported by clinical practice patterns (varies by payer and region)

Commercial assumptions that typically govern projection

A credible projection framework for amantadine hydrochloride usually rests on:

• Unit demand trends tied to neurologic disease prevalence and prescribing density
• Price compression from generic competition
• Sensitivity to safety label updates and guideline changes
• Potential uptake shifts from updated evidence in clinical trials

Pricing expectation under generic competition

In most established small-molecule generics, revenue growth tends to follow:

• Stable or declining pricing per unit
• Offset via modest unit growth (if any) or by replacement of older generics with lower-cost entrants

Clinical trial outcomes could change market outlook: what are the most decision-relevant trial signals?

For a legacy molecule, the “decision signals” that influence market projections are usually:

• Replication of symptomatic benefit at clinically meaningful magnitude versus comparator
• Safety tolerability improvements, particularly in older adults
• Evidence supporting guideline updates or payer coverage changes for specific populations or regimens

What trial results can do

Trial results can shift:

• Formulary positioning
• Prescriber comfort and guideline inclusion
• Reimbursement pathways, which affects utilization
• Uptake of specific dosing schedules or formulation types

Which companies manufacture and supply amantadine hydrochloride, and how does supply affect forecast?

Supply matters because revenue is linked to who can reliably manufacture and ship approved generic products at low cost. For legacy molecules, market performance is influenced by:

• ANDA ownership distribution
• Manufacturing capacity and batch release reliability
• Competitive pricing in wholesaler and pharmacy channels

What to watch in forecast modeling

• Price leader behavior (who sets the low-cost benchmark)
• Any supply disruptions that cause temporary market pricing rebounds
• Evidence of premiumization around certain formulations (when available)

What patent litigation, settlements, or Paragraph IV challenges affect amantadine hydrochloride generics?

For amantadine hydrochloride, litigation typically relates to:

• Para IV challenges against Orange Book-listed patents for reference or long-term branded or “listed” generic products
• Method-of-use or formulation disputes where design-around is debated

Practical litigation impact on projections

Litigation affects:

• Launch date clearance for specific applicants
• Settlement-driven payoffs and delayed entry
• Temporary price fluctuations post-launch due to market rebalancing

What formulation-specific patents and development efforts exist for amantadine hydrochloride?

Lifecycle strategy for small molecules can include:

• Formulation stability enhancements
• Bioavailability optimization to ensure interchangeability
• Tablet strength and excipient system improvements for manufacturability

Why formulation matters even with generic competition

Even when active ingredient competition is generic, formulation can:

• Affect bioequivalence study requirements for new applicants
• Influence rate of adoption if patients experience tolerability differences
• Create narrow patent corridors tied to product-specific composition or process

Key takeaways

• Amantadine hydrochloride remains a neurologic symptomatic agent with clinical trial activity focused on refinement of use rather than transformative repositioning.
• Market outlook is primarily shaped by generic penetration, pricing compression, and supply stability rather than long-duration exclusivity cliffs.
• Patent barriers, where present, are most likely to be product-specific lifecycle claims tied to Orange Book listings for specific NDCs, with generic entry risk dependent on whether any still-listed patents block substitution or require design-arounds.
• Clinical trial endpoints that can alter utilization are those supporting meaningful symptomatic benefit with acceptable tolerability, especially in older adults and real-world comedication settings.
• Near-term commercial projections should model unit demand sensitivity and price compression, with scenario adjustments for any Orange Book patent listings that could delay or accelerate specific generic launches.

FAQs

1. Are there any still-listed Orange Book patents for specific amantadine hydrochloride NDCs that could delay generic entry?
2. Which neurologic indications have the highest current clinical trial density for amantadine hydrochloride?
3. How do formulation differences (tablet strength, excipients, dissolution characteristics) affect amantadine hydrochloride interchangeability and uptake?
4. What endpoints in Parkinson’s and drug-induced movement disorder trials most strongly predict guideline and formulary adoption for amantadine hydrochloride?
5. How does generic supply continuity influence amantadine hydrochloride pricing and revenue in US pharmacy channels?

References

No sources were provided in the prompt, and no authoritative, citable dataset (e.g., FDA Orange Book listing IDs, ClinicalTrials.gov trial results, or company/market data) is included here.