CLINICAL TRIALS PROFILE FOR COMTAN

All Clinical Trials for COMTAN

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00262470 ↗	Treatment of Orthostatic Intolerance	Active, not recruiting	National Institutes of Health (NIH)	Phase 1/Phase 2	1997-04-01	This trial is designed to study the effects of various mechanistically unique medications in controlling excessive increases in heart rate with standing and in improving the symptoms of orthostatic intolerance in patients with this disorder.
NCT00262470 ↗	Treatment of Orthostatic Intolerance	Active, not recruiting	Satish R. Raj	Phase 1/Phase 2	1997-04-01	This trial is designed to study the effects of various mechanistically unique medications in controlling excessive increases in heart rate with standing and in improving the symptoms of orthostatic intolerance in patients with this disorder.
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.
NCT02058966 ↗	Pilot Study of Entacapone for Methamphetamine Abuse	Completed	Portland VA Medical Center	Early Phase 1	2014-06-01	Addiction to methamphetamine is a serious health problem. There are no medications that a doctor can give someone to help them stop using methamphetamine. Entacapone (Comtan©) is a medication that could help people addicted to methamphetamine. This study will see how entacapone works in healthy people who are given methamphetamine. We think that the study drug will be well tolerated, and that it will prevent some of the effects of methamphetamine that make it so addictive. We also want to see how differences in people's genes may cause differences in the ways the study drug and methamphetamine work for them. The study has six total visits. The first visit is for screening. Tests and procedures will make sure it is safe for subjects to participate. The second visit is a familiarization day. Subjects will receive methamphetamine, but no entacapone. This is done to make sure they can tolerate the drug and recognize its effects before being given a second drug on the same day. Subjects will take surveys and computer tests to see how the medications change mood, thinking, and liking the drug. The final four visits are the actual study days. Subjects will be randomly assigned (like the flip of a coin) to the different ways to get either 1) study medication or placebo (placebo contains no active study medication) and then 2) methamphetamine or placebo. Subjects will be in all four groups during the study, which means that each day a subject will get a different group.

Clinical Trial Conditions for COMTAN

Condition Name

Condition Name for COMTAN
Intervention	Trials
Multiple System Atrophy	2
Parkinson Disease	2
Dementia With Lewy Bodies	1
Gastrointestinal Stromal Tumor, Malignant	1

Condition MeSH

Condition MeSH for COMTAN
Intervention	Trials
Parkinson Disease	3
Multiple System Atrophy	2
Atrophy	2
Shy-Drager Syndrome	2

Clinical Trial Locations for COMTAN

Trials by Country

Trials by Country for COMTAN
Location	Trials
United States	4
China	2

Trials by US State

Trials by US State for COMTAN
Location	Trials
Tennessee	2
Oregon	1
Maryland	1

Clinical Trial Progress for COMTAN

Clinical Trial Phase

Clinical Trial Phase for COMTAN
Clinical Trial Phase	Trials
Phase 2	1
Phase 1/Phase 2	3
Phase 1	1

Clinical Trial Status

Clinical Trial Status for COMTAN
Clinical Trial Phase	Trials
Completed	2
Unknown status	2
Recruiting	1

Clinical Trial Sponsors for COMTAN

Sponsor Name

Sponsor Name for COMTAN
Sponsor	Trials
Satish R. Raj	1
National Institute of Neurological Disorders and Stroke (NINDS)	1
Portland VA Medical Center	1

Sponsor Type

Sponsor Type for COMTAN
Sponsor	Trials
Other	6
NIH	2
U.S. Fed	1

COMTAN (entacapone) Clinical Trials Update, Market Analysis, and Exclusivity/Generic Entry Outlook

Last updated: July 30, 2026

COMTAN (entacapone) is an older, small-molecule adjunct to levodopa/carbidopa in Parkinson’s disease. Because COMTAN’s key commercial basis is tied to established dispensing and older regulatory exclusivity windows, market risk today is driven mainly by generic availability, price compression, and formulary status rather than near-term patent expirations. No current, material COMTAN-specific late-stage development pipeline is evidenced in the public clinical trial record as a driver of future expansion.

What is COMTAN (entacapone) and what is it used for?

COMTAN is entacapone, a catechol-O-methyltransferase (COMT) inhibitor used with levodopa/carbidopa to treat Parkinson’s disease, including off episodes. It is marketed in tablet form.

Which regimen does COMTAN support?

• Levodopa/carbidopa + entacapone for “wearing-off” and off-period management
• Standard adult use is oral dosing with each levodopa/carbidopa dose (per label)

What does the clinical trial landscape look like for COMTAN right now?

Primary market implication: the clinical development profile is no longer dominated by new COMTAN pivotal trials. For an older drug, the practical “clinical trials update” is usually dominated by:

• comparative studies vs other COMT/adjunct strategies,
• real-world effectiveness/brain symptom outcomes,
• switching/retention and adherence studies,
• pharmacokinetic and formulation comparability work that supports generic/brand continuity.

Are there any active late-stage trials for COMTAN?

A true “late-stage” (Phase 3) COMTAN development program is not showing up as a near-term catalyst in the public trial landscape for new registrations or label expansions. That means projected growth in COMTAN revenues is unlikely to come from fresh registrational trial milestones.

What trial endpoints are being studied in older COMTAN work?

Common endpoints in COMT-inhibitor research include:

• off-time reduction,
• Unified Parkinson’s Disease Rating Scale (UPDRS) changes,
• caregiver and patient quality-of-life measures,
• dyskinesia and adverse event profiles (including dopaminergic side effects).

How big is the COMTAN market and what drives demand?

COMTAN’s demand is driven by:

• Parkinson’s disease prevalence in treated markets,
• the size of the subset on levodopa therapy,
• clinical practice patterns for adjunct COMT inhibition versus alternative strategies (other COMT inhibitors, MAO-B inhibitors, optimized levodopa scheduling, device-aided therapies).

What is the revenue model for COMTAN?

For mature brands, revenue typically comes from:

• ongoing maintenance prescriptions,
• conversion between brand and generics based on pricing,
• formulary and payer contracting dynamics.

What is the main structural risk to COMTAN sales growth?

• Generic entacapone availability and price competition, which compresss net pricing and reduces incremental brand share.
• Shifts to alternative COMT-adjunct strategies or other classes depending on patient characteristics and local payer preferences.

When does COMTAN lose exclusivity and what matters for generic entry?

COMTAN is an older product. In the US, the primary exclusivity levers that matter historically are patent terms (composition, use, and formulation) and any data exclusivity periods if applicable. In practice, for a drug at this lifecycle stage, generic entry risk is already realized. The market now functions under generic-based competition.

Where does Orange Book status typically matter for COMTAN today?

For older products, Orange Book listings often show:

• expired composition and use patents,
• remaining method/formulation patents only if any were sustained by later filings,
• possible continued listing for specific dosage forms or manufacturing-related claims.

Because COMTAN is widely available as a generic, near-term Orange Book-driven “first generic” timing is usually not a current expansion variable.

What generic entry risks exist for COMTAN now?

The “risk” is largely limited to:

• new entrants targeting specific strengths/dosage forms,
• label carve-outs or manufacturing equivalency,
• payer-driven switching at lower price points.

Given that entacapone is a mature generic, incremental entrants rarely create step-function market share changes for the brand.

How does COMTAN compare with other COMT inhibitors and adjunct PD drugs?

From a competitive dynamics standpoint, COMT-inhibitor choice often depends on:

• dosing convenience,
• adverse event profile tolerability,
• payer formularies and negotiated rebates,
• clinician familiarity and patient response history.

Key comparison set:

• Entacapone (COMTAN) versus alternative COMT inhibitors (notably opicapone where available)
• Adjunct strategies: MAO-B inhibitors (e.g., selegiline/rasagiline), other add-ons, and device therapies in advanced disease

What patent estate strength does COMTAN have, and how does it affect the market?

COMTAN’s patent estate impact is mostly historic. Today, patent strength typically shows up as:

• residual branded protection in select markets if any later-use/formulation claims remain,
• differentiation via protected formulations or specific dosing schedules only if claims were updated and sustained.

For COMTAN specifically, the commercialization reality is that entacapone is already broadly genericized, so patent barriers have not prevented generic market presence.

What is the current FDA status of COMTAN?

COMTAN is an approved drug with a marketed label supporting adjunct use with levodopa/carbidopa in Parkinson’s disease. The functional regulatory question in 2026 is less about approval novelty and more about:

• generic labeling consistency (bioequivalence),
• substitution and interchangeability under state pharmacy rules,
• any ongoing REMS-like requirements (if applicable to the product category, though COMT inhibitor products generally do not carry REMS in the US).

Market projection for COMTAN: 2026-2031

Base-case projection

• Net sales: low growth or flat-to-declining trajectory, driven by generic price compression and substitution effects.
• Volume: modest stability if Parkinson’s growth offsets price pressure; otherwise gradual decline if prescriber preference shifts to other adjuncts or if formularies favor lower-cost alternatives.

Bull-case projection

• Better-than-market pricing stability in selected formularies through contracting.
• Local brand retention for subsets of patients where switches are avoided.
• Continued levodopa-based treatment penetration.

Bear-case projection

• Additional price cuts and more aggressive payer switching.
• Expanded preference for alternative adjuncts such as other COMT inhibitors (where clinically used and payer favored).
• Increased guideline or formulary alignment away from entacapone in certain managed-care plans.

Commercial drivers and KPIs to monitor

1. US and EU net pricing vs wholesale acquisition price (WAC) and generic parity pricing
2. Formulary placement in top payers and PBMs
3. Script growth in Parkinson’s segments (older age cohort drivers)
4. Switching rates: brand-to-generic and generic-to-other adjunct therapy
5. Real-world adverse event reporting trends that influence clinician comfort

Key takeaways

• COMTAN is a mature Parkinson’s adjunct with growth constrained by generic competition and payer price pressure.
• The clinical trial update is not signaling a near-term registrational catalyst; late-stage expansion appears unlikely to drive meaningful incremental growth.
• Market projection for 2026-2031 is best modeled as flat-to-slight decline in net sales with limited upside from contracting and stable volume.

FAQs

1. What is COMTAN (entacapone) mechanism of action in Parkinson’s disease?
   COMT inhibition prolongs levodopa availability by reducing peripheral conversion to 3-O-methyldopa.

2. Are there active Phase 3 trials for entacapone to expand indications?
   No clear late-stage registrational catalyst is apparent in the current public trial record.

3. Does COMTAN have REMS or major US risk-management requirements?
   COMT inhibitor products are generally managed through standard prescribing and labeling rather than REMS, but confirm for the specific label used in current markets.

4. How does entacapone compare to newer COMT inhibitors for “off” episodes?
   Choice is driven by dosing and tolerability plus payer preference; newer agents can win in formulary contests depending on market access.

5. What drives whether a payer keeps the brand COMTAN versus generic entacapone?
   Net price and contracting terms, PBM rebate economics, and formulary tier placement.

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References

1. https://clinicaltrials.gov/ (accessed for COMTAN/entacapone trial record review)
2. FDA Drugs@FDA: COMTAN (entacapone) product label and approval record. https://www.accessdata.fda.gov/scripts/cder/daf/ (accessed for label/status review)