CLINICAL TRIALS PROFILE FOR NAPROXEN SODIUM

505(b)(2) Clinical Trials for naproxen sodium

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
OTC	NCT00751400 ↗	Naproxen Sodium Extended-Release Actual Use Study	Completed	Pegus Research, Inc.	Phase 3	2008-07-01	The purpose of this Study is to assess how subjects will use the investigational product in an uncontrolled, naturalistic environment.
OTC	NCT00751400 ↗	Naproxen Sodium Extended-Release Actual Use Study	Completed	Bayer	Phase 3	2008-07-01	The purpose of this Study is to assess how subjects will use the investigational product in an uncontrolled, naturalistic environment.
OTC	NCT01365052 ↗	Safety Trial of Naproxen Sodium/ Diphenhydramine	Completed	Bayer	Phase 3	2011-05-01	The purpose of this trial is to see how safe the combination of naproxen sodium 440 mg and diphenhydramine hydrochloride (DPH) 50 mg (the investigational product) is compared to placebo (capsules containing no drug) when taken for 10 days.
OTC	NCT01383486 ↗	Self Selection Trial of Naproxen Sodium	Completed	Bayer	Phase 3	2011-07-01	A pilot trial to demonstrate that consumers can appropriately select Aleve 24 Hour for their own use based on expected duration of pain greater than 12 hours.
OTC	NCT01427803 ↗	Actual Use Trial of Naproxen Sodium	Completed	Bayer	Phase 3	2011-09-01	An actual use trial to demonstrate that consumers will not exceed the labeled daily dose of Aleve 24 Hour at an unacceptable rate. Two aspects of consumer use will be evaluated: 1) the frequency at which consumers exceed the label-defined daily dose, thus putting themselves at clinical risk, and 2) the reasons for exceeding the labeled daily dose.
OTC	NCT02519231 ↗	Copper IUD Treatment Observation Study	Completed	Cook County Hospital	Phase 4	2016-02-01	Studies indicate that bleeding irregularities and dysmenorrhea are common reasons for copper IUD method discontinuation. Some evidence suggests that non-steroidal anti-inflammatory medications (NSAIDs) can help improve bleeding during Cu-IUD use. However, these studies did not examine NSAID use with the TCu380A specifically, nor did they evaluate readily available NSAIDs such as over-the-counter naproxen. For this reason, the investigators propose a pilot trial in which new TCu380A users complaining of heavy or prolonged menstrual bleeding or spotting after 1 month of use are randomized to naproxen or placebo to be taken the first 7 days of menstruation for three consecutive cycles, and then observed for one cycle without treatment.
OTC	NCT02519231 ↗	Copper IUD Treatment Observation Study	Completed	Teva Pharmaceuticals USA	Phase 4	2016-02-01	Studies indicate that bleeding irregularities and dysmenorrhea are common reasons for copper IUD method discontinuation. Some evidence suggests that non-steroidal anti-inflammatory medications (NSAIDs) can help improve bleeding during Cu-IUD use. However, these studies did not examine NSAID use with the TCu380A specifically, nor did they evaluate readily available NSAIDs such as over-the-counter naproxen. For this reason, the investigators propose a pilot trial in which new TCu380A users complaining of heavy or prolonged menstrual bleeding or spotting after 1 month of use are randomized to naproxen or placebo to be taken the first 7 days of menstruation for three consecutive cycles, and then observed for one cycle without treatment.

All Clinical Trials for naproxen sodium

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00092729 ↗	An Investigational Drug Study in the Treatment of Primary Dysmenorrhea (0663-064)	Completed	Merck Sharp & Dohme Corp.	Phase 3	2002-06-07	The purpose of this study is to evaluate the pain relieving effect and safety of an investigational drug in women with moderate to severe primary dysmenorrhea (painful menstruation).
NCT00114049 ↗	Dental Pain (Following Third Molar Tooth Extraction) Study	Completed	GlaxoSmithKline	Phase 3	2004-12-01	The purpose of this study is to evaluate the effectiveness of GW406381 (a COX-2 inhibitor) in treating the signs and symptoms of dental pain following third molar tooth extraction.
NCT00240617 ↗	Study Of Treximet, Formerly Known as Trexima, In The Acute Treatment Of Multiple Migraine Attacks	Completed	GlaxoSmithKline	Phase 3	2005-10-01	The purpose of this study is to determine the consistency of response for Treximet (formerly known as Trexima) when treating four acute migraine attacks at the mild pain phase and within 1 hour of onset of head pain.
NCT00240630 ↗	Treximet (Sumatriptan/Naproxen Sodium), Formerly Known as Trexima, In The Acute Treatment Of Multiple Migraine Attacks	Completed	GlaxoSmithKline	Phase 3	2005-10-01	The purpose of this study is to determine the consistency of response for Treximet (sumatriptan/naproxen sodium), formerly known as Trexima, when treating four acute migraine attacks at the mild pain phase and within 1 hour of onset of head pain.
NCT00261586 ↗	A Safety Trial to Compare Different Analgesics in Combination With Low Dose Aspirin to Study Their Bleeding Properties and Their Effects on the Stomach	Completed	Johnson & Johnson Consumer and Personal Products Worldwide	Phase 4	1969-12-31	The purpose of this study is to compare several analgesics given in approved daily doses in combination with a daily cardioprotective dose of aspirin (81 mg), to study their bleeding properties and their effects on the stomach in healthy volunteers.
NCT00329355 ↗	Menstrual Migraine Treatment With TREXIMET (Formerly Known as TREXIMA)	Completed	GlaxoSmithKline	Phase 3	2006-05-01	This study was designed to determine efficacy of TREXIMET (sumatriptan/naproxen sodium), formerly known as TREXIMA compared to placebo for the treatment of a menstrual migraine.
NCT00329459 ↗	Treximet (Sumatriptan/Naproxen Sodium), Formerly Known as TREXIMA, for Menstrual Migraine in Women With Dysmenorrhea	Completed	GlaxoSmithKline	Phase 3	2006-05-01	This study was designed to determine efficacy of TREXIMA compared to placebo for the treatment of a menstrual migraine.

Clinical Trial Conditions for naproxen sodium

Condition Name

Condition Name for naproxen sodium
Intervention	Trials
Migraine Disorders	16
Pain	14
Healthy	12
Migraine	7

Condition MeSH

Condition MeSH for naproxen sodium
Intervention	Trials
Migraine Disorders	28
Pain, Postoperative	10
Toothache	9
Dysmenorrhea	5

Clinical Trial Locations for naproxen sodium

Trials by Country

Trials by Country for naproxen sodium
Location	Trials
United States	406
India	4
Canada	4
Pakistan	4
Turkey	3

Trials by US State

Trials by US State for naproxen sodium
Location	Trials
Utah	29
Texas	28
Florida	17
California	17
Ohio	15

Clinical Trial Progress for naproxen sodium

Clinical Trial Phase

Clinical Trial Phase for naproxen sodium
Clinical Trial Phase	Trials
PHASE4	4
PHASE3	1
PHASE2	1

Clinical Trial Status

Clinical Trial Status for naproxen sodium
Clinical Trial Phase	Trials
Completed	87
Recruiting	7
Not yet recruiting	6

Clinical Trial Sponsors for naproxen sodium

Sponsor Name

Sponsor Name for naproxen sodium
Sponsor	Trials
Bayer	25
GlaxoSmithKline	23
Dr. Reddy's Laboratories Limited	4

Sponsor Type

Sponsor Type for naproxen sodium
Sponsor	Trials
Industry	79
Other	65
NIH	4

Naproxen Sodium Clinical Trials Update, Market Analysis, and Launch/Exclusivity Projections for NSAID Competitors

Last updated: May 21, 2026

Naproxen sodium (OTC and Rx NSAID) has no meaningful patent-led exclusivity barriers for standard immediate-release and established delayed-release oral tablets/capsules, and clinical development visibility is mostly tied to new formulations, fixed-dose combinations, or delivery improvements rather than new active ingredient approvals. Near-term market dynamics are driven by generic penetration, OTC switching, payer formularies, and safety-focused label usage.

What clinical trials have been reported for naproxen sodium recently?

Naproxen sodium’s clinical-trials footprint is dominated by (1) formulation and bioequivalence studies, (2) comparative NSAID safety and tolerability work, and (3) appropriateness-of-use or real-world outcomes research rather than pivotal “new drug” development. In practice, these studies do not reset exclusivity because the active ingredient is long established and most development is not tied to a first-in-class new chemical entity.

What types of studies show up in naproxen sodium trial activity?

Common recurring categories for naproxen sodium include:

• Bioequivalence and pharmacokinetic bridging after formulation changes (strength, coating, release profile, excipients).
• Comparative pain studies versus other oral NSAIDs (ibuprofen, naproxen, diclofenac, ketoprofen) in indications such as acute musculoskeletal pain.
• GI and cardiovascular risk characterization in cohorts using NSAIDs, sometimes in combination with gastroprotective strategies.
• Switching studies for OTC access and adherence (dose timing, persistence, and self-medication patterns).

What is the practical meaning for a patent or investment view?

• Trials that support generic approvals typically do not create enforceable exclusivity for naproxen sodium.
• Trials that support label expansions are usually limited by already-established safety and prescribing frameworks for NSAIDs.
• Formulation-specific differentiation affects market share only if it solves a patient or prescriber barrier (fewer GI events, improved onset, lower pill burden), not if it changes the underlying drug IP position.

What patents protect naproxen sodium and its common formulations?

Naproxen sodium is an established active ingredient; the main “IP map” in the US is historically anchored to original naproxen and naproxen sodium compositions-of matter, but for business planning the more relevant question is which formulation, process, or method-of-use patents still have enforceable coverage. For an established NSAID, most broad composition-of matter claims are expired or near-expired, and remaining enforceable IP tends to be narrow and formulation/process specific.

Where does remaining IP usually live for naproxen sodium products?

• Proprietary release technologies (delayed-release or special coatings), when tied to specific brand products.
• Manufacturing process steps or controlled particle size/surface properties for certain generics under specific assignments.
• Method-of-use or regimen patents are uncommon for old NSAIDs, but may appear for niche combinations (for example, naproxen sodium with an additional active agent) or specific dosing regimens.

What does that mean for enforcement risk and licensing?

• For standalone naproxen sodium tablets/capsules, litigation and licensing are typically low relative to novel drug classes.
• The main licensing exposure is when a product uses a still-protected delivery system or fixed-dose combination that is separately patented.

When does naproxen sodium lose exclusivity in the US and key markets?

For naproxen sodium as an active ingredient, exclusivity is not a core gating factor in modern markets because generic supply is established. The meaningful “timeline” for competitive entry is usually:

• expiration of any brand-specific formulation/process patents still listed for a particular NDA product,
• any relevant pediatric exclusivity or orphan exclusivity (rare for NSAIDs),
• and any ongoing brand settlement constraints (if they exist for a specific NDA/product).

Because naproxen sodium is widely available, the realistic projection is that entry and substitution occur rapidly after any remaining product-specific IP expires, with most competition driven by pricing and distribution rather than legal timing.

What is the Orange Book status of naproxen sodium products?

Orange Book status for naproxen sodium depends on the specific NDA holder and dosage form/strength. In practice, you should treat “Orange Book status” for naproxen sodium as a granular product mapping exercise:

• Different brands or NDA submissions for delayed-release, combination products, or reformulated versions can have different patent lists.
• Many classic naproxen sodium presentations have no active unexpired patents in force, but a subset may still show listed patents for formulation/process claims.

At the portfolio level, the market reality is generic dominance with limited brand exclusivity.

How do naproxen sodium clinical, safety, and label dynamics affect prescribing?

NSAIDs face ongoing prescriber and payer sensitivity to GI risk and cardiovascular risk. This changes market share even when IP is expired.

What label elements most affect commercial use?

Typical constraints across NSAIDs that affect uptake:

• GI warning language and the need for lowest effective dose.
• Cardiovascular risk disclosures.
• Contraindications or cautions in patients with certain comorbidities.
• Guidance on concomitant use with anticoagulants, antiplatelets, and other NSAIDs.

How does that translate into market behavior?

• Payers steer utilization toward lower-cost generics and sometimes toward preferred NSAIDs with better cost-effectiveness profiles.
• Clinicians may shift to topical NSAIDs or non-NSAID alternatives in higher-risk patients, reducing oral naproxen sodium share in those cohorts.
• “On-label” use tends to preserve volume, while any off-label restrictions or warnings can reduce sustained prescriptions.

What generic entry risks exist for naproxen sodium?

For naproxen sodium, generic entry risk is typically low because:

• API is established and widely manufactured.
• Most remaining IP, if present, is formulation or NDA-specific rather than blocking active ingredient replication.

The principal risk for a market entrant is product-level:

• a still-enforceable formulation/process patent for a specific dosage form,
• a still-active REMS or Risk Evaluation/ Mitigation Strategy requirement (rare for NSAIDs compared with biologics, but label-driven risk communications exist),
• or supply-chain constraints around particular strength offerings.

How does naproxen sodium compare with ibuprofen and celecoxib on market position?

Market share is shaped by both clinical practice and pricing.

Pricing and switching

• Naproxen sodium and ibuprofen compete in OTC and prescription-adjacent settings.
• Switching often follows cost and availability rather than pharmacologic novelty.

Safety-driven differentiation

• Celecoxib (COX-2 selective) often competes for patients where prescribers want reduced GI risk, while balancing cardiovascular considerations.
• Naproxen sodium remains a go-to NSAID when cost and prescriber familiarity dominate.

Business implication

If your goal is market projection, assume naproxen sodium’s volume follows generic NSAID demand plus OTC elasticity, with share shifts driven by payer preference and safety communications rather than brand exclusivity.

What market size and demand drivers should be used to project naproxen sodium revenue?

Naproxen sodium revenue projection should be built from:

• baseline generic NSAID demand by pain indication category,
• OTC versus Rx channel mix,
• pharmacy benefit management (PBM) formulary positioning,
• competitive pricing and promotional intensity,
• and substitution against topical NSAIDs and non-NSAID alternatives.

Key demand drivers

• Aging population and musculoskeletal pain prevalence.
• OTC access and self-treatment habits for minor pain.
• Seasonality effects in musculoskeletal and cold-related pain demand.
• Changes in NSAID risk perception in clinical guidelines.

Key headwinds

• Competitive encroachment from topical NSAIDs (reduced systemic exposure).
• Growth of non-NSAID options (acetaminophen alternatives, adjuvant pain meds) and shifting guideline patterns.
• Tightening payer prior authorization or preference management for oral NSAIDs in high-risk groups.

What do clinical development and formulation innovation signal for future naproxen sodium competitiveness?

Although active-ingredient exclusivity is not the lever, formulation development can still shift economics:

• Extended or delayed-release versions can support “once-daily” or improved tolerability positioning in specific segments.
• Fixed-dose combinations can create small but sticky differentiation if patents protect the combination or if the combination aligns with guideline-based prescribing.
• Taste, swallowing, and pill-burden improvements affect OTC conversion rates in some segments.

In a projection model, treat these as share-shift inputs rather than as new demand creation.

How strong is the patent estate for naproxen sodium versus other NSAIDs?

Compared with newer NSAID development (for example, specialized delivery systems or combination regimens), naproxen sodium’s patent estate is typically:

• mostly expired for the active ingredient,
• concentrated in narrow product-specific protections for particular presentations.

For a competitor analysis, the “patent strength” takeaway is that legal barriers are usually not the long pole for generic entry. The long pole is product economics: supply capacity, manufacturing cost, distribution, and price erosion dynamics.

What patent litigation affects naproxen sodium products?

For established generic NSAIDs, litigation is frequently historical and product-specific. For current business decisions, the key value is mapping:

• any active or recently concluded Paragraph IV disputes for NDA-specific products,
• any settlement constraints that delayed generic entry for a particular branded NDA.

For naproxen sodium as an active ingredient, the expectation is that litigation is not currently the primary driver of market supply because generic availability is already widespread.

Key Takeaways

• Naproxen sodium’s clinical trials activity is mostly formulation, bioequivalence, and comparative outcomes work, with limited relevance to new exclusivity creation.
• Generic competition is structurally entrenched; revenue outlook is driven by OTC/Rx channel dynamics, formulary positioning, pricing, and safety-focused prescribing behaviors.
• Any remaining enforceable IP is likely narrow and product-specific (formulation or process), so entry timing and licensing exposure are granular to dosage form/NDA presentation rather than the active ingredient.
• Market projection should model NSAID demand plus substitution against topical NSAIDs and non-NSAID options, with channel mix as the main forecasting lever.

FAQs

1. Do naproxen sodium delayed-release and extended-release versions have different IP protection than immediate-release?
2. Which NSAID class tends to capture share from oral naproxen sodium in higher GI-risk patients?
3. How should a revenue model separate OTC volume elasticity from prescription formularies for naproxen sodium?
4. What types of clinical studies most often support regulatory submissions for naproxen sodium after reformulation?
5. Are Paragraph IV challenges common for naproxen sodium NDA presentations in the current market cycle?

References (APA)

1. FDA. (n.d.). Drugs@FDA. U.S. Food and Drug Administration.
2. FDA. (n.d.). Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations. U.S. Food and Drug Administration.
3. EMA. (n.d.). European Medicines Agency medicines database. European Medicines Agency.