CLINICAL TRIALS PROFILE FOR PROPOXYPHENE HYDROCHLORIDE

505(b)(2) Clinical Trials for PROPOXYPHENE 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.

All Clinical Trials for PROPOXYPHENE HYDROCHLORIDE

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00240786 ↗	An Effectiveness and Safety Study of Two Doses of Acetaminophen Extended Release Caplets in the Treatment of Osteoarthritis of the Hip or Knee	Completed	Johnson & Johnson Consumer and Personal Products Worldwide	Phase 3	2002-04-01	The purpose of this study is to determine the safety and effectiveness of 650 mg and 1300 mg acetaminophen extended release given three times a day for the relief of signs and symptoms of osteoarthritis of the hip or knee for a period of 12 weeks.
NCT00240799 ↗	An Effectiveness and Safety Study of Acetaminophen Extended Release Caplets in the Treatment of Osteoarthritis of the Hip or Knee.	Completed	McNeil Consumer & Specialty Pharmaceuticals, a Division of McNeil-PPC, Inc.	Phase 3	1969-12-31	The purpose of this study is to evaluate acetaminophen extended release (3900 mg/day) compared to placebo for safety and effectiveness in the relief of signs and symptoms of osteoarthritis of the hip or knee over 12 weeks
NCT00240799 ↗	An Effectiveness and Safety Study of Acetaminophen Extended Release Caplets in the Treatment of Osteoarthritis of the Hip or Knee.	Completed	Johnson & Johnson Consumer and Personal Products Worldwide	Phase 3	1969-12-31	The purpose of this study is to evaluate acetaminophen extended release (3900 mg/day) compared to placebo for safety and effectiveness in the relief of signs and symptoms of osteoarthritis of the hip or knee over 12 weeks
NCT00317447 ↗	The Efficacy of Oral Steroids in the Treatment of Acute Sciatica	Completed	Kaiser Permanente	Phase 3	2002-02-01	Sciatica (lumbosacral radiculopathy) is a common diagnosis in primary care, occurring in approximately one percent of all patients with acute low back pain. (1, 2) Traditional treatment generally involves pain control (acetominophen, NSAID's, or narcotics), activity as tolerated, and time. (1, 3-8 ) The general consensus is that fifty percent of patients with sciatica recover within six weeks, and that ninety percent are better in twelve weeks.(4, 8) Those patients with intractable pain or progressive neurologic symptoms usually receive epidural steroid injections and, if necessary, decompressive laminectomy or discectomy. (2, 8, 9) Low back pain and sciatica result in tremendous losses to our society in terms of decreased productivity and cost of treatment. (1, 12) Oral steroids are inexpensive and relatively safe medications that, if effective in reducing the pain and disability associated with sciatica, could improve the quality of patients' lives, and result in significant cost savings to society at large. We hypothesize that the use of oral steroids to treat acute sciatica will speed patients' recovery as measured by: changes in physical findings, rates of return to work and activities of daily living, pain and disability assessment scores, and decreases in the use of narcotic and non-steroidal anti-inflammatory drugs (NSAID's), and in the need for epidural injection or surgical intervention.

Clinical Trial Conditions for PROPOXYPHENE HYDROCHLORIDE

Condition Name

Condition Name for PROPOXYPHENE HYDROCHLORIDE
Intervention	Trials
Osteoarthritis	2
Atrial Fibrillation	1
Bariatric Surgery Candidate	1
Healthy	1

Condition MeSH

Condition MeSH for PROPOXYPHENE HYDROCHLORIDE
Intervention	Trials
Osteoarthritis, Hip	2
Osteoarthritis	2
Constriction, Pathologic	1
Parkinson Disease	1

Clinical Trial Locations for PROPOXYPHENE HYDROCHLORIDE

Trials by Country

Trials by Country for PROPOXYPHENE HYDROCHLORIDE
Location	Trials
United States	6
Egypt	1
Brazil	1

Trials by US State

Trials by US State for PROPOXYPHENE HYDROCHLORIDE
Location	Trials
California	2
Utah	1
New York	1
Texas	1
Florida	1

Clinical Trial Progress for PROPOXYPHENE HYDROCHLORIDE

Clinical Trial Phase

Clinical Trial Phase for PROPOXYPHENE HYDROCHLORIDE
Clinical Trial Phase	Trials
Phase 4	4
Phase 3	3
Phase 1/Phase 2	1

Clinical Trial Status

Clinical Trial Status for PROPOXYPHENE HYDROCHLORIDE
Clinical Trial Phase	Trials
Completed	5
Terminated	2
Suspended	1

Clinical Trial Sponsors for PROPOXYPHENE HYDROCHLORIDE

Sponsor Name

Sponsor Name for PROPOXYPHENE HYDROCHLORIDE
Sponsor	Trials
Johnson & Johnson Consumer and Personal Products Worldwide	2
Endo Pharmaceuticals	1
University of Rochester	1

Sponsor Type

Sponsor Type for PROPOXYPHENE HYDROCHLORIDE
Sponsor	Trials
Other	6
Industry	5

PROPOXYPHENE HYDROCHLORIDE: Clinical Trials Update, Market Analysis, and Projection

Last updated: April 26, 2026

What is propoxyphene hydrochloride and where is it authorized?

Propoxyphene hydrochloride is an oral opioid analgesic (prodrug/analogue class used for pain) that historically held regulatory authorizations in multiple markets. Its clinical and commercial trajectory changed materially after safety findings tied to cardiac toxicity and overdose risk led to product withdrawals and major restrictions in key jurisdictions.

Regulatory and market status (high level)

• United States: Propoxyphene products were withdrawn from the market following FDA action on safety (cardiac rhythm risk and lethality in overdose scenarios). FDA notes that the drugs are no longer marketed.
• European Union and other major markets: Access tightened materially after safety actions. Practical availability became limited, and long-term commercial presence declined relative to safer opioid alternatives.

Source: FDA communications on propoxyphene product withdrawal status and safety basis. [1]

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What does the clinical trial landscape look like now?

Propoxyphene’s late-stage and confirmatory development activity is no longer the center of the R&D pipeline in the way it was historically. The current “clinical trials update” is best described as a shift from active development to legacy data re-evaluation, pharmacovigilance review, and comparative safety positioning against alternative analgesics.

Evidence base characteristics used in market decisions

Clinical decisions and guideline placement (where relevant) have been driven by:

• Cardiovascular safety signals associated with QT-prolongation risk and arrhythmias.
• Overdose lethality concerns, including impairment of respiration and central nervous system depression.
• Therapeutic risk-benefit mismatch versus other opioid and non-opioid analgesics.

Source: FDA safety rationale and withdrawal basis for propoxyphene. [1]

Current trials (active development)

A current active global phase development program is not identifiable in publicly tracked registries at a level that would support an R&D-forward market projection. The remaining clinical work is largely retrospective or regulatory pharmacovigilance oriented.

Source: FDA action and ongoing non-marketed status are consistent with a lack of contemporary phase development momentum. [1]

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Why did propoxyphene lose commercial traction?

The commercial decline is explainable by three concrete factors that show up in regulator decisions and payer behavior.

1) Safety-driven market exit

• Withdrawal in the US ended mainstream sales growth and constrained any re-entry strategy for new development.
• Label tightening and restrictions in other jurisdictions reduced prescriber confidence and insurer acceptance.

Source: FDA withdrawal decision and safety basis for propoxyphene. [1]

2) Competitive substitution

After withdrawal, pain management shifted further toward:

• safer opioid options,
• combination strategies that reduce opioid exposure,
• and non-opioid analgesics.

3) Litigation and risk premium

High-profile safety actions tend to increase risk premia for manufacturers, deter brand expansion, and accelerate generic displacement only after major compliance and risk mitigation steps.

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How big was the market and what remains after withdrawal?

Because propoxyphene is no longer marketed in the United States and is heavily constrained elsewhere, the “market” is now best framed as:

• residual historical demand (pre-withdrawal),
• and any remaining access through legacy channels in limited geographies (not a stable growth market).

Market sizing method for a withdrawn product (what matters)

For investment and R&D decisions, size estimates depend on:

• regulatory access status (market withdrawal means the base becomes effectively zero in the jurisdiction),
• global availability (if non-marketed, there is no current addressable commercial TAM),
• and switch rates (patients move to alternatives).

With the US market closed, any credible forward-looking projection must treat propoxyphene as a declining non-core asset rather than an addressable growth drug.

Source: FDA confirms non-marketed status due to safety withdrawal. [1]

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What is the forward market projection?

Base case (most actionable)

• Near-term global revenue: Minimal to none in major regulated markets due to withdrawal and constrained access.
• Long-term revenue: Structurally impaired; any upside requires new reformulation and fresh regulatory pathway, which is incompatible with the current non-marketed status trajectory.

Projection table (practical, jurisdictional framing)

Horizon	Addressable market in US	Addressable market in major EU markets	Expected sales trajectory
0 to 12 months	0 (not marketed)	Limited / constrained	Declining or flat near zero
1 to 3 years	0	Limited / constrained	Near-zero continuation
3 to 7 years	0	Limited / constrained	Structural decline unless re-authorized

Source: FDA non-marketed status and withdrawal basis. [1]

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What development path would be required to restart commercialization?

No credible path exists under the current market status without a substantial regulatory reset. In practice, the only scenarios that can change the commercial outlook are:

• New molecular entity or substantially different formulation with safety risk reduction (cardiac and overdose risk mitigation).
• New clinical program designed for risk management (thorough QT strategy, abuse-deterrent design where relevant, and robust safety characterization).
• Regulatory re-approval after showing a corrected risk-benefit profile.

Given the established safety concerns that triggered withdrawal, the bar for re-entry is high, and the near-term probability is low.

Source: FDA withdrawal and safety rationale. [1]

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What competitive landscape does propoxyphene face today?

Propoxyphene is functionally displaced by:

• safer opioids with clearer benefit-risk frameworks,
• and broad classes of analgesics that reduce opioid reliance.

From a business perspective, any remaining demand would be absorbed by substitutable therapies with better regulatory standing.

Source: FDA withdrawal rationale drives substitute selection and prescriber/Payer behavior. [1]

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Key Takeaways

• Propoxyphene hydrochloride is withdrawn and no longer marketed in the United States due to safety concerns, which removes the primary driver for forward revenue growth. [1]
• The clinical trial landscape is not consistent with an active, future development program; the remaining work is primarily legacy and safety-oriented. [1]
• Forward market projection is near-zero in major markets, with any upside requiring a new, safety-reset development and re-approval pathway. [1]

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FAQs

1. Is propoxyphene hydrochloride currently marketed in the United States?
   No. FDA states propoxyphene products are withdrawn and no longer marketed. [1]

2. What safety issues drove the withdrawal?
   FDA cites safety concerns including cardiac rhythm risk and overdose-related lethality. [1]

3. Are there active late-stage clinical trials for propoxyphene?
   The current publicly documented trajectory supports a legacy posture rather than active, new late-stage development. [1]

4. What is the realistic global revenue outlook?
   In major regulated markets, the outlook is near-zero given non-marketed status and constrained access. [1]

5. What would need to happen for commercialization to resume?
   A new safety-forward development package and regulatory re-approval with substantially improved risk-benefit evidence. [1]

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References

[1] U.S. Food and Drug Administration. (n.d.). Propoxyphene (Darvon/Darvocet) information and safety-related actions. FDA. APA-style source compiled from FDA communications describing withdrawal and non-marketed status.