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.
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.

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
Atrial Fibrillation	1
Spinal Stenosis	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
McNeil Consumer & Specialty Pharmaceuticals, a Division of McNeil-PPC, Inc.	1
Kaiser Permanente	1

Sponsor Type

Sponsor Type for propoxyphene hydrochloride
Sponsor	Trials
Other	6
Industry	5

Propoxyphene Hydrochloride: Clinical Trials Update, Market Analysis, and Future Projections

Last updated: October 27, 2025

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Introduction

Propoxyphene Hydrochloride, a synthetic opioid analgesic historically used for pain relief, has experienced significant regulatory and market shifts over recent years. Once a common prescription drug, inherited regulatory concerns have prompted its withdrawal in multiple jurisdictions. This article offers a comprehensive analysis of current clinical trial activities, market landscape, and future market projections for Propoxyphene Hydrochloride, emphasizing strategic considerations for pharmaceutical industry stakeholders.

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Clinical Trials Landscape

Historical Clinical Profile

Propoxyphene Hydrochloride was approved in the mid-20th century, predominantly marketed under brand names such as Darvon and Darvocet. Its clinical efficacy in moderate pain management was established through extensive but now outdated trials, which lack modern safety and efficacy assessments.

Current Clinical Trial Initiatives

As of 2023, active clinical trials involving Propoxyphene Hydrochloride are virtually nonexistent. Past trials explored its analgesic properties, pharmacokinetics, and safety profile but were discontinued following safety concerns raised in the late 20th and early 21st centuries.

• Regulatory Scrutiny and Discontinuation: In 2010, the U.S. Food and Drug Administration (FDA) withdrew approval of Propoxyphene due to its association with serious cardiac toxicity, including arrhythmias linked to the active metabolite norpropoxyphene [1].

• Post-Marketing Monitoring: Only retrospective observational studies and pharmacovigilance reports remain, focusing on adverse effects and overdose risks rather than new clinical testing.

• Future Trial Prospects: No current proprietary or pharmaceutical industry-sponsored trials are underway, aligning with the global trend of phased-out opioid use in favor of safer alternatives.

Research and Development Outlook

Given the safety concerns and regulatory bans, Propoxyphene Hydrochloride is unlikely to re-enter clinical development for pain management. Any investigational efforts would require extensive reformulation or safety modifications, possibly positioning it as a candidate for abuse-deterrent formulations or in non-analgesic therapeutic areas, although such initiatives currently do not exist.

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Market Analysis

Historical Market Dynamics

Propoxyphene Hydrochloride was once a staple in analgesic therapy, with a global market peak in the 1980s and 1990s. Its low cost and perceived efficacy contributed to widespread prescription, especially in the United States, Canada, and parts of Europe.

• Market Size (Pre-2010): The U.S. analgesic market valued at approximately $20 billion, with Propoxyphene products once accounting for a notable segment before regulatory actions. Revenue peaked before declining sharply post-2010.

• Regulatory Impact: The FDA's 2010 decision to remove Propoxyphene from the market caused a rapid decline in prescription volume, leading to a near-complete market exit [2].

• Pharmaceutical Manufacturers: Major companies like Eli Lilly and Whitehall-Robins ceased manufacturing and discontinued Propoxyphene-containing products, leading to limited availability and substitute therapies.

Current Market Environment

• Market Replacement: The analgesic space has shifted towards safer NSAIDs, acetaminophen combinations, and opioids with improved safety profiles, such as controlled-release formulations of oxycodone and hydromorphone. The demand for Propoxyphene has effectively vanished.

• Unapproved Uses and Black Market: Despite formal withdrawal, illicit use persists in some regions, fueled by addiction and abuse issues. However, this is not reflected in legitimate market statistics.

• Generic and OTC Availability: No licensed proprietary formulations exist; over-the-counter availability is nonexistent due to safety concerns and regulatory bans.

Regulatory and Legal Environment

Global regulatory agencies have adopted stringent controls on opioid analgesics, especially those with cardiotoxicity risks. The rescheduling or banning of Propoxyphene has been reinforced in numerous jurisdictions, including:

• United States: Withdrawn by FDA (2010) [1].
• European Union: Market removal coordinated by EMA.
• Canada: Market withdrawal by Health Canada.

This environment significantly constrains any potential resurgence or new market entry.

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Future Market Projections

Market Outlook (Next 5–10 Years)

Based on current trends and regulatory trajectories, the prospects for Propoxyphene Hydrochloride litigation, development, or market resurgence are exceedingly slim.

• Market Absence: No foreseeable legitimate market for Propoxyphene at the global level. Existing users have transitioned to alternative medications.

• Research and Reformulation Potential: Although theoretical reformulation could mitigate cardiotoxicity, there is little industry interest due to recent opioid misuse crises and regulatory hurdles.

• Legal and Liability Risks: Potential liability associated with past adverse events continues to influence industry stance, discouraging re-entry.

• Niche or Non-Analgesic Uses: No emerging therapeutic areas or patent opportunities are apparent for Propoxyphene, diminishing R&D incentives.

Implications for Stakeholders

Pharmaceutical companies are unlikely to allocate R&D resources toward Propoxyphene development. Conversely, legal entities involved in past litigation may see ongoing claims but limited future commercial opportunities.

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Strategic Considerations

• Regulatory Vigilance: Companies should monitor regulatory updates closely, especially related to opioid derivatives and analogs.

• Alternative Analgesics: Focus should shift to developing or marketing newer, safer analgesic options with improved safety profiles and lower abuse potential.

• Market Exit Strategies: Stakeholders with existing assets or formulations should consider exit strategies, including licensing or de-marketing plans.

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Key Takeaways

• Clinical Trials: No current or planned clinical trials involve Propoxyphene Hydrochloride; historical safety concerns have halted ongoing development.

• Market Status: The global market for Propoxyphene has effectively disappeared following regulatory bans due to safety risks, particularly cardiotoxicity.

• Future Outlook: Virtually no prospects exist for market revival; reformulation or new clinical development is unlikely given the current regulatory climate and public health priorities.

• Industry Focus: Pharma ventures are better directed toward safer analgesic options and abuse-deterrent opioids, aligning with global opioid stewardship initiatives.

• Legal and Public Health Considerations: Remaining liabilities and societal concerns about opioids further diminish the appeal of Propoxyphene-related products or research.

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FAQs

1. Is Propoxyphene Hydrochloride still available on the market?
No. Extensive safety reviews led to its withdrawal in major markets, including the U.S. and EU, making it unavailable through legitimate channels.

2. Why was Propoxyphene withdrawn from the market?
Because of its association with serious cardiac toxicity, including arrhythmia risk, which outweighs its analgesic benefits [1].

3. Are there ongoing clinical trials for Propoxyphene or its derivatives?
Currently, no known clinical trials are active or planned. The focus has shifted toward developing safer analgesics.

4. Could Propoxyphene be reformulated for better safety?
While theoretically possible, there is little current industry or regulatory interest due to safety concerns and alternative therapeutic options.

5. What are the implications for investors or pharmaceutical companies?
Investors should avoid positioning in Propoxyphene-related assets, given the lack of market viability and regulatory barriers.

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References

[1] U.S. Food and Drug Administration. (2010). FDA Announces Removal of Darvon and Darvocet from the Market.

[2] National Institute on Drug Abuse. (2016). The Opioid Crisis: Impact and Response.

Note: The citation links to authoritative regulatory and health sources, underpinning the analysis provided.