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	2
Osteoarthritis, Hip	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
New York	1
Texas	1
Florida	1
Utah	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

Clinical Trials Update, Market Analysis, and Projection for Propoxyphene Hydrochloride

Last updated: January 25, 2026

Summary

Propoxyphene Hydrochloride, formerly marketed as Darvon and Darvocet, is an opioid analgesic once widely prescribed for mild to moderate pain. However, regulatory agencies globally, notably the U.S. Food and Drug Administration (FDA), have decisively curtailed its use due to safety concerns—primarily cardiovascular risks—and its addictive potential. Currently withdrawn from the U.S. market, its active exploration in clinical trials remains minimal. This article offers a comprehensive review of existing clinical data, regulatory decisions, current market status, and future projections for Propoxyphene Hydrochloride.

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Clinical Trials Update for Propoxyphene Hydrochloride

Aspect	Details
Historical Clinical Trials	Conducted predominantly in the 1950s–1970s, involving safety, efficacy, and dosage studies. These early trials established its analgesic properties but also revealed significant adverse effects.
Regulatory Actions	The FDA issued a final rule in late 2010 (21 CFR Part 310, Docket No. FDA-2010-N-0072) withdrawing approval for Propoxyphene-containing products, citing increased risk of serious cardiac events.
Current Clinical Trials (2023+)	No active federally registered trials evaluating Propoxyphene's safety or efficacy are ongoing in major clinical trial registries such as ClinicalTrials.gov. Historically, some experimental studies on analogues or formulations might exist but are not underway presently.
Phase Investigations	No recent Phase I–III trials registered since 2010, reflecting the regulatory withdrawal and market disuse. Some preclinical research on opioid receptor interaction and analog development exists but is not aimed at drug approval.

Key Features of Past Clinical Trials

Trial Aspect	Findings
Efficacy	Effective for mild/moderate pain in early studies; comparable to codeine but with less sedative effect.
Adverse Outcomes	Increased incidence of cardiac arrhythmias linked to QT interval prolongation; overdose risks; rapid development of dependency.
Regulatory Response	Market withdrawal, classification as a controlled substance, and removal from formularies.

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Market Analysis of Propoxyphene Hydrochloride

Historical Market Dynamics (Pre-2010)

Market Indicator	Details
Market Launch	Introduced in 1957, rapidly gained popularity as an over-the-counter (OTC) and prescription analgesic.
Peak Sales	Estimated global peak sales occurred around the early 2000s, with US sales reaching approximately $100 million annually—mainly via prescription channels.
Manufacturers	Divided primarily between Eli Lilly, Shore Ltd., and other generics; Lilly ceased production post-2010.
Distribution Channel	Widely available over-the-counter initially, moving primarily to prescription status before market withdrawal.
Indicative User Base	Primarily adult patients aged 18–65 with mild to moderate pain; usage often in outpatient settings.

Regulatory Impact on Market

• FDA and EMA Decisions | The FDA's 2010 decision to withdraw approval effectively eliminated legal sales in the U.S. and discouraged international marketing. The European Medicines Agency (EMA) also recommended restrictions or removal.
• Impact on Prescriptions | Substitution therapies, including NSAIDs, acetaminophen, and alternative opioids, increased post-withdrawal.

Post-Withdrawal Market Landscape

Status	Data/Trends
Market Presence	Non-existent officially; illegal manufacturing and trafficking remain a minor concern in illicit markets.
Off-Label/Counterfeit	Rare reports; no significant data on counterfeit distribution.
Generic Replacements	No direct replacements under the same chemical entity; some reformulated opioids have gained prominence.

Future Market Projection (2023–2030)

Scenario	Projection	Supporting Factors
Continued Withdrawal	Near-zero legal market activity	Ongoing regulatory bans, safety concerns, and negative publicity.
Potential Resurgence (Hypothetical)	Low; primarily in illicit trade or unregulated markets	Historical dependence and its pharmacological profile could provoke criminal use if reintroduced.
Development of Analogues or Derivatives	Moderate; limited R&D toward safer opioids	Focus on developing safer analgesics, but Propoxyphene itself unlikely to return.

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Comparison with Similar Analgesics

Agent	Approval Status	Reason for Withdrawal/Restrictions	Market Status
Propoxyphene	Withdrawn (U.S., 2010); European restrictions	Cardiac toxicity, overdose risk	Absent from legal market
Codeine	Widely available	Addiction potential	Prescriptions and OTC in many countries
Tramadol	Approved globally	Seizures, dependence	Market leader in opioids for mild/moderate pain
Oxycodone	Approved	Abuse potential	Major opioid market segment

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FAQs

1. Why was Propoxyphene Hydrochloride withdrawn from the market?
The FDA withdrew approval in 2010 due to evidence linking Propoxyphene with increased cardiovascular risks—specifically, QT prolongation and arrhythmias—and its potential for overdose and dependency.[1]

2. Are there ongoing clinical trials involving Propoxyphene?
No. Current clinical trial registries show no active investigations since the 2010 market withdrawal, indicating that Propoxyphene is not under development or evaluation in regulated clinical settings.

3. Can Propoxyphene still be legally prescribed or obtained?
No. Following regulatory bans, Propoxyphene-containing products are no longer approved for sale or prescription in the USA, Europe, and many other jurisdictions.

4. Are there any attempts to develop Propoxyphene analogues or safer derivatives?
Limited research exists aiming to design analogues with better safety profiles, but none have entered advanced clinical phases or regulatory approval as of 2023.

5. What lessons does the Propoxyphene case provide for new analgesic development?
It underscores the critical importance of comprehensive cardiovascular safety profiling and post-market surveillance in opioid drug approval, as well as the need for alternative, safer pain management therapies.

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Key Takeaways

• Regulatory verdicts have decisively ended Propoxyphene Hydrochloride's market presence due to safety issues.
• Clinical trials are inactive since 2010; no new research efforts are currently underway targeting Propoxyphene itself.
• Market landscape demonstrates a complete retreat; future projections show negligible legal use and high potential for illicit activity if reintroduced.
• Drug developers are cautious, focusing on alternative opioids with improved safety profiles.
• Industry implications emphasize the importance of rigorous safety assessment and post-marketing surveillance in opioid pharmacotherapy.

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References

[1] U.S. Food and Drug Administration (FDA). (2010). Final Rule: Withdrawal of Approval for Propoxyphene-Containing Products. Federal Register, 75(241), 78952–78956.