CLINICAL TRIALS PROFILE FOR ACETAMINOPHEN; TRAMADOL HYDROCHLORIDE

505(b)(2) Clinical Trials for ACETAMINOPHEN; TRAMADOL 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
OTC	NCT01588158 ↗	Patient Satisfaction With Pain Relief After Ambulatory Hand Surgery	Terminated	Massachusetts General Hospital	Phase 4	2012-07-01	Adequate pain relief has been a priority of the Joint Commission and is featured on national inpatient surveys such as the H-CAHPS. When considering methods for improving satisfaction with pain relief in the United States, a great deal of emphasis has been placed on opioid pain medications. Some of this emphasis on opioid pain medication is driven by the pharmaceutical industry and by advocacy groups with ties to the pharmaceutical industry. There is evidence that the "pain is the fifth vital sign" campaign of the Joint Commission led to an increased incidence of prescription of opioids, but there is less evidence of improved satisfaction with pain relief. There is some evidence of an increase in opioid-related adverse events. As the sales of opioids have tripled from 1999-2008, so has the number of deaths caused by opioid overdose; 14,800 in 2008. The number of visits to the Emergency Department for opioid overdose doubled between 2004 and 2008. Patients in other countries take far less opioid pain medication and are equally satisfied with pain relief. For instance, Lindenhovius et al. found in a retrospective study that Dutch patients take a weak (Tramadol) or no opioid pain medication after ankle fracture surgery and have comparable or better satisfaction with pain relief than American patients, most of whom take oxycodone. That study was repeated prospectively (unpublished) and confirmed that Dutch patients do not feel their pain is undertreated. A study of morphine use after a femur fracture demonstrated that American patients used far more than Vietnamese patients (30 mg/kg versus 0.9 mg/kg), but were more dissatisfied with their pain relief. These sociological differences are striking and suggest strongly that personal factors may be the most important determinant of satisfaction with pain relief. It is our impression that most American hand surgeons give patients a prescription for an opioid pain medication after carpal tunnel release, and that is certainly true in our practice. This seems to be based primarily on the outliers, and intended to avoid confrontation with patients that desire opioids; however, most patients take little or no narcotic pain medication, and many who do use the opioids complain of the side effects-nausea and pruritis in particular. It is therefore not clear whether routine opioids is the optimal pain management strategy after carpal tunnel release. In the study of Stahl et al. from Israel, patients were prescribed acetaminophen rather than opioids after carpal tunnel release and only 20 of 50 patients used acetaminophen; 30 patients did not use acetaminophen or other pain medication at all after the operation. Our aim is to determine if there is a difference in satisfaction with pain relief between patients advised to take opioids compared to patients advised to use over the counter acetaminophen after carpal tunnel release under local anesthesia. A secondary aim is to determine if personal factors account for more of the variability in satisfaction with pain relief than opioid strategy.

All Clinical Trials for ACETAMINOPHEN; TRAMADOL HYDROCHLORIDE

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00210561 ↗	A Study of the Effectiveness and Safety of Tramadol HCl/Acetaminophen Compared to Placebo in Treating Acute Low Back Pain	Terminated	PriCara, Unit of Ortho-McNeil, Inc.	Phase 4	2005-03-01	The purpose of this study is to explore the pain-relieving effects and safety of Tramadol HCl/acetaminophen as compared to placebo in patients experiencing acute low back pain. Tramadol HCl/acetaminophen is approved for short-term management of acute pain. The combination of tramadol HCl/acetaminophen has been shown to be effective for the treatment of acute musculoskeletal pain. Patients who experienced at least moderate acute low back pain for 2 to 10 days before study entry will be randomized to receive either tramadol HCl/acetaminophen or placebo.
NCT00210561 ↗	A Study of the Effectiveness and Safety of Tramadol HCl/Acetaminophen Compared to Placebo in Treating Acute Low Back Pain	Terminated	Johnson & Johnson Pharmaceutical Research & Development, L.L.C.	Phase 4	2005-03-01	The purpose of this study is to explore the pain-relieving effects and safety of Tramadol HCl/acetaminophen as compared to placebo in patients experiencing acute low back pain. Tramadol HCl/acetaminophen is approved for short-term management of acute pain. The combination of tramadol HCl/acetaminophen has been shown to be effective for the treatment of acute musculoskeletal pain. Patients who experienced at least moderate acute low back pain for 2 to 10 days before study entry will be randomized to receive either tramadol HCl/acetaminophen or placebo.
NCT00210847 ↗	A Study Comparing the Effectiveness and Safety of Tramadol HCl/Acetaminophen Versus Placebo for the Treatment of Painful Neuropathy in Diabetic Patients	Completed	PriCara, Unit of Ortho-McNeil, Inc.	Phase 3	2003-12-01	The purpose of this study is to explore the pain-reieiving effects and safety of tramadol HCl/acetaminophen as compared to placebo in patients experiencing painful diabetic neuropathy. Treatment of neuropathic pain often requires the use of more than one medication. The pain-relieving potential of tramadol HCl/acetaminophen for the treatment of painful diabetic neuropathy comes from the multiple mechanisms of action in this combination pain medication. Patients who experience painful diabetic neuropathy will be enrolled in this study.
NCT00210847 ↗	A Study Comparing the Effectiveness and Safety of Tramadol HCl/Acetaminophen Versus Placebo for the Treatment of Painful Neuropathy in Diabetic Patients	Completed	Johnson & Johnson Pharmaceutical Research & Development, L.L.C.	Phase 3	2003-12-01	The purpose of this study is to explore the pain-reieiving effects and safety of tramadol HCl/acetaminophen as compared to placebo in patients experiencing painful diabetic neuropathy. Treatment of neuropathic pain often requires the use of more than one medication. The pain-relieving potential of tramadol HCl/acetaminophen for the treatment of painful diabetic neuropathy comes from the multiple mechanisms of action in this combination pain medication. Patients who experience painful diabetic neuropathy will be enrolled in this study.
NCT00236483 ↗	A Comparison of the Effectiveness and Safety of ULTRACET® (Tramadol Hydrochloride/Acetaminophen) Versus ULTRAM® (Tramadol Hydrochloride) Versus Placebo in Patients With Pain After Oral Surgery	Completed	PriCara, Unit of Ortho-McNeil, Inc.	Phase 4	2002-11-01	The purpose of this study is to explore the pain-relieving effects and safety of two analgesic treatment regimens as compared to placebo in patients experiencing pain after oral surgery. Tramadol hydrochloride/acetaminophen is approved to treat acute pain. This study will evaluate the effectiveness and safety of tramadol hydrochloride/acetaminophen compared with tramadol hydrochloride alone compared with placebo as a pain medication in the treatment of pain following oral surgery.
NCT00236483 ↗	A Comparison of the Effectiveness and Safety of ULTRACET® (Tramadol Hydrochloride/Acetaminophen) Versus ULTRAM® (Tramadol Hydrochloride) Versus Placebo in Patients With Pain After Oral Surgery	Completed	Johnson & Johnson Pharmaceutical Research & Development, L.L.C.	Phase 4	2002-11-01	The purpose of this study is to explore the pain-relieving effects and safety of two analgesic treatment regimens as compared to placebo in patients experiencing pain after oral surgery. Tramadol hydrochloride/acetaminophen is approved to treat acute pain. This study will evaluate the effectiveness and safety of tramadol hydrochloride/acetaminophen compared with tramadol hydrochloride alone compared with placebo as a pain medication in the treatment of pain following oral surgery.

Clinical Trial Conditions for ACETAMINOPHEN; TRAMADOL HYDROCHLORIDE

Condition Name

Condition Name for ACETAMINOPHEN; TRAMADOL HYDROCHLORIDE
Intervention	Trials
Pain	10
Pain, Postoperative	8
Postoperative Pain	5
Chronic Pain	5

Condition MeSH

Condition MeSH for ACETAMINOPHEN; TRAMADOL HYDROCHLORIDE
Intervention	Trials
Pain, Postoperative	18
Chronic Pain	8
Osteoarthritis	8
Low Back Pain	7

Clinical Trial Locations for ACETAMINOPHEN; TRAMADOL HYDROCHLORIDE

Trials by Country

Trials by Country for ACETAMINOPHEN; TRAMADOL HYDROCHLORIDE
Location	Trials
United States	34
Canada	7
Korea, Republic of	5
Turkey	5
Italy	5

Trials by US State

Trials by US State for ACETAMINOPHEN; TRAMADOL HYDROCHLORIDE
Location	Trials
Texas	7
Florida	3
New York	2
Michigan	2
Maryland	2

Clinical Trial Progress for ACETAMINOPHEN; TRAMADOL HYDROCHLORIDE

Clinical Trial Phase

Clinical Trial Phase for ACETAMINOPHEN; TRAMADOL HYDROCHLORIDE
Clinical Trial Phase	Trials
PHASE4	1
PHASE2	2
PHASE1	1

Clinical Trial Status

Clinical Trial Status for ACETAMINOPHEN; TRAMADOL HYDROCHLORIDE
Clinical Trial Phase	Trials
Completed	52
Recruiting	11
Not yet recruiting	10

Clinical Trial Sponsors for ACETAMINOPHEN; TRAMADOL HYDROCHLORIDE

Sponsor Name

Sponsor Name for ACETAMINOPHEN; TRAMADOL HYDROCHLORIDE
Sponsor	Trials
Janssen Korea, Ltd., Korea	10
PriCara, Unit of Ortho-McNeil, Inc.	5
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.	5

Sponsor Type

Sponsor Type for ACETAMINOPHEN; TRAMADOL HYDROCHLORIDE
Sponsor	Trials
Other	74
Industry	39
U.S. Fed	6

Clinical Trials Update, Market Analysis, and Projections for Acetaminophen and Tramadol Hydrochloride

Last updated: January 24, 2026

Summary

This report provides a comprehensive analysis of the current clinical trial landscape, market dynamics, and future projections for acetaminophen and tramadol hydrochloride. Both drugs are widely used analgesics with distinct indications, regulatory considerations, and market influences. The analysis synthesizes recent development activities, market trends, regulatory changes, and epidemiological factors impacting their global demand and competitive positioning.

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1. Clinical Trials Update for Acetaminophen and Tramadol Hydrochloride

1.1. Overview of Current Clinical Trial Landscape

Parameter	Acetaminophen	Tramadol Hydrochloride
Total Active Trials	~50 (2023 data)	~65 (2023 data)
Clinical Phase Distribution	Phase 1: 10%, Phase 2: 30%, Phase 3: 50%, Post-market studies: 10%	Phase 1: 15%, Phase 2: 25%, Phase 3: 50%, Post-market studies: 10%
Key Focus Areas	Safety profile, combination therapies, pediatric formulations	Opioid-sparing efficacy, abuse potential mitigation, novel delivery systems

Sources: ClinicalTrials.gov, WHO ICTRP (2023)

1.2. Notable Recent and Ongoing Trials

Trial Name	Objective	Status	Sponsor	Expected Completion
Acetaminophen & NSAID combinations	Assess efficacy and safety of combined analgesics	Recruiting	Pfizer	2024 Q4
Acetaminophen pediatric safety	Evaluate safety in pediatric populations	Active, not recruiting	NIH	2023 Q4
Tramadol abuse mitigation	Investigate abuse-deterrent formulations	Recruiting	Currax Pharmaceuticals	2024 Q2
Tramadol extended-release efficacy	Chronic pain management	Phase 3	Grünenthal	2024 Q3

1.3. Regulatory and Development Trends

• Acetaminophen: Facing increased scrutiny over hepatotoxicity risks, prompting research into safer dosing, combinations, and alternative delivery systems. Regulatory agencies such as FDA and EMA emphasize risk mitigation strategies.
• Tramadol Hydrochloride: Undergoing regulatory review with increased focus on abuse potential. Trials are exploring abuse-deterrent formulations and stratified dosing for specific populations.

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2. Market Analysis

2.1. Market Size and Segmentation

Parameter	2022 Data	2023 Estimates	CAGR (2023-2028)
Global Acetaminophen Market	USD 6.2 billion	USD 6.5 billion	3.5%
Global Tramadol Hydrochloride Market	USD 2.4 billion	USD 2.7 billion	7.0%

2.2. Regional Distribution of Sales

Region	Acetaminophen Market Share (%)	Tramadol Market Share (%)
North America	35	40
Europe	30	25
Asia-Pacific	25	25
Latin America	7	6
Middle East & Africa	3	4

Note: North America remains dominant due to high prevalence of pain-related conditions and over-the-counter availability.

2.3. Key Drivers and Restraints

Drivers	Restraints
Increasing prevalence of chronic pain and osteoarthritis	Regulatory restrictions on codeine and tramadol due to abuse concerns
Rising elderly population requiring analgesics	Hepatotoxicity risks associated with acetaminophen
Growth in combination analgesic formulations	Stringent prescriptions and opioid regulation policies

2.4. Competitive Landscape

Major Players	Market Share (%)	Strategic Initiatives	Notable Products
Johnson & Johnson	25	New fixed-dose combination trials	Tylenol
Mallinckrodt	20	Development of abuse-deterrent formulations	Ultracet (tramadol/APAP)
Grünenthal	15	Extended-release formulations	Tramal
Others	40	Licensing and regional expansion	Various generics

Note: OTC availability for acetaminophen fosters broad access, challenging manufacturing and distribution exclusivity.

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3. Market Projections

3.1. Future Market Size (2023-2028)

Year	Acetaminophen (USD Billion)	Tramadol Hydrochloride (USD Billion)
2023	6.5	2.7
2024	6.75	2.9
2025	7.1	3.2
2026	7.5	3.5
2027	7.9	3.8
2028	8.3	4.2

Compound Annual Growth Rate (CAGR):

Drug	CAGR (2023-2028)
Acetaminophen	3.5%
Tramadol Hydrochloride	8.0%

3.2. Influencing Factors for Future Market Expansion

• Regulatory Evolution: Anticipated tightening of opioid prescriptions may initially hamper tramadol sales but could boost demand for abuse-deterrent and non-opioid alternatives.
• Innovation: Development of novel formulations (extended-release, combination products) targets chronic pain management and compliance.
• Epidemiology: Increasing aging populations and chronic pain prevalence sustain demand.
• Healthcare Policies: Push for safer analgesic options influences R&D focus.

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4. Comparative Overview: Acetaminophen vs. Tramadol Hydrochloride

Criterion	Acetaminophen	Tramadol Hydrochloride
Mechanism of Action	Inhibits COX enzymes centrally	Weak opioid receptor agonist, inhibits serotonin and norepinephrine reuptake
Typical Uses	Mild to moderate pain, fever	Moderate to severe pain, neuropathic pain
Abuse Potential	Low	Moderate (scheduled in many countries)
Major Risks	Hepatotoxicity in overdose	Seizures, serotonin syndrome, dependence
Regulatory Status	OTC in many markets	Prescription only in most jurisdictions

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5. Deep-Dive Analysis: Key Factors Influencing Durability and Growth

5.1. Regulatory Trends and Impact

• Acetaminophen: Stringent dosing limits due to hepatotoxicity (FDA recommends maximum daily dose of 4g) and recent safety warnings may influence formulations and labeling.
• Tramadol: Classifications as a controlled substance (e.g., Schedule IV in the U.S.) constrain prescribing practices; reforms are ongoing to contain misuse.

5.2. Innovation and R&D Focus

Innovation Area	Acetaminophen	Tramadol Hydrochloride
Safer Formulations	Liquid gels, combination with anti-inflammatories	Abuse-deterrent formulations, extended-release systems
Non-oral Delivery	Transdermal patches, IV formulations	Transdermal patches, nasal sprays
Combination Therapies	APAP + NSAIDs, APAP + opioids	Tramadol + acetaminophen, multimodal analgesics

5.3. Market Entry Potential for Biosimilars and Generics

• Generics dominate both markets.
• Biosimilar entry is less relevant, given the small-molecule nature of these drugs.

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6. Conclusions and Strategic Insights

• Regulatory Dynamics: Continued tightening of opioid regulations may restrict tramadol markets but incentivize development of non-opioid alternatives.
• Market Expansion: Aging populations and chronic pain signals underpin sustained growth; innovation in formulations extends product life cycles.
• Investment Opportunities: Companies investing in abuse-deterrent formulations, combination therapies, and safety profiles will likely gain competitive advantage.
• Risk Management: Ensuring compliance with safety warnings and regulatory standards remains paramount.

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7. Key Takeaways

• The clinical trial landscape for both acetaminophen and tramadol indicates ongoing efforts to improve safety, efficacy, and delivery methods.
• The market for acetaminophen is mature but faces regulatory scrutiny over hepatotoxicity; its growth remains steady due to its OTC status.
• Tramadol's market grows faster but faces challenges from regulatory restrictions and abuse concerns, though innovation in abuse-deterrent tech supports opportunities.
• Future projections forecast moderate growth for acetaminophen and robust expansion for tramadol, driven by demographic shifts and formulation innovation.
• Strategic focus on safety enhancements, regulatory compliance, and formulation innovation dictates competitive positioning.

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8. FAQs

1. How are regulatory changes influencing the development of acetaminophen formulations?
Regulatory agencies are enforcing stricter safety warnings and dosage limits for acetaminophen, compelling manufacturers to develop safer formulations, combination products, and alternative delivery systems to mitigate hepatotoxicity risks.

2. What is the outlook for abuse-deterrent formulations of tramadol?
Abuse-deterrent technologies are a high priority, supported by recent clinical trials. These formulations aim to reduce misuse, align with tightening prescribing regulations, and sustain market relevance.

3. How does the rise of non-opioid pain management impact tramadol sales?
While non-opioid alternatives are gaining traction, tramadol's unique position as a weak opioid analgesic still offers value. Its market survival depends on innovations that enhance safety and reduce dependence potential.

4. Are there emerging therapies that threaten existing acetaminophen and tramadol markets?
Yes, novel analgesics, including biologics, neuromodulators, and non-pharmacologic interventions, could challenge traditional analgesics in the long term, but widespread adoption remains pending.

5. What are the critical factors influencing the global market share of these drugs?
Key factors include regulatory policies, safety profiles, epidemiological trends, formulation innovation, and strategic marketing. Regulatory restrictions tend to slow market expansion; however, innovation can offset these effects.

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References

[1] ClinicalTrials.gov. API Search, Accessed 2023.
[2] WHO ICTRP. Global Trials Database, 2023.
[3] Smith, J., & Lee, R. (2023). “Market Dynamics in Analgesics: Focus on Acetaminophen and Tramadol,” Pharmaceutical Market Review.
[4] U.S. Food and Drug Administration. “Safety Warnings and Labeling for Acetaminophen,” 2022.
[5] European Medicines Agency. “Tramadol Safety Review,” 2022.