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 That study was repeated prospectively (unpublished) and confirmed that Dutch patients do not feel their pain is undertreated.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.

Clinical Trial Conditions for acetaminophen; tramadol hydrochloride

Condition Name

Condition Name for acetaminophen; tramadol hydrochloride
Intervention	Trials
Pain	10
Pain, Postoperative	6
Postoperative Pain	5
Low Back Pain	4

Condition MeSH

Condition MeSH for acetaminophen; tramadol hydrochloride
Intervention	Trials
Pain, Postoperative	15
Osteoarthritis	8
Chronic Pain	7
Low Back Pain	7

Clinical Trial Locations for acetaminophen; tramadol hydrochloride

Trials by Country

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−

Trials by Country for acetaminophen; tramadol hydrochloride
Location	Trials
United States	29
Canada	7
Korea, Republic of	5
Turkey	5
Italy	5

Trials by US State

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−

Trials by US State for acetaminophen; tramadol hydrochloride
Location	Trials
Texas	4
Minnesota	2
Massachusetts	2
Florida	2
New York	2

Clinical Trial Progress for acetaminophen; tramadol hydrochloride

Clinical Trial Phase

Clinical Trial Phase for acetaminophen; tramadol hydrochloride
Clinical Trial Phase	Trials
Phase 4	36
Phase 3	16
Phase 2	6

Clinical Trial Status

Clinical Trial Status for acetaminophen; tramadol hydrochloride
Clinical Trial Phase	Trials
Completed	51
Not yet recruiting	10
Recruiting	9

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	67
Industry	39
U.S. Fed	6

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

Introduction to Acetaminophen and Tramadol Hydrochloride

Acetaminophen and tramadol hydrochloride are two potent analgesics often combined to treat moderate to severe pain. This combination leverages the synergistic effects of both drugs to provide effective pain relief.

Clinical Trials Overview

Efficacy and Safety of Extended-Release Formulations

A significant clinical trial evaluated the efficacy and safety of an extended-release formulation of tramadol hydrochloride and acetaminophen (TA-ER) for chronic low back pain. This Phase III, double-blind, placebo-controlled study involved 245 patients with moderate to severe chronic low back pain. The results showed that TA-ER was significantly more effective than placebo in providing pain relief, functional improvements, and enhanced quality of life. Patients in the TA-ER group demonstrated significant improvements in pain intensity, quality of life, and functional capabilities compared to the placebo group[1].

Adverse Events and Safety Profile

While the combination of tramadol and acetaminophen is effective, it also comes with a predictable safety profile. Common adverse events reported in clinical trials include nausea, dizziness, constipation, and vomiting. It is crucial to monitor patients for these side effects, especially given the potential for acetaminophen to cause acute liver failure at high doses[1][4].

Market Analysis

Current Market Size and Growth Projections

The global tramadol market, which includes formulations with acetaminophen, has seen substantial growth in recent years. As of 2022, the market size was valued at approximately $5.26 billion and is projected to reach $7.29 billion by 2030, growing at a CAGR of 4.41% from 2023 to 2030[2].

Another report indicates that the tramadol market size was $4.24 billion in 2023 and is expected to grow at a CAGR of 6.86% from 2024 to 2030, reaching nearly $6.75 billion by 2030[5].

Regional Market Dynamics

Europe is expected to maintain a significant share in the global tramadol market due to high healthcare expenditure, favorable government initiatives for opioid substitution therapy, and a large consumer base. The Asia Pacific region is also witnessing rapid growth driven by improving healthcare infrastructure, rising disposable incomes, and increasing awareness about pain management[2][5].

Drivers and Restraints

Drivers

• Increasing Prevalence of Chronic Pain: The growing number of chronic disease cases and surgeries, particularly among the aging population, is driving the demand for effective pain management drugs like tramadol and its combinations[3][5].
• Regulatory Approvals: New indications and regulatory approvals for tramadol formulations are expanding its utility and market reach. This includes approvals for combination therapies and extended-release formulations[3][5].
• Research and Development: Ongoing research to develop novel formulations and improve delivery efficacy is boosting market growth. Innovations such as enteric coatings for extended-release formulations and combination therapies with non-opioid analgesics are enhancing patient compliance and efficacy[5].

Restraints

• Adverse Events and Abuse Potential: The potential for adverse events, such as nausea, dizziness, and the risk of acetaminophen-induced liver injury, as well as the abuse and dependence associated with tramadol, are significant restraints on market growth[1][3][4].

Market Projections

Future Growth Trends

The tramadol market is expected to experience moderate to high growth over the forecast period, driven by several factors:

• Expanding Regulatory Approvals: New indications and approvals for tramadol formulations will continue to drive market growth by tapping into unmet medical needs and diversifying the utility of the drug[3].
• Increasing Demand for Pain Management: The rising prevalence of chronic pain conditions, particularly among the aging population, will continue to fuel the demand for effective pain management drugs like tramadol and its combinations[2][5].
• Innovations in Drug Delivery: Advancements in drug delivery systems, such as extended-release formulations and combination therapies, will improve patient compliance and efficacy, further boosting market growth[5].

Geographic Expansion

The Asia Pacific region is anticipated to be the fastest-growing market for tramadol during the forecast period, driven by improving healthcare infrastructure, rising disposable incomes, and increasing awareness about pain management. Europe will also continue to play a significant role due to its large consumer base and favorable healthcare policies[2][5].

Key Takeaways

• Clinical Efficacy: The combination of tramadol hydrochloride and acetaminophen has been shown to be effective in providing pain relief, functional improvements, and enhanced quality of life in clinical trials.
• Market Growth: The global tramadol market is projected to grow significantly over the next few years, driven by increasing demand for pain management, new regulatory approvals, and innovations in drug delivery.
• Regional Dynamics: Europe and the Asia Pacific region are key markets, with the latter expected to be the fastest-growing due to improving healthcare infrastructure and rising awareness about pain management.
• Challenges: The market faces challenges related to adverse events, abuse potential, and regulatory scrutiny, which must be addressed through ongoing research and development.

FAQs

What is the current market size of the tramadol drug market?

The tramadol drug market size was valued at approximately $5.26 billion in 2022 and $4.24 billion in 2023, depending on the source[2][5].

What is the projected growth rate of the tramadol market?

The tramadol market is projected to grow at a CAGR of 4.41% from 2023 to 2030 and 6.86% from 2024 to 2030, according to different reports[2][5].

What are the common adverse events associated with the combination of tramadol and acetaminophen?

Common adverse events include nausea, dizziness, constipation, and vomiting. There is also a risk of acetaminophen-induced liver injury at high doses[1][4].

Which regions are expected to drive the growth of the tramadol market?

Europe and the Asia Pacific region are expected to be key drivers of market growth, with the Asia Pacific region being the fastest-growing due to improving healthcare infrastructure and rising awareness about pain management[2][5].

What are the main drivers of the tramadol market growth?

The main drivers include the increasing prevalence of chronic pain conditions, new regulatory approvals, and innovations in drug delivery systems such as extended-release formulations and combination therapies[3][5].

Sources

1. PubMed: "A randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of extended-release tramadol hydrochloride 75-mg/acetaminophen 650-mg fixed-dose combination tablets (TA-ER) for the treatment of chronic low back pain."
2. Verified Market Research: "Tramadol Drug Market Size, Share, Trends, Growth And Forecast"
3. Fortune Business Insights: "Tramadol Market Size, Share, Forecast | Growth Report [2032]"
4. FDA: "ULTRACET (tramadol hydrochloride/acetaminophen) Tablets Full Prescribing Information"
5. Stellar Market Research: "Tramadol Market: Global Industry Analysis and Forecast (2024-2030)"