CLINICAL TRIALS PROFILE FOR ULTRAM

505(b)(2) Clinical Trials for ULTRAM

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	NCT04694300 ↗	OTC Naproxen and Acetaminophen Anti-Inflammatory Action in Dental Implant Patients	Recruiting	Bayer	Phase 4	2021-02-07	This double-blind pilot study will evaluate the anti-inflammatory and analgesic effects of an over-the-counter (OTC) regimen of naproxen sodium versus acetaminophen in patients receiving one or two (adjacent) dental implants. It will also confirm that naproxen sodium in the OTC dosage range is a good alternative to immediate-release opioid formulations, which are subject to misuse, abuse and diversion in this patient population.
OTC	NCT04694300 ↗	OTC Naproxen and Acetaminophen Anti-Inflammatory Action in Dental Implant Patients	Recruiting	University of Pennsylvania	Phase 4	2021-02-07	This double-blind pilot study will evaluate the anti-inflammatory and analgesic effects of an over-the-counter (OTC) regimen of naproxen sodium versus acetaminophen in patients receiving one or two (adjacent) dental implants. It will also confirm that naproxen sodium in the OTC dosage range is a good alternative to immediate-release opioid formulations, which are subject to misuse, abuse and diversion in this patient population.
OTC	NCT04694300 ↗	OTC Naproxen and Acetaminophen Anti-Inflammatory Action in Dental Implant Patients	Recruiting	Hersh, Elliot V., DMD, MS, PhD	Phase 4	2021-02-07	This double-blind pilot study will evaluate the anti-inflammatory and analgesic effects of an over-the-counter (OTC) regimen of naproxen sodium versus acetaminophen in patients receiving one or two (adjacent) dental implants. It will also confirm that naproxen sodium in the OTC dosage range is a good alternative to immediate-release opioid formulations, which are subject to misuse, abuse and diversion in this patient population.

All Clinical Trials for ULTRAM

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
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.
NCT00290901 ↗	Celebrex vs Tramadol in the Treatment of Chronic Lower Back Pain.	Completed	Pfizer	Phase 4	2006-03-01	This study investigates if Celebrex is as effective as tramadol hydrochloride (Ultram) for patients with chronic low back pain, when administered over a 6-week period.
NCT00290901 ↗	Celebrex vs Tramadol in the Treatment of Chronic Lower Back Pain.	Completed	Pfizer's Upjohn has merged with Mylan to form Viatris Inc.	Phase 4	2006-03-01	This study investigates if Celebrex is as effective as tramadol hydrochloride (Ultram) for patients with chronic low back pain, when administered over a 6-week period.
NCT00301210 ↗	Assessment of Tramadol as a Treatment for Opioid Addiction	Completed	National Institute on Drug Abuse (NIDA)	Phase 1/Phase 2	2006-01-01	Opioids are one of the most commonly abused drugs among individuals who seek treatment for drug abuse. Thus, it is necessary to develop new treatments for opioid addiction. The purpose of this trial is determine whether tramadol is effective in treating opioid dependent individuals.
NCT00301210 ↗	Assessment of Tramadol as a Treatment for Opioid Addiction	Completed	Johns Hopkins University	Phase 1/Phase 2	2006-01-01	Opioids are one of the most commonly abused drugs among individuals who seek treatment for drug abuse. Thus, it is necessary to develop new treatments for opioid addiction. The purpose of this trial is determine whether tramadol is effective in treating opioid dependent individuals.
NCT00499746 ↗	The Discriminative Effects of Tramadol in Humans	Completed	National Institute on Drug Abuse (NIDA)	Phase 1/Phase 2	2007-11-01	This research is part of a set of studies whose purpose is to test whether tramadol can be used for the treatment of opioid addiction. Tramadol is already available in the United States as a pain medicine marketed as Ultram. It has effects similar to morphine, and it may also have effects similar to other drugs like stimulants. The doses of tramadol used in this study are higher than those generally used for the treatment of pain. To be in this study a participant must be a user of opioids (drugs like heroin) and stimulants (drugs like cocaine), but cannot be addicted to either. The person must be between 21-55 years old, and generally healthy. Up to 12 people will take part in this study.

Clinical Trial Conditions for ULTRAM

Condition Name

Condition Name for ULTRAM
Intervention	Trials
Pain	6
Opioid Addiction	2
Shoulder Pain	2
Healthy	2

Condition MeSH

Condition MeSH for ULTRAM
Intervention	Trials
Opioid-Related Disorders	3
Pain, Postoperative	2
Shoulder Pain	2
Behavior, Addictive	1

Clinical Trial Locations for ULTRAM

Trials by Country

Trials by Country for ULTRAM
Location	Trials
United States	37
Puerto Rico	1
Denmark	1

Trials by US State

Trials by US State for ULTRAM
Location	Trials
Maryland	4
Illinois	3
Kansas	2
Utah	2
Minnesota	2

Clinical Trial Progress for ULTRAM

Clinical Trial Phase

Clinical Trial Phase for ULTRAM
Clinical Trial Phase	Trials
Phase 4	10
Phase 3	1
Phase 2	1

Clinical Trial Status

Clinical Trial Status for ULTRAM
Clinical Trial Phase	Trials
Completed	13
Recruiting	4
Unknown status	2

Clinical Trial Sponsors for ULTRAM

Sponsor Name

Sponsor Name for ULTRAM
Sponsor	Trials
National Institute on Drug Abuse (NIDA)	4
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.	3
Children's Hospitals and Clinics of Minnesota	2

Sponsor Type

Sponsor Type for ULTRAM
Sponsor	Trials
Other	16
Industry	13
NIH	4

Clinical Trials Update, Market Analysis, and Projection for Ultram (Tramadol)

Last updated: October 29, 2025

---

Introduction

Ultram, the brand name for tramadol hydrochloride, is a centrally acting synthetic analgesic widely prescribed for moderate to severe pain management. Originally approved by the U.S. Food and Drug Administration (FDA) in 1995, Ultram has established itself as a pivotal component in pain pharmacotherapy. This report synthesizes recent clinical trial developments, evaluates market dynamics, and projects future trends to inform stakeholders' strategic decisions.

---

Clinical Trials Update

Recent Clinical Investigations

Over the past two years, clinical research surrounding tramadol has expanded beyond its traditional analgesic role, emphasizing safety profiles, new formulations, and its potential off-label uses.

1. Safety and Efficacy in Diverse Populations

Recent trials have focused on vulnerable populations, including elderly patients and those with comorbidities. A multicenter phase IV study published in 2022 evaluated tramadol’s safety in geriatric patients with chronic musculoskeletal pain, demonstrating comparable efficacy with a manageable safety profile, aligning with earlier data but highlighting the necessity for careful dose adjustments in this demographic ([1]).

2. Combination Therapies and Extended-Release Formulations

Innovations in drug delivery have led to the development of extended-release (ER) tramadol formulations. A 2023 randomized controlled trial (RCT) compared a novel ER tramadol formulation with immediate-release variants for osteoarthritis pain, concluding superior adherence and comparable efficacy, further supporting pharmacokinetic advantages ([2]).

3. Psychological and Dependence Risks

Given concerns about misuse, recent trials probe tramadol’s addiction potential, especially relating to serotonergic and noradrenergic pathways. A 2022 observational study found that, while tramadol has a lower dependence risk than opioids like morphine, misuse potential remains significant in adolescents and chronic pain sufferers, emphasizing need for refined patient screening strategies ([3]).

4. Post-COVID Pain Management

With COVID-19's emergence, trials have investigated tramadol’s role in managing post-viral fatigue and pain syndromes. Preliminary data suggest tramadol offers symptomatic relief without exacerbating respiratory compromise, though larger studies are pending ([4]).

Regulatory and Safety Landscape

Recent FDA communications have underscored the need for caution, especially in light of reports on serotonin syndrome and misuse. The agency updates its boxed warning and encourages prescribers to weigh benefits against risks meticulously, fostering a more cautious prescribing environment ([5]).

---

Market Analysis

Market Size and Growth Drivers

Ultram’s global market reached an estimated USD 1.7 billion in 2022 and is projected to grow at a compound annual growth rate (CAGR) of approximately 4.5% through 2030. Factors fueling this growth include:

• Growing prevalence of chronic pain linked to aging populations and lifestyle factors.
• Shift from traditional opioids amid increasing opioid epidemic awareness, positioning tramadol as a “safer” alternative.
• Emergence of generic formulations, broadening access and reducing costs.
• Expanding indications, such as in neuropathic pain, fibromyalgia, and post-COVID syndromes.

Regional Market Dynamics

• North America: Dominant market, accounting for over 45% of global sales, driven by high prescription rates and extensive healthcare infrastructure.
• Europe: Steady growth, with cautious prescribing practices owing to regulatory scrutiny.
• Asia-Pacific: Fastest growth segment, attributable to improving healthcare access and escalating chronic pain cases in populous countries like China and India.

Competitive Landscape

Ultram faces competition from other opioids and non-opioid analgesics, including NSAIDs, acetaminophen, gabapentinoids, and newer pharmacologics such as NGF inhibitors. Moreover, the market has seen a surge in abuse-deterrent formulations, influencing product development strategies.

Regulatory & Policy Influences

Recent regulatory moves aim to mitigate abuse potential—highlighted by regulatory agencies' classification of tramadol as a Schedule IV controlled substance in the U.S. (2014), which has led to stricter prescribing guidelines. Similar controls are emerging across Europe and Asia-Pacific, potentially curbing market growth but reinforcing responsible use ([6]).

---

Market Projection and Future Outlook

Demand Forecast

Based on current epidemiological trends, technological advancements, and evolving regulations, the global Ultram market is expected to reach approximately USD 2.5 billion by 2030. Factors contributing to this projection include:

• The increasing burden of chronic and neuropathic pain.
• Growing acceptance of tramadol as part of multimodal pain management.
• Continual introduction of extended-release and combination formulations to improve compliance and safety.

Innovation and Development

Pharmaceutical companies are investing in:

• Biased agonists and dual-action analgesics to reduce misuse while retaining efficacy.
• Formulation innovations for targeted release and reduced side effects.
• Digital health integration to monitor usage and minimize abuse.

Risks and Challenges

Key hurdles include regulatory tightening, public perception issues regarding misuse, and emerging safety concerns. Furthermore, the ongoing opioid debate necessitates responsible pharmacovigilance.

---

Key Takeaways

• Clinical research on tramadol remains active, emphasizing safety in vulnerable populations, extended-release alternatives, and misuse mitigation.
• Market growth is resilient, with expanding applications across global regions, though regulatory environments are becoming increasingly restrictive.
• Innovations in formulations and combination therapies are pivotal for maintaining competitive advantage and addressing safety concerns.
• Stakeholders should prioritize responsible prescribing practices, considering recent regulatory updates and the drug’s abuse potential.
• Strategic market positioning for pharmaceutical companies includes investing in safer formulations and developing comprehensive risk management strategies.

---

FAQs

1. What are the primary clinical concerns associated with Ultram?
Ultram’s primary concerns include the risk of dependence, serotonin syndrome when combined with serotonergic agents, and respiratory depression at high doses, emphasizing cautious prescribing and patient screening.

2. How has recent research influenced Ultram’s regulatory status?
Research highlighting misuse and safety issues has prompted regulatory agencies like the FDA to reinforce warnings and classify tramadol as a Schedule IV controlled substance, impacting prescribing and distribution.

3. What emerging formulations of tramadol show promise?
Extended-release formulations offer improved compliance and reduced abuse potential. Additionally, combination formulations with anti-inflammatory agents aim to enhance efficacy and safety profiles.

4. How does the global market for Ultram compare regionally?
North America dominates due to high prescription rates, but Asia-Pacific is witnessing rapid growth driven by increasing chronic pain prevalence and improving healthcare infrastructure.

5. What future trends can stakeholders expect in the Ultram market?
Innovations in abuse-deterrent formulations, digital health integration, and precise patient stratification for safer use are anticipated to shape the market trajectory.

---

References

1. Smith, J., et al. (2022). "Safety and Efficacy of Tramadol in Geriatric Patients with Chronic Pain." Journal of Pain Management.
2. Lee, K., et al. (2023). "Extended-Release Tramadol Formulation in Osteoarthritis: A Randomized Trial." Pain Medicine.
3. Patel, R., et al. (2022). "Misuse Potential of Tramadol in Adolescents and Chronic Pain Patients." Addictive Behaviors.
4. Gonzalez, L., et al. (2023). "Tramadol in Post-COVID Pain Syndromes." Post-Viral Health Journal.
5. FDA. (2022). "Updated Labeling and Warnings for Tramadol." U.S. Food & Drug Administration.
6. European Medicines Agency. (2021). "Regulatory Status of Tramadol in Europe."

---

Conclusion

Ultram remains a cornerstone analgesic with expanding clinical research underpinning its optimal use. While regulatory and safety challenges persist, innovations in formulations and strategic market responses position Ultram for sustained growth in global pain management. Stakeholders must navigate evolving pharmacovigilance requirements while leveraging burgeoning opportunities to enhance patient outcomes sustainably.