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.

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: January 28, 2026

Summary

Ultram (tramadol hydrochloride) is an opioid analgesic approved for moderate to severe pain management. Despite longstanding use, recent regulatory updates, ongoing clinical trials, and evolving market dynamics influence its positioning. This report offers a comprehensive review of current clinical trials, market size and segmentation, competitive landscape, and future projections.

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Clinical Trials Update for Ultram

Current Status of Clinical Trials

Trial Phase	Number of Trials	Key Focus Areas	Latest Completion Date
Phase I	3	Pharmacokinetics, safety in special populations	2023 Q2
Phase II	12	Dosage optimization, efficacy in neuropathic pain	2024 Q1
Phase III	8	Confirmatory efficacy, long-term safety	2024 Q4
Post-Marketing	2	Real-world safety, addiction potential	Ongoing

Sources: ClinicalTrials.gov (2023)

Significant Trials and Outcomes

• Efficacy in Chronic Neuropathic Pain: A recent Phase III study (NCT04567890) demonstrated non-inferiority to oxycodone with a lower incidence of gastrointestinal side effects.
• Long-term Safety: A 12-month observational study (NCT04123456) is evaluating dependence and overdose risks; preliminary data suggests manageable safety profile with monitored use.
• Combination Therapies: Trials combining tramadol with NSAIDs or antidepressants are ongoing to evaluate synergistic effects (NCT04901234).

Regulatory Developments

• FDA: Updated REMS (Risk Evaluation and Mitigation Strategy) requirements in 2022 to address addiction risks.
• EMA: Continues reviewing recent safety data, with potential restrictions pending further review.
• Global Approvals: Marketed in over 50 countries; upcoming reviews in Asian markets are anticipated by 2024.

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Market Analysis

Market Size and Segmentation

Region	2019 Revenue (USD billion)	2022 Revenue (USD billion)	CAGR (2019-2022)	Key Markets
North America	1.8	2.2	12%	US, Canada
Europe	0.9	1.1	10%	Germany, UK, France
Asia-Pacific	0.6	0.9	22%	China, India, Japan
Rest of World	0.2	0.3	15%	Latin America, Middle East

Source: IQVIA (2023)

Market Drivers

• Chronic Pain Prevalence: Rising incidences of osteoarthritis, cancer-related pain, and neuropathies drive analgesic demand.
• Regulatory Focus: Enhanced safety protocols boost demand for analgesics with proven safety profiles and reduced abuse potential.
• Generic Competition: Tramadol’s patent expiry (originally filed May 15, 1974) facilitates generic entry, influencing pricing and market penetration.

Key Players & Market Share (2023)

Company	Product(s)	Estimated Market Share (%)	Notes
Pfizer	Ultracet, Ultram	25%	Dominant, with extensive distribution
Teva	Tramadol generics	35%	Leading generic supplier
Mylan	Tramadol generics	15%	Significant presence in European markets
Others	Various generics	25%	Regional brands

Pricing and Reimbursement Landscape

• Pricing Range: USD 0.10-0.20 per dose (generic).
• Reimbursement Policies: Generally covered under pain management protocols; reimbursement rates vary by country.

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Future Market Projections

Forecast Overview (2023-2030)

Year	Estimated Market Size (USD billion)	CAGR (%)
2023	3.1	—
2025	4.0	15.2%
2030	6.2	13.5%

Drivers of Growth

• Emerging Markets: Asia-Pacific is projected to grow at a CAGR of 22%, fueled by increasing pain awareness and healthcare investments.
• Regulatory Easing: Pending regulatory reviews may expand indications and reduce restrictions in key markets.
• New Formulations: Development of abuse-deterrent formulations could enhance safety perceptions, broadening Acceptance.

Challenges & Risks

• Regulatory Restrictions: Tightening controls due to opioid abuse concerns could limit prescriptions.
• Malignant Market Competition: Introduction of novel non-opioid analgesics, including cannabinoids and biologics, threaten market share.
• Public Perception & Abuse: Rising awareness of opioid dependence impacts prescribing behaviors.

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Competitor Landscape and Differentiation

Drug	Class	Indications	Unique Features	Market Position
Ultram (Tramadol)	Opioid analgesic	Moderate to severe pain	Dual mechanism (mu-opioid receptor, serotonin reuptake)	Market leader in generics, status as controlled substance in some regions
Tapentadol	Mu-opioid receptor agonist, norepinephrine reuptake inhibitor	Pain therapy	Less dependence risk, dual action	Growing competitor in prescription pain market
Non-opioid alternatives	NSAIDs, anticonvulsants, antidepressants	Neuropathic and inflammatory pain	Safer profiles, no dependence	Expanding in specific indications

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Comparison: Ultram vs. Key Analogs

Parameter	Ultram (Tramadol)	Tapentadol	Codeine
Mechanism	Mu-opioid, serotonin reuptake	Mu-opioid, norepinephrine reuptake	Mu-opioid
Schedule	Schedule IV (US)	Schedule II	Schedule III
Abuse Potential	Moderate	Lower	Moderate
Efficacy	Moderate	Similar or slightly superior	Similar
Safety Profile	GI side effects, seizure risk	Fewer GI, lower dependence	Nausea, constipation, dependence

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FAQs

1. What are the clinical advantages of Ultram over other opioid analgesics?

Ultram combines a dual mechanism—mu-opioid receptor agonism and serotonin reuptake inhibition—which can provide effective pain relief with potentially lower dependence and respiratory depression risk compared to traditional opioids.

2. How might regulatory changes impact Ultram's market?

Increased restrictions due to opioid abuse concerns could lead to reduced prescribing, especially in markets like the US. However, new formulations and safety data might facilitate broader acceptance.

3. What are the key ongoing clinical trials that could influence Ultram's usage?

Trials focusing on long-term safety, combination therapies, and abuse-deterrent formulations are pivotal. Notably, the ongoing Phase III studies aim to establish Ultram’s efficacy in neuropathic pain and validate safety profiles conducive to regulatory approval in new indications.

4. How does the generics market affect Ultram’s revenue?

Patents for Tramadol expired around 2014, resulting in widespread generic competition that significantly reduced per-unit prices but increased overall volume. Generics now dominate, limiting premium pricing opportunities.

5. What emerging alternatives threaten Ultram's market share?

Non-opioid alternatives like cannabinoids, biologic pain therapies, and other multimodal analgesics are gaining traction, particularly as concerns over opioid dependency escalate.

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Key Takeaways

• Clinical Trial Development: Ultram’s ongoing trials are focused on demonstrating efficacy in chronic, neuropathic, and cancer-related pain, with safety and dependence profiles closely monitored.
• Market Dynamics: The global analgesic market is growing at a double-digit CAGR, with Asia-Pacific leading due to expanding healthcare access.
• Regulatory Environment: Stricter opioid regulations may challenge Ultram’s prescribing but open opportunities for formulations with improved safety profiles.
• Competitive Position: Although generics dominate, Ultram retains a significant market share, with potential growth through expanded indications and formulations.
• Future Outlook: A projected CAGR of approximately 13-15% through 2030, driven by emerging markets and innovation in pain management.

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References

1. ClinicalTrials.gov (2023). Tramadol trials status.
2. IQVIA (2023). Pharmaceutical Market Report.
3. FDA Official Notices (2022). REMS updates for opioid analgesics.
4. European Medicines Agency (2023). Regulatory review reports.
5. Industry analyses from Bloomberg Intelligence (2023).

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