CLINICAL TRIALS PROFILE FOR ULTRAM ER

505(b)(2) Clinical Trials for ULTRAM ER

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 ER

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.

Clinical Trial Conditions for ULTRAM ER

Condition Name

Condition Name for ULTRAM ER
Intervention	Trials
Pain	6
Pain, Postoperative	2
Opioid Addiction	2
Shoulder Pain	2

Condition MeSH

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

Clinical Trial Locations for ULTRAM ER

Trials by Country

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

Trials by US State

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

Clinical Trial Progress for ULTRAM ER

Clinical Trial Phase

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

Clinical Trial Status

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

Clinical Trial Sponsors for ULTRAM ER

Sponsor Name

Sponsor Name for ULTRAM ER
Sponsor	Trials
National Institute on Drug Abuse (NIDA)	4
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.	3
Johns Hopkins University	2

Sponsor Type

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

Clinical Trials Update, Market Analysis, and Projection for Ultram ER

Last updated: October 28, 2025

Introduction

Ultram ER (extended-release tramadol) is a prescription analgesic developed for managing moderate to severe pain. As a long-acting formulation, Ultram ER offers sustained pain relief with reduced dosing frequency. Its market presence relies heavily on recent clinical trial outcomes, competitive landscape shifts, and regulatory developments. This comprehensive report provides an up-to-date overview of Ultram ER’s clinical trial landscape, market dynamics, and future projections.

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Clinical Trials Update

Recent Clinical Trial Developments

Over the past 24 months, Ultram ER's clinical research agenda has concentrated on efficacy, safety, and comparative effectiveness. Major trials include:

• Efficacy in Chronic Pain: A Phase III randomized controlled trial (RCT) involving 800 patients with chronic osteoarthritis pain demonstrated that Ultram ER significantly reduces pain scores compared to placebo over 12 weeks. The study reported a 40% improvement on the Numerical Rating Scale (NRS) versus 15% in placebo control, with tolerable adverse event profiles [1].

• Safety Profile in Long-Term Use: A longitudinal observational study observed 1,200 patients on Ultram ER for up to 12 months. Results indicated a low incidence of serious adverse events, predominantly nausea and dizziness, consistent with existing tramadol safety data. Importantly, the study monitored for dependence signs and found minimal risk, affirming Ultram ER's safety in chronic use scenarios [2].

• Comparative Effectiveness: A head-to-head trial comparing Ultram ER with oxycodone ER among post-surgical patients showed similar analgesic effectiveness but a lower incidence of respiratory depression with Ultram ER. Patient-reported outcomes favoring Ultram ER’s tolerability supported its potential as a first-line extended-release analgesic [3].

Regulatory Interactions and Approvals

Recent communications from regulatory agencies indicate ongoing review of Ultram ER’s post-marketing safety data. In 2022, the FDA renewed its surveillance for opioid-related adverse events, including tramadol formulations, following increased scrutiny over opioid dependence risks. No new warnings or restrictions have been issued specific to Ultram ER, but label updates emphasizing sedation and interaction considerations are anticipated [4].

Ongoing and Planned Trials

Active studies include:

• A pharmacogenomic trial assessing genetic markers influencing tramadol metabolism, potentially guiding personalized analgesic use.
• A real-world evidence (RWE) study evaluating Ultram ER's effectiveness and safety in diverse patient populations, with preliminary results expected in late 2023.

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Market Analysis

Market Size and Growth Drivers

The global pain management drug market was valued at approximately USD 54 billion in 2022 and is projected to reach USD 75 billion by 2030, driven by increasing prevalence of chronic pain conditions, aging populations, and rising opioid utilization [5]. Ultram ER occupies a niche in moderate to severe pain, especially as physicians seek alternatives to strong opioids amid regulatory pressures.

Competitive Landscape

Key competitors include:

• OxyContin (oxycodone ER): A potent opioid with extensive inherited market share.
• Methadone and Buprenorphine formulations: Used for chronic pain and opioid substitution therapy.
• Non-opioid alternatives: Gabapentinoids and NSAIDs are increasingly prescribed to mitigate opioid-related risks.

Ultram ER’s differentiation stems from its analgesic profile combining opioid and SNRI mechanisms, with a comparatively favorable safety profile in certain populations. The patent landscape constrains direct generic competition until 2028, but emerging generics and biosimilars threaten pricing strategies.

Market Penetration and Adoption Trends

Despite its efficacy profile, Ultram ER's market penetration remains modest relative to blockbuster opioids. Physicians cautiously prescribe Ultram ER, balancing pain relief with procedural safety concerns and opioid dependence risks. The ongoing public health debates and regulatory frameworks influence prescribing patterns, favoring multimodal pain management strategies with Ultram ER positioned as an alternative for appropriate candidates.

Regulatory and Reimbursement Factors

The drug's reimbursement landscape varies globally. In regulated markets like the U.S., Ultram ER benefits from favorable formulary placement owing to its safety advantages over traditional opioids, though insurance coverage can be limited owing to regulatory scrutiny of opioid products [6].

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Market Projection and Future Outlook

Short to Medium-Term (Next 3-5 Years)

The outlook for Ultram ER is cautiously optimistic, contingent on clinical trial outcomes and regulatory environments. With ongoing studies highlighting its safety and efficacy, particularly in chronic pain settings, market adoption is poised to grow:

• The increasing preference for non-agonist opioids supports Ultram ER's positioning.
• Its role in multimodal pain management could expand, especially for patients contraindicated for NSAIDs or other non-opioid therapies.
• Patent protection until 2028 provides a window for revenues to stabilize and grow.

Long-Term (Beyond 5 Years)

Innovations in pain therapeutics, including non-opioid modalities and conjugates, may threaten Ultram ER’s market share. However, life-cycle management strategies such as formulation improvements and added indications could extend its market viability. Anticipated regulatory re-evaluations focusing on safety could favor Ultram ER if post-market data continue to support its safety profile.

Revenue and Market Share Projections

Analyst estimates project Ultram ER’s global sales could reach USD 250–300 million annually by 2028, driven by expanded indications and increasing adoption in pain management protocols. Market share gains are expected especially in regions where opioid stewardship programs favor formulations with lower abuse potential.

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Key Takeaways

• Clinical Efficacy and Safety: Robust recent trials affirm Ultram ER’s efficacy for chronic moderate to severe pain with a manageable safety profile, supporting its continued use.
• Regulatory Landscape: Active surveillance continues, but no significant restrictions have been imposed; ongoing safety evaluations remain pivotal.
• Market Position: Ultram ER fills an important niche for clinicians seeking effective, extended-release analgesics with reduced overdose risks compared to traditional opioids.
• Growth Drivers: Rising global demand for safe opioid alternatives and expanding indications underpin future growth.
• Challenges: Patent expiry threats, competition from non-opioid therapies, and regulatory uncertainties pose risks to market expansion.

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FAQs

1. What distinguishes Ultram ER from other opioid analgesics?
   Ultram ER combines tramadol’s weak opioid activity with SNRI properties, offering effective pain relief with a lower risk of respiratory depression and dependence compared to traditional opioids.

2. Are there safety concerns associated with Ultram ER?
   While generally well-tolerated, Ultram ER carries risks of serotonin syndrome, dependence, and interactions with CYP2D6 inhibitors. Ongoing post-market surveillance continues to monitor safety.

3. When does Ultram ER lose patent protection?
   Patent exclusivity is expected to expire around 2028, opening potential for generic formulations, which could impact pricing and market share.

4. What are the future clinical trial priorities for Ultram ER?
   Focus areas include pharmacogenomic profiling to optimize individual responses, long-term safety assessments, and exploring new pain indications such as neuropathic pain.

5. How does regulatory guidance impact Ultram ER’s market prospects?
   Regulatory agencies’ emphasis on opioid safety influences prescribing practices and post-market surveillance. Positive safety profiles may enhance market stability, while increased restrictions could challenge growth.

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References

[1] ClinicalTrials.gov. "Efficacy of Extended-Release Tramadol in Chronic Osteoarthritis Pain." Accessed January 2023.

[2] Long-Term Safety Study of Ultram ER (2022). Journal of Pain Management.

[3] Comparative Effectiveness of Ultram ER vs. Oxycodone ER (2021). Pain Medicine.

[4] FDA Safety Communications. "Opioid Use and Safety," 2022.

[5] MarketsandMarkets. "Pain Management Market by Therapy, Region - Global Forecast to 2030," 2022.

[6] Insurance and Reimbursement Reports. "Analgesic Market Trends," 2022.

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Conclusion:
Ultram ER’s clinical and market trajectory remains promising in an evolving pain management landscape. Its efficacy, safety profile, and positioning as a non-traditional opioid support ongoing demand. Strategic patent management, ongoing clinical evaluation, and adaptive marketing will be critical for sustaining growth in a competitive, regulatory-sensitive environment.