CLINICAL TRIALS PROFILE FOR TRAMADOL HYDROCHLORIDE

505(b)(2) Clinical Trials for 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
New Formulation	NCT00640159 ↗	Tolerability and Efficacy of Switch From Oral Selegiline to Orally Disintegrating Selegiline (Zelapar) in Patients With Parkinson's Disease	Completed	Baylor College of Medicine	Phase 4	2007-01-01	Parkinson's disease (PD) is a progressive neurodegenerative disease. Symptomatic therapy is primarily aimed at restoring dopamine function in the brain. Oral selegiline in conjunction with L-dopa has been a mainstay of therapy for PD patients experiencing motor fluctuations for many years. The mechanisms accounting for selegiline's beneficial adjunctive action in the treatment of PD are not fully understood. Inhibition of monoamine oxidase (MAO) type B (MAO-B) activity is generally considered to be of primary importance. Oral selegiline has low bio-availability and is typically dosed BID, for a total of 5-10 mg daily. Recently, the FDA approved a new orally disintegration tablet (ODT) formulation of selegiline, called ZelaparTM. This new formulation utilizes Zydis technology to dissolve in the mouth, with absorption through the oral mucosa, thereby largely bypassing the gut and avoiding first pass hepatic metabolism. This allows more active drug to be delivered at a lower dose. Consequently, Zelapar is dosed once-daily, up to 2.5 mg per day. There are no empirical data indicating whether the use of the new approved formulation of selegiline ODT (Zelapar) is superior or preferred by patients compared to traditional oral selegiline. It is believed that clinical efficacy will be preserved or enhanced, by delivering more active drug, with improved patient preference for the ODT formulation due to the once-daily dosing . The effectiveness of orally disintegrating selegiline as an adjunct to carbidopa/levodopa in the treatment of PD was established in a multicenter randomized placebo-controlled trial (n=140; 94 received orally disintegrating selegiline, 46 received placebo) of three months' duration. Patients randomized to orally disintegrating selegiline received a daily dose of 1.25 mg for the first 6 weeks and a daily dose of 2.5 mg for the last 6 weeks. Patients were all treated with levodopa and could additionally have been on dopamine agonists, anticholinergics, amantadine, or any combination of these during the trial. At 12 weeks, orally disintegrating selegiline-treated patients had an average of 2.2 hours per day less "OFF" time compared to baseline. Placebo treated patients had 0.6 hours per day less "OFF" time compared to baseline. These differences were significant (p < 0.001). Adverse events were very similar between drug and placebo.
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.
New Formulation	NCT03766984 ↗	Pharmacokinetic Non-interaction Study With a Fixed-dose Combination Tablet With Tramadol and Diclofenac	Completed	Grünenthal Colombiana S.A.	Phase 1	2015-06-07	The objective of the study was to evaluate whether or not there is a substantial pharmacokinetic interaction between diclofenac and tramadol in a new formulation of a fixed-dose combination of diclofenac 25 milligrams (mg) and tramadol 25 mg for oral administration. The study was conducted in healthy participants of both genders.
New Formulation	NCT03766984 ↗	Pharmacokinetic Non-interaction Study With a Fixed-dose Combination Tablet With Tramadol and Diclofenac	Completed	Grünenthal S.A.	Phase 1	2015-06-07	The objective of the study was to evaluate whether or not there is a substantial pharmacokinetic interaction between diclofenac and tramadol in a new formulation of a fixed-dose combination of diclofenac 25 milligrams (mg) and tramadol 25 mg for oral administration. The study was conducted in healthy participants of both genders.
New Formulation	NCT03766984 ↗	Pharmacokinetic Non-interaction Study With a Fixed-dose Combination Tablet With Tramadol and Diclofenac	Completed	Grünenthal GmbH	Phase 1	2015-06-07	The objective of the study was to evaluate whether or not there is a substantial pharmacokinetic interaction between diclofenac and tramadol in a new formulation of a fixed-dose combination of diclofenac 25 milligrams (mg) and tramadol 25 mg for oral administration. The study was conducted in healthy participants of both genders.
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.

All Clinical Trials for Tramadol Hydrochloride

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00058357 ↗	Lidocaine Patch in Treating Cancer Patients With Neuropathic Pain After Surgery	Completed	National Cancer Institute (NCI)	Phase 3	2004-05-01	RATIONALE: A lidocaine patch may be effective in relieving numbness, tingling, and other symptoms of neuropathy. It is not yet known whether a lidocaine patch is effective in treating neuropathy in patients who have undergone surgery for cancer. PURPOSE: This randomized phase III trial is studying lidocaine patch to see how well it works compared to a placebo patch in relieving numbness, tingling, and other symptoms of neuropathy in patients who have undergone surgery for cancer.
NCT00058357 ↗	Lidocaine Patch in Treating Cancer Patients With Neuropathic Pain After Surgery	Completed	Alliance for Clinical Trials in Oncology	Phase 3	2004-05-01	RATIONALE: A lidocaine patch may be effective in relieving numbness, tingling, and other symptoms of neuropathy. It is not yet known whether a lidocaine patch is effective in treating neuropathy in patients who have undergone surgery for cancer. PURPOSE: This randomized phase III trial is studying lidocaine patch to see how well it works compared to a placebo patch in relieving numbness, tingling, and other symptoms of neuropathy in patients who have undergone surgery for cancer.
NCT00111046 ↗	Pain Relief - Tramadol Versus Ibuprofen	Unknown status	Royal Liverpool University Hospital	Phase 1/Phase 2	2001-02-01	The purpose of this study is to assess post operative pain following the insertion of radioactive plaque for choroidal melanoma in patients after receiving either ibuprofen or tramadol.
NCT00115752 ↗	Genetic Basis For Variation In NSAID Analgesia In A Clinical Model Of Acute Pain	Completed	National Institute of Nursing Research (NINR)	Phase 2	2005-06-20	This study will evaluate how genetic makeup contributes to the variation in people regarding their sensitivity to and experience of pain. Scientists believe that differences in information found in genes may explain why an analgesic drug, that is, one that treats pain, works effectively for some people but not for others. The study will explore pain that is acute (fast and short period). Knowledge gained from this ongoing study may permit development of an individualized analgesic drug prescription. Patients ages 16 to 35 who are in good health and have been referred for removal of impacted wisdom teeth; who are not allergic to aspirin or other nonsteroidal anti-inflammatory drugs (known as NSAIDs), sulfites, or certain anesthetics; who are not pregnant or nursing; and who are willing to have a biopsy before and after dental surgery are eligible for this study. Patients will come to the clinic for one test visit and one treatment visit. During the first visit, a questionnaire will evaluate patients' psychological state, including mood and depression. There will be a clinical examination of their wisdom teeth. A blood sample of 10 milliliters (about 0.4 ounces) will be collected from the forearm to provide DNA material containing genes stored in cells. The primary genetic analysis will be done at NIH, although the DNA collected might also be sent to a laboratory outside NIH. DNA samples will be coded so that names of patients cannot be traced. During the second visit, two of the patients' lower wisdom teeth will be removed. Patients will be given a local anesthetic in the mouth and a sedative given through a vein in the arm. While the mouth is numb, a small piece of tissue will be removed from inside the cheek, near the wisdom tooth. It is the first biopsy. After the two wisdom teeth are removed, a small piece of tubing will be placed into both sides of the mouth where the teeth were removed. Every 20 minutes, for the next 3 hours, the researchers will collect inflammatory fluid from the tubing, to measure the chemicals thought to cause pain and swelling. Also every 20 minutes, patients will rate the pain they feel by answering questions. If there is pain before 3 hours following surgery, they will receive a dose of fentanyl to relieve moderate to severe pain. A second biopsy will occur 3 hours after surgery, to measure changes in chemicals produced in response to surgery. Immediately afterward, patients will receive 30 mg of ketorolac (Toradol) whether or not pain is felt. They will answer questionnaires about pain for 3 hours after receiving the drug, to rate how well it works. They will stay at the clinic up to 6 hours after the surgery. If pain is not relieved with ketorolac, patients will receive a one-time dose of tramadol, a pain medication for moderate to severe pain. After the study procedures are completed, patients will receive pain medication for pain after surgery. Patients will be monitored closely, because all drugs have side effects. Ketorolac is a nonsteroidal anti-inflammatory drug, one that may cause gastrointestinal upset. Fentanyl is a powerful narcotic drug that is safe at the dosage used in this study, but stomach upset, dizziness, and breathing trouble may occur. Also, risks from the biopsy include discomfort from injecting the numbing medicine, infection, and bleeding. There may be discomfort from the sedative injected into the vein, and there may be bruising. Benefits from participating are having wisdom teeth removed at no cost as well as close monitoring before and after surgery. There are no plans to give patients the results of genetic tests or questionnaires. Years of research may be needed before such information has the chance to become meaningful.
NCT00142896 ↗	Tramadol to Reduce Opioid Withdrawal Symptoms	Completed	National Institute on Drug Abuse (NIDA)	Phase 2	2005-02-01	Individuals with opioid addiction often experience serious withdrawal symptoms that may make relapse unavoidable. Tramadol, a medication that is currently used to treat pain caused by chronic conditions such as cancer or joint pain, may also be effective at reducing opioid withdrawal symptoms. This study will evaluate the effectiveness of tramadol at reducing withdrawal symptoms in individuals addicted to opioid drugs.
NCT00163553 ↗	Neuraxial Pethidine After Lumbar Surgery Trial	Unknown status	Austin Health	Phase 3	2004-12-01	The hypothesis is that epidural pethidine is an effective form of pain relief following lumbar spinal surgery, resulting in significantly lower usage of concomitantly administered (intravenous) patient-controlled analgesia (PCA) pethidine.
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.

Clinical Trial Conditions for Tramadol Hydrochloride

Condition Name

Condition Name for Tramadol Hydrochloride
Intervention	Trials
Pain	60
Postoperative Pain	46
Pain, Postoperative	32
Healthy	20

Condition MeSH

Condition MeSH for Tramadol Hydrochloride
Intervention	Trials
Pain, Postoperative	97
Osteoarthritis	31
Acute Pain	21
Chronic Pain	20

Clinical Trial Locations for Tramadol Hydrochloride

Trials by Country

Trials by Country for Tramadol Hydrochloride
Location	Trials
United States	147
Turkey	47
Egypt	36
Brazil	20
Italy	17

Trials by US State

Trials by US State for Tramadol Hydrochloride
Location	Trials
Maryland	12
Texas	11
California	9
Pennsylvania	8
New York	8

Clinical Trial Progress for Tramadol Hydrochloride

Clinical Trial Phase

Clinical Trial Phase for Tramadol Hydrochloride
Clinical Trial Phase	Trials
Phase 4	184
Phase 3	75
Phase 2/Phase 3	10

Clinical Trial Status

Clinical Trial Status for Tramadol Hydrochloride
Clinical Trial Phase	Trials
Completed	277
Unknown status	58
Recruiting	57

Clinical Trial Sponsors for Tramadol Hydrochloride

Sponsor Name

Sponsor Name for Tramadol Hydrochloride
Sponsor	Trials
Labopharm Inc.	15
Cairo University	13
Janssen Korea, Ltd., Korea	10

Sponsor Type

Sponsor Type for Tramadol Hydrochloride
Sponsor	Trials
Other	450
Industry	140
U.S. Fed	17

Tramadol Hydrochloride: Clinical Trials, Market Analysis, and Projections

Last updated: January 1, 2025

Introduction

Tramadol hydrochloride, a centrally-acting opioid agonist and serotonin/norepinephrine reuptake inhibitor, is widely used for managing moderate to severe pain. This article provides an update on the clinical trials, market analysis, and projections for tramadol hydrochloride, highlighting its current status, market dynamics, and future outlook.

Clinical Trials and Regulatory Approvals

Recent Developments

Clinical trials for tramadol hydrochloride have been ongoing to explore its efficacy and safety in various indications. A notable example is the development of a fixed-dose combination product, E-58425, which combines celecoxib and tramadol hydrochloride. This product was reviewed by the FDA for the management of acute pain in adults, with the committee voting evenly on its approval due to concerns about comparative effectiveness and abuse potential[1].

Ongoing and Future Trials

There is a significant focus on conducting clinical trials to address the risks associated with tramadol, such as abuse and dependence. These trials aim to develop novel formulations and combinations that reduce these risks while maintaining the drug's efficacy. For instance, studies are being conducted to evaluate the safety and effectiveness of different tramadol formulations, including intravenous (IV) formulations, which are gaining traction[2][3].

Regulatory Considerations

Tramadol hydrochloride, as a Schedule IV controlled substance, is subject to the Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS) to mitigate its potential for abuse. Regulatory bodies continue to monitor and evaluate the benefit-risk profile of tramadol, particularly in subpopulations with mental health and substance use disorders[1].

Market Analysis

Market Size and Forecast

The global tramadol hydrochloride market has been experiencing steady growth. As of 2022, the market was valued at approximately USD 5.26 billion and is projected to reach USD 7.29 billion by 2030, growing at a Compound Annual Growth Rate (CAGR) of 4.41% from 2023 to 2030. Another estimate suggests the market will reach USD 7.190 billion by 2032, with a CAGR of 6.87% during this period[2][3].

Geographical Segmentation

The market is segmented geographically, with Europe and Asia Pacific expected to dominate due to high healthcare expenditure and increasing product consumption, respectively. Europe is anticipated to maintain a significant share, while the Asia Pacific region is expected to see lucrative growth driven by growing disposable income levels and increasing chronic pain prevalence[2][3].

Market Segmentation by Type and Application

The tramadol market is segmented by type (oral, injection, rectal) and application (hospital pharmacy, retail pharmacy, online pharmacy). The oral type is the most common, but the injection type, particularly the IV formulation, is gaining traction. Hospital pharmacies are a significant segment due to the use of tramadol in postoperative pain management[2][3].

Driving Factors

Increasing Prevalence of Chronic Pain

The rise in chronic pain cases, driven by lifestyle changes and an aging population, is a key driver of the tramadol market. Tramadol is increasingly prescribed for managing pain associated with chronic diseases such as neuropathic pain, dental pain, and pain related to surgeries[2][3].

Innovations in Drug Delivery

Continuous innovation in drug delivery systems and formulations is driving market growth. The development of IV formulations and other delivery methods is expected to stimulate further investment and expand the market[2][3].

Regulatory Approvals for New Indications

New indications and regulatory approvals are strategic expansions that tap into unmet medical needs and diversify the utility of the drug. This trend is expected to propel market growth during the forecast period[3].

Public Health Impact

Pain Management

Tramadol fills a critical gap in pain management, especially for moderate to moderately severe pain, providing an alternative to more potent opioids. Its efficacy in relieving pain associated with various chronic diseases and surgeries makes it a valuable option for healthcare professionals[2][3].

Abuse Potential

As a Schedule IV drug, tramadol has less abuse potential compared to Schedule II opioids, which could help in reducing the overall opioid abuse crisis. However, safety concerns, particularly around the IV formulation, are being addressed through regulatory reviews and ongoing clinical trials[1][2].

Adverse Events and Safety Concerns

Common Adverse Events

Clinical studies have reported common adverse events associated with tramadol hydrochloride, including nausea, vomiting, somnolence, and dizziness. These events are comparable to those reported with other tramadol products[1].

IV Formulation Safety

The IV formulation of tramadol has raised concerns about delayed onset of analgesia, which can lead to the need for additional analgesics and potentially increase the risk of opioid stacking and related adverse reactions. Regulatory bodies and clinical trials are focusing on addressing these safety concerns[2].

Investment and Innovation

Research and Development

Major pharmaceutical companies are investing heavily in the development and marketing of tramadol hydrochloride. Continuous innovation in drug delivery systems and formulations is driving market growth. The development of novel products, such as fixed-dose combinations and IV formulations, is expected to stimulate further investment[2][3].

Market Expansion

Companies are expanding their product lines and entering new markets, particularly in developing countries where there is a growing demand for pain management drugs. This expansion is driven by the increasing prevalence of chronic pain and the need for effective pain management solutions[2][3].

Impact of COVID-19

The COVID-19 pandemic had a negative impact on the tramadol market, primarily due to the decrease in patient visits for pain management and the reduction in elective and non-elective surgeries. However, the market rebounded to pre-pandemic levels in 2022 and is projected to experience moderate growth throughout the forecast period[3].

Key Takeaways

• Market Growth: The global tramadol hydrochloride market is projected to grow significantly, driven by increasing chronic pain prevalence, an aging population, and innovations in drug delivery.
• Geographical Dominance: Europe and Asia Pacific are expected to dominate the market due to high healthcare expenditure and increasing product consumption.
• Safety Concerns: Regulatory reviews and clinical trials are addressing safety concerns, particularly around the IV formulation.
• Investment and Innovation: Major pharmaceutical companies are investing in research and development to expand the market.
• Public Health Impact: Tramadol has a lower abuse potential compared to other opioids, making it a valuable option for pain management.

Frequently Asked Questions

1. What is the projected market size of the tramadol hydrochloride market by 2030?

The global tramadol drug market is projected to reach USD 7.29 billion by 2030[2].

2. What are the primary drivers of the tramadol market growth?

The primary drivers include the increasing prevalence of chronic pain, the growing geriatric population, and innovations in drug delivery systems[2][3].

3. Which regions are expected to see significant growth in the tramadol market?

Europe and Asia Pacific are expected to see significant growth due to high healthcare expenditure and increasing product consumption, respectively[2][3].

4. What are the key market segments for tramadol hydrochloride?

The market is segmented by type (oral, injection, rectal) and application (hospital pharmacy, retail pharmacy, online pharmacy)[2][3].

5. What are the safety concerns associated with the IV formulation of tramadol hydrochloride?

The IV formulation has a delayed onset of analgesia, which can lead to the need for additional analgesics and potentially increase the risk of opioid stacking and related adverse reactions[2].

Sources

1. FDA Division Director Summary Review for Regulatory Action - "Seglentis (Celecoxib and tramadol hydrochloride oral tablets)"[1].
2. DrugPatentWatch - "Tramadol Hydrochloride Market Dynamics and Financial Trajectory"[2].
3. Fortune Business Insights - "Tramadol Market Size, Share, Forecast | Growth Report [2032]"[3].
4. DrugBank Online - "Tramadol: Uses, Interactions, Mechanism of Action"[4].
5. Cognitive Market Research - "Tramadol Hydrochloride Market Report 2024 (Global Edition)"[5].