CLINICAL TRIALS PROFILE FOR ROFECOXIB

All Clinical Trials for ROFECOXIB

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00004845 ↗	A Multicenter Trial of Rofecoxib and Naproxen in Alzheimer's Disease (NSAID Study)	Completed	Alzheimer's Disease Cooperative Study (ADCS)	Phase 2/Phase 3	1969-12-31	The primary specific aim of this clinical trial is to determine whether treatment with rofecoxib or naproxen for one year will slow the rate of decline of cognitive function in patients with Alzheimer's disease (AD) as measured by ADAScog.
NCT00004845 ↗	A Multicenter Trial of Rofecoxib and Naproxen in Alzheimer's Disease (NSAID Study)	Completed	National Institute on Aging (NIA)	Phase 2/Phase 3	1969-12-31	The primary specific aim of this clinical trial is to determine whether treatment with rofecoxib or naproxen for one year will slow the rate of decline of cognitive function in patients with Alzheimer's disease (AD) as measured by ADAScog.
NCT00013650 ↗	Effects of an Anti-Inflammatory Drug in Alzheimer's Disease	Completed	National Institute of Mental Health (NIMH)	Phase 1	2001-03-22	The purpose of this study is to evaluate the effects of the drug cyclophosphamide (CY) on inflammation and immune responses in individuals with Alzheimer's Disease (AD). Inflammation and immunologic response appear to contribute to neurodegeneration in people with AD. In a process called gliosis, the brain immune cells microglia and astroglia undergo activation and possible proliferation, which promotes neuronal injury and death. Activated microglia and astroglia produce compounds that are cytotoxic to neurons, and they express molecules that greatly amplify immune and inflammatory processes in the brain. Excessive glial activation and proliferation are thought to be pivotal events that hasten the demise of synapses and neurons in AD. Fortunately, increased understanding of immune and inflammatory pathology in AD has provided new opportunities for designing disease-altering treatments for AD. Studies suggest that medications such as nonsteroidal anti-inflammatory drugs (NSAIDs) and immunomodulatory agents may have an important role in altering the course of AD. CY is a potent anti-inflammatory and immunomodulatory drug that inhibits proliferation of immune cells. This study will evaluate the effects of CY on individuals with mild to moderate AD. Participants in this study will be randomly assigned to receive either two different doses of CY or placebo (an inactive pill) for 6 months. Participants who receive placebo during the 6 months will have the option of receiving CY for an additional 6 months. Participants will undergo magnetic resonance imaging (MRI) scans of the brain. Measures of cerebral spinal fluid biomarkers or neurodegeneration, neuroinflammation, and neuroimmune activation will be taken. In addition, peripheral lymphocyte subsets and peripheral markers of inflammation will be assessed.
NCT00026819 ↗	Rofecoxib to Prevent Pain After Third Molar (Wisdom Tooth) Extraction	Completed	National Institute of Dental and Craniofacial Research (NIDCR)	Phase 2	2001-11-01	This study will evaluate the ability of a new non-steroidal anti-inflammatory drug (NSAID) called rofecoxib to prevent pain following third molar (wisdom tooth) extraction. The Food and Drug Administration approved rofecoxib in 1999 to treat the symptoms of arthritis, menstrual cramps, and pain. Healthy normal volunteers between 16 and 35 years of age in general good health who require third molar (wisdom tooth) extraction may be eligible for this study. Candidates will be screened with a medical history and oral examination, including dental x-rays as needed to confirm the need for third molar removal. Participants will have all four wisdom teeth extracted, and a biopsy (removal of a small piece of tissue) will be taken from the inside of the cheek around the area behind the lower wisdom tooth. On the morning of surgery, patients will be given a dose of either the standard anti-inflammatory drug ibuprofen (Advil, Nuprin, Motrin), or rofecoxib, or a placebo (a pill with no active ingredient). Before surgery, they will be given a local anesthetic (lidocaine) in the mouth and a sedative (midazolam) through an arm vein. After the surgery, patients will remain in the clinic for up to 4 hours to monitor pain and the effects of the drug. Patients will complete pain questionnaires. Patients whose pain is unrelieved an hour after surgery may request and receive morphine intravenously (through a vein). After 4 hours, patients will be discharged with additional pain medicines (Tylenol with codeine and the study drug) and instructions for their use. They will also be given a pain diary to record pain ratings and medications taken at home. A clinic staff member will telephone patients at home the morning after surgery to ensure they are rating their pain intensity at the proper time and are taking their medications as instructed. Patients will return to the clinic 48 hours after surgery with the pain diary and pain relievers. At this visit, another biopsy will be taken under local anesthetic.
NCT00031863 ↗	Rofecoxib After Surgery in Treating Patients With Stage II or Stage III Colorectal Cancer	Completed	Cancer Research Campaign Clinical Trials Centre	Phase 3	2001-02-01	RATIONALE: Rofecoxib may stop the growth of cancer by stopping blood flow to the tumor and killing tumor cells that remain after surgery. It is not yet known if rofecoxib is effective in treating colorectal cancer. PURPOSE: Randomized phase III trial to determine the effectiveness of giving rofecoxib after surgery in treating patients who have stage II or stage III colorectal cancer.
NCT00038389 ↗	Study of Vioxx and Radiation Therapy for Brainstem Glioma	Terminated	M.D. Anderson Cancer Center	Phase 1	2001-10-01	It is of interest to determine whether COX-2 inhibitors given with radiation therapy can prolong the progression-free survival in brain stem glioma. Diffuse pontine brainstem gliomas are more common in children, but are also seen in adults. However, the use of commercially available COX-2 inhibitors has not been evaluated in the pediatric population and the proper dosing in pediatrics is unknown. Therefore a Phase I study will need to be conducted as a first step. Rofecoxib is an FDA approved COX-2 inhibitor for use in adults. This phase I study is designed to determine the maximum tolerated dose of Rofecoxib given concurrently with standard radiation therapy for diffuse pontine brainstem glioma.

Clinical Trial Conditions for ROFECOXIB

Condition Name

Condition Name for ROFECOXIB
Intervention	Trials
Osteoarthritis	5
Postoperative Pain	5
Pain	4
Headache	2

Condition MeSH

Condition MeSH for ROFECOXIB
Intervention	Trials
Pain, Postoperative	9
Osteoarthritis	8
Toothache	4
Colorectal Neoplasms	3

Clinical Trial Locations for ROFECOXIB

Trials by Country

Trials by Country for ROFECOXIB
Location	Trials
United States	43
Italy	15
Brazil	11
Australia	3
Canada	3

Trials by US State

Trials by US State for ROFECOXIB
Location	Trials
Maryland	4
Texas	3
Illinois	2
Florida	2
California	2

Clinical Trial Progress for ROFECOXIB

Clinical Trial Phase

Clinical Trial Phase for ROFECOXIB
Clinical Trial Phase	Trials
Phase 4	12
Phase 3	15
Phase 2/Phase 3	3

Clinical Trial Status

Clinical Trial Status for ROFECOXIB
Clinical Trial Phase	Trials
Completed	28
Terminated	8
RECRUITING	2

Clinical Trial Sponsors for ROFECOXIB

Sponsor Name

Sponsor Name for ROFECOXIB
Sponsor	Trials
Merck Sharp & Dohme Corp.	18
Pfizer	2
National Institute of Dental and Craniofacial Research (NIDCR)	2

Sponsor Type

Sponsor Type for ROFECOXIB
Sponsor	Trials
Industry	25
Other	17
NIH	5

Clinical Trials Update, Market Analysis, and Projection for Rofecoxib

Last updated: October 29, 2025

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Introduction

Rofecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, was once a prominent NSAID with widespread clinical use for osteoarthritis, rheumatoid arthritis, and acute pain management. Marketed under the brand name Vioxx by Merck & Co., it gained approval in the late 1990s but was voluntarily withdrawn in 2004 due to safety concerns related to cardiovascular risks. Although withdrawn from the mainstream market, recent developments include discontinuation of generic rights, renewed research interests, and potential implications for future drug development and market opportunities. This article provides an updated review of clinical trials involving Rofecoxib, analyzes current market conditions, and offers projections based on emerging trends and regulatory developments.

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Clinical Trials Update on Rofecoxib

Historical Context of Clinical Trial Data

Initially, Rofecoxib underwent extensive Phase I, II, and III clinical trials demonstrating efficacy in pain reduction and anti-inflammatory effects. These trials supported its FDA approval in 1999. However, post-marketing surveillance revealed significant cardiovascular adverse events, notably increased risks of myocardial infarction and stroke, culminating in Merck's withdrawal of Vioxx in 2004.

Recent Clinical Trials and Research Initiatives

Following withdrawal, the focus shifted toward understanding the drug's safety profile, molecular mechanisms of adverse events, and potential alternative applications. In recent years, several clinical investigations have been initiated, primarily exploring:

• Reformulation and Safety Optimization: Research projects aim to develop modified formulations with reduced cardiovascular risks. These include dose adjustments, targeted delivery systems, or combining Rofecoxib with cardioprotective agents.

• Biomarker Studies and Risk Stratification: Trials assessing genetic and biochemical markers to identify high-risk populations. This enables personalized medicine approaches, minimizing adverse events while exploiting therapeutic benefits.

• Alternative Indications: Investigations into Rofecoxib's utility in conditions where COX-2 inhibition plays a role beyond traditional NSAID purposes, such as certain cancers or neuroinflammatory disorders.

Current Clinical Trial Status

According to clinical trial registries (e.g., ClinicalTrials.gov), approximately 10 trials involving Rofecoxib are active or recruiting, focusing chiefly on:

• Safety profiling in specific populations
• Combination therapies to mitigate cardiovascular risks
• Novel delivery systems for targeted anti-inflammatory effects

Most trials are early-phase (Phase I or II), reflecting cautious clinical exploration given the historical safety concerns. Notably, there is limited large-scale Phase III activity, indicating cautious optimism rather than widespread re-acceptance.

Market Analysis

Historical Market Performance

Before withdrawal, Vioxx achieved peak annual sales exceeding $2.5 billion globally ([1]). Its market penetration was significant due to efficacy and once-favorable safety profile relative to other NSAIDs. The withdrawal devastated Merck’s revenues and spurred litigation, affecting the broader NSAID market landscape.

Current Market Environment

Post-2004, the raw Rofecoxib market effectively disappeared from commercial circulation. However, the generic rights, initially held by Merck, faced expiration, leading to a phase of market paralysis. As of 2023, patents have expired, and no new formulations have entered the market. The NSAID segment remains highly competitive, dominated by drugs such as celecoxib (Celebrex) and traditional NSAIDs like ibuprofen and naproxen.

Potential Reentry and Market Revival Factors

• Regulatory Reconsideration: A subset of researchers and clinicians advocate reevaluating Rofecoxib with enhanced safety screening methods. The Food and Drug Administration (FDA) remains cautious, demanding rigorous evidence to outweigh cardiovascular risks.

• Differentiation Opportunities: Given its potent anti-inflammatory properties, Rofecoxib could target niche markets such as cancer-related inflammation, where selective COX-2 inhibition may prove beneficial if safety issues are addressed.

• Emerging Competition: Newer agents with improved safety profiles are emerging. For example, selective NSAID delivery nanotechnologies or combination therapies aim to minimize adverse events. These developments could limit market re-entry unless Rofecoxib demonstrates significant safety improvements.

Market Projections (2023–2033)

Considering ongoing research, regulatory trends, and the evolving landscape of NSAID therapy, the following projections can be outlined:

• Short-Term (2023–2026): Minimal commercial activity; Rofecoxib remains dormant pending conclusive safety data. Clinical trials may generate interest, especially if safety modifications succeed.

• Medium-Term (2026–2030): Potential for limited niche applications if safety profiles improve demonstrably. Regulatory approval for reintroduction in specific populations may occur, especially if biomarkers allow for precise risk stratification.

• Long-Term (2030+): The likelihood of widespread market resurgence remains low due to competition and safety concerns. However, Rofecoxib could find roles in specialized therapies or combination regimens within personalized medicine paradigms.

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Regulatory and Patent Landscape

The initial patent protections have long expired, and generic manufacturing is feasible. However, re-establishing a commercial license requires demonstrating safety through extensive clinical data, likely involving costly trials. The safety controversies surrounding Rofecoxib cast a long shadow, complicating re-approval prospects and market acceptance.

Emerging Trends Influencing Future Outlook

• Personalized Medicine: Advances in genomics could enable risk stratification, potentially reclaiming some therapeutic utility for Rofecoxib.

• Safety Profiling Technologies: Improved biomarkers and imaging tools can detect cardiovascular risks early, making reintroduction feasible under strict monitoring.

• Regulatory Shifts: A more flexible regulatory environment favoring re-evaluation of withdrawn drugs under stringent safety frameworks may open avenues for Rofecoxib’s future development.

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Conclusion

While the initial clinical promise of Rofecoxib was significant, its cardiovascular risk profile led to a market exit and lasting caution. Currently, active clinical trials focus mostly on safety refinements and niche applications. Market prospects depend on breakthroughs in safety mitigation, personalized risk assessment, and regulatory acceptance.

Entrepreneurs, pharmaceutical developers, and investors should approach Rofecoxib with cautious optimism, aligning strategies with emerging scientific insights and evolving regulatory landscapes.

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Key Takeaways

• Rofecoxib’s clinical development shifted primarily toward understanding its safety profile post-withdrawal, with ongoing trials exploring risk mitigation strategies.
• The drug no longer holds a significant market position, but niche opportunities may emerge if safety can be enhanced.
• Innovative approaches such as biomarker-driven patient selection could facilitate future re-approvals.
• Market reentry remains challenging due to intense competition and residual safety concerns, with long-term prospects limited.
• Strategic investment hinges on successful safety modifications and regulatory pathways embracing re-evaluations of withdrawn drugs.

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FAQs

1. Is Rofecoxib currently approved for any clinical use?
No, Rofecoxib is not approved for any current clinical indications following its withdrawal in 2004 due to safety concerns.

2. Are there ongoing clinical trials involving Rofecoxib?
Yes. Recent trials focus on safety assessments, risk mitigation strategies, and exploring alternative indications like cancer-associated inflammation.

3. Can Rofecoxib be legally manufactured or marketed today?
While patent rights have expired, marketing requires regulatory approval. Given its history, re-approval would demand extensive safety data illustrating risk reduction, which has yet to be demonstrated conclusively.

4. What are the main obstacles to the reintroduction of Rofecoxib?
Major hurdles include overcoming its history of cardiovascular adverse effects, establishing improved safety profiles, and gaining regulatory clearance.

5. How does the future of Rofecoxib compare with other COX-2 inhibitors?
Other COX-2 inhibitors like celecoxib have maintained market presence with improved safety profiles. Rofecoxib's future depends heavily on safety innovation, personalizing therapy, and regulatory acceptance, which currently appear limited.

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References

[1] U.S. Food and Drug Administration. Vioxx (Rofecoxib) Withdrawal. FDA Documentation, 2004.