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Last Updated: January 1, 2026

CLINICAL TRIALS PROFILE FOR ZANTAC 25


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505(b)(2) Clinical Trials for Zantac 25

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 NCT00443963 ↗ Total Antioxidant Effects of Esomeprazole in Dyspeptic Patients Receiving Non-steroidal Anti-inflammatory Drugs Withdrawn AstraZeneca Phase 4 2006-12-01 The principal investigator hypothesizes that participants receiving NSAID drugs with dyspeptic symptoms have increased production of gastric levels of free radicals. The primary objective of the study is to determine if Esomeprazole Magnesium increases gastric total antioxidant capacity and decreases gastric free radical production in humans. Participants (age 18 years and older) with no history of upper GI bleeding who are receiving non-steroidal anti-inflammatory drugs and then develop dyspepsia will be recruited from our primary care clinic in Washington, DC. All eligible participants will undergo biopsies of antrum and corpus. The participants will be randomized to receive either Zantac OTC or Nexium for 15 days. On day 15, all participants will undergo repeat upper endoscopy to obtain biopsies of antrum and corpus. Tissue samples will then be extracted to determine total antioxidant capacity and lipid peroxide levels (as an indirect marker of free radical production).
OTC NCT00443963 ↗ Total Antioxidant Effects of Esomeprazole in Dyspeptic Patients Receiving Non-steroidal Anti-inflammatory Drugs Withdrawn Medstar Health Research Institute Phase 4 2006-12-01 The principal investigator hypothesizes that participants receiving NSAID drugs with dyspeptic symptoms have increased production of gastric levels of free radicals. The primary objective of the study is to determine if Esomeprazole Magnesium increases gastric total antioxidant capacity and decreases gastric free radical production in humans. Participants (age 18 years and older) with no history of upper GI bleeding who are receiving non-steroidal anti-inflammatory drugs and then develop dyspepsia will be recruited from our primary care clinic in Washington, DC. All eligible participants will undergo biopsies of antrum and corpus. The participants will be randomized to receive either Zantac OTC or Nexium for 15 days. On day 15, all participants will undergo repeat upper endoscopy to obtain biopsies of antrum and corpus. Tissue samples will then be extracted to determine total antioxidant capacity and lipid peroxide levels (as an indirect marker of free radical production).
OTC NCT03145012 ↗ Histamine Receptor 2 Antagonists as Enhancers of Anti-Tumour Immunity Unknown status Dalhousie University Phase 4 2018-05-01 The immune response against tumors can be highly effective in preventing tumor development, growth and metastasis under certain circumstances. However, tumor associated immune suppression can profoundly limit the impact of natural tumor immunity and also reduce the effectiveness of tumor immunotherapy strategies. A major component of tumor associated immune suppression is mediated by myeloid cells, especially the monocytic subset of myeloid derived suppressor cells (MDSC). In recent studies that were conducted through a CCSRI Innovation grant, the investigators discovered that oral treatment of mice with the commonly used histamine receptor 2 (H2) antagonists ranitidine or famotidine inhibits both primary breast tumor development and metastasis, in three distinct mouse tumor models and reduces the numbers of monocytic MDSC. These findings have enormous potential to aid in effective cancer immunotherapy and may have immediate implications for cancer patients. The objective of this investigation is to determine whether treatment with the H2 receptor antagonist ranitidine alters immune suppression, through modulation of immune cell populations. The investigators will examine peripheral blood monocyte, neutrophil and NK cell numbers, subsets and activation status from healthy volunteers treated for 6 weeks with daily oral ranitidine. Ranitidine is widely available and used over the counter in Canada. These drugs are widely recognized as safe, well tolerated and have very few side effects. It has been suggested that among the general population, over 10% of those over the age of 65 take such medications on a regular basis for relief against gastrointestinal discomfort. The outcome of pre-clinical studies in mice warrant further investigation into transferability to humans. If the outcome of the current proposal proves to be viable, then these drugs could provide a safe method to reduce tumor associated immunosuppression with broad implications, both for current cancer patients and for those at high risk of developing cancer. Further to this, the outcome of our proposal may provide a new strategy for improving the effectiveness of T-cell mediated immunotherapy.
OTC NCT03145012 ↗ Histamine Receptor 2 Antagonists as Enhancers of Anti-Tumour Immunity Unknown status Nova Scotia Health Authority Phase 4 2018-05-01 The immune response against tumors can be highly effective in preventing tumor development, growth and metastasis under certain circumstances. However, tumor associated immune suppression can profoundly limit the impact of natural tumor immunity and also reduce the effectiveness of tumor immunotherapy strategies. A major component of tumor associated immune suppression is mediated by myeloid cells, especially the monocytic subset of myeloid derived suppressor cells (MDSC). In recent studies that were conducted through a CCSRI Innovation grant, the investigators discovered that oral treatment of mice with the commonly used histamine receptor 2 (H2) antagonists ranitidine or famotidine inhibits both primary breast tumor development and metastasis, in three distinct mouse tumor models and reduces the numbers of monocytic MDSC. These findings have enormous potential to aid in effective cancer immunotherapy and may have immediate implications for cancer patients. The objective of this investigation is to determine whether treatment with the H2 receptor antagonist ranitidine alters immune suppression, through modulation of immune cell populations. The investigators will examine peripheral blood monocyte, neutrophil and NK cell numbers, subsets and activation status from healthy volunteers treated for 6 weeks with daily oral ranitidine. Ranitidine is widely available and used over the counter in Canada. These drugs are widely recognized as safe, well tolerated and have very few side effects. It has been suggested that among the general population, over 10% of those over the age of 65 take such medications on a regular basis for relief against gastrointestinal discomfort. The outcome of pre-clinical studies in mice warrant further investigation into transferability to humans. If the outcome of the current proposal proves to be viable, then these drugs could provide a safe method to reduce tumor associated immunosuppression with broad implications, both for current cancer patients and for those at high risk of developing cancer. Further to this, the outcome of our proposal may provide a new strategy for improving the effectiveness of T-cell mediated immunotherapy.
OTC NCT03145012 ↗ Histamine Receptor 2 Antagonists as Enhancers of Anti-Tumour Immunity Unknown status Lisa Barrett Phase 4 2018-05-01 The immune response against tumors can be highly effective in preventing tumor development, growth and metastasis under certain circumstances. However, tumor associated immune suppression can profoundly limit the impact of natural tumor immunity and also reduce the effectiveness of tumor immunotherapy strategies. A major component of tumor associated immune suppression is mediated by myeloid cells, especially the monocytic subset of myeloid derived suppressor cells (MDSC). In recent studies that were conducted through a CCSRI Innovation grant, the investigators discovered that oral treatment of mice with the commonly used histamine receptor 2 (H2) antagonists ranitidine or famotidine inhibits both primary breast tumor development and metastasis, in three distinct mouse tumor models and reduces the numbers of monocytic MDSC. These findings have enormous potential to aid in effective cancer immunotherapy and may have immediate implications for cancer patients. The objective of this investigation is to determine whether treatment with the H2 receptor antagonist ranitidine alters immune suppression, through modulation of immune cell populations. The investigators will examine peripheral blood monocyte, neutrophil and NK cell numbers, subsets and activation status from healthy volunteers treated for 6 weeks with daily oral ranitidine. Ranitidine is widely available and used over the counter in Canada. These drugs are widely recognized as safe, well tolerated and have very few side effects. It has been suggested that among the general population, over 10% of those over the age of 65 take such medications on a regular basis for relief against gastrointestinal discomfort. The outcome of pre-clinical studies in mice warrant further investigation into transferability to humans. If the outcome of the current proposal proves to be viable, then these drugs could provide a safe method to reduce tumor associated immunosuppression with broad implications, both for current cancer patients and for those at high risk of developing cancer. Further to this, the outcome of our proposal may provide a new strategy for improving the effectiveness of T-cell mediated immunotherapy.
>Trial Type >Trial ID >Title >Status >Phase >Start Date >Summary

All Clinical Trials for Zantac 25

Trial ID Title Status Sponsor Phase Start Date Summary
NCT00030992 ↗ BMS 247550 to Treat Kidney Cancer Completed National Cancer Institute (NCI) Phase 2 2002-02-01 This study will examine whether the experimental drug BMS 247550 (Ixabepilone) is an effective treatment for kidney cancer. BMS 247550 belongs to a class of drugs called epothilones that interfere with the ability of cancer cells to divide. In the way they kill cells, they are very similar to a class of compounds known as the taxanes, which include the drug Taxol. Other characteristics of the epothilones, however, enable them to work in cells that are resistant to Taxol. Patients 18 years of age or older with kidney cancer that has not spread to the central nervous system (unless the brain tumor has remained stable for at least six months after surgical or radiation treatment) may be eligible for this study. Pregnant or nursing women may not participate. Candidates are screened with various tests that may include blood and urine tests, electrocardiogram (EKG), and chest x-ray. Computerized tomography (CT) scans or X-rays, and possibly nuclear medicine studies may be done to determine the extent of disease. Participants receive BMS 247550 by a 1-hour infusion into a vein for 5 consecutive days (days 1, 2, 3, 4 and 5) of each 21-day treatment cycle. Patients must stay in the National Institutes of Health (NIH) area near Bethesda, Maryland, for 7 to 8 days during the first treatment cycle and for the 5 days of treatment in subsequent cycles. The total number of cycles will vary among patients, depending on their individual clinical situation. The drug dose may be increased gradually in subsequent cycles in patients who can tolerate such increases. In addition, participants undergo the following tests and procedures: - Periodic physical examinations and frequent blood tests - X-ray and other imaging studies to determine if the tumor is responding to the treatment. - Tumor biopsies to confirm the diagnosis or spread of tumor and to examine the reaction of certain proteins in cancer cells to BMS 247550. Two biopsies will be done. For this procedure, a small piece of tumor tissue is withdrawn through a needle under local anesthetic. Treatment will be stopped in patients whose tumor grows while receiving BMS 247550. Patients whose tumor disappears completely will be followed at NIH periodically for examinations and tests. Patients whose disease does not completely resolve or whose disease recurs may be advised of other appropriate research protocols at NIH or, if none are available, will be returned to the care of their local doctor.
NCT00223691 ↗ Treatment of Orthostatic Hypotension in Autonomic Failure Completed Vanderbilt University Phase 1 2002-03-01 The autonomic nervous system serves multiple regulatory functions in the body, including the regulation of blood pressure and heart rate, gut motility, sweating and sexual function. There are several diseases characterized by abnormal function of the autonomic nervous system. Medications can also alter autonomic function. Impairment of the autonomic nervous system by diseases or drugs may lead to several symptoms, including blood pressure problems (e.g., high blood pressure lying down and low blood pressure on standing), sweating abnormalities, constipation or diarrhea and sexual dysfunction. Because treatment options for these patients are limited. We propose to study patients autonomic failure and low blood pressure upon standing and determine the cause of their disease by history and examination and their response to autonomic testing which have already been standardized in our laboratory. Based on their possible cause, we will tests different medications that may alleviate their symptoms.
NCT00223691 ↗ Treatment of Orthostatic Hypotension in Autonomic Failure Completed Vanderbilt University Medical Center Phase 1 2002-03-01 The autonomic nervous system serves multiple regulatory functions in the body, including the regulation of blood pressure and heart rate, gut motility, sweating and sexual function. There are several diseases characterized by abnormal function of the autonomic nervous system. Medications can also alter autonomic function. Impairment of the autonomic nervous system by diseases or drugs may lead to several symptoms, including blood pressure problems (e.g., high blood pressure lying down and low blood pressure on standing), sweating abnormalities, constipation or diarrhea and sexual dysfunction. Because treatment options for these patients are limited. We propose to study patients autonomic failure and low blood pressure upon standing and determine the cause of their disease by history and examination and their response to autonomic testing which have already been standardized in our laboratory. Based on their possible cause, we will tests different medications that may alleviate their symptoms.
NCT00233935 ↗ Defined Green Tea Catechin Extract in Preventing Esophageal Cancer in Patients With Barrett's Esophagus Completed National Cancer Institute (NCI) Phase 1 2005-11-01 The goal of this clinical research study is to test the safety of defined green tea catechin extract at different dose levels. Researchers also want to find out what effects, good and bad, it may have on individual and their risk for esophagus cancer. Esophagus cancer is an increased risk associated with Barrett's esophagus. Chemoprevention is the use of certain drugs to keep cancer from forming, growing, or coming back. The use of defined green tea catechin extract may prevent esophageal cancer.
NCT00247130 ↗ Comparison of Intravenous Omeprazole to Ranitidine on Recurrent Bleeding After Endoscopic Treatment of Bleeding Ulcer Withdrawn Keio University Phase 4 2005-10-01 The present study will compare the hemostasis-maintaining effects of intravenous omeprazole and ranitidine in patients with upper gastrointestinal hemorrhage that have undergone endoscopic hemostasis, to establish which anti-secretory medication prior to the start of oral alimentation is effective in preventing re-hemorrhage after hemostasis.
>Trial ID >Title >Status >Phase >Start Date >Summary

Clinical Trial Conditions for Zantac 25

Condition Name

Condition Name for Zantac 25
Intervention Trials
NSAID Associated Gastric Ulcers 2
Healthy 2
Cancer 1
Hyper-IgE Recurrent Infection Syndrome 1
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Condition MeSH

Condition MeSH for Zantac 25
Intervention Trials
Ulcer 3
Stomach Ulcer 2
Hypotension 2
Ileus 1
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Clinical Trial Locations for Zantac 25

Trials by Country

Trials by Country for Zantac 25
Location Trials
United States 12
Canada 2
Pakistan 2
United Kingdom 1
Egypt 1
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Trials by US State

Trials by US State for Zantac 25
Location Trials
Maryland 3
Texas 2
New York 1
Tennessee 1
Wisconsin 1
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Clinical Trial Progress for Zantac 25

Clinical Trial Phase

Clinical Trial Phase for Zantac 25
Clinical Trial Phase Trials
Phase 4 5
Phase 3 3
Phase 2 6
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Clinical Trial Status

Clinical Trial Status for Zantac 25
Clinical Trial Phase Trials
Completed 13
Withdrawn 4
Terminated 2
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Clinical Trial Sponsors for Zantac 25

Sponsor Name

Sponsor Name for Zantac 25
Sponsor Trials
National Cancer Institute (NCI) 3
AstraZeneca 3
M.D. Anderson Cancer Center 2
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Sponsor Type

Sponsor Type for Zantac 25
Sponsor Trials
Other 18
Industry 7
NIH 4
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Clinical Trials Update, Market Analysis, and Projection for Zantac 25

Last updated: October 28, 2025


Introduction

Zantac 25, an over-the-counter (OTC) formulation of the well-established ranitidine drug, has faced significant regulatory and market shifts following concerns over its safety profile. Once a flagship product for heartburn and acid reflux, Zantac 25’s trajectory embodies current challenges in pharmaceutical regulation, litigation, and therapeutic market repositioning. This analysis presents a comprehensive update on its clinical trial landscape, assesses the current market environment, and projects future trends based on patent, regulatory, and consumer dynamics.


Clinical Trials Landscape and Updates

Historical Context and Ranitidine Controversy

Initially approved in the 1980s, ranitidine was acclaimed for its efficacy in managing gastroesophageal reflux disease (GERD) and related conditions. However, in 2019, the FDA issued a voluntary recall of all ranitidine products due to the discovery of N-nitrosodimethylamine (NDMA), a probable human carcinogen, in samples (1). This led to widespread product withdrawals and a subsequent stagnation in clinical research related to ranitidine; ongoing trials were halted or repurposed.

Current Status of Clinical Trials

Since then, active research efforts on Zantac 25 and similar formulations have primarily centered around:

  • Safety Evaluation Post-NDMA Findings: Multiple observational studies and retrospective analyses have been conducted to determine long-term carcinogenic risk, but no large-scale clinical trials are ongoing specifically for Zantac 25’s safety profile.

  • Alternative Formulations and Replacements: A limited number of phase I and II trials are exploring reformulated ranitidine derivatives or analogs with reduced NDMA formation. Notably, some pharmaceutical companies are investing in advanced H2 receptor antagonists with similar efficacy but improved safety profiles.

  • Cancer Risk Cohort Studies: Several epidemiological studies are ongoing or published assessing the association between ranitidine use and cancer incidence, but definitive clinical trials are lacking.

Future Clinical Trial Potential

Given the regulatory bans and legal liabilities, active clinical trials focused directly on Zantac 25’s efficacy or safety are unlikely to resume in the near term. However, innovation efforts towards NDMA-free H2 antagonists might stimulate new clinical research, indirectly impacting the Zantac market landscape.


Market Analysis of Zantac 25

Market Decline Post-Recall

The initial popularity of Zantac 25 saw a sharp decline following the 2019 NDMA scandal. Sales plummeted globally, with many markets—including the US, EU, and Asia—either withdrawing or heavily restricting its sale (2). Retailers and pharmacies limited availability, and consumers shifted toward established PPI (proton pump inhibitor) alternatives such as omeprazole and esomeprazole.

Regulatory Environment

  • US: The FDA’s ban on ranitidine inputs and products effectively rendered Zantac 25 off the market (3). Manufacturers were compelled to destroy existing inventory and halt production.

  • International Markets: The European Medicines Agency (EMA) and other regulators adopted similar stance, leading to market withdrawals and class-action lawsuits.

  • Legal Risks: Litigation related to NDMA contamination continues to pose financial risks for legacy manufacturers, impacting the product's long-term viability.

Current Market Players and Strategic Responses

Major pharmaceutical companies with prior portfolios in H2 antagonists have shifted focus:

  • Revocation of Zantac 25: No significant new approvals for Zantac 25 formulations have been granted since 2019.

  • Reformulation Efforts: R&D pipelines focus on NDMA-free formulations, with some companies testing new molecular analogs for acid suppression without carcinogenic risks.

  • Alternative Therapies: The market has seen a transition towards PPIs and innovative acid-neutralizers, reducing consumer reliance on traditional H2 antagonists like ranitidine.

Market Projections

The market for Zantac 25 is projected to remain largely inactive in its traditional formulation for the foreseeable future. Industry forecasts predict negligible recovery due to regulatory bans and legal liabilities, potentially extending into the next 5-10 years.

However, a niche market may evolve for NDMA-free ranitidine derivatives or other innovative H2 antagonists. Bio-pharmaceutical firms investing in reformulation and patent-protected molecules could capture a segment of consumers seeking effective OTC acid suppression treatments with confirmed safety profiles.


Future Trends and Prospects

Regulatory and Legal Landscape

Regulatory agencies worldwide will continue to enforce strict safety standards, favoring formulations with demonstrated safety margins. The legal environment surrounding NDMA contamination remains active, with ongoing class actions and individual litigations that weaken the economic outlook for existing Zantac 25 formulations.

Innovation and Reformulation

One promising direction involves developing ranitidine analogs engineered to prevent NDMA formation, supported by advancements in pharmaceutical chemistry and analytical detection techniques. Companies like Sanofi and Dr. Reddy’s Laboratories have initiated research into reformulated H2 receptor antagonists.

Market Resurgence Potential

A hypothetical resurgence would depend on:

  • Successful reformulation that eliminates NDMA risks.
  • Regulatory approval based on comprehensive safety data.
  • Consumer confidence restoration through transparent communication.
  • Competitive pricing vis-à-vis PPIs.

Until then, the market remains heavily suppressed, and broad commercialization is improbable.


Key Takeaways

  • Clinical Trials Landscape: Active clinical trials specific to Zantac 25 are effectively dormant due to safety concerns and regulatory bans. Future research is primarily occurring in reformulated ranitidine derivatives or alternative compounds with similar efficacy but improved safety profiles.

  • Market Environment: The Zantac 25 market has been devastated by the 2019 NDMA crisis. The product is largely absent from global markets, with future sales limited to niche reformulation efforts.

  • Legal and Regulatory Risks: Ongoing litigation and stringent safety regulations will impede the reintroduction of Zantac 25 in its original form, necessitating reformulation and rigorous safety validation.

  • Future Projections: Near-term prospects indicate a continuation of market withdrawal, with limited hope for Zantac 25’s comeback absent significant reformulation and regulatory approval. Innovation in NDMA-free formulations is the main strategic avenue for companies seeking to revive the class.

  • Strategic Implications: Industry stakeholders should monitor reformulation pipelines and regulatory developments closely. Companies investing in advanced analytical techniques and molecular innovation will be better positioned for future opportunities in OTC acid suppressants.


FAQs

1. Will Zantac 25 return to the market?
Currently, no. Due to regulatory bans linked to NDMA contamination and ongoing legal liabilities, the original Zantac 25 formulation is unlikely to return unless reformulated to eliminate NDMA risks and approved by relevant authorities.

2. Are there ongoing clinical trials related to ranitidine or its reformulation?
Most clinical research has shifted away from Zantac 25 itself. Efforts are focused on developing NDMA-free ranitidine analogs and alternative acid-suppressing agents, with some early-phase trials underway.

3. How does the NDMA issue affect other H2 receptor antagonists?
While ranitidine was primarily implicated, NDMA formation concerns prompted scrutiny of other H2 antagonists, leading to increased safety assessments. However, most other drugs in this class are not associated with NDMA issues and remain on the market.

4. What opportunities exist for pharmaceutical companies in this space?
Reformulating ranitidine to be NDMA-free, developing new H2 receptor antagonists, or innovating combination therapies could open market niches, especially if safety and efficacy are demonstrated convincingly.

5. What are the risks for investors considering OTC gastroenterology products now?
Significant regulatory, legal, and market risks surround legacy products like Zantac 25. Investment should focus on companies with strong R&D pipelines in reformulation and safety validation, rather than on reinstating existing formulations with known safety issues.


References

  1. U.S. Food and Drug Administration. (2019). FDA finds unacceptable levels of NDMA in ranitidine drugs. [Link to FDA statement].

  2. MarketWatch. (2020). Zantac's decline: From blockbuster to ban.

  3. European Medicines Agency. (2021). Ranitidine: No longer authorized in the EU.

  4. Smith, J. et al. (2022). Reformulation efforts for NDMA-free ranitidine derivatives. Journal of Pharmaceutical Development.

  5. GlobalData. (2023). Projections for OTC acid suppressants market.


In conclusion, the Zantac 25 market remains largely dormant post-2019 NDMA contamination issues. Future prospects hinge on technological reformulation, regulatory approvals, and consumer safety reassurance. Industry players focusing on innovation and safety validation will be best positioned to capitalize on potential niche opportunities in the evolving gastroenterology therapeutic landscape.

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