CLINICAL TRIALS PROFILE FOR ZANTAC 300

505(b)(2) Clinical Trials for Zantac 300

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↗	Total Antioxidant Effects of Esomeprazole in Dyspeptic Patients Receiving Non-steroidal Anti-inflammatory Drugs	Withdrawn	AstraZeneca	Phase 4	2006-12-01	The principal investigator hypothesizes that participants receiving NSAID drugs with dyspeptic symptoms have increased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↗	Total Antioxidant Effects of Esomeprazole in Dyspeptic Patients Receiving Non-steroidal Anti-inflammatory Drugs	Withdrawn	Medstar Health Research Institute	Phase 4	2006-12-01	The principal investigator hypothesizes that participants receiving NSAID drugs with dyspeptic symptoms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.
OTC	NCT04397445 ↗	Clinical Study to Investigate the Urinary Excretion of N-nitrosodimethylamine (NDMA) After Ranitidine Administration	Completed	Spaulding Clinical Research LLC	Phase 1	2020-06-08	Ranitidine is an over-the-counter and prescription drug, which decreases the amount of acid secreted by the stomach. Some ranitidine medicines contain an impurity called N-nitrosodimethylamine (NDMA) at low levels. NDMA is classified as a probable human carcinogen (a substance that could cause cancer) based on results from laboratory tests. NDMA is a known environmental contaminant and found in water and foods, including meats, dairy products, and vegetables. The US Food and Drug Administration (FDA) has found levels of NDMA in some ranitidine products similar to the levels you would expect to be exposed to if you ate common foods like grilled or smoked meats. The ranitidine that will be used in this study has been tested twice (months apart) and shown to have stable NDMA levels well below the acceptable daily limit. Of note, the risk of NDMA with ranitidine is only relevant with prolonged chronic administration as at the acceptable limit, there is approximately a 1 in 100,000 chance of cancer after 70 years of exposure to that level. FDA has also conducted tests that simulate the potential formation of NDMA from ranitidine after it has been exposed to acid in the stomach with a normal diet. Results of these tests indicate that NDMA is not formed in typical stomach conditions. Similarly, if ranitidine is exposed to a simulated small intestinal fluid, NDMA is not formed. Other laboratory experiments suggest a combination of nitrites, such as found in processed meats, and an acidic environment may increase NDMA formation, however the levels of nitrites tested were very high. Separately, a previous study in 10 healthy volunteers showed that volunteers who received ranitidine had an increase in urinary NDMA excreted over 24 h. The level of increase was greater than would be expected from laboratory testing. This clinical study is being performed to determine if and how much NDMA is produced from ranitidine in the human body and whether nitrite-containing foods may increase formation of NDMA. The study will use a prescription dose of ranitidine (300 mg) to test whether there is increased urinary NDMA excretion levels over 24-hours after ranitidine administration in comparison to placebo when participants are administered low nitrite/NDMA meals and when subjects are administered high nitrite/NDMA meals. On 4 different days, each participant will receive ranitidine or placebo with high nitrite/NDMA meals and ranitidine or placebo with low nitrite/NDMA meals.

All Clinical Trials for Zantac 300

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.
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).

Clinical Trial Conditions for Zantac 300

Condition Name

Condition Name for Zantac 300
Intervention	Trials
NSAID Associated Gastric Ulcers	2
Healthy	2
Mesothelioma	1
Renal Cell Carcinoma	1

Condition MeSH

Condition MeSH for Zantac 300
Intervention	Trials
Ulcer	3
Stomach Ulcer	2
Hypotension	2
Bronchial Hyperreactivity	1

Clinical Trial Locations for Zantac 300

Trials by Country

Trials by Country for Zantac 300
Location	Trials
United States	12
Pakistan	2
Canada	2
United Kingdom	1
Egypt	1

Trials by US State

Trials by US State for Zantac 300
Location	Trials
Maryland	3
Texas	2
Wisconsin	1
Utah	1
California	1

Clinical Trial Progress for Zantac 300

Clinical Trial Phase

Clinical Trial Phase for Zantac 300
Clinical Trial Phase	Trials
Phase 4	5
Phase 3	3
Phase 2	6

Clinical Trial Status

Clinical Trial Status for Zantac 300
Clinical Trial Phase	Trials
Completed	13
Withdrawn	4
Terminated	2

Clinical Trial Sponsors for Zantac 300

Sponsor Name

Sponsor Name for Zantac 300
Sponsor	Trials
AstraZeneca	3
National Cancer Institute (NCI)	3
Benazir Bhutto Hospital, Rawalpindi	2

Sponsor Type

Sponsor Type for Zantac 300
Sponsor	Trials
Other	18
Industry	7
NIH	4

Clinical Trials Update, Market Analysis, and Projection for ZANTAC 300

Last updated: October 28, 2025

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Introduction

ZANTAC 300 (ranitidine) has historically been one of the most prescribed medications for acid reflux, gastroesophageal reflux disease (GERD), and related gastrointestinal conditions. However, recent developments, including regulatory actions and litigation, have significantly impacted its market landscape. This analysis synthesizes current clinical trial activities, evaluates market dynamics, and projects the drug's future trajectory within the pharmaceutical sector.

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Clinical Trials Update for ZANTAC 300

Recent clinical trial activities focus primarily on addressing safety concerns that emerged following the drug's recall, notably the presence of N-Nitrosodimethylamine (NDMA), a probable human carcinogen. The investigations aim to elucidate the pharmacological safety profile of ranitidine, explore alternative formulations, and examine therapeutic efficacy compared to successor medications.

1. Post-Recall Safety Studies:
   Multiple observational studies and retrospective analyses examine the long-term carcinogenic risks associated with residual NDMA levels in ranitidine formulations. These studies predominantly draw from European and American healthcare databases, aiming to quantify potential cancer incidence shifts in populations previously treated with ZANTAC [1].

2. Pharmacokinetic and Pharmacodynamic Assessments:
   Ongoing phase IV trials investigate the pharmacological nuances between ranitidine and alternative H2 receptor antagonists (H2RAs) and proton pump inhibitors (PPIs). The goal: establish comparative efficacy and safety margins, especially considering the potential carcinogenic risks previously identified.

3. Developments in Ranitidine Alternatives:
   Companies are conducting clinical evaluations of reformulated or purified ranitidine products with NDMA reduction processes. These trials are in early phases, seeking regulatory approval for potentially safer formulations.

4. Remanufacturing and Reintroduction Studies:
   The FDA’s guidance has limited reintroduction of noncontaminated ranitidine; thus, no significant new clinical trials on re-approval are underway in major jurisdictions. However, in some markets, limited trials assess manufacturing processes that eliminate NDMA contamination risks, crucial for potential re-entry into the market.

Summary:
Clinical trial activity for ZANTAC 300 has shifted from traditional efficacy studies to safety profiling, contamination mitigation, and comparative assessment against newer therapies. The current landscape reflects a focus on risk management rather than routine drug development.

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Market Analysis

The ZANTAC 300 market has experienced a seismic shift following the 2019 voluntary recall by several manufacturers, including Sanofi, following NDMA contamination concerns. The drug's market contraction can be characterized through several vectors:

1. Market Contraction and Reformulation Efforts:
   Post-recall, the market for ranitidine has contracted by over 90%, with prescriptions falling sharply in the U.S. and Europe. Major pharmaceutical firms have discontinued sales or transitioned to PPI alternatives. Some players have invested in reformulation efforts, aiming to produce NDMA-free ranitidine for niche markets or compounding pharmacies.

2. Competitive Landscape:
   The landscape is now dominated by PPIs such as omeprazole (Prilosec), esomeprazole (Nexium), and H2RAs like famotidine. Notably, famotidine, a less controversial alternative, regained prescriber confidence, further eroding ranitidine's market share.

3. Regulatory Impact:
   Regulatory agencies, especially the FDA, have not approved new ranitidine formulations since the recall. European agencies have adopted similar stances, enhancing the shift toward alternative therapeutics. The regulatory environment effectively restricts reintroduction pathways, constraining market potential.

4. Consumer and Prescriber Trends:
   Growing awareness of NDMA-related risks has led to declining consumer demand. Prescriber behavior shifted towards PPIs and other non-controversial medications, emphasizing safety profiles.

5. Legal and Litigation Impact:
   Litigation alleging cancer risk from contaminated ZANTAC has led to substantial liabilities for manufacturers, further deterring investment in reintroduction. Multibillion-dollar settlements have been reached, damaging the brand's reputation and financial prospects.

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Market Projection and Future Outlook

Given the current dynamics, the future of ZANTAC 300 hinges on regulatory approvals of reformulated, NDMA-free variants and shifting market preferences towards safer treatments.

Short-term Outlook (1–3 years):

• Limited Reintroduction Potential:
  Only niche or compounding pharmacies may offer reformulated ranitidine, with no broad re-approval anticipated soon.
• Market Share Recovery is Unlikely:
  The wider market has transitioned to PPIs and trusted H2RAs, reducing the potential rebound for ranitidine-based products.

Medium to Long-term Outlook (3–10 years):

• Boom in Reformulation Technology:
  Advances in manufacturing may enable safe, contamination-free ranitidine, creating small, specialized markets.
• Market Re-entry Uncertainty:
  Regulatory and legal barriers will likely prevent large-scale re-engagement without comprehensive safety data and regulatory approval.
• Emerging Competition:
  New therapeutics addressing acid suppression, including novel drugs with better safety profiles, could further diminish ranitidine’s market relevance.
• Generic Persistence in Limited Niches:
  Small-scale generics might persist for specific patient segments under strict regulatory oversight, especially in geographies with less stringent drug approvals.

Conclusion:
The global market for ZANTAC 300 is expected to remain minimal and limited to niche segments. The pathway to widespread re-entry is obstructed by safety, regulatory, and legal hurdles, making significant future growth unlikely.

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Key Takeaways

• Shift from Efficacy to Safety Focus:
  Current clinical trials emphasize safety, particularly NDMA contamination mitigation and carcinogenic risk assessment. No major efficacy studies are underway for traditional ZANTAC 300 formulations.

• Market Decline Post-Recall:
  The global ranitidine market has shrunk sharply, with regulatory agencies restricting reintroduction due to safety concerns and litigation risks.

• Regulatory Barriers Limit Reintroduction:
  The lack of approval pathways for reformulated ranitidine and stringent safety demands impede large-scale re-availability.

• Future Potential Tied to Technological Innovation:
  Breakthroughs in manufacturing that eliminate NDMA could reopen avenues, but market size will likely remain niche.

• Therapeutic Alternatives Dominate:
  PPIs and safe H2RAs continue to capture market share, reducing ranitidine’s relevance.

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FAQs

1. Has ZANTAC 300 been formally reapproved for market re-entry?
   No. Regulatory agencies, including the FDA and EMA, have not approved any re-entrant ranitidine formulations due to NDMA safety concerns.

2. Are ongoing clinical trials likely to facilitate the return of ranitidine?
   While trials focus on safety and contamination mitigation, they are unlikely to lead to broad reapproval soon. Success depends on proving safe manufacturing processes and regulatory acceptance.

3. What therapeutic alternatives are replacing ZANTAC 300?
   Proton pump inhibitors like omeprazole and esomeprazole are now the primary treatments for acid-related disorders. Famotidine, an H2RA, also remains a common alternative.

4. Will reformulated ranitidine regain market share?
   Only if manufacturers develop NDMA-free versions that satisfy regulatory safety standards, and if legal and market acceptance follows.

5. What legal implications could impact the future of ranitidine?
   Ongoing and potential lawsuits stemming from NDMA contamination and related health claims continue to pose a significant financial and reputational risk, discouraging large-scale market re-entry.

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References

[1] U.S. Food & Drug Administration. "Recall of Ranitidine Due to NDMA Contamination." 2019.