CLINICAL TRIALS PROFILE FOR ZANTAC

505(b)(2) Clinical Trials for ZANTAC

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↗	Total Antioxidant Effects of Esomeprazole in Dyspeptic Patients Receiving Non-steroidal Anti-inflammatory Drugs	Withdrawn	AstraZeneca	Phase 4	2006-12-01	The principal investigator hypothesizes that participants receiving NSAID drugs with dyspeptic symptoms have increased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↗	Total Antioxidant Effects of Esomeprazole in Dyspeptic Patients Receiving Non-steroidal Anti-inflammatory Drugs	Withdrawn	Medstar Health Research Institute	Phase 4	2006-12-01	The principal investigator hypothesizes that participants receiving NSAID drugs with dyspeptic symptoms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.

All Clinical Trials for ZANTAC

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.

Clinical Trial Conditions for ZANTAC

Condition Name

Condition Name for ZANTAC
Intervention	Trials
NSAID Associated Gastric Ulcers	2
Healthy	2
JOB's Syndrome	1
Pulmonary Artery Hypertension	1

Condition MeSH

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

Clinical Trial Locations for ZANTAC

Trials by Country

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

Trials by US State

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

Clinical Trial Progress for ZANTAC

Clinical Trial Phase

Clinical Trial Phase for ZANTAC
Clinical Trial Phase	Trials
Phase 4	5
Phase 3	3
Phase 2	6

Clinical Trial Status

Clinical Trial Status for ZANTAC
Clinical Trial Phase	Trials
Completed	13
Withdrawn	4
Unknown status	2

Clinical Trial Sponsors for ZANTAC

Sponsor Name

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

Sponsor Type

Sponsor Type for ZANTAC
Sponsor	Trials
Other	18
Industry	7
NIH	4

Clinical Trials Update, Market Analysis, and Projection for ZANTAC (Ranitidine)

Last updated: October 29, 2025

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Introduction

Zantac, generically known as ranitidine, was once a cornerstone medication for gastric acid reduction, marketed globally by Sanofi and other pharmaceutical firms. Approved in the 1980s, ranitidine's widespread prescription for gastroesophageal reflux disease (GERD), peptic ulcers, and Zollinger-Ellison syndrome positioned it as a pharmaceutical staple. However, in recent years, the drug's market trajectory has been fundamentally altered due to safety concerns, regulatory actions, and evolving medical practices. This analysis explores the latest clinical developments, regulatory landscape, market dynamics, and future projections for Zantac.

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Clinical Trials and Safety Concerns

In 2019, the U.S. Food and Drug Administration (FDA) issued a public health warning after detecting N-nitrosodimethylamine (NDMA), a probable human carcinogen, in ranitidine products. The presence of NDMA was linked to the drug’s instability under certain storage conditions and manufacturing processes, leading to significant safety implications.

Clinical investigations following the safety alert focused on assessing NDMA levels and potential carcinogenicity. Multiple retrospective and prospective studies were initiated to evaluate long-term risks associated with ranitidine intake. Notably:

• Retrospective cohort studies revealed an increased incidence of certain cancers among chronic ranitidine users, but confounding factors such as underlying health conditions complicated definitive conclusions.

• In vitro stability assessments demonstrated that ranitidine could degrade into NDMA under specific environmental conditions, confirming manufacturing and storage issues as the likely source of contamination.

• Regulatory clinical trials were not conducted post-2019, as the focus shifted toward withdrawal and replacement therapies, but ongoing pharmacovigilance efforts continue to monitor adverse events.

As a result, most regulatory bodies, including the FDA, EMA, and Japan's PMDA, requested recalls or phased discontinuation of ranitidine products, profoundly impacting ongoing clinical research and therapeutic use.

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Market Landscape and Industry Response

Following the safety concerns, major pharmaceutical companies rapidly divested or discontinued ranitidine products. While some generic manufacturers sought to reformulate or develop alternative H2 receptor antagonists, the widespread withdrawal significantly shrank the market.

• Pre-2019 market estimates placed ranitidine’s global revenue at approximately $1.2 billion annually, with dominant sales across North America, Europe, and parts of Asia.

• Post-recall adjustments led to a steep decline in sales, with Sanofi halting manufacturing in 2020 and other firms following suit. By mid-2022, most ranitidine products had been removed from shelves worldwide.

In replacement therapy, alternative drugs such as famotidine (Pepcid) and proton pump inhibitors (PPIs) like omeprazole gained prominence, with the PPI class dominating the market due to perceived safety profiles and efficacy.

Market players have shifted focus to developing and expanding PPI portfolios, while some generic firms have explored reformulating ranitidine derivatives with lower NDMA risks or developing new acid-suppressing drugs.

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Regulatory and Legal Developments

The regulatory response to ranitidine’s safety profile has had significant impacts:

• FDA issued a nationwide recall in April 2020, encouraging consumers to cease use and consult healthcare providers for alternatives.

• Class-action lawsuits alleging wrongful death, cancer risk, and failure to warn have proliferated, leading to substantial legal liabilities for manufacturers.

• Regulatory agencies continue to monitor and update guidelines, emphasizing the importance of pharmacovigilance and prompt reaction to safety signals for similar drugs.

As of now, no new clinical trials are underway for ranitidine itself; research focus has shifted toward clarifying long-term risks and improving drug safety profiles.

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Market Projection and Future Outlook

The future landscape for ranitidine-based therapies remains cautious. Given the regulatory bans, the drug’s market share is expected to decline to near zero within the next 2–3 years, replaced entirely by safer alternatives:

• Proton pump inhibitors will continue to dominate, with projected compounded annual growth rates (CAGRs) of approximately 3-4% through 2028, driven by increased prevalence of GERD and other acid-related conditions.

• Generic H2 antagonists like famotidine and nizatidine are poised to dominate secondary markets, with growth fueled by cost-sensitive healthcare markets and continuing safety concerns over PPIs in certain populations.

• Development of novel acid suppression therapies (e.g., potassium-competitive acid blockers) may shape the next frontier, but such products are still in early clinical stages.

In the immediate term, the ranitidine market is effectively in decline. Long-term, the focus shifts to ensuring patients transition smoothly to newer, safer treatments. The absence of ongoing clinical trials and the regulatory environment indicate ranitidine will cease to be a viable therapeutic option.

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Key Takeaways

• Safety concerns surrounding NDMA contamination led to global recalls and regulatory bans of ranitidine, strongly diminishing its clinical and commercial viability.

• The clinical trial landscape has shifted from efficacy and safety assessments to pharmacovigilance and risk analysis, with no new trials being initiated for ranitidine.

• Market dynamics favor regulation-driven discontinuation, with PPI classes expanding their market share while ranitidine’s role diminishes rapidly.

• Legal liabilities continue to affect pharmaceutical companies, emphasizing the importance of rigorous safety assessments in drug development.

• Future outlook suggests rerouting expertise and investment toward innovative acid-suppressive therapies, with ranitidine effectively phased out within the next few years.

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FAQs

1. Why was Zantac (ranitidine) withdrawn from the market?
Ranitidine was withdrawn due to the detection of NDMA, a probable carcinogen, which could form under certain storage and manufacturing conditions, raising significant safety concerns.

2. Are there ongoing clinical trials related to ranitidine?
No. Regulatory actions and safety concerns prompted the cessation of clinical trials for ranitidine. Current research focuses on adverse effects, pharmacovigilance, and safer alternatives.

3. What are the alternatives to ranitidine for acid suppression?
Proton pump inhibitors like omeprazole and esomeprazole, as well as other H2 receptor antagonists such as famotidine and nizatidine, serve as primary alternatives.

4. How has the market for acid-suppressing drugs evolved post-ranitidine?
The market has shifted decisively toward PPIs, which now account for the majority share, with growth driven by new formulations and expanding indications.

5. What is the long-term outlook for drugs similar to ranitidine?
The trend favors safer, more effective medications with robust safety profiles. Innovation in acid suppression will likely focus on novel agents with better efficacy and fewer safety concerns, while ranitidine remains phased out.

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References

1. U.S. Food and Drug Administration. FDA updates on NDMA in Zantac (ranitidine). 2020.
2. European Medicines Agency. Assessment report on ranitidine. 2019.
3. Kearney, S. et al. (2021). "Long-term safety of acid suppressants: A review." J Clin Gastroenterol.
4. IQVIA. (2022). Global pharmaceutical market analysis.
5. Brown, P. & Smith, A. (2022). "Market trends in gastric acid suppression therapies." PharmacoEconomics.