CLINICAL TRIALS PROFILE FOR RANITIDINE

505(b)(2) Clinical Trials for ranitidine

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↗	Total Antioxidant Effects of Esomeprazole in Dyspeptic Patients Receiving Non-steroidal Anti-inflammatory Drugs	Withdrawn	AstraZeneca	Phase 4	2006-12-01	The principal investigator hypothesizes that participants receiving NSAID drugs with dyspeptic symptoms have increased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↗	Total Antioxidant Effects of Esomeprazole in Dyspeptic Patients Receiving Non-steroidal Anti-inflammatory Drugs	Withdrawn	Medstar Health Research Institute	Phase 4	2006-12-01	The principal investigator hypothesizes that participants receiving NSAID drugs with dyspeptic symptoms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

All Clinical Trials for ranitidine

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00000964 ↗	The Effect of Stomach Acid on Foscarnet	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	Phase 1	1969-12-31	To see if ranitidine, by reducing stomach acidity, can enhance the effectiveness of foscarnet, by making foscarnet more available to the body. Foscarnet is an antiviral compound. Laboratory studies have shown it to be active against HIV. However, only 12 - 22 percent of an oral foscarnet dose is absorbed by the body. Ranitidine suppresses gastric acid output, increasing gastric pH. Thus by increasing gastric pH (decreasing stomach acidity), less foscarnet is expected to be decomposed or broken down in the stomach. Thus, more foscarnet should be absorbed into the body.
NCT00002106 ↗	A Pilot Randomized, Double-Blind, Placebo-Controlled, Parallel Design, Multicenter Trial to Evaluate the Effect of Ranitidine on Immunologic Indicators in Asymptomatic HIV-1 Infected Subjects With a CD4 Cell Count Between 400-700 Cells/mm3	Completed	Glaxo Wellcome	Phase 2	1969-12-31	To evaluate the effect of ranitidine on immunologic indicators in asymptomatic HIV-1 infected patients with CD4 counts of 400-700 cells/mm3.
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.

Clinical Trial Conditions for ranitidine

Condition Name

Condition Name for ranitidine
Intervention	Trials
Healthy	7
Postoperative Pain	6
Dyspepsia	4

Condition MeSH

Condition MeSH for ranitidine
Intervention	Trials
Hypotension	9
Ulcer	8
Pain, Postoperative	8

Clinical Trial Locations for ranitidine

Trials by Country

Trials by Country for ranitidine
Location	Trials
United States	87
Egypt	25
China	20
Korea, Republic of	12
Italy	8

Trials by US State

Trials by US State for ranitidine
Location	Trials
California	13
Texas	10
Florida	6
Illinois	4
Pennsylvania	4

Clinical Trial Progress for ranitidine

Clinical Trial Phase

Clinical Trial Phase for ranitidine
Clinical Trial Phase	Trials
PHASE4	1
PHASE1	1
Phase 4	39

Clinical Trial Status

Clinical Trial Status for ranitidine
Clinical Trial Phase	Trials
Completed	89
Unknown status	18
Terminated	10

Clinical Trial Sponsors for ranitidine

Sponsor Name

Sponsor Name for ranitidine
Sponsor	Trials
AstraZeneca	6
Cairo University	5
Kasr El Aini Hospital	5

Sponsor Type

Sponsor Type for ranitidine
Sponsor	Trials
Other	134
Industry	47
NIH	6

Ranitidine Clinical Trials Update, Market Analysis and Expiration Outlook (U.S. and Key Geographies)

Last updated: July 27, 2026

Ranitidine’s clinical development pipeline is effectively closed after regulatory withdrawal in multiple markets and a sustained stop in new enrollment. Commercial activity has shifted to last-time inventory clearance and transition to alternative H2-receptor antagonists and class-competitive generics. Patent-driven exclusivity is not the primary determinant of availability; regulatory action is.

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Is ranitidine still being studied in clinical trials (2025 update)?

No meaningful new ranitidine clinical trial enrollment is observable in the current period, and the effective development position is “paused/ended” in practice because major regulators required withdrawal tied to NDMA (N-nitrosodimethylamine) contamination concerns.

What caused the development shutdown?

• U.S. FDA required removal of ranitidine products from the market (and blocked new product distribution under prevailing actions), after it determined there was a risk of unacceptable NDMA exposure from ranitidine.
• EU and other jurisdictions adopted parallel restrictions and withdrawals, leading sponsors to discontinue trials and halt new studies.

What clinical trial activity typically remains post-withdrawal?

When a product is withdrawn, remaining studies usually fall into one of these buckets:

• Regulatory-required pharmacovigilance follow-up
• Narrow, investigator-initiated pharmacokinetic work with alternate supply sources (rare post-withdrawal)
• Retrospective observational studies using historical datasets

For ranitidine specifically, current commercial relevance is tied to availability and labeling transitions rather than new clinical evidence generation.

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What happened to ranitidine’s regulatory status, NDMA risk, and withdrawals (Orange Book and beyond)?

Ranitidine’s regulatory standing changed materially after NDMA risk findings. The key market impact is product discontinuation rather than patent expiry.

U.S. FDA status and market effect

• FDA announced market withdrawal from the U.S. based on NDMA formation concerns.
• This action ended routine commercial distribution and constrained new FDA-facing lifecycle activities tied to the original NDA pathway.

EU and UK treatment of the product

• European authorities implemented suspensions/withdrawals across member states, also tied to NDMA impurity risk.

What happens to remaining brand/generic supply?

• Last-time stock clearance and substitution by alternative H2 antagonists (famotidine, cimetidine in some markets) and PPI regimens.
• In some countries, products were relisted only after reformulation and impurity controls, where allowed, but the overall category demand shifted away from ranitidine.

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How does ranitidine’s market size and demand profile change after NDMA withdrawals?

The category demand persists, but the “share of stomach acid suppression” shifted away from ranitidine to:

• Famotidine (where available and supported by supply continuity)
• PPIs (omeprazole, esomeprazole, lansoprazole, pantoprazole, and generics)

Demand substitution dynamics

• When an H2 blocker is removed, prescribers and OTC users typically switch to an alternative H2 blocker or PPI based on symptom profile and dosing convenience.
• Risk communication around NDMA accelerated substitution because it affected both prescription and OTC users.

Market projection framing

Near-term revenue projections for ranitidine depend on:

• Remaining inventory
• Whether any jurisdictions retain stock or continued approvals
• Regulatory enforcement intensity on distribution
• Competitive capture by famotidine and PPIs

The higher-order driver is regulatory permissibility, not patent posture.

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What is the competitive landscape for ranitidine: famotidine vs omeprazole vs cimetidine?

Ranitidine’s competitive set is mostly the same patients on acid suppression regimens.

H2 blocker substitution: famotidine

• Famotidine has remained a primary alternative in many markets because it did not face the same NDMA-specific withdrawal outcome.
• Generic famotidine availability supports broad access.

PPI substitution: omeprazole and other PPIs

• PPIs have stronger acid suppression and are widely used for GERD and ulcer indications.
• Patients seeking symptom control often move to OTC and generic PPI options after ranitidine withdrawal.

Clinical practice impact

• For mild, intermittent GERD or dyspepsia: H2 blocker options get faster pickup.
• For chronic GERD/ulcer prevention: PPIs retain share.

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When does ranitidine lose exclusivity: patent expiration vs regulatory withdrawal?

Ranitidine’s exclusivity question resolves differently than for typical Rx brands because the product’s availability was disrupted by regulatory action.

Key point: exclusivity is not the constraint

Even if patents had remaining terms, FDA withdrawal removed or curtailed distribution. The practical impact is market access termination regardless of remaining patent life.

Practical exclusivity timeline

• Brand ranitidine exclusivity and subsequent generic entry occurred years earlier; the NDMA-driven withdrawal is what ended the meaningful commercial presence rather than impending patent expiry.

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What patents protect ranitidine and do they affect market access today?

Ranitidine is an older active ingredient with extensive generic availability history. Patent estates, where still present in certain jurisdictions, rarely govern current access because regulators have already constrained distribution.

How to interpret “patent protection” for ranitidine now

• For active-ingredient ranitidine, patents are generally legacy and not the main barrier to generic supply.
• For any remaining jurisdictions or legacy formulations, the controlling factor is regulatory approval status and product impurity controls, not patent life.

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What formulations of ranitidine existed and how did product versions matter for NDMA risk?

NDMA risk is tied to impurity formation and storage/processing conditions. Formulation and manufacturing controls matter.

Dosage forms historically marketed

• Oral tablets
• Oral capsules
• Syrup formulations for pediatric use (where marketed)

Manufacturing controls

• NDMA impurity management requires tight control of sourcing, synthesis route impurities, and analytical release testing thresholds.

Because regulatory withdrawal applied at the product level, formulation-specific “next-gen” ranitidine development did not scale the category back.

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What generic entry risks exist for ranitidine after withdrawal?

In typical Hatch-Wax or Paragraph IV scenarios, entry risk centers on patent litigation. For ranitidine, the dominant risk is regulatory permissibility.

Generic entry risk categories

• Regulatory status risk: whether the specific product remains authorized for sale
• Impurity control risk: NDMA formation and release specs
• Supply chain risk: continued availability of acceptable API lots under compliant testing

Bottom line

• If regulators require withdrawal, Paragraph IV and patent strategies do not restore market access. The bottleneck is regulatory authorization for a safe product.

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What patent litigation affected ranitidine, and is it driving outcomes now?

Ranitidine is an older drug where active litigation is not the principal driver of current market availability. The market narrative is regulatory, not litigation.

• The litigation impact, where any existed historically, does not override a withdrawal that cuts off distribution.

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How much market revenue exposure does ranitidine have in 2025–2028?

Ranitidine revenue exposure in this window is primarily:

• Clearance of residual supply
• Any remaining approved stock in specific countries
• Limited niche sales where the product was not fully displaced

Projection logic

• Demand shifted to substitutes after withdrawal.
• Remaining ranitidine sales are likely to be small relative to earlier years and are inventory-dependent.

A robust forward projection by geography and product form requires live market datasets tied to current distribution and authorization. Without that dataset, a defensible numeric forecast cannot be produced.

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What is the path forward: will ranitidine return to major markets?

Return is constrained by:

• Regulatory standards for NDMA
• Feasibility of manufacturing controls at scale
• Willingness of sponsors and generics to relaunch after withdrawal

In most major markets, ranitidine did not return as a dominant therapy, and the category shifted structurally to other H2 blockers and PPIs.

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Key Takeaways

• Ranitidine clinical development is effectively shut down in practice due to NDMA-driven market withdrawal.
• Market access is governed by regulatory status, not by remaining exclusivity or patent life.
• Commercial demand moved to famotidine and PPIs, reducing ranitidine’s forward revenue base to residual inventory and limited regional availability.
• Any future ranitidine reintroduction would require regulatory clearance tied to impurity controls; patent strategy is not the gating factor.

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FAQs

1) Did the NDMA issue come from ranitidine itself or storage conditions?

Regulators concluded NDMA risk related to ranitidine exposure, including conditions that allowed NDMA formation, leading to market withdrawal actions.

2) Are there approved H2 blockers in the same therapeutic category as ranitidine that gained share?

Yes. Famotidine and PPIs captured the displaced patient demand in most markets.

3) Can generic manufacturers still sell ranitidine where it was previously available?

Only if a specific product remains authorized and can meet impurity specifications tied to NDMA risk.

4) Do Paragraph IV filings meaningfully affect ranitidine market access today?

Not in the way they do for active FDA-authorized products with intact regulatory supply. Withdrawal and authorization status dominate.

5) What patient populations are most likely to switch away from ranitidine?

GERD, dyspepsia, ulcer-related maintenance users, and OTC buyers often switch to PPIs or alternative H2 blockers depending on symptom pattern and dosing convenience.

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References (APA)

1. U.S. Food and Drug Administration. (2019). FDA requests removal of all ranitidine products (Zantac) from the market. https://www.fda.gov
2. European Medicines Agency. (2019). EMA issues recommendations on use of ranitidine. https://www.ema.europa.eu