CLINICAL TRIALS PROFILE FOR HYDROCORTISONE

505(b)(2) Clinical Trials for hydrocortisone

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	NCT00754247 ↗	A Randomized Comparative Study Evaluating the Tolerability and Efficacy of Two Topical Therapies for the Treatment of Keloids and Hypertrophic Scars	Completed	University of Miami	Phase 4	2006-03-01	Keloids are thought to result from derailments in the typical wound healing process following cutaneous injury. Current treatment options for keloids include intralesional corticosteroids, silicone gel sheeting, compression, surgery and adjuvants to surgery, including radiation and cryotherapy. 0.5% hydrocortisone, silicone, vitamin E lotion (HSE) and onion extract gel (OE) are widely used over-the-counter medications for the treatment of keloids and hypertrophic scars. However, their efficacy and safety have not been compared in a blinded, placebo-controlled, prospective fashion. This study is being undertaken to determine the efficacy and safety of HSE versus OE versus placebo (Cetearyl alcohol; CEA) in subjects with hypertrophic scars and keloids. This is an investigator-blinded study, which means that the doctor evaluating you will not know if you are receiving the study medication or not. Another doctor will be supplying you with the medication and discussing any problems that you may have with the medication. You will be assigned to one of the three treatment groups: HSE, OE, or CEA. The group will be assigned by chance and you will have two in three chances of receiving treatment with a study medication, HSE or OE. The no treatment group will receive CEA, a bland lotion, containing no active ingredients such as steroids, silicone, vitamin E, or onion extract.

All Clinical Trials for hydrocortisone

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00001409 ↗	Genetically Modified Lymphocytes to Treat HIV-Infected Identical Twins - Study Modifications	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	Phase 1	1994-09-01	Certain patients enrolled in NIH protocol 94-I-0206 at the Clinical Center may be eligible to participate in one or more of the following new options: - Donor/recipient extension phase - Both the recipient (HIV-infected twin) and donor (non-infected twin) will participate in this extension of the CD4-zeta gene therapy study. It will evaluate the safety and activity of infusing gene-modified CD4+ cells as well as the modified CD8+ cells. - Corticosteroid administration - A corticosteroid, such as prednisone, hydrocortisone or prednisolone, will be added to the interleukin-2 (IL-2) regimen for preventing or treating side effects of IL-2 such as fever and other flu-like symptoms. - Extended follow-up - A more intensive follow-up will be scheduled for patients with substantial numbers of lymphocytes that harbor the CD4-zeta gene. Every 3 months, participants will have blood tests and specialized tests of CD4 counts, HIV-1 viral load and numbers of circulating cells containing the CD4-zeta gene every 3 months> the frequency of follow-up visits may be reduced as time goes by. - IL-2 continuation - Participants will continue to receive periodic treatment with IL-2 to see how long the genetically modified cells persist in the bloodstream and to evaluate the long-term response to IL-2. - Home treatment with interleukin-2 - Participants may receive future IL-2 treatment cycles at home. Home treatment involves less frequent data and safety monitoring and no medical evaluations at the Clinical Center except at the beginning of each cycle.
NCT00001521 ↗	Three Drug Combination Therapy Versus Conventional Treatment of Children With Congenital Adrenal Hyperplasia	Active, not recruiting	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)	Phase 2	1995-06-08	This study was developed to determine if a combination of four drugs (flutamide, testolactone, reduced hydrocortisone dose, and fludrocortisone) can normalize growth in children with congenital adrenal hyperplasia. The study will take 60 children, boys and girls and divide them into 2 groups based on the medications given. Group one will receive the new four- drug combination. Group two will receive the standard treatment for congenital adrenal hyperplasia (hydrocortisone and fludrocortisone). The boys in group one will take the medication until the age of 14 at which time they will stop taking the four drug combination and begin receiving the standard treatment for congenital adrenal hyperplasia. Girls in group one will take the four drug combination until the age of 13, at which time they will stop and begin receiving the standard treatment for congenital adrenal hyperplasia plus flutamide. Flutamide will be given to the girls until six months after their first menstrual period. All of the children will be followed until they reach their final adult height. The effectiveness of the treatment will be determined by measuring the patient's adult height, body mass index, and bone density. ...
NCT00002471 ↗	Combination Chemotherapy in Treating Patients With Acute B-Lymphoblastic Leukemia or Non-Hodgkin's Lymphoma	Completed	Memorial Sloan Kettering Cancer Center	Phase 2	1990-02-01	RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells. PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy in treating patients who have acute B-lymphoblastic leukemia or recurrent non-Hodgkin's lymphoma.
NCT00002494 ↗	Combination Chemotherapy in Treating Patients With Non-Hodgkin's Lymphoma or Acute Lymphocytic Leukemia	Completed	National Cancer Institute (NCI)	Phase 2	1992-05-01	RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells. PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy and alternating regimens of chemotherapy in treating patients who have non-Hodgkin's lymphoma or acute lymphocytic leukemia.
NCT00002494 ↗	Combination Chemotherapy in Treating Patients With Non-Hodgkin's Lymphoma or Acute Lymphocytic Leukemia	Completed	Alliance for Clinical Trials in Oncology	Phase 2	1992-05-01	RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells. PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy and alternating regimens of chemotherapy in treating patients who have non-Hodgkin's lymphoma or acute lymphocytic leukemia.
NCT00002700 ↗	Chemotherapy With or Without Bone Marrow Transplantation in Treating Patients With Acute Lymphoblastic Leukemia	Completed	Acute Leukemia French Association	Phase 3	1995-08-01	RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with radiation therapy may kill more tumor cells. Bone marrow transplantation can replace immune cells that were destroyed by chemotherapy. PURPOSE: Randomized phase III trial to study the effectiveness of chemotherapy compared with or without bone marrow transplantation in treating patients with acute lymphoblastic leukemia.

Clinical Trial Conditions for hydrocortisone

Condition Name

Condition Name for hydrocortisone
Intervention	Trials
Septic Shock	37
Leukemia	31
Adrenal Insufficiency	26
Sepsis	24

Condition MeSH

Condition MeSH for hydrocortisone
Intervention	Trials
Leukemia	90
Leukemia, Lymphoid	70
Precursor Cell Lymphoblastic Leukemia-Lymphoma	69
Shock, Septic	46

Clinical Trial Locations for hydrocortisone

Trials by Country

Trials by Country for hydrocortisone
Location	Trials
Canada	153
Australia	65
United Kingdom	45
France	45
Spain	38

Trials by US State

Trials by US State for hydrocortisone
Location	Trials
California	77
Texas	69
Tennessee	56
New York	55
Massachusetts	49

Clinical Trial Progress for hydrocortisone

Clinical Trial Phase

Clinical Trial Phase for hydrocortisone
Clinical Trial Phase	Trials
PHASE4	9
PHASE3	5
PHASE2	9

Clinical Trial Status

Clinical Trial Status for hydrocortisone
Clinical Trial Phase	Trials
Completed	237
Recruiting	73
Terminated	37

Clinical Trial Sponsors for hydrocortisone

Sponsor Name

Sponsor Name for hydrocortisone
Sponsor	Trials
National Cancer Institute (NCI)	60
Children's Oncology Group	20
St. Jude Children's Research Hospital	20

Sponsor Type

Sponsor Type for hydrocortisone
Sponsor	Trials
Other	659
Industry	119
NIH	98

Hydrocortisone Clinical Trials Update, Market Analysis, and 2025–2035 Projection

Last updated: July 26, 2026

Hydrocortisone is a long-established corticosteroid used across dermatology, ophthalmology, otology, pulmonology/allergy, gastroenterology, and adrenal insufficiency. The commercial outlook in the near term is driven by (1) continued demand for legacy generics and authorized generics, (2) recurrent FDA/market access cycles for ophthalmic and topical formulations, and (3) incremental uptake of reformulated or device-combination products. Long-horizon growth is constrained by mature patent status for the core drug and by sustained generic competition in most dosage forms.

A clinical-trials “update” at the brand level is fragmented because hydrocortisone spans many reference listed drug (RLD) products and active-ingredient equivalents. Trial activity is therefore best read through formulation and route-specific studies (ophthalmic suspensions/ointments, otic solutions, rectal formulations, and novel delivery systems) and through studies in adrenal insufficiency cohorts, where there is ongoing optimization of dosing regimens and diagnostic strategies.

What are the latest hydrocortisone clinical trials (phase, indications, endpoints)?

Hydrocortisone trials cluster in four buckets that repeat across registries and sponsor decks:

1. adrenal insufficiency and steroid replacement optimization (including stress dosing and adherence)
2. ophthalmic inflammation and post-surgical protocols (with product comparisons and tolerability)
3. otic inflammatory conditions (often in pediatrics and otitis externa subtypes)
4. topical dermatology (vehicle optimization, irritation mitigation, and vehicle-controlled efficacy comparisons)

Where are new hydrocortisone studies concentrated by route of administration?

• Ophthalmic: trials and post-approval studies frequently evaluate post-cataract or post-ocular surgery inflammation control, keratoconjunctivitis indicators, and steroid-safety monitoring (IOP rise, cataract risk proxies).
• Otic: studies target pain reduction and symptom resolution in inflammatory ear conditions, typically with microbiology arms or exclusion criteria designed around otic infections.
• Topical/dermatologic: vehicle and concentration comparisons, time-to-improvement endpoints, and safety under occlusion or sensitive-site use.
• GI/rectal: studies focus on rectal delivery performance, stool frequency endpoints, and corticosteroid tolerability.

What endpoints are most common in hydrocortisone trials?

• ophthalmic: anterior chamber cell/flare reductions; pain and photophobia scales; intraocular pressure (IOP) monitoring
• adrenal insufficiency: adrenal crisis incidence, dosing adherence, quality-of-life measures, biochemical markers (when included)
• otic/topical: time-to-symptom improvement; lesion clearance or erythema/scaling scores; patient-reported outcomes; safety (skin/ear irritation, infection rates)

How does hydrocortisone trial design typically differ across competitors?

• Generics and authorized generics often aim at bioequivalence or comparative safety/tolerability rather than novel efficacy claims.
• Reformulation developers emphasize local tolerability and vehicle consistency (particle size for suspensions, uniformity for ointments, and steadier viscosity/suspension stability for drops).
• Adrenal insufficiency studies often include real-world adherence components and structured stress dosing education as an outcome driver.

What does the hydrocortisone market look like today by dosage form and geography?

Hydrocortisone’s market is dominated by older, off-patent products with broad generic penetration. That makes the market more “portfolio and distribution” than “patent and breakthrough pipeline.”

Key commercial segments

1. Topical hydrocortisone (over-the-counter and prescription strength across mild inflammatory dermatoses)
2. Ophthalmic hydrocortisone (prescription anti-inflammatory role)
3. Otic hydrocortisone combinations (often paired with antibiotics/antifungals depending on the product)
4. Adrenal replacement products (oral tablets and injectable hydrocortisone sodium succinate)
5. Respiratory/allergy and other niche uses via systemically active or route-specific formulations

Geographic market dynamics

• United States: high generic share in most dosage forms, with continued branded presence where combination products or formulations stay competitive.
• EU5 (DE, FR, IT, ES, UK): similar generic dominance with jurisdiction-specific approvals for specific strengths and presentations.
• Emerging markets: growth tracks access and procurement cycles, with supply concentration risks in sterile injectables and ophthalmics.

Competitive structure

• Most competition is low-cost generic and authorized generic activity.
• Differentiation is more frequently tied to formulation stability, packaging, and patient handling than to new pharmacology.

When does hydrocortisone lose exclusivity, and what drives new competition?

Because hydrocortisone as a molecule is mature, “exclusivity” usually means:

• formulation-specific exclusivity (if any exists for a given RLD and filing history)
• data exclusivity and patent protection around the specific marketed product presentation
• exclusivity or patent protection around combinations (hydrocortisone with other actives)

What timing matters in hydrocortisone generics in practice?

• ANDA approval cycles and product-specific patent/Orange Book listings
• FDA labeling carve-outs that permit generics to enter without changing the active ingredient
• Manufacturing facility readiness and inspection outcomes for sterile products (especially ophthalmics and injectables)

What is the Orange Book status of hydrocortisone products?

Hydrocortisone’s Orange Book profile is best addressed product-by-product because:

• hydrocortisone appears across many RLDs and strengths
• each RLD has its own patent and exclusivity listing footprint

A single “hydrocortisone Orange Book status” statement is not actionable. The relevant question for market entry is whether a specific RLD presentation has unexpired:

• method-of-use patents
• formulation/process patents
• listed patents tied to the specific formulation (particle size, suspension characteristics, sterility assurance methods for ophthalmic or injectable products)

How many patents protect hydrocortisone formulations, and what is typical patent scope?

For older corticosteroids, patent estates tend to be:

• small and presentation-specific for many genericable formats
• stronger in sterile manufacturing/process for ophthalmics and injectables (where regulator and CGMP requirements create practical barriers)
• more likely to exist around combination products rather than hydrocortisone monotherapy

Typical patent categories you should expect

• formulation patents: composition of suspensions/ointments, viscosity modifiers, stabilizers
• process patents: sterilization and terminal processing methods, container closures and fill processes
• method-of-use: limited, usually tied to specific dosing or clinical protocols for particular indications or combinations
• device-related: for delivery systems that are co-packaged or integrated (less common in legacy hydrocortisone)

Which hydrocortisone companies are challenging patents or launching generics via Paragraph IV?

Paragraph IV challenges for hydrocortisone monotherapy are less common than for novel drugs because most monotherapy presentations are long off-patent. The more realistic focal points are:

• hydrocortisone in combination products
• ophthalmic/otic reformulations tied to specific RLDs
• injectable presentations with sterile manufacturing complexity

A defensible competitor map requires product-level Orange Book review, because the Paragraph IV landscape varies by RLD, strength, and dosage form.

What hydrocortisone patent litigation affects market entry?

Hydrocortisone litigation tends to be:

• product-specific
• concentrated around sterile formulations and combination actives
• resolved through stipulations and settlement agreements that preserve limited label niches

For market projection, the practical risk is not whether hydrocortisone is protected, but whether a specific RLD presentation is protected on the day a generic is ready for launch, including any stay of FDA approval.

How strong is the hydrocortisone patent estate (brand vs generic risk)?

Hydrocortisone is not expected to have a broad, multi-decade monopoly estate for core monotherapy across major routes. Strength is largely:

• narrow in scope
• tied to formulation/process and product-specific listings
• increasingly outmatched by generic manufacturing maturity and distribution scale

For an R&D or licensing strategy, the “estate” value is usually in:

• securing rights to a specific presentation with commercially meaningful differentiation
• or acquiring/defending rights to a combination product where IP protection and label differentiation matter.

How does hydrocortisone compare with other topical and steroid options (market share and substitution)?

Hydrocortisone competes directly with:

• other topical corticosteroids (different potency classes)
• non-steroidal anti-inflammatories in some dermatologic segments
• ophthalmic steroids and combinations with antibiotics/antivirals in eye care
• systemic steroids in adrenal replacement and inflammatory disease contexts (where hydrocortisone is differentiated by replacement physiology and dosing practice)

Substitution risk is high at the molecule level but lower when:

• clinical protocols require a specific formulation (e.g., suspension vs ointment)
• combination labels dictate specific indications
• route-specific handling affects adherence.

What hydrocortisone biosimilar or biologic risk exists?

Hydrocortisone is a small-molecule steroid and is not a biologic. There is no biosimilar framework risk.

What formulations are most commercially important for hydrocortisone growth?

Commercial value is concentrated in:

• ocular sterile suspensions and ointments (prescription)
• otic formulations (often combinations)
• injectable hydrocortisone sodium succinate (acute adrenal crisis and perioperative stress dosing)
• mild topical OTC/prescription spectrum (high volume, low price, broad competition)

Reformulation that improves:

• patient handling (drop size, consistency)
• stability (suspension uniformity, shelf life)
• tolerability (vehicle irritation profile) can protect share even after IP expiration.

Clinical trial-to-market: what evidence tends to translate into hydrocortisone uptake?

For mature steroids, uptake typically follows:

• improved convenience (dosing regimen, pack usability)
• demonstrated safety in real use (especially for ophthalmics and pediatrics)
• stable supply reliability and pharmacist/payer preferences
• payer contracting and pharmacy channel distribution

Clinical efficacy improvements are harder to demonstrate in a molecule with well-understood pharmacodynamics, so development that proves local tolerability and consistent performance often carries more weight.

2025–2035 hydrocortisone market projection: revenue drivers, constraints, and scenarios

Base case projection logic (what will likely happen)

• Volume growth modestly positive in most mature markets due to ongoing needs and demographic factors.
• Value growth limited by persistent generic pricing pressure.
• Growth concentration shifts toward higher-value sterile presentations, combination products, and channel-driven uptake.

Constraints that cap growth

• sustained generic competition in monotherapy hydrocortisone
• limited scope for blockbuster-level pricing power
• formulation-specific regulatory pathways that slow refresh cycles for sterile products
• product supply and manufacturing QA bottlenecks (sterile and ophthalmic)

Upside scenario (what could improve the trajectory)

• successful launches of reformulated ophthalmic/otic presentations with meaningful patient handling or stability differentiation
• limited but real opportunities in combination products and niche disease protocols
• improved payer recognition of specific RLDs tied to consistent outcomes and lower discontinuation rates

Downside scenario (what could worsen the trajectory)

• supply chain disruptions in sterile manufacturing
• higher-than-expected regulatory remediation cost or inspection impact
• rapid price erosion in remaining higher-value presentations if additional entrants arrive

Projection table (framework for business planning)

Year	Expected market direction	Main growth contributors	Main headwinds
2025–2026	Low single-digit value growth in mature markets	mix shift to sterile presentations, combination products	generic price compression
2027–2029	Flat to modest growth	incremental reformulation launches, channel re-contracting	sustained erosion in monotherapy
2030–2033	Modest growth or stabilization	targeted niche indications and reformulations	ongoing entry cycles and supply normalization
2034–2035	Stabilization	replacement and maintenance therapies; new product refresh	continued generic saturation

What generic entry risks exist for hydrocortisone products?

Generic entry risk is product-specific and depends on:

• whether the marketed RLD presentation has unexpired listed patents or exclusivity
• whether there are regulatory or labeling barriers (sterile, viscosity, suspension uniformity, container closure)
• whether competitors can replicate the same quality attributes at scale

For planning, the risk concentration is highest in:

• ophthalmics and injectables (manufacturing complexity)
• combination products (patent and label scope more likely to be present)

What commercial actions make the most sense for a hydrocortisone portfolio?

• Treat hydrocortisone as a product-presentation portfolio business.
• Build defensibility through formulation performance, supply reliability, and contract access, not through molecule-level patent strategy.
• For new development, target routes and presentations where clinical handling or stability can be differentiated and where product-specific regulatory scrutiny leaves room for differentiation.

Key Takeaways

• Hydrocortisone market growth is constrained by maturity and generic competition; value depends more on presentation mix and channel contracting than on new pharmacology.
• Clinical trial activity is best read by route and formulation (ophthalmic, otic, topical, adrenal replacement) rather than by molecule-level novelty.
• Patent and exclusivity risk is product-specific; market entry timing hinges on Orange Book listings and formulation-specific constraints for sterile and combination products.
• 2025–2035 projections point to low-to-moderate value growth with stabilization, driven by mix shift into higher-value sterile and combination presentations and limited by persistent price erosion.

FAQs

1. Which hydrocortisone dosage forms are most exposed to generic substitution in the US?
2. Do hydrocortisone ophthalmic products have higher regulatory or manufacturing barriers than topical creams?
3. What drives payer decisions for prescription hydrocortisone suspensions and ointments?
4. How do combination products (hydrocortisone plus antibiotics/antifungals) change patent and labeling risk?
5. What clinical evidence endpoints matter most for approving hydrocortisone formulation changes?

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References (APA)

1. FDA. Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations. https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm
2. U.S. FDA. Drug Development and Drug Interactions guidance and generic drug review resources (various). https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs