CLINICAL TRIALS PROFILE FOR URSODIOL

505(b)(2) Clinical Trials for URSODIOL

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	NCT00125281 ↗	SAMe to Treat Biliary Cirrhosis Symptoms	Terminated	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)	Phase 2	2005-07-25	This study will examine the effect of S-adenosyl methionine (SAMe) on itching and fatigue in patients with primary biliary cirrhosis, a disease of the small bile ducts in the liver. Ursodiol, the only currently available treatment for biliary cirrhosis, does not cure the disease, and many people continue to have symptoms or liver test abnormalities despite treatment. SAMe is a naturally occurring substance found in most cells of the body. The highest levels of the substance are produced by the liver, where it helps to rid the body of toxins and breakdown products of metabolism. Studies in Europe suggest that SAMe may help to: 1) decrease the fatigue and itching that are common in persons with liver problems, and 2) decrease levels of liver enzymes in the blood, suggesting that it may decrease the amount of liver injury. Patients 21 years of age or older with primary biliary cirrhosis who are taking ursodiol and have symptoms of itching or fatigue may be eligible for this study. Candidates are screened with a medical history, physical examination, review of medical records, routine blood tests, and a symptoms rating scale. Participants stop all medications for itching 4 weeks before starting the study, but continue to take ursodiol during the 42-week trial. On entering the study, patients are assigned to take either SAMe or placebo tablets twice a day for 12 weeks. While taking the medications, they are followed in the clinic every 2 weeks for the first month and then every 4 weeks to fill out symptoms questionnaires and have a short medical evaluation and blood tests. At the end of 12 weeks, treatment is interrupted for a 2-week "wash-out" period, after which patients begin a 12-week crossover treatment; that is, patients who were taking SAMe are switched to placebo, and those who were taking placebo are switched to SAMe. After completing the second 12-week treatment course, patients come to the clinic at 4, 8, and 12 weeks to fill out symptoms questionnaires and have a medical evaluation and blood tests. At the last visit, patients are told which type of tablet they received during the two courses of treatment. SAMe is available without prescription in many forms as an over-the-counter medication.

All Clinical Trials for URSODIOL

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00004315 ↗	Phase II Pilot Study to Compare the Bioavailability of Buffered, Enteric-Coated Ursodiol With Unmodified Ursodiol for Chronic Cholestatic Liver Disease and Cystic Fibrosis-Associated Liver Disease	Unknown status	Children's Hospital Medical Center, Cincinnati	Phase 2	1995-11-01	OBJECTIVES: I. Compare the bioavailability of polymer-coated and buffered ursodiol (ursodeoxycholic acid) to unmodified ursodiol in patients with cystic fibrosis-associated liver disease or chronic cholestatic liver disease. II. Compare the differences in pruritus, weight gain, and liver function for both treatments.
NCT00004315 ↗	Phase II Pilot Study to Compare the Bioavailability of Buffered, Enteric-Coated Ursodiol With Unmodified Ursodiol for Chronic Cholestatic Liver Disease and Cystic Fibrosis-Associated Liver Disease	Unknown status	National Center for Research Resources (NCRR)	Phase 2	1995-11-01	OBJECTIVES: I. Compare the bioavailability of polymer-coated and buffered ursodiol (ursodeoxycholic acid) to unmodified ursodiol in patients with cystic fibrosis-associated liver disease or chronic cholestatic liver disease. II. Compare the differences in pruritus, weight gain, and liver function for both treatments.
NCT00004441 ↗	Study of Tauroursodeoxycholic Acid for Hepatobiliary Disease in Cystic Fibrosis	Completed	Children's Hospital Medical Center, Cincinnati	N/A	1997-09-01	OBJECTIVES: I. Determine the optimum dose of tauroursodeoxycholic acid (TUDCA) required to achieve maximal bioavailability for patients with cystic fibrosis-associated liver disease. II. Compare optimized doses of TUDCA with ursodiol (ursodeoxycholic acid; UDCA) for effects on biliary bile acid composition and metabolism, serum biochemistries, fat absorption, and fat-soluble vitamin status in these patients.
NCT00004442 ↗	Study of Bile Acids in Patients With Peroxisomal Disorders	Terminated	Children's Hospital Medical Center, Cincinnati	N/A	1969-12-31	OBJECTIVES: I. Determine the effectiveness of oral bile acid therapy with cholic acid, chenodeoxycholic acid, and ursodeoxycholic acid in patients with peroxisomal disorders involving impaired primary bile acid synthesis. II. Determine whether suppression of synthesis of atypical bile acids and enrichment of bile acid pool with this regimen is effective in treating this patient population and improving quality of life.
NCT00004442 ↗	Study of Bile Acids in Patients With Peroxisomal Disorders	Terminated	University of Cincinnati	N/A	1969-12-31	OBJECTIVES: I. Determine the effectiveness of oral bile acid therapy with cholic acid, chenodeoxycholic acid, and ursodeoxycholic acid in patients with peroxisomal disorders involving impaired primary bile acid synthesis. II. Determine whether suppression of synthesis of atypical bile acids and enrichment of bile acid pool with this regimen is effective in treating this patient population and improving quality of life.

Clinical Trial Conditions for URSODIOL

Condition Name

Condition Name for URSODIOL
Intervention	Trials
Healthy	5
Liver Cirrhosis, Biliary	4
Cholestasis	2
Primary Biliary Cirrhosis	2

Condition MeSH

Condition MeSH for URSODIOL
Intervention	Trials
Fibrosis	8
Liver Cirrhosis, Biliary	6
Liver Cirrhosis	6
Cholangitis	2

Clinical Trial Locations for URSODIOL

Trials by Country

Trials by Country for URSODIOL
Location	Trials
United States	51
Canada	6
Egypt	2
Italy	2
Germany	1

Trials by US State

Trials by US State for URSODIOL
Location	Trials
Texas	5
Minnesota	4
Arizona	3
Washington	3
Virginia	3

Clinical Trial Progress for URSODIOL

Clinical Trial Phase

Clinical Trial Phase for URSODIOL
Clinical Trial Phase	Trials
PHASE4	1
Phase 4	4
Phase 3	6

Clinical Trial Status

Clinical Trial Status for URSODIOL
Clinical Trial Phase	Trials
Completed	18
Terminated	8
Recruiting	4

Clinical Trial Sponsors for URSODIOL

Sponsor Name

Sponsor Name for URSODIOL
Sponsor	Trials
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)	5
National Cancer Institute (NCI)	4
Children's Hospital Medical Center, Cincinnati	3

Sponsor Type

Sponsor Type for URSODIOL
Sponsor	Trials
Other	52
NIH	13
Industry	9

Ursodiol Clinical Trials Update, Market Analysis and Patent/Exclusivity Projection

Last updated: May 21, 2026

Ursodiol (ursodeoxycholic acid, UDCA) is an established bile-acid therapy with long-standing regulatory presence and broad generic availability in key markets. Clinical development activity is concentrated in new indications, higher-yield trial designs (biomarker endpoints and stratification), and formulation or dosing refinements rather than first-in-class breakthroughs. Commercial upside is driven by prescription retention in approved uses, label expansion in cholestatic and liver conditions, and uptake in specialty pathways where payers favor guideline-aligned bile acid therapy.

What clinical trials are ongoing for ursodiol right now and what endpoints are being used?

Most public ursodiol “clinical trials” activity falls into three buckets: (1) studies in cholestatic liver diseases and bile-duct injury states, (2) comparative or add-on studies with biomarker and imaging endpoints, and (3) protocol adaptations (dose-ranging, adherence, and patient stratification). Trial selection has shifted toward measurable biochemical readouts such as alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), bilirubin, bile acid profiles, and noninvasive liver measures.

Common endpoints used in ursodiol studies

• Biochemical response: ALP, GGT, ALT, AST, total and direct bilirubin
• Safety/tolerability: pruritus, fatigue, gastrointestinal adverse events
• Imaging/clinical surrogate: cholestatic markers, liver stiffness, ultrasound/MR-based morphology in some cohorts
• Composite outcomes: biochemical response thresholds and progression proxies used in cholestatic disease trials

Key trial design trend

• Longer follow-up windows to map biochemical responders to downstream outcomes (disease progression and complications), using stratification by baseline severity.

How does ursodiol perform in cholestatic liver indications based on the most recent evidence?

Ursodiol is best established in primary biliary cholangitis (PBC) where it is standard-of-care for many patients and is used across historical guideline pathways. In other cholestatic contexts, evidence is more heterogeneous and often depends on disease stage, baseline biomarkers, and whether patients are receiving combination therapy.

Performance factors that drive clinical outcomes

• Baseline cholestasis severity (ALP and bilirubin at entry)
• Adherence and dose tolerability
• Disease subtype and stage (early vs advanced cholestasis)
• Concomitant therapies (especially when UDCA is part of a broader regimen)

What has changed in practice

• Clinicians increasingly use biochemical response criteria to decide whether patients remain on UDCA alone or are escalated to additional agents where indicated by guidelines.
• Trials lean into responder definitions to improve signal detection and reduce “noise” from non-responding baseline subgroups.

Which new ursodiol studies target label expansion or new patient segments?

Where incremental development exists, it tends to focus on:

• Earlier-stage patients where UDCA response rates are higher
• Combination strategies or add-on designs where UDCA is compared as part of optimized standard-of-care
• Novel endpoints or enrichment strategies for cholestatic phenotypes

Because ursodiol is off-patent in most jurisdictions, new trials are less about exclusivity creation and more about sustaining guideline positioning, payer relevance, and post-approval evidence depth.

What is the current market size for ursodiol and what does the demand mix look like?

Ursodiol demand is driven by chronic prescription patterns in cholestatic and bile-duct–related indications, supported by ongoing use in PBC and related cholestasis populations. Generic supply underpins pricing pressure, but utilization is resilient due to chronic treatment duration and entrenched guideline status.

Demand drivers

• Chronic use in guideline-aligned cholestatic disease management
• Treatment continuity for responders
• Broad availability of generics that lowers access barriers
• Specialty prescribing concentration (hepatology and gastroenterology)

Demand headwinds

• Generic price compression in major markets
• Competition from other bile-acid–modulating therapies in selected subgroups where they are guideline recommended
• Regulatory or guideline shifts that adjust where UDCA remains first-line vs combination/add-on

What market projection applies to ursodiol through 2030: base case, bull case, bear case?

Given generic saturation, projection is best expressed as utilization-driven with modest revenue growth (units grow faster than revenue) unless a meaningful label expansion occurs or reimbursement shifts favor UDCA.

Projection structure for a generic-dominant product

• Units: expected to grow modestly with incidence and improved diagnosis
• ASP/revenue: grow slower due to generic price pressure
• Share: sensitive to payer formularies and specialty guideline alignment

Base case (most likely)

• Low single-digit annual revenue growth through 2030 driven by utilization stability and modest unit growth
• Revenue gains limited by continued generic price compression

Bull case

• Faster unit growth from guideline expansions or earlier adoption in cholestatic subtypes
• Improved payer coverage for UDCA in combination pathways
• Revenue outperforms units if some manufacturers gain favorable distribution/contract pricing

Bear case

• Stronger substitution to non-UDCA therapies in guideline-recommended combination pathways
• Additional price declines from generic entrants and contracting pressure
• Units flat due to reduced initiation rates or tighter payer criteria

How much of ursodiol revenue is at risk from generic erosion and price compression?

Market risk is structural because ursodiol is widely generic. The principal revenue threat is not sudden entry, but incremental ASP dilution from:

• additional generic launches in fragmented markets,
• contract renegotiations,
• pharmacy benefit manager (PBM) re-formulary cycles,
• channel mix shifts toward lower-cost authorized generics and multi-source products.

Practical risk framing

• Revenue per patient tends to be vulnerable.
• Utilization per patient is comparatively stable due to chronic treatment patterns.

What is the Orange Book status of ursodiol and which companies hold listed patents?

For ursodiol, the practical Orange Book takeaway is usually “multi-source generics with limited active exclusivity.” In high-level licensing and litigation terms, the active patent estate is typically narrow or expired, which shifts value from litigation-driven exclusivity to brand differentiation, supply reliability, and contracting.

If no dataset is supplied that maps specific NDA numbers, strength/dosage form listings, and patent expiration dates, a precise Orange Book patent list cannot be stated without risking inaccuracies.

When does ursodiol lose exclusivity by formulation, strength, and route in major markets?

Ursodiol’s exclusivity situation is generally dominated by historical foundational approvals and broad generic availability. Precision requires NDA/BLA-specific Orange Book data and country-level patent status by formulation (capsules/tablets), strength, and route (oral).

Without a provided dossier of specific products/NDA numbers, a complete exclusivity timeline by jurisdiction and dosage form cannot be produced.

What patents protect ursodiol in the US and what formulation or method-of-use IP still matters?

In many older small-molecule drugs that are broadly generic, remaining IP tends to concentrate on:

• specific formulations or controlled-release systems,
• manufacturing processes,
• method-of-use claims tied to particular patient subgroups or dosing regimens.

However, the exact patent coverage for ursodiol requires a confirmed patent estate map by product listing.

Which Paragraph IV challenges exist for ursodiol, and what does that imply for generic entry risk?

UDCA is generally not the kind of asset where new Paragraph IV challenges frequently drive near-term entry, given multi-source availability. Generic entry risk is more about:

• supply expansions by existing generic manufacturers,
• contract cycles and channel shifts,
• sporadic reformulation launches that can affect competitive dynamics.

A real risk map requires confirmation of pending ANDAs with Paragraph IV allegations and litigation dockets.

What litigation affects ursodiol patent enforcement and settlement behavior?

For established off-patent generics, litigation is usually sporadic and fact-specific. A defensible litigation assessment requires:

• current district court cases,
• Federal Circuit history,
• settlement agreements tied to specific ANDA filings.

No verified litigation list is available in the prompt.

How does ursodiol compare with competing bile-acid therapies for cholestatic disease in efficacy, tolerability, and use patterns?

Comparators typically include other bile-acid pathway agents and disease-modifying therapies used in cholestatic liver diseases depending on guideline positioning and patient phenotype. In practice:

• UDCA retains role as foundational therapy in PBC and certain bile-duct disorders.
• Other agents can be used for inadequate responders or specific disease segments, driving substitution risk.

Because exact comparator trial outcomes and guideline alignment depend on indication and patient stage, a precise head-to-head comparison requires indication-specific evidence and up-to-date guideline snapshots.

What does the commercial projection imply for R&D strategy: where should investment focus for ursodiol?

For an already generic, mature molecule, R&D ROI typically shifts to:

• formulation improvements that can win payers and pharmacies on tolerability, adherence, or stability,
• evidence generation that tightens responder definitions and supports earlier escalation,
• life-cycle evidence in subgroups that payers and guideline bodies prioritize.

From a business standpoint, the best investment targets are those that reduce discontinuation, improve patient adherence, or create differentiated access contracts rather than attempting to restart primary exclusivity.

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Key Takeaways

• Ursodiol clinical activity is oriented around cholestatic liver disease evidence refinement: biochemical endpoints, responder stratification, and longer follow-up rather than first-in-class innovation.
• Market growth is expected to be utilization-led with modest revenue growth due to entrenched generic competition and ongoing price compression.
• Near-term generic entry risk is structurally lower because multi-source availability is already established; competitive dynamics are driven by contracting, channel distribution, and incremental supply.
• Patent/exclusivity and litigation assessments require NDA/product-specific Orange Book and docket data; without it, only high-level directional conclusions are supportable.

FAQs

1. How do clinicians define ursodiol biochemical response in cholestatic liver disease trials?
2. What dosing and tolerability factors most influence adherence to ursodiol in chronic use?
3. Which payer criteria typically determine formulary placement for ursodiol in specialty liver pathways?
4. Do ursodiol formulations (tablet vs capsule) change bioavailability or real-world outcomes?
5. What competitive threats matter most for ursodiol: additional generics, substitution by other agents, or guideline changes?

References

No sources were provided in the prompt.