CLINICAL TRIALS PROFILE FOR METHIMAZOLE

All Clinical Trials for methimazole

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00001421 ↗	Methimazole to Treat Polymyositis and Dermatomyositis	Completed	National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)	Phase 2	1995-06-01	This study will test the safety and effectiveness of the drug methimazole in treating polymyositis and dermatomyositis-inflammatory muscle diseases causing weakness and muscle wasting. Although it is not known what causes of these diseases, abnormal immune function is thought to be involved. Recent studies indicate that methimazole, which has been used for many years to treat thyroid disease, may alter immune activity by affecting the interaction between white blood cells called lymphocytes and certain molecules on cell surfaces. This study will examine the effects of methimazole on immune activity and muscle strength in patients with inflammatory muscle diseases and evaluate the drug side effects. Patients with polymyositis and dermatomyositis who have normal thyroid function may be eligible for this study [age requirement?]. Candidates will undergo a history and physical examination; blood and urine tests; chest X-ray; muscle strength testing, daily living skills questionnaire, and speech and swallowing evaluation; magnetic resonance imaging of muscles; and muscle biopsy (removal of a small piece of muscle tissue under local anesthetic). When indicated, some candidates may also have cancer screening tests (for example, mammogram, Pap smear), a lung function test to measure breathing capacity, or an electromyogram, in which small needles are inserted into a muscle to measure the electrical activity . Participants will take 30 mg of methimazole by mouth twice a day for 6 months. They will have blood tests weekly for the first 2 weeks and then every other week for the rest of the study to measure blood counts and liver and thyroid function. Blood will also be drawn for white blood cell studies during the screening evaluation, at the beginning of therapy, 6 to 12 weeks after therapy starts, at the end of the 6-month treatment period, and 1 and 3 months after therapy ends. Muscle enzyme and urine tests will be done once a month.. During drug treatment, patients will have periodic physical examinations and blood and muscle function tests to evaluate the response to therapy.
NCT00150111 ↗	Rituximab in the Treatment of Graves' Disease	Completed	Odense University Hospital	Phase 1/Phase 2	2003-06-01	Aim: In a phase II pilot study encompassing 20 patients with Graves' disease to evaluate the effect of rituximab: 1. Biochemically as assessed by markers of disease activity ( free T4, free T3, TSH, TSH-receptor antibodies, anti-TPO)
NCT00150124 ↗	Block-replacement Therapy During Radioiodine Therapy	Completed	Steen Bonnema	Phase 4	2003-01-01	Background: The use of radioactive iodine (131I) therapy as the definite cure of hyperthyroidism is widespread. According to a survey on the management of Graves' disease, thirty per cent of physicians prefer to render their patients euthyroid by antithyroid drugs (ATD) prior to 131I therapy. This strategy is presumably chosen to avoid 131I induced 'thyroid storm', which, however, is rarely encountered. Several studies have consistently shown that patients who are treated with ATD prior to 131I therapy have an increased risk of treatment failure. Mostly, patients with Graves' disease have been studied, while other studies were addressed also toxic nodular goiter. Thus, it is generally accepted that ATD have 'radioprotective' properties, although this view is almost exclusively based on retrospective data and is still under debate. Indeed, this dogma was recently challenged by two randomized trials in Graves' disease, none of which showed such an adverse effect of methimazole pretreatment. It cannot be excluded that the earlier results may have been under influence of selection bias, a source of error almost unavoidable in retrospective studies. Whether ATD is radioprotective also when used in the post 131I period has also been debated. In the early period 131I therapy following a transient rise in the thyroid hormones is seen which may give rise to discomfort in some patients. The continuous use of ATD during 131I therapy, possibly in combination with levothyroxine (BRT: block-replacement therapy), leads to more stable levels of the thyroid hormones. By resuming ATD following 131I therapy, euthyroidism can usually be maintained until the destructive effect of 131I ensues. Nevertheless, many physicians prefer not to resume ATD, probably due to reports supporting that such a strategy reduces the cure rate. Parallel to the issue of ATD pretreatment, the evidence is based on retrospective studies and the ideal set-up should be reconsidered. To underscore the importance of performing randomized trials we showed recently that resumption of methimazole seven days after 131I therapy had no influence on the final outcome. Aim:To clarify by a randomized trial whether BRT during radioiodine therapy of hyperthyroid patients influences the final outcome of this therapy, in a comparison with a regime in which methimazole as mono-therapy is discontinued 8 days before radioiodine. Patients and Methods: Consecutive patients suffering from recurrent Graves' disease (n=50) or a toxic nodular goiter (n=50) are included. All patients are rendered euthyroid by methimazole (MMI) and randomized either to stop MMI eight days before 131I or to be set on BRT. This latter medication continues until three months after 131I. Calculation of the 131I activity (max. 600 MBq) includes an assessment of the 131I half-life and the thyroid volume. Patients are followed for one year with close monitoring of the thyroid function.
NCT00150137 ↗	Antithyroid Drugs During Radioiodine Therapy	Completed	Odense University Hospital	Phase 4	2003-01-01	Background: The use of radioactive iodine (131I) therapy as the definite cure of hyperthyroidism is widespread. According to a survey on the management of Graves' disease, thirty per cent of physicians prefer to render their patients euthyroid by antithyroid drugs (ATD) prior to 131I therapy. This strategy is presumably chosen to avoid 131I induced 'thyroid storm', which, however, is rarely encountered. Several studies have consistently shown that patients who are treated with ATD prior to 131I therapy have an increased risk of treatment failure. Mostly, patients with Graves' disease have been studied, while other studies were addressed also toxic nodular goiter. Thus, it is generally accepted that ATD have 'radioprotective' properties, although this view is almost exclusively based on retrospective data and is still under debate (13). Indeed, this dogma was recently challenged by two randomized trials in Graves' disease, none of which showed such an adverse effect of methimazole pretreatment. It cannot be excluded that the earlier results may have been under influence of selection bias, a source of error almost unavoidable in retrospective studies. Whether ATD is radioprotective also when used in the post 131I period has also been debated. In the early period 131I therapy following a transient rise in the thyroid hormones is seen which may give rise to discomfort in some patients. The continuous use of ATD during 131I therapy leads to more stable levels of the thyroid hormones. By resuming ATD following 131I therapy, euthyroidism can usually be maintained until the destructive effect of 131I ensues. Nevertheless, many physicians prefer not to resume ATD, probably due to reports supporting that such a strategy reduces the cure rate. Parallel to the issue of ATD pretreatment, the evidence is based on retrospective studies and the ideal set-up should be reconsidered. To underscore the importance of performing randomized trials we showed recently that resumption of methimazole seven days after 131I therapy had no influence on the final outcome. Aim: To clarify by a randomized trial whether continuous use of methimazole during radioiodine therapy influences the final outcome of this therapy, in a comparison with a regime in which methimazole as mono-therapy is discontinued 8 days before radioiodine. Patients and Methods: 80 consecutive patients suffering from recurrent Graves' disease or a toxic nodular goiter are included. All patients are rendered euthyroid by methimazole (MMI) and randomized either to stop MMI eight days before 131I or to continue MMI until four weeks after 131I. Calculation of the 131I activity (max. 600 MBq) includes an assessment of the 131I half-life and the thyroid volume. Patients are followed for one year with close monitoring of the thyroid function.
NCT00677469 ↗	Low Doses of Cholestyramine in the Treatment of Hyperthyroidism	Completed	Shiraz University of Medical Sciences	N/A	2007-07-01	The enterohepatic circulation of thyroid hormones is increased in thyrotoxicosis.Bile-salt sequestrants (ionic exchange resins) bind thyroid hormones in the intestine and thereby increase their fecal excretion. Based on these observations, the use of cholestyramine has been tried. The present study evaluates the effect of low doses of cholestyramine as an adjunctive therapy in the management of hyperthyroidism
NCT00725946 ↗	Pilot Study to Determine Radioiodide Accumulation and Dosimetry in Breast Cancers Using 124I PET/CT	Terminated	Stanford University	Early Phase 1	2008-02-01	This is a pilot imaging study for women whose tumors express NIS [Na+I- symporter, sodium iodide symporter]. Eligibility is limited to the presence of strong (3+) and/or plasma membrane staining in > 20% of cells as determined by immunohistochemical methods. A total of 10 patients will be imaged with 124I PET/CT (serial scans over 24 hour period) to determine radioiodide uptake and distribution in tumor tissue. Thyroid iodide uptake and retention will be blocked beginning one week prior to 124I PET/CT scan with thyroid hormone (T3) and methimazole (impedes organification). Tumor, organ and whole body dosimetry will be calculated in each patient.

Clinical Trial Conditions for methimazole

Condition Name

Condition Name for methimazole
Intervention	Trials
Graves Disease	8
Graves' Disease	4
Hyperthyroidism	2
Graves Ophthalmopathy	2

Condition MeSH

Condition MeSH for methimazole
Intervention	Trials
Graves Disease	14
Hyperthyroidism	7
Graves Ophthalmopathy	5
Eye Diseases	4

Clinical Trial Locations for methimazole

Trials by Country

Trials by Country for methimazole
Location	Trials
United States	10
Denmark	4
China	4
Malaysia	3
Iran, Islamic Republic of	2

Trials by US State

Trials by US State for methimazole
Location	Trials
California	2
Texas	1
Ohio	1
New Mexico	1
Florida	1

Clinical Trial Progress for methimazole

Clinical Trial Phase

Clinical Trial Phase for methimazole
Clinical Trial Phase	Trials
PHASE2	1
Phase 4	5
Phase 3	3

Clinical Trial Status

Clinical Trial Status for methimazole
Clinical Trial Phase	Trials
Completed	11
Not yet recruiting	4
Terminated	3

Clinical Trial Sponsors for methimazole

Sponsor Name

Sponsor Name for methimazole
Sponsor	Trials
University of Pisa	2
Odense University Hospital	2
Shiraz University of Medical Sciences	1

Sponsor Type

Sponsor Type for methimazole
Sponsor	Trials
Other	32
Industry	1
NIH	1

Last updated: July 25, 2026

THIMAZOLE Clinical Trials Update, Market Analysis & Forecast (2026) Methimazole is an established generic antithyroid drug with no meaningful patent-led exclusivity tail. Current commercial dynamics are driven by (1) prevalence of Graves’ disease and toxic multinodular goiter, (2) generic pricing, (3) supply and manufacturing reliability, and (4) ongoing physician preference for established oral dosing regimens. Clinical development activity is largely limited to formulation, bioequivalence, and comparative/observational studies rather than new molecular entities.

What is the current clinical trials landscape for methimazole?

Direct development pipeline visibility for methimazole is low because methimazole is long off innovative patent protection in most markets and marketed as multiple immediate-release generics. Public clinical trials tend to be:

• Bioequivalence and formulation comparisons for new generics (FDA-oriented).
• Comparative effectiveness studies among antithyroid approaches.
• Observational registries around safety and thyroid outcomes in special populations (pregnancy/offspring monitoring, pediatrics, and comorbidities).

Key implication for strategy: trial activity around methimazole is less likely to support market differentiation via new indications and more likely to support market entry via product lifecycle extension tactics (strength range, dosing convenience, stability, and patient adherence).

Which trial types dominate methimazole studies?

• Bioequivalence and formulation optimization
  • Often oral solid dose comparisons (tablet strength, excipient systems, dissolution profiles).
• Clinical comparative studies
  • Studies comparing antithyroid drug strategies, monitoring frequency, and safety management rather than testing methimazole against a new drug class.
• Special population monitoring
  • Thyroid function endpoints, adverse event rates (agranulocytosis, hepatotoxicity), and monitoring protocols.

What endpoints and safety signals show up most often?

Common endpoints in observational and comparative work:

• Time to achieve euthyroidism (TSH suppression reversal, Free T4 and Free T3 normalization).
• Relapse rates after dose reduction or discontinuation.
• Adverse events:
  • Agranulocytosis monitoring triggers and incidence.
  • Hepatic injury signals and management thresholds.
  • Minor rash and gastrointestinal intolerance rates.

What market factors drive methimazole demand by indication?

Demand is driven by treated hyperthyroidism incidence, primarily:

• Graves’ disease
• Toxic multinodular goiter
• Toxic adenoma
• Off-label use and bridging therapy where clinicians use antithyroid drugs to stabilize thyroid status before definitive therapy (radioiodine or surgery).

How do guideline patterns shape prescribing?

Clinical practice is shaped by:

• Initial disease control needs (normalize thyroid hormones before definitive therapy).
• Monitoring tolerance and safety protocols.
• Radioiodine and surgical referral patterns.

Commercial takeaway: methimazole demand follows thyroid disease epidemiology more than it follows differentiated pharma marketing.

Where does methimazole sit in the competitive set?

Methimazole competes with:

• Propylthiouracil (PTU): used more selectively, especially in specific clinical contexts (including pregnancy protocols in guideline frameworks).
• Radioiodine and thyroidectomy: substitute demand when used as definitive treatments earlier rather than as later-stage options.
• Other antithyroid generics at equivalent dosing strengths.

How strong is the Orange Book and patent estate for methimazole?

Methimazole is a generic antithyroid without a meaningful, enforceable innovation patent estate supporting long-term exclusivity. Product differentiation is typically excipient and manufacturing-specification based.

Practical effect: market power is concentrated in supply chain reliability and price positioning, not patent exclusivity.

What does this mean for exclusivity and entry barriers?

• No durable regulatory exclusivity for the active substance is expected because methimazole is established.
• Entry barriers are mostly CMC, bioequivalence, and inspection outcomes, not IP.

When do methimazole products lose exclusivity and can generics launch immediately?

Generics are already standard-of-care for methimazole globally. For new entrants, the relevant question is not “loss of exclusivity” but:

• Whether a specific branded product has any remaining exclusivity-like protections (rare for this molecule).
• Whether the planned product is tied to a specific FDA listing with unique labeling or specific dosing formats.

Commercial reality: new generic launches typically require FDA bioequivalence work and listing compliance rather than Paragraph IV litigation.

Is there Paragraph IV litigation risk for methimazole generics?

Paragraph IV risk is typically low for methimazole because:

• Most Abbreviated New Drug Applications (ANDAs) for methimazole are for products where patent disputes are not central.
• The IP landscape is mature and largely settled.

Business takeaway: competitive disputes are more likely to be supply, quality, and pricing driven.

What is the biosimilar or biologics risk for methimazole?

Not applicable. Methimazole is a small-molecule antithyroid drug, not a biologic.

What formulations are used commercially, and what formulation IP barriers exist?

Commercially, methimazole is sold as immediate-release oral tablets in various strengths. Formulation barriers are generally:

• Bioequivalence requirements for generic tablets.
• Stability and dissolution specifications tied to quality systems.
• Manufacturing capacity and batch release performance.

Do reformulations create meaningful market advantages?

For methimazole, reformulations usually do not create sustained pricing power because:

• Therapeutic equivalence is expected.
• Substitution is common when payers manage generics.

How does methimazole compare with propylthiouracil (PTU) in market role?

Methimazole is generally the default antithyroid option in many non-pregnancy clinical contexts in standard practice frameworks, while PTU is used more selectively based on clinical scenario.

Competitive implication: methimazole has broader utilization, but PTU can still capture share in specific patient subsets governed by guideline-based safety considerations.

What does the methimazole commercial forecast look like through 2027?

Base-case forecast: modest growth with pricing pressure, because:

• The market is mature and generic.
• Demand grows with thyroid disease prevalence and treatment coverage, but unit prices trend downward.
• Volume can rise modestly even as revenue growth stays limited.

Revenue drivers and headwinds

• Drivers
  • Increasing diagnosis rates of thyroid dysfunction.
  • Ongoing treatment continuity for Graves’ disease over multi-month horizons.
  • Stabilization needs before radioiodine/surgery.
• Headwinds
  • Generic price compression.
  • Tighter procurement and payer substitution rules.
  • Manufacturing disruptions that can cause temporary shortages but not sustainable revenue uplift.

Scenario structure (no patent-driven uplift)

• Base case: steady volume, low single-digit revenue growth, continuing net price decline.
• Upside: temporary supply constraints widen margin briefly; contract wins by higher-availability manufacturers.
• Downside: further price compression and increased procurement-driven switching to lowest-cost suppliers.

Which companies control supply and how does that affect pricing?

Because methimazole is generic, the market can be concentrated by:

• Companies with stable manufacturing throughput and consistent lot release.
• Firms with broader distribution network coverage and payer contracting success.
• Suppliers with lower incidence of FDA warning letters or consent decrees tied to manufacturing compliance.

Effect on pricing: in periods of supply stress, margin can improve for compliant manufacturers. In normal conditions, price returns toward competitive equilibrium.

What generic entry risks exist for methimazole tablets?

Key risks are not IP, but operational:

• AND A approval delays
• Bioequivalence batch failures
• Manufacturing inspection outcomes
• Stability/dissolution issues during scale-up
• Labeling inconsistencies and supply chain constraints

What FDA regulatory status matters most for methimazole products?

For generic methimazole tablets, regulatory considerations that affect market access:

• Abbreviated approval and bioequivalence to a listed reference.
• Ongoing compliance with cGMP and post-approval changes.
• Lot release and supply continuity.

Commercial consequence: products with superior regulatory/CMC performance tend to retain shelf placement and payer access.

Key Takeaways

• Methimazole is a mature generic antithyroid drug where clinical trial activity is largely formulation, bioequivalence, and observational safety/outcomes work.
• Demand is driven by Graves’ disease and toxic hyperthyroidism epidemiology plus bridging needs before definitive therapy.
• The patent estate and exclusivity tail are not the basis for market power; competitive advantage is supply reliability, quality performance, and pricing execution.
• Forecast through 2027 is most consistent with modest revenue growth and ongoing price compression.
• Entry barriers for new suppliers are primarily regulatory/CMC and distribution contracting, not Paragraph IV litigation or exclusivity fights.

FAQs

1. Do methimazole clinical trials focus on efficacy, safety, or formulation?
   Most public activity clusters around safety monitoring protocols, clinical outcomes in observational cohorts, and formulation/bioequivalence studies for generic products.

2. What are the most common clinical endpoints reported for methimazole-treated patients?
   Thyroid hormone normalization (Free T4/Free T3 and TSH trends), time-to-euthyroidism, and relapse after dose reduction, alongside adverse event incidence.

3. Is methimazole used as a bridge therapy before radioiodine or surgery?
   Yes, commonly to control thyroid status prior to definitive management, which supports baseline volume even in mature markets.

4. Are patents a meaningful barrier to new methimazole generic launches?
   Typically not; barriers are more operational (bioequivalence, manufacturing quality, inspection outcomes) than IP-driven.

5. How do supply shortages influence methimazole pricing and access?
   Shortages can temporarily improve pricing and contract leverage for compliant manufacturers, but competitive equilibrium generally returns once supply normalizes.

---

References (APA)

1. FDA Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations. U.S. Food and Drug Administration. https://www.accessdata.fda.gov/scripts/cder/daf/
2. ClinicalTrials.gov. Methimazole. National Library of Medicine. https://clinicaltrials.gov/
3. American Thyroid Association (ATA) Guidelines and publications on management of hyperthyroidism and Graves’ disease. https://www.thyroid.org/