CLINICAL TRIALS PROFILE FOR LEVOTHYROXINE SODIUM

505(b)(2) Clinical Trials for levothyroxine sodium

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
New Formulation	NCT04037748 ↗	Bioequivalence of Two Formulations of Levothyroxine Sodium 200 Micrograms (mcg) Under Tablet Form	Completed	Merck Healthcare KGaA, Darmstadt Germany, an affiliate of Merck KGaA, Darmstadt, Germany	Phase 1	2019-06-25	The study was to verify if the test formulation of Levothyroxine sodium presents an equivalent rate and extension of absorption to the comparator formulation when administered with the same dosage and under fasting conditions and after baseline correction concentrations.
New Formulation	NCT04037748 ↗	Bioequivalence of Two Formulations of Levothyroxine Sodium 200 Micrograms (mcg) Under Tablet Form	Completed	Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany	Phase 1	2019-06-25	The study was to verify if the test formulation of Levothyroxine sodium presents an equivalent rate and extension of absorption to the comparator formulation when administered with the same dosage and under fasting conditions and after baseline correction concentrations.

All Clinical Trials for levothyroxine sodium

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00311987 ↗	Study of 3,5-Diiodothyropropionic Acid (DITPA) in Hypercholesterolemic Patients	Terminated	Johns Hopkins University	Phase 1/Phase 2	2006-04-01	The natural thyroid hormones, thyroxine (T4) and triiodothyronine (T3), are known to have a cholesterol-lowering effect. Their pharmacologic use for this purpose is limited, however, by their actions on other organs, including the heart, bone, and brain, where there can be side effects of excessive thyroid hormone action. 3,5-diiodothyropropionic acid (DITPA) is a thyroid hormone analog with relative selectivity for a form of the thyroid hormone receptor expressed in the liver, where it regulates several aspects of lipid metabolism, including the clearance of low-density lipoprotein (LDL) cholesterol. This study is designed to determine whether DITPA is safe and effective in achieving LDL cholesterol levels that are consistent with the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) guidelines in patients who have not achieved those levels on conventional therapy, due to drug-resistant disease, drug intolerance, or both. This is a single-center, randomized, double-blind, placebo-controlled study. Following a 4-week Pre-Randomization Phase with dietary counseling and a 2-week placebo run-in, eligible patients will be randomized (1:1:1) to receive DITPA (90 mg/day, 180 mg/day), or placebo for a total treatment duration of 12 weeks. Sixty (60) patients will be randomized to 1 of 3 treatment groups in a 1:1:1 ratio (i.e., 20 patients per treatment group): - DITPA at 90 mg/day (45 mg twice a day [BID] taken orally) - DITPA at 180 mg/day (90 mg BID taken orally) - Placebo (BID taken orally) Those patients randomized to receive DITPA at 90 mg/day will receive 45 mg/day for the first 2 weeks, followed by 90 mg/day for 10 weeks. Those patients randomized to receive DITPA at 180 mg/day will receive 45 mg/day for the first 2 weeks, followed by 90 mg/day for the next 2 weeks, and then 180 mg/day for 8 weeks.
NCT00647855 ↗	Fasting Study of Levothyroxine Sodium Tablets 300 μg to Synthroid® Tablets 300 μg	Completed	Mylan Pharmaceuticals	Phase 1	2003-05-01	The objective of this study was to investigate the bioequivalence of Mylan's levothyroxine sodium 300 μg tablets to Abbott's Synthroid® 300 μg tablets following a single 600 μg (2 x 300 μg) dose administered in healthy volunteers under fasting conditions. Single-dose pharmacokinetic parameters for baseline corrected total L-thyroxine and non-baseline corrected total L-triiodothyronine were calculated using noncompartmental techniques.
NCT00648557 ↗	Fasting Study of Levothyroxine Sodium Tablets 200 mg to Synthroid Tablets 200 mg	Completed	Mylan Pharmaceuticals	Phase 1	2003-01-01	The objective of this study was to investigate the bioequivalence of Mylan's levothyroxine sodium 200 μg tablets to Abbott's Synthroid® 200 μg tablets following a single 600 μg (3 x 200 μg) dose administration in healthy volunteers under fasting conditions. Twenty-nine healthy, non-smoking, subjects between the ages of 18 and 47 completed this open-label, randomized, two-period, two-treatment, single-dose crossover study conducted by Dr. James D. Carlson at PRACS Institute, Ltd., Fargo, ND. Statistical analysis of the data revealed that 90% confidence intervals were within the acceptable bioequivalent range of 80% and 125% for the natural log transformed parameters LNAUC0-48hr and LNCPEAK for baseline corrected total L-thyroxine. This study demonstrated that Mylan's 200 μg levothyroxine sodium tablets are bioequivalent to Abbott's Synthroid® 200 μg tablets following a single, oral 600 μg (3 x 200 μg) dose under fasting conditions
NCT00648700 ↗	Fasting Study of Levothyroxine Sodium Tablets 300 μg to Levothroid® Tablets 300 μg	Completed	Mylan Pharmaceuticals	Phase 1	2005-08-01	The objective of this study was to investigate the bioequivalence of Mylan's levothyroxine sodium 300 μg tablets to Lloyd's Levothroid® 300 μg tablets following a single 600 μg (2 x 300 μg) dose administered in healthy adult volunteers under fasting conditions. Statistical analysis of the data revealed that 90% confidence intervals were within the acceptable bioequivalent range of 80% and 125% for the natural log transformed parameters LNAUC0-48hr and LNCPEAK for baseline corrected total levothyroxine.
NCT00648882 ↗	Fasting Study of Levothyroxine Sodium Tablets 300 Mcg to Synthroid® Tablets 300 Mcg	Completed	Mylan Pharmaceuticals	Phase 1	2007-03-01	The objective of this study was to investigate the bioequivalence of Mylan's levothyroxine sodium 300 mcg tablets to Abbott's Synthroid® 300 mcg tablets following a single, oral 600 mcg dose (2 × 300 mcg) administered under fasting conditions.
NCT00921050 ↗	Subclinical Hypothyroidism and Mind in the Elderly	Completed	Universidad Autonoma de Nuevo Leon	Phase 2/Phase 3	2009-06-01	Some recommendations of expert consensus on subclinical hypothyroidism (SH) are controversial in those areas with not enough information to reach a conclusion, such as not recommending treatment with thyrotrophic hormone of 4-10 mUI/L and free thyroxin in normal range. The body changes or symptoms at this stage are often mistaken as aging. There are studies showing significant changes in heart (slow rate, lower ejection fraction, diastolic dysfunction); hypercholesterolemia, dysfunction cognitive abilities (memory attention…). The prevalence of SH increases with age, reaching 14% over 65 years old. This age group increase as the population ages highlights the need for evidence to improve recommendations for the elderly. NEUROPSI is a validated neuropsychological test sensible for mild cognitive alterations. It can be applied to individuals with little schooling. This study aims to determine positive change in cognitive abilities (NEUROPSI), ejection fraction, and body percent of lean and adipose tissue without adverse effects, placebo versus thyroxin supplement to keep thyroid-stimulating hormone (TSH) between 0.5-2.5 mUI/L in elderly with TSH 4-10 mIU/L.

Clinical Trial Conditions for levothyroxine sodium

Condition Name

Condition Name for levothyroxine sodium
Intervention	Trials
Healthy	10
Hypothyroidism	5
Thyroid Disease	1
Hypothyroidism;Postablative	1

Condition MeSH

Condition MeSH for levothyroxine sodium
Intervention	Trials
Hypothyroidism	8
Thyroid Diseases	3
Diabetes Mellitus, Type 2	1
Poisoning	1

Clinical Trial Locations for levothyroxine sodium

Trials by Country

Trials by Country for levothyroxine sodium
Location	Trials
United States	19
China	4
Brazil	2
Colombia	1
Mexico	1

Trials by US State

Trials by US State for levothyroxine sodium
Location	Trials
California	4
North Dakota	4
District of Columbia	2
Maryland	2
Pennsylvania	1

Clinical Trial Progress for levothyroxine sodium

Clinical Trial Phase

Clinical Trial Phase for levothyroxine sodium
Clinical Trial Phase	Trials
PHASE1	1
Phase 4	8
Phase 2/Phase 3	1

Clinical Trial Status

Clinical Trial Status for levothyroxine sodium
Clinical Trial Phase	Trials
Completed	13
Recruiting	6
Not yet recruiting	3

Clinical Trial Sponsors for levothyroxine sodium

Sponsor Name

Sponsor Name for levothyroxine sodium
Sponsor	Trials
Mylan Pharmaceuticals	4
IBSA Institut Biochimique SA	2
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)	2

Sponsor Type

Sponsor Type for levothyroxine sodium
Sponsor	Trials
Other	27
Industry	16
NIH	3

Levothyroxine Sodium Clinical Trials Update, Market Analysis, and 2030 Forecast: Patent/Generic and Competitive Landscape

Last updated: July 26, 2026

Levothyroxine sodium is a mature, high-volume thyroid hormone replacement with ongoing incremental trials focused on dosing strategies, formulation performance (brand vs. generic comparability), and special populations. The U.S. market is dominated by longstanding brands and multiple authorized generics, with competition driven by bioequivalence, payer contracting, and interchangeability rather than new mechanism breakthroughs. Projected growth through 2030 is tied mainly to population aging, thyroid disorder prevalence, and continued penetration of lower-cost multisource products.

What is the clinical trial landscape for levothyroxine sodium in 2024-2026?

The clinical trials footprint for levothyroxine sodium is largely incremental: bioequivalence, formulation behavior (tablet disintegration/dissolution, absorption under food or gastric conditions), adherence/persistence studies, and observational effectiveness or safety work in hypothyroid subtypes and comorbidities (pregnancy, bariatric surgery, GI disease).

What are the dominant trial types?

• Bioequivalence and formulation performance: comparative studies among brand and generic levothyroxine tablets, softgels, and liquid presentations where available.
• Dosing optimization: once-daily consistency, titration algorithms, and dose conversion practices after switching formulations.
• Absorption modifiers: studies addressing simultaneous ingestion with PPIs, calcium/iron, bile acid sequestrants, and changes after GI surgeries.
• Special populations: pregnancy monitoring schedules, postpartum dose adjustments, elderly tolerability, and pediatric titration.

What endpoints are typically used?

• TSH suppression and normalization with time-matched pharmacodynamic assessments.
• Free T4 response and stability of biochemical control.
• Adherence metrics (missed doses, persistence) and real-world regimen adherence proxies.
• Pharmacokinetics in BE studies: Cmax/AUC of levothyroxine.

Where do trials usually run?

• Multi-center sites for BE and food-effect studies.
• Endocrinology-heavy recruitment patterns for comparative effectiveness and switch studies.

(No specific trial dataset is provided in the prompt, so this section is limited to the established clinical development pattern for levothyroxine sodium and does not enumerate individual NCTs.)

Which formulations of levothyroxine sodium are in focus (tablet vs softgel vs liquid) and why?

Clinical interest is increasingly concentrated on delivery formats that can reduce variability in absorption and address real-world challenges where patients take levothyroxine with food or interacting medications.

Tablets

• Largest market footprint.
• High confidence in therapeutic effect after stable dosing.
• Main differentiators in practice are manufacturing controls and switch stability.

Softgels and liquids

• Target improved consistency in absorption, particularly in patients with GI comorbidities or those requiring morning dosing changes.
• Trials and postmarketing evaluations often emphasize reduction in absorption variability and stabilization of TSH.

Switching and interchangeability

• A recurring clinical theme is the risk of TSH excursions after switching between products, even with BE.
• Studies often measure “switch outcomes” in the first 6 to 12 weeks after transition, when dose recalibration is most likely.

How do levothyroxine sodium absorption studies affect clinical outcomes?

Absorption variability drives a meaningful portion of real-world hypothyroidism control issues, shaping both clinical trial design and payer/labeling policies.

Common absorption problem scenarios studied

• Food co-administration (breakfast timing effects).
• PPI use (reduced gastric acidity can affect dissolution and absorption).
• Calcium and iron supplements (chelation interactions).
• Bile acid sequestrants (binding).
• Celiac disease and inflammatory GI disease (malabsorption patterns).
• Bariatric surgery (anatomical and physiological changes).

How trials translate into practice

• Clinicians often use TSH targets and retitration schedules after interacting medication changes or formulation switches.
• Trials typically support more structured monitoring windows (early TSH check and follow-up titration).

What is the levothyroxine sodium market size, growth drivers, and demand outlook through 2030?

Levothyroxine sodium is a volume product: a stable, long-term treatment for hypothyroidism and thyroid hormone replacement after thyroidectomy. Growth is driven by incidence and aging demographics rather than clinical breakthrough.

Growth drivers

• Population aging: higher prevalence of hypothyroidism and autoimmune thyroid disease.
• Incidence of thyroid cancer treatment: post-surgical hypothyroidism replacement.
• Pregnancy and pediatric demand: ongoing need for careful dosing and monitoring.
• Chronic disease management: long duration therapy creates baseline demand stability.

Downside and constraints

• Generic erosion continues across strengths and dosage forms.
• Payer formularies prioritize lowest-cost options with maintained coverage.
• Therapy substitution (brand-to-generic switches) can lead to short-term monitoring costs that may affect real-world adherence and physician behavior.

2030 projection framework (what drives the forecast)

A credible 2030 projection is typically built from:

• Baseline patient pool for hypothyroidism and post-thyroidectomy replacement
• Switching rates across brands and multisource products
• Average selling price pressure as authorized generics expand
• Mix shift between tablets and alternative formats where available

(No numeric market share or dollar figures are included because the prompt does not supply source data and the response is constrained to avoid fabricating proprietary estimates.)

How does levothyroxine sodium price erosion impact revenue projections?

Revenue exposure is mainly a function of ASP compression and volume retention. For mature therapies:

• Generics typically reduce net revenue per tablet.
• Mix shift can occur toward lower-cost authorized generics.
• Wholesale and pharmacy network contracting can drive rapid price convergence.

Revenue projection mechanics used by market teams

• Estimate total units from patient demand trends.
• Apply expected ASP decline from competitive bidding and generic entries.
• Model shift in share between:
  • original brands
  • authorized generics
  • OTC/alternatives where applicable
  • specialty formats (if premium pricing persists)

What patents protect levothyroxine sodium in the U.S., and when do they expire?

Levothyroxine sodium itself is not a new molecular entity and the core API is off-patent in most major markets. Market competition is shaped by:

• legacy patents that may have expired
• formulation-specific patents for particular delivery formats
• method-of-use or dosing regimen patents where still active
• manufacturing process and stability patents that can extend market exclusivity for certain products

Where patent protection usually matters in levothyroxine today

• Formulation patents for softgel/liquid variants where relevant
• Manufacturing process patents affecting stability or bioavailability
• Coloring, coatings, excipients, and dissolution profile claims

How the patent estate affects commercial risk

• When the API is off-patent, legal strategy focuses on product-specific patents.
• Payer and prescriber behavior tends to neutralize premium pricing once multisource access expands.

(A full patent list and expiration timeline cannot be produced from the prompt alone without specific brand/product identifiers and Orange Book data.)

What is the Orange Book status of levothyroxine sodium products and generics?

Levothyroxine sodium has many listed products and multiple strengths. Orange Book status is typically dominated by:

• drug substance and drug product listings with long-expired exclusivities
• residual formulation/manufacturing listings for select presentations

Why Orange Book status is still relevant

• It identifies what patents are listed for each strength and product.
• It drives Paragraph IV challenge risk for the specific NDA/NDC, not the API globally.

(No product-level NDC/NDA identifier is provided, so an accurate Orange Book table with patents, expiration dates, and MAH assignments is not possible here.)

What generic entry risks exist for levothyroxine sodium?

Generic entry risk is generally lower than for new drugs, but it remains meaningful at the presentation and strength level, especially for:

• alternative formats where a premium product exists
• products with ongoing formulation-related patent listings
• any product with unexpired formulation or manufacturing patents

What would trigger new entry or litigation

• FDA approval of additional ANDAs for specific NDCs
• Patent listings that support or deny eligibility for certain generics
• Court outcomes affecting exclusivity for a specific formulation

How does levothyroxine sodium compare with competitors (liothyronine, desiccated thyroid, and combination therapies)?

Competitive substitution pressure is shaped by guideline preferences, tolerability profiles, and payer coverage.

Standard comparator: liothyronine (T3)

• Often used as an adjunct rather than monotherapy in practice.
• Different PK and clinical monitoring needs.

Desiccated thyroid extract

• Continued use in some segments.
• Quality and dosing variability concerns drive guideline-recommended caution.

Combination therapy (T4/T3)

• Clinical evidence is mixed.
• Interest persists, but most care pathways continue to rely on levothyroxine as first-line.

Practical impact on levothyroxine market

• Unless combination therapy gains broader guideline/payer adoption, levothyroxine maintains market dominance.

What dosing and patient management developments are most likely to change prescribing through 2030?

Prescribing is influenced by practical management rather than new pharmacology.

Likely changes

• More structured TSH monitoring after:
  • switching manufacturers
  • starting/stopping PPIs and supplements
  • pregnancy and postpartum transitions
  • bariatric and malabsorptive procedures
• Gradual adoption of alternative formats where they demonstrably improve stability for subgroups.

What does not typically change

• Levothyroxine remains the reference standard due to dosing predictability and clinician familiarity.

Key Takeaways

• Levothyroxine sodium clinical development is dominated by incremental BE, absorption interaction, and special-population studies focused on biochemical stability (TSH/free T4).
• Market growth through 2030 is expected to be driven mainly by aging and chronic hypothyroidism prevalence, with revenue constrained by ongoing generic ASP erosion.
• Product differentiation is increasingly about formulation and switch stability rather than new mechanism innovation.
• Patent and Orange Book strategy is product- and formulation-specific; broad API exclusivity is largely not the driver in mature competition.

FAQs

1. What is the most common clinical trial endpoint used for levothyroxine sodium formulations?
   TSH normalization and free T4 response, with PK endpoints (Cmax/AUC) in bioequivalence studies.

2. Do levothyroxine softgel or liquid formulations have evidence for reduced variability?
   Clinical focus centers on improved absorption consistency, particularly in patients with absorption modifiers and adherence constraints.

3. How often should TSH be rechecked after switching levothyroxine products?
   Trials and clinical practice typically concentrate retesting in the early post-switch period (commonly within weeks) followed by titration to target.

4. How do PPIs, calcium, and iron influence levothyroxine sodium absorption and trial design?
   They drive food and interaction studies and influence structured monitoring and dosing separation protocols.

5. What drives levothyroxine sodium market share among generics and authorized generics?
   Contracting, formulary placement, price, and perceived switch stability at the NDC/strength level.

References

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. FDA. Bioequivalence Studies. Guidance for Industry. U.S. Food and Drug Administration. https://www.fda.gov/