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
Hypothyroidism;Postablative	1
Thyroid; Functional Disturbance	1

Condition MeSH

Condition MeSH for Levothyroxine Sodium
Intervention	Trials
Hypothyroidism	8
Thyroid Diseases	3
Substance Withdrawal Syndrome	1
Kidney Diseases	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
Belgium	1
Argentina	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
North Carolina	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
University of California, Irvine	2
Tecnoquimicas	2

Sponsor Type

Sponsor Type for Levothyroxine Sodium
Sponsor	Trials
Other	27
Industry	16
NIH	3

Levothyroxine Sodium: Clinical Trials Update, Market Analysis, and Projection

Last updated: April 27, 2026

What is levothyroxine sodium’s clinical and regulatory landscape?

Levothyroxine sodium is a long-established synthetic thyroid hormone used to treat hypothyroidism and other thyroid-related indications. As an active, commodity-class therapy, the clinical-trials pipeline is dominated by:

• Line extensions tied to formulation/absorption (not new molecular entities).
• Bioequivalence and pharmacokinetic studies across manufacturers and dosing forms.
• Special population studies (pediatrics, pregnancy, switching).

Because levothyroxine is widely available as generics and branded products, the most investable “clinical updates” in practice are formulation durability, switching outcomes, and controlled trials comparing absorption across newer formulations (including soft-gel and liquid presentations).

What clinical trial activity should investors watch?

Investors typically track three “clinical outcome buckets” for levothyroxine platform plays:

1) Bioavailability and TSH stability after switching

• Comparative PK/PD endpoints often center on TSH time course and achievement of therapeutic ranges after transitions between formulations.
• Real-world adherence and “missed dose” patterns tend to be reflected through comparator designs using controlled dosing regimens.

2) Formulation performance

• Key differentiators are often absorption in the presence of food or GI factors and consistency of systemic exposure.
• Studies frequently evaluate performance versus reference levothyroxine tablets and across administration conditions.

3) Special populations

• Pregnancy: dose titration timing and attainment of target thyroid physiology.
• Pediatrics: growth-linked dosing stability and monitoring intervals.
• Geriatrics: tolerability and biochemical target control.

Representative regulatory evidence base (how dosing is typically justified)

In practice, levothyroxine approvals rely on established efficacy with verification via:

• Bioequivalence (for generics and reformulations)
• Labeling consistent with monograph standards and thyroid function test targets.

For business decisions, trial relevance is judged less by “novel efficacy” and more by whether a formulation improves dose-to-dose exposure consistency and reduces the risk of clinically meaningful TSH drift, especially in switching scenarios.

Which trial types dominate and what endpoints appear most?

Across levothyroxine studies, the repeated endpoint structure is:

• Primary PK endpoints: Cmax and AUC (often with Tmax as secondary).
• PD/clinical endpoints: change in TSH with time to biochemical stabilization.
• Safety endpoints: adverse event rates, vital signs, and thyroid-related symptom reporting.

The practical investor takeaway: trials are designed to show pharmacologic equivalence and biochemical control under real administration constraints, not new disease-modifying biology.

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Levothyroxine Sodium: Market Analysis

How big is the levothyroxine market and what drives demand?

Levothyroxine demand tracks global prevalence of hypothyroidism and, in developed markets, the high share of treated patients. The market is structurally characterized by:

• Patent-expired originators in most geographies.
• Large generic volumes, which compress price growth and shift competition to packaging, availability, and brand/formulation positioning.
• Branded formulation differentiation (where present) built on perceived stability, switching convenience, or adherence.

Supply and price structure

• Generic entry drives market volume but constrains revenue.
• Branded reformulations can defend margins through payer positioning and patient-switching friction.
• Wholesale acquisition cost (WAC) vs net varies materially with rebates and tendering in national systems.

Where is growth most likely to come from?

Given the commodity nature, growth tends to be “share and mix” rather than total category expansion:

1) Formulation mix shift

• Increased adoption of presentations marketed as easier to use or more consistent under non-ideal administration conditions.

2) Switching and persistence

• Patients and clinicians often resist switching due to concern about TSH stability. That creates pockets where formulation-specific products can retain share.

3) Payer and national formulary behavior

• Formularies can temporarily favor specific presentations based on tender cycles or evidence packages (bioequivalence plus patient-focused labeling language).

Competitive landscape: how products win

Competition in levothyroxine is typically won through:

• Availability and supply reliability
• Tender competitiveness for generics
• Brand trust and formulation differentiation for branded presentations
• Ecosystem coverage (pharmacy channel availability, patient support)

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Projections (Revenue and Growth)

What does a realistic projection model look like for levothyroxine sodium?

A viable projection framework for a commodity thyroid hormone reflects three layers:

1) Category volume growth

• Driven by prevalence trends and aging demographics.

2) Net revenue per unit

• Pressured by generic competition and tender pricing.
• Stabilized by mix (branded/formulation share) and channel constraints.

3) Share shift

• Formulation-specific products can capture share where clinicians or payers prefer a particular presentation.

Base-case projection logic used by market models

• Total category growth is typically mid-single-digit in volume terms in many markets.
• Value growth is typically low to mid-single-digit or lower, dominated by price compression offset by mix gains.

What are the key downside and upside drivers?

Upside:

• Sustained uptake of differentiated formulations with strong switching performance data.
• Payer preference for specific presentations due to tender wins.

Downside:

• Aggressive generic pricing in major markets.
• Loss of branded mix through formulary changes or heightened substitution rules.

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Clinical and Commercial Implications

How should R&D teams position levothyroxine programs?

Programs tied to levothyroxine that stay investable generally focus on:

• Demonstrating consistent absorption under realistic administration conditions.
• Reducing switching risk through improved exposure stability.
• Targeting adherence and patient experience with dosing convenience.

How should investors underwrite commercial value?

Underwriting should separate:

• Generic category exposure (volume, tender dynamics, margin compression) from
• Formulation differentiation (share capture, resistance to switching, payer channel fit).

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Key Takeaways

• Levothyroxine sodium’s pipeline is dominated by formulation, bioequivalence, switching, and special population studies rather than novel efficacy.
• Market growth is primarily mix and share with value constrained by generic price compression.
• Commercial upside hinges on whether differentiated presentations improve TSH stability after switching and maintain payer and clinician preference across tender cycles.

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FAQs

1) Are there ongoing late-stage efficacy trials for levothyroxine sodium?

Levothyroxine development typically does not run late-stage “new mechanism” trials; most clinical activity is centered on formulation performance and biochemical control.

2) What endpoints matter most in levothyroxine switching studies?

The most decision-relevant endpoints are changes in TSH over time plus PK comparators such as Cmax and AUC, with follow-up designed to confirm biochemical stabilization.

3) Why does generic substitution impact levothyroxine value?

Generic substitution can shift prescribing away from specific branded presentations, compressing net pricing and reducing differentiated mix.

4) What is the main commercial strategy for differentiated levothyroxine formulations?

Clinicians and payers respond to evidence that a formulation produces consistent exposure and lowers the risk of clinically meaningful TSH drift, particularly during switching.

5) What markets are most sensitive to tender pricing?

Public and quasi-public formularies and countries with centralized procurement are usually more sensitive to tender outcomes than highly fragmented private channels.

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References

[1] World Health Organization. (n.d.). Hypothyroidism and thyroid hormone treatment information. World Health Organization. https://www.who.int/
[2] U.S. Food and Drug Administration. (n.d.). Abbreviated applications and bioequivalence guidance for generic drugs. U.S. FDA. https://www.fda.gov/
[3] European Medicines Agency. (n.d.). Guidance and regulatory framework for bioequivalence and generic medicines. EMA. https://www.ema.europa.eu/
[4] U.S. National Library of Medicine. (n.d.). ClinicalTrials.gov (levothyroxine sodium searches and trial listings). https://clinicaltrials.gov/
[5] American Thyroid Association. (n.d.). Guidelines and patient information on levothyroxine therapy. https://www.thyroid.org/