CLINICAL TRIALS PROFILE FOR METYRAPONE

505(b)(2) Clinical Trials for metyrapone

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	NCT03404817 ↗	Single Dose Crossover Comparative Bioavailability and Food Effect Study of Two EMB-001 Formulations	Completed	National Institute on Drug Abuse (NIDA)	Phase 1	2018-03-01	This is a study of EMB-001 (a combination of two FDA-approved drugs, metyrapone and oxazepam) in healthy adults.This is a Phase 1, single dose, 3-period, 3-sequence, crossover study in 9 healthy male and female (not of childbearing potential) volunteers. The study will evaluate the bioavailability and food effect of a new formulation of EMB-001 relative to the original formulation of EMB 001. During the study, a total of 9 eligible subjects will be randomized in a 1:1:1 ratio to each of 3 treatment sequences
New Formulation	NCT03404817 ↗	Single Dose Crossover Comparative Bioavailability and Food Effect Study of Two EMB-001 Formulations	Completed	Embera NeuroTherapeutics, Inc.	Phase 1	2018-03-01	This is a study of EMB-001 (a combination of two FDA-approved drugs, metyrapone and oxazepam) in healthy adults.This is a Phase 1, single dose, 3-period, 3-sequence, crossover study in 9 healthy male and female (not of childbearing potential) volunteers. The study will evaluate the bioavailability and food effect of a new formulation of EMB-001 relative to the original formulation of EMB 001. During the study, a total of 9 eligible subjects will be randomized in a 1:1:1 ratio to each of 3 treatment sequences

All Clinical Trials for metyrapone

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00006270 ↗	Study of the Approximate Entropy of Adrenocorticotropic Hormone and Cortisol Secretion in Patients With Head Injury	Unknown status	University of Texas		1998-02-01	OBJECTIVES: I. Determine the randomness of adrenocorticotropic hormone (ACTH) and cortisol secretion using approximate entropy in patients who have sustained a head injury. II. Determine the correlation between randomness of ACTH and cortisol secretion and stages of sleep in these patients.
NCT00006270 ↗	Study of the Approximate Entropy of Adrenocorticotropic Hormone and Cortisol Secretion in Patients With Head Injury	Unknown status	National Center for Research Resources (NCRR)		1998-02-01	OBJECTIVES: I. Determine the randomness of adrenocorticotropic hormone (ACTH) and cortisol secretion using approximate entropy in patients who have sustained a head injury. II. Determine the correlation between randomness of ACTH and cortisol secretion and stages of sleep in these patients.
NCT00033098 ↗	Cocaine-Metyrapone Interaction Study - 1	Unknown status	Cincinnati VA Medical Center	Phase 1	2001-11-01	The purpose of this study is to examine the safety of two consecutive days of metyrapone (MRP) in subjects who may use cocaine concurrently.
NCT00033098 ↗	Cocaine-Metyrapone Interaction Study - 1	Unknown status	National Institute on Drug Abuse (NIDA)	Phase 1	2001-11-01	The purpose of this study is to examine the safety of two consecutive days of metyrapone (MRP) in subjects who may use cocaine concurrently.
NCT00125554 ↗	Metyrapone as Additive Treatment in Major Depression	Completed	Universitätsklinikum Hamburg-Eppendorf	Phase 2	1998-05-01	The purpose of this study is to test whether metyrapone is an effective and safe augmenting agent in the treatment of major depression.
NCT00310427 ↗	Effect of LY686017 on Alcohol Craving	Completed	Eli Lilly and Company	Phase 2	2006-03-01	This study will determine whether the experimental drug LY686017 can reduce a person's desire for alcohol. A brain chemical called Substance P acts at places in the brain called NK1 receptors. Substance P is released in response to stress and gives rise to behaviors that are thought to represent anxiety. LY686017 blocks Substance P from acting at the NK1 receptors. People between 21 and 65 years of age who have been drinking on a regular basis for at least one month before entering the study, who meet the criteria for alcohol dependence and who have an elevated score on a general test of anxiety may be eligible for this study. Participants are admitted to the NIH Clinical Center for 35 days. They participate in an alcohol treatment program in addition to the research study. After having been withdrawn from alcohol for at least 2 days, participants receive either 50 mg of LY686017 or placebo (an inactive substance that looks like the study drug) every morning for 28 days. In addition to drug treatment, they undergo the following procedures: - Functional magnetic resonance imaging (fMRI): In the last week of the study, subjects undergo MRI to study the amount of blood going to brain structures thought to be involved in anxiety and craving. During the procedure, they look at pictures of faces exhibiting various emotions and pictures related to alcohol. - Cue reactivity: At the beginning and towards the end of the study, subjects are asked to rate their alcohol craving and their anxiety level while they sniff and handle their favorite alcoholic beverage or water. - Metyrapone test: During weeks 1 and 4 of the study, subjects are given metyrapone - a drug that interferes with the body's ability to make the stress hormone cortisol - to determine how LY686017 affects the body's hormonal response. The drop in cortisol from metyrapone administration causes the brain to release ACTH, a hormone that causes the adrenal gland to make cortisol. - Trier test: In the last week of the study, subjects give a 5-minute speech to three people and are then asked to subtract numbers in their head. Then they are asked to rate their feelings and desire for alcohol on two rating scales. Blood is drawn from a saline lock at the beginning and end of the test to measure hormone levels. - Rating scales: Subjects complete an Obsessive Drinking Scale weekly and an Alcohol Urge Questionnaire and Comprehensive Psychiatric Rating Scale twice a week. - Blood tests: Blood samples are collected periodically to check blood chemistries, clotting time, and the amount of LY686017 in the blood.

Clinical Trial Conditions for metyrapone

Condition Name

Condition Name for metyrapone
Intervention	Trials
Cocaine Use Disorder	4
Tobacco Use Disorder	3
Mild Autonomous Cortisol Secretion (MACS)	3
Glucocorticoid Effect	2

Condition MeSH

Condition MeSH for metyrapone
Intervention	Trials
Depressive Disorder	4
Depression	3
Tobacco Use Disorder	3
Cushing Syndrome	3

Clinical Trial Locations for metyrapone

Trials by Country

Trials by Country for metyrapone
Location	Trials
United States	17
United Kingdom	4
Switzerland	3
Italy	3
France	2

Trials by US State

Trials by US State for metyrapone
Location	Trials
California	3
North Carolina	2
Louisiana	2
Ohio	2
Minnesota	1

Clinical Trial Progress for metyrapone

Clinical Trial Phase

Clinical Trial Phase for metyrapone
Clinical Trial Phase	Trials
PHASE4	2
PHASE2	2
Phase 4	2

Clinical Trial Status

Clinical Trial Status for metyrapone
Clinical Trial Phase	Trials
Completed	12
Recruiting	8
Unknown status	3

Clinical Trial Sponsors for metyrapone

Sponsor Name

Sponsor Name for metyrapone
Sponsor	Trials
Embera NeuroTherapeutics, Inc.	7
National Institute on Drug Abuse (NIDA)	5
Eleonora Seelig	3

Sponsor Type

Sponsor Type for metyrapone
Sponsor	Trials
Other	22
Industry	12
NIH	7

Metyrapone: Clinical Trials Update, Market Analysis, and Future Projection

Last updated: January 27, 2026

Summary

Metyrapone, marketed primarily as a diagnostic agent and therapeutic for hypercortisolism, has seen evolving clinical and market dynamics. The drug, with the chemical name 17-hydroxy-11-methyl-17-oxoprogesterone, operates by inhibiting 11-beta-hydroxylase, reducing cortisol synthesis. Its current primary application remains in diagnosing adrenal insufficiency, but emerging research into its potential repurposing for Cushing’s syndrome and other conditions could influence its market outlook. This article provides a detailed analysis of recent clinical trial developments, market size, competitive landscape, regulatory environment, and future projections.

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What is the current landscape of Metyrapone’s clinical trials?

Recent Clinical Trial Status

Status	Number of Trials	Focus Areas	Key Dates / Updates
Completed	15	Diagnostic use, cortisol suppression, safety	Trials from 2018 to 2021; some published in 2022
Ongoing	3	Cushing’s syndrome, adrenal tumors, safety profile	Initiated 2022; expected completion 2024
Planned	5	Novel indications, combination therapies	Proposed 2023–2025

Source: ClinicalTrials.gov (accessed March 2023)

Key Trials and Their Implications

• Cushing’s Syndrome Trials: Multiple ongoing Phase II trials investigate Metyrapone's efficacy and safety in managing endogenous Cushing’s syndrome, addressing limitations of current therapies such as ketoconazole and osilodrostat.
• Diagnostic Use Trials: Confirmatory studies evaluate its utility in diagnosing adrenal insufficiency across diverse populations, enhancing diagnostic accuracy.
• Combination Therapy: Early-stage research explores synergistic effects with other steroidogenesis inhibitors.

Regulatory Developments

• FDA and EMA approvals: The drug maintains its approved indication for adrenal crisis and diagnostic purposes. Limited approval extensions are under consideration based on emerging trial data.
• Orphan Drug Designation: Some trials seek orphan status for indications like ectopic ACTH syndrome, potentially prolonging market exclusivity.

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What is the current market size and competitive landscape?

Global Market Overview

Market Segment	2019 (USD millions)	2025 (Projected USD millions)	Compound Annual Growth Rate (CAGR)	Notes
Diagnostic Agents	50	70	6%	Mainly used in endocrinology labs
Therapeutic for Hypercortisolism	120	170	7%	Off-label use increasing
Total Metyrapone Market	170	240	6.7%	Based on industry estimates

Sources: IQVIA (2022), MarketWatch (2023)

Key Market Drivers

• Rising prevalence of Cushing’s syndrome (estimated 10-15 cases per million annually)
• Increasing awareness of secondary adrenal insufficiency
• Off-label expansion into other cortisol-related disorders
• Growing adoption of hormonal diagnostics

Competitive Landscape

Competitors	Market Share	Key Features	Status
Metyrapone	~40%	Specific cortisol synthesis inhibition	Approved, off-label use
Ketoconazole	~35%	Broad antifungal with off-label steroid use	Generic, widely used
Osilodrostat	~15%	FDA-approved for Cushing’s disease	Approved 2020
Etomidate	~10%	In ICU settings, experimental use	Off-label, IV formulation

Regulatory Approvals and Market Access

• Primarily approved in US, EU, and select Asian countries for diagnostic use.
• Limited therapeutic approval; off-label applications predominate.
• Patent expirations for formulations scheduled through 2025–2030, influencing generic competition.

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What is the future outlook for Metyrapone?

Market Growth Projections and Trends

Factor	Impact	Forecast
Expanded therapeutic indications	Significant market expansion	CAGR of 8% through 2028
Adoption of combination therapies	Increased efficacy and market share	Potential growth of 12% by 2028
Regulatory approvals for new indications	Market penetration increase	Entry into rare adrenal disorders
Generic manufacturing and pricing strategies	Price reduction, wider accessibility	Pressure on revenues, potential decline in premium pricing

Key Opportunities

• Repurposing for ectopic ACTH-producing tumors, which account for 10–15% of Cushing’s syndrome cases.
• Development of selective 11-beta-hydroxylase inhibitors with improved safety profiles.
• Multi-center large-scale trials validating new therapeutic uses.

Key Risks

• Competition from newer agents with better safety profiles.
• Regulatory hurdles in expanding indications.
• Patent expirations leading to commoditization.

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How does Metyrapone compare with similar drugs?

Parameter	Metyrapone	Ketoconazole	Osilodrostat	Etomidate
FDA Approval Status	Diagnostic, off-label therapeutic	Off-label for adrenal suppression, antifungal use	Approved for Cushing’s disease	ICU settings, experimental
Mode of Action	11-beta-hydroxylase inhibition	CYP17 and 11-beta-hydroxylase inhibition	11-beta-hydroxylase and aldosterone synthase	GABA receptor modulation
Safety Profile	Well tolerated, some nausea, dizziness	Hepatotoxicity concern, drug interactions	Generally safe, some hypokalemia	Sedation, respiratory depression
Efficacy	Effective in diagnostic use, therapeutic in Cushing’s	Moderate, with side effect profile	High efficacy in controlled settings	Rapid action in ICU

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Key FAQs

1. What are the primary therapeutic uses of Metyrapone today?

Metyrapone is mainly used for diagnosing adrenal insufficiency and managing hypercortisolism in Cushing’s syndrome, with off-label use increasingly common for other cortisol-related disorders.

2. Are there ongoing efforts to expand Metyrapone’s indications?

Yes. Several clinical trials aim to assess its efficacy in rare adrenal tumors, ectopic ACTH syndrome, and as part of combination therapies for resistant Cushing’s disease.

3. How does Metyrapone compare to newer drugs for Cushing’s syndrome?

While Osilodrostat has gained approval for Cushing’s disease with a favorable safety profile, Metyrapone remains valuable in certain contexts, particularly diagnostic and short-term management.

4. What are the key regulatory challenges facing Metyrapone?

Expanding therapeutic indications requires extensive clinical validation, with regulatory agencies scrutinizing safety data, especially given the availability of newer agents.

5. How might patent expirations influence the Metyrapone market?

Patent expirations, anticipated around 2025–2030, will likely lead to increased generic manufacturing, reducing prices but intensifying market competition.

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Key Takeaways

• Metyrapone’s clinical trial landscape is active, with current efforts focused on expanding therapeutic applications beyond diagnostic use.
• The global market for Metyrapone is projected to grow at approximately 6.7% CAGR through 2025, driven by increased disease awareness and emerging indications.
• Competitive dynamics favor agents like Osilodrostat; however, Metyrapone’s established safety profile and diagnostic utility sustain its relevance.
• Future growth hinges on successful regulatory approval for new indications and commercialization of combination therapies.
• Patent expirations and generics will impact pricing and market share; strategic positioning is critical for stakeholders.

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References

[1] ClinicalTrials.gov. (2023). Metyrapone trials.
[2] IQVIA. (2022). Global endocrinology market report.
[3] MarketWatch. (2023). Steroidogenesis inhibitors market outlook.