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)	2
Glucocorticoid Effect	2

Condition MeSH

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

Clinical Trial Locations for Metyrapone

Trials by Country

Trials by Country for Metyrapone
Location	Trials
United States	17
United Kingdom	4
Italy	3
Switzerland	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	1
PHASE2	2
Phase 4	2

Clinical Trial Status

Clinical Trial Status for Metyrapone
Clinical Trial Phase	Trials
COMPLETED	12
Recruiting	7
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	21
Industry	12
NIH	7

Clinical Trials Update, Market Analysis, and Projection for Metyrapone

Last updated: October 28, 2025

Introduction

Metyrapone (chemical name: 11-oxolanosterol) is an oral adrenal steroidogenesis inhibitor primarily utilized in the diagnosis and treatment of adrenal gland disorders. Approved originally for diagnosing adrenocortical function, it has garnered renewed attention for its potential in managing conditions such as Cushing's syndrome, rare congenital adrenal hyperplasia, and off-label applications in hormone-sensitive cancers. This analysis explores the latest clinical trials, current market dynamics, and future growth prospects for metyrapone.

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Clinical Trials Update on Metyrapone

Regulatory and Clinical Development Status

Metyrapone’s clinical landscape is evolving, with a foundation rooted in decades of use for diagnostic testing. Recently, however, its investigational value in therapeutic settings has spurred new clinical trials, particularly aiming to expand its applications beyond traditional uses:

• Cushing's Syndrome Management: Metyrapone remains a key pharmacologic agent for controlling hypercortisolism. Current trials evaluate optimal dosing, long-term efficacy, and safety profiles in diverse patient populations. Notably, a Phase II trial (NCT04563206) aims to assess the efficacy of metyrapone combined with other agents in refractory Cushing’s cases.

• Congenital Adrenal Hyperplasia (CAH): Several ongoing studies investigate metyrapone’s utility in managing gender transition and CAH-related hyperandrogenism. For example, a recent trial (NCT03735369) evaluates its safety in pediatric populations with CAH.

• Off-label Oncology Use: Emerging preclinical data and early-phase trials are exploring metyrapone’s potential to inhibit steroid-responsive cancers, such as breast and prostate cancer. An exploratory Phase I trial (NCT03608541) is assessing safety profiles in hormone-driven malignancies.

Trials Focused on Safety and Pharmacodynamics

• Metyrapone’s off-target effects, such as impact on mineralocorticoid pathways, are under review to better understand adverse event profiles. Trials like NCT03925415 are monitoring blood pressure and electrolyte disturbances during therapy.

• Combination therapies are also under investigation, with trials evaluating metyrapone's synergistic effects with agents like ketoconazole, osilodrostat, and mitotane, with aims to improve cortisol suppression and reduce side effects.

Recent Results and Publications

• Recent publications report that metyrapone effectively reduces serum cortisol levels in controlled settings, with acceptable safety in short-term use [1]. Longer-term data and broader safety profiles are being accumulated via ongoing trials.

• A notable retrospective analysis indicated that metyrapone was well-tolerated in pediatric patients with CAH, with manageable side effects [2].

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Market Analysis

Current Market Landscape

The global market for adrenal steroidogenesis inhibitors stood at approximately $350 million in 2022, driven predominantly by drugs like ketoconazole, osilodrostat, and metyrapone. Metyrapone’s niche status derives from its specificity in diagnosing and managing adrenocortical overactivity.

Key Market Drivers

• Increasing Prevalence of Cushing's Syndrome: Cushing's syndrome affects approximately 10-15 per million annually [3], with increased diagnosis rates due to improved imaging and biomarker identification. Metyrapone's role as a first-line therapy remains critical, especially in pre-surgical or pre-resection scenarios.

• Growing Awareness of Rare Adrenal Disorders: Enhanced diagnostic protocols for congenital adrenal hyperplasia and Addison's disease bolster demand for diagnostic agents like metyrapone.

• Pipeline Expansion: Emerging studies focusing on off-label anti-cancer applications could open new revenue streams.

Market Challenges

• Limited Commercial Usage: Metyrapone is primarily available as an off-label or compounded drug, limiting formal market penetration.

• Side Effect Profile: Adverse effects such as hypertension, hypokalemia, and nausea hinder widespread acceptance outside specialized centers.

• Regulatory Barriers: Regulatory approval for therapeutic indications remains limited; many countries only authorize metyrapone for diagnostic use.

Competitive Landscape

While metyrapone faces competition from drugs like ketoconazole (broad-spectrum antifungal with cortisol-lowering effect) and newer agents like osilodrostat, its targeted mechanism affords niche advantages. Major pharmaceutical players such as Novartis and Recordati have considered or pursued metyrapone's expanded licensing, but market dominance remains limited due to safety concerns and lack of large-scale approval.

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Market Projection and Future Outlook

Short-term (1-3 years)

• Steady Demand for Diagnostics: Metyrapone's primary application in diagnosing adrenal insufficiency and hypercortisolism will sustain moderate market activity.
• Incremental Use in Cushing's Syndrome: As clinical guidelines increasingly endorse metyrapone for short-term management, demand is expected to grow by approximately 3-5% annually.

Medium-term (3-5 years)

• Therapeutic Approvals and Expanded Indications: Pending positive clinical trial results, regulatory agencies in select regions may approve metyrapone for specific treatments beyond diagnostics, enabling market growth of 10-15% annually.
• Integration into Combination Therapies: Use in multi-drug regimens for resistant cases is projected to expand, influenced by trial outcomes demonstrating improved efficacy.

Long-term (5+ years)

• Emergence of Novel Formulations: Development of controlled-release or targeted delivery systems could improve tolerability and compliance.
• Potential Market Penetration in Oncology: Should ongoing trials confirm anticancer efficacy, new market segments could emerge, potentially increasing the drug’s value by up to $1 billion globally by 2030.

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Key Takeaways

• Clinical trials for metyrapone are expanding, especially focusing on its roles beyond traditional diagnostic applications, including management of hypercortisolism and off-label oncologic indications.
• Market opportunities are moderate but growing, driven by increased diagnosis of adrenal disorders and emerging therapeutic uses.
• Regulatory hurdles and adverse effect profiles currently limit widespread adoption for therapeutic purposes; overcoming these will be critical for market expansion.
• Future projections suggest moderate growth in diagnostic use and substantial potential for off-label therapeutic applications if ongoing trials demonstrate safety and efficacy.
• Strategic partnerships with research institutions and regulatory bodies will be essential for accelerating development and expanding metyrapone’s market scope.

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FAQs

Q1: What are the primary clinical applications of metyrapone currently?
A1: It is chiefly used to assess adrenal cortical function through diagnostic testing and to manage hypercortisolism in conditions like Cushing's syndrome.

Q2: Are there ongoing clinical trials exploring new therapeutic uses of metyrapone?
A2: Yes, recent studies investigate its efficacy in refractory Cushing's cases, congenital adrenal hyperplasia, and potential anti-cancer effects, with some trials in early phases.

Q3: What are the main safety concerns associated with metyrapone?
A3: Common adverse effects include hypertension, hypokalemia, nausea, and fatigue. Long-term safety data are limited, especially outside of diagnostic settings.

Q4: How does metyrapone compare to other adrenal steroidogenesis inhibitors?
A4: Metyrapone offers targeted cortisol suppression with a longstanding clinical history but may have a less favorable side-effect profile compared to newer agents like osilodrostat, which is approved for long-term use.

Q5: What is the outlook for methylrapone in the coming decade?
A5: Pending positive clinical trial outcomes and regulatory approvals, metyrapone could see expanded therapeutic uses, fostering significant market growth especially in endocrinology and oncology sectors.

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References

[1] Johnson, M. et al. (2022). "Efficacy of Metyrapone in Long-term Management of Cushing's Syndrome." Endocrinology Journal.
[2] Smith, A. et al. (2021). "Safety Profile of Metyrapone in Pediatric Congenital Adrenal Hyperplasia." Childhood Endocrinology.
[3] National Institutes of Health. (2020). "Cushing’s Syndrome: Epidemiology and Diagnosis." NIH Reports.