CLINICAL TRIALS PROFILE FOR COPPER HISTIDINATE

All Clinical Trials for COPPER HISTIDINATE

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00811785 ↗	Molecular Bases of Response to Copper Treatment in Menkes Disease, Related Phenotypes, and Unexplained Copper Deficiency	Completed	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)	Phase 3	2009-02-27	Menkes disease and occipital horn syndrome are two forms of copper deficiency that must be diagnosed and treated very early in life to prevent serious developmental problems. However, these and other forms of copper deficiency are not very well understood, and further research is needed to determine whether certain treatments are useful in treating copper deficiency. One such treatment is copper histidine, a copper replacement that can be injected directly into the body to avoid absorption through the gastrointestinal tract. This study will investigate the effectiveness, side effects, and dosage of copper histidine treatment for patients with copper deficiency. It will also collect medical history information from patients to allow researchers to study possible genetic and nongenetic origins of copper deficiency. This study will include 100 subjects, all of whom will be children and adults who have been diagnosed with Menkes disease, occipital horn syndrome, or other unexplained copper deficiency. Patients will receive a prescribed dose of copper histidine, which will be administered daily as an injection. During the study, patients will be admitted to the NIH Clinical Center on an outpatient basis to evaluate their response to the copper histidine treatment. These evaluations will take place every 8 months, with a final evaluation performed after 3 years of treatment. During the outpatient visits, patients will be required to give blood and urine samples for testing and undergo ultrasound testing. They will also undergo brain MRI scans at the initial visit and at the 16-month and 36-month visits. Patients who agree will give additional blood samples for genetic research purposes.
NCT00811785 ↗	Molecular Bases of Response to Copper Treatment in Menkes Disease, Related Phenotypes, and Unexplained Copper Deficiency	Completed	National Center for Complementary and Integrative Health (NCCIH)	Phase 3	2009-02-27	Menkes disease and occipital horn syndrome are two forms of copper deficiency that must be diagnosed and treated very early in life to prevent serious developmental problems. However, these and other forms of copper deficiency are not very well understood, and further research is needed to determine whether certain treatments are useful in treating copper deficiency. One such treatment is copper histidine, a copper replacement that can be injected directly into the body to avoid absorption through the gastrointestinal tract. This study will investigate the effectiveness, side effects, and dosage of copper histidine treatment for patients with copper deficiency. It will also collect medical history information from patients to allow researchers to study possible genetic and nongenetic origins of copper deficiency. This study will include 100 subjects, all of whom will be children and adults who have been diagnosed with Menkes disease, occipital horn syndrome, or other unexplained copper deficiency. Patients will receive a prescribed dose of copper histidine, which will be administered daily as an injection. During the study, patients will be admitted to the NIH Clinical Center on an outpatient basis to evaluate their response to the copper histidine treatment. These evaluations will take place every 8 months, with a final evaluation performed after 3 years of treatment. During the outpatient visits, patients will be required to give blood and urine samples for testing and undergo ultrasound testing. They will also undergo brain MRI scans at the initial visit and at the 16-month and 36-month visits. Patients who agree will give additional blood samples for genetic research purposes.
NCT00811785 ↗	Molecular Bases of Response to Copper Treatment in Menkes Disease, Related Phenotypes, and Unexplained Copper Deficiency	Completed	Cyprium Therapeutics, Inc.	Phase 3	2009-02-27	Menkes disease and occipital horn syndrome are two forms of copper deficiency that must be diagnosed and treated very early in life to prevent serious developmental problems. However, these and other forms of copper deficiency are not very well understood, and further research is needed to determine whether certain treatments are useful in treating copper deficiency. One such treatment is copper histidine, a copper replacement that can be injected directly into the body to avoid absorption through the gastrointestinal tract. This study will investigate the effectiveness, side effects, and dosage of copper histidine treatment for patients with copper deficiency. It will also collect medical history information from patients to allow researchers to study possible genetic and nongenetic origins of copper deficiency. This study will include 100 subjects, all of whom will be children and adults who have been diagnosed with Menkes disease, occipital horn syndrome, or other unexplained copper deficiency. Patients will receive a prescribed dose of copper histidine, which will be administered daily as an injection. During the study, patients will be admitted to the NIH Clinical Center on an outpatient basis to evaluate their response to the copper histidine treatment. These evaluations will take place every 8 months, with a final evaluation performed after 3 years of treatment. During the outpatient visits, patients will be required to give blood and urine samples for testing and undergo ultrasound testing. They will also undergo brain MRI scans at the initial visit and at the 16-month and 36-month visits. Patients who agree will give additional blood samples for genetic research purposes.
NCT04977388 ↗	NORTHERA (DROXIDOPA) for Dysautonomia in Adult Survivors of Menkes Disease and Occipital Horn Syndrome	Recruiting	Stephen G. Kaler, MD	Phase 1/Phase 2	2021-07-12	The purpose of this study is to evaluate whether Northera (Droxidopa) is safe and effective in young adults with Menkes disease who survived the most severe complications of their illness or adults with occipital horn syndrome (OHS), who have trouble with intermittent low blood pressure and other symptoms of dysautonomia. The outcomes and information from this study may help adult survivors of Menkes disease and individuals with OHS lead more normal day-to-day lives.

Clinical Trial Conditions for COPPER HISTIDINATE

Condition Name

Condition Name for COPPER HISTIDINATE
Intervention	Trials
Menkes Disease	2
Occipital Horn Syndrome	2
Unexplained Copper Deficiency	1

Condition MeSH

Condition MeSH for COPPER HISTIDINATE
Intervention	Trials
Cutis Laxa	2
Menkes Kinky Hair Syndrome	2
Ehlers-Danlos Syndrome	2
Syndrome	1

Clinical Trial Locations for COPPER HISTIDINATE

Trials by Country

Trials by Country for COPPER HISTIDINATE
Location	Trials
United States	2

Trials by US State

Trials by US State for COPPER HISTIDINATE
Location	Trials
Ohio	1
Maryland	1

Clinical Trial Progress for COPPER HISTIDINATE

Clinical Trial Phase

Clinical Trial Phase for COPPER HISTIDINATE
Clinical Trial Phase	Trials
Phase 3	1
Phase 1/Phase 2	1

Clinical Trial Status

Clinical Trial Status for COPPER HISTIDINATE
Clinical Trial Phase	Trials
Recruiting	1
Completed	1

Clinical Trial Sponsors for COPPER HISTIDINATE

Sponsor Name

Sponsor Name for COPPER HISTIDINATE
Sponsor	Trials
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)	2
National Center for Complementary and Integrative Health (NCCIH)	1
Cyprium Therapeutics, Inc.	1

Sponsor Type

Sponsor Type for COPPER HISTIDINATE
Sponsor	Trials
NIH	3
Industry	1
Other	1

Last updated: July 27, 2026

Copper Histidinate Clinical Trials Update, Market Analysis, and Revenue Projections

Copper histidinate is a copper(II) salt complexed with the amino acid histidine. It is developed and marketed across multiple customer segments (dietary supplement, medical nutrition, and drug-like formulations in certain jurisdictions). Public trial visibility is limited relative to large, late-stage pharmaceuticals; the most accessible evidence is typically label claims, observational use, and small clinical studies rather than large Phase 3 programs.

What clinical trials exist for copper histidinate and what are the latest updates?

Answer (featured snippet): Public updates for copper histidinate are mostly confined to small, sponsor-driven studies and formulation/absorption work. Large-scale, late-stage registrational trials (Phase 3 with broad endpoints) are not consistently identifiable from public registries, and many programs appear to sit in early clinical or product-dossier stages rather than in Phase 3.

Which trial phases are most commonly reported?

• Early clinical work focused on bioavailability, absorption, tolerance, and copper homeostasis biomarkers.
• Some studies support use in pediatric or malnutrition/enteral nutrition contexts or as a component of parenteral/enteral nutrition formulations, where copper is used as an essential micronutrient.

What endpoints do copper histidinate trials typically use?

• Serum copper and ceruloplasmin changes
• Urinary copper excretion
• Copper balance markers during controlled nutrition regimens
• Safety endpoints: liver enzymes, gastrointestinal tolerance, and micronutrient interaction signals

Why do trial listings look sparse?

Copper histidinate programs frequently present as:

• Ingredient-level clinical evidence to support formulation dossiers
• Use-case trials embedded in broader nutrition or metabolic programs
• Regional studies not consistently mirrored into global public registries

Is copper histidinate an FDA-approved drug, and what is its regulatory status?

Answer (featured snippet): In the US, copper histidinate is typically regulated as a dietary ingredient or through medical nutrition product pathways, not as a single, centrally approved “drug” with an Orange Book exclusivity map. Where it appears in prescription-grade products, it is usually within combination nutrition or specialized formulations under product-level approvals rather than a standalone active ingredient drug story.

How is copper histidinate commonly positioned in regulation?

• As a micronutrient source of copper in medical nutrition frameworks in some markets
• As a dietary supplement ingredient in other markets
• As a component of formulations that need bioavailability support rather than patent-heavy drug-like claims

Orange Book status

Copper histidinate does not map cleanly to a single, well-known Orange Book “blockbuster” listing pattern; the absence of a prominent, centralized Orange Book framework typically implies:

• Limited standalone drug exclusivity
• Greater emphasis on formulation, supplier qualification, and manufacturing controls
• Licensing and exclusivity claims driven by process/formulation and clinical dossier rather than classic “new chemical entity” structures

What patents protect copper histidinate and how strong is the patent estate?

Answer (featured snippet): For copper histidinate, the patent landscape is generally concentrated in formulation/process and method-of-use niches tied to specific product presentations (nutrition regimens, delivery systems, and manufacturing parameters). A dense “core compound” patent estate is less common than for novel molecular entities.

Patent clusters that typically matter

• Chelation/complex formation and purity specifications
• Stabilization in finished dosage forms (capsules, powders, nutrition mixes)
• Manufacturing methods controlling particle characteristics and solubility
• Use in nutrition regimens, including pediatric or enteral/parenteral protocols

What does this mean for competitive entry?

• Competitive risk is usually supplier-to-supplier and formulation-to-formulation, not generic-to-brand in a single FDA-NDA bottleneck.
• IP barriers skew toward process know-how, regulatory dossier ownership, and finished product line differentiation.

How does copper histidinate compare with other copper sources (copper sulfate, copper gluconate)?

Answer (featured snippet): Copper histidinate is positioned for enhanced absorption and tolerability relative to inorganic copper salts in some contexts, because amino acid complexation can affect dissolution, stability, and transport.

Typical tradeoffs by copper source

Copper source	Common rationale	Primary risk	Where it matters most
Copper histidinate	Complexation can improve absorption/tolerability; supports nutrition formulations	Ingredient supply and formulation stability	Medical nutrition and supplements
Copper sulfate	Widely used, low cost, established dosing	GI irritation/tolerability in some users	Supplements, cost-driven programs
Copper gluconate	Moderate bioavailability, commonly used	Variable performance by formulation	Nutrition and OTC markets

Market analysis: How big is the copper histidinate opportunity and what segments drive demand?

Answer (featured snippet): The economic opportunity for copper histidinate is driven by micronutrient fortification and medical nutrition ingredient demand, not by blockbuster prescription utilization. Growth tracks with:

• Medical nutrition volume expansion
• Pediatric nutrition demand
• Specialized nutrition regimens
• Premiumization of supplements toward “better tolerated/absorbed” copper forms

Demand drivers

• Growth in enteral nutrition and clinical nutrition protocols
• Increasing use of micronutrient-formulated products in pediatric and geriatric markets
• Consumer preference for complexed minerals in supplements

Constraints

• Price sensitivity in commodity micronutrient markets
• Ingredient substitution risk: copper salts and other chelates compete on supply and cost
• Regulatory scrutiny of label claims tied to absorption or efficacy

Revenue projection: What is the 3-to-7-year market outlook for copper histidinate?

Answer (featured snippet): A reasonable projection framework for copper histidinate is ingredient revenue, using topline growth assumptions aligned to medical nutrition and premium supplement penetration. However, without authoritative global volume and unit-price datasets for copper histidinate specifically, projections cannot be stated as a single quantified forecast with defensible numerics.

Actionable projection model (structure)

Use a three-driver model:

1. Clinical nutrition volume growth (hospital and home enteral nutrition adoption)
2. Supplement premiumization rate (share shift from copper salts to complexed copper)
3. Net realizable price (ingredient-grade cost curve minus competitive discounting)

Where the forecast tends to break

• Public sources often report copper in aggregate, not histidinate specifically.
• Supplier-level disclosures are inconsistent.
• Many sales are captured as part of blended nutrition SKUs rather than separately itemized as copper histidinate.

What generic or alternative-entry risks exist for copper histidinate?

Answer (featured snippet): The primary “generic” risk is not Paragraph IV litigation. It is ingredient equivalency and formulation replication: alternative copper chelates or salts can substitute if they meet specifications and deliver comparable performance in dossiers and in-use tolerability.

Entry barriers that slow substitution

• Regulatory dossier ownership for a specific use case
• Demonstrated bioavailability/tolerability in the target population
• Manufacturing consistency: particle size/solubility, impurity profile, and stability in finished goods

Competitive dynamics

• Multiple copper chelates compete. Substitution happens when compliance and cost are favorable.

What clinical evidence gaps matter most for commercialization?

Answer (featured snippet): For commercialization outside niche medical nutrition claims, the most valuable evidence is:

• Replicated bioavailability/tolerability comparisons versus common copper salts
• Outcomes linked to copper repletion and clinically meaningful endpoints in relevant populations

Evidence that typically accelerates adoption

• Controlled studies showing copper status improvement in the intended demographic
• Safety data supporting long-term supplementation or regimen-based use
• Stability and manufacturability data for the finished form

Key Takeaways

• Copper histidinate’s development and market footprint are typically ingredient- and formulation-driven, with less consistent identification of large Phase 3 registrational trials.
• Regulatory handling is usually medical nutrition and dietary ingredient frameworks, which reduces Orange Book-style exclusivity mechanics as a centerpiece of competitive strategy.
• The patent estate is generally process/formulation/method-of-use rather than a dominant, single-compound protection moat.
• Market growth is best modeled through nutrition volume expansion and premium copper-complex substitution, but precise numeric projections require product-level and ingredient-level sales visibility.

FAQs

1. Is copper histidinate the same as copper histidine chelate, and how does nomenclature affect search and regulatory filings?
2. What bioavailability markers best demonstrate copper repletion for copper histidinate versus copper sulfate?
3. How do copper histidinate formulations differ in stability and solubility across powders, capsules, and nutrition mixes?
4. What labeling claims are most commonly challenged for complexed copper ingredients in supplements or medical nutrition?
5. Which regions show the highest uptake of complexed minerals in clinical nutrition and why?

References

1. FDA. Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations. U.S. Food and Drug Administration.
2. ClinicalTrials.gov. Search results for “copper histidinate” and “copper histidine” trials. U.S. National Library of Medicine.