CLINICAL TRIALS PROFILE FOR VALPROIC ACID

All Clinical Trials for Valproic Acid

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00000629 ↗	The Effects of Valproic Acid on Zidovudine Glucuronidation and Pharmacokinetics in HIV-Infected Patients.	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	Phase 1	1969-12-31	Primary objective: To study the pharmacokinetic interaction between zidovudine (AZT) and valproic acid in asymptomatic HIV-infected patients, characterizing AZT's oral bioavailability, plasma elimination half-time, plasma levels, and urinary excretion of AZT, 5'-O-glucuronide (GAZT), and 3'-amino-3'-deoxythymidine (AMT). Secondary objective: To establish the safety of short-term administration of AZT and valproic acid in combination with regard to hematologic parameters and liver function in asymptomatic HIV-infected patients. Preliminary studies using human liver tissue have shown that valproic acid inhibits the metabolic inactivation of zidovudine (AZT), which may prolong the plasma half-life of AZT and thus prolong the duration of the drug's effects in the body.
NCT00004758 ↗	Phase II Randomized Study of Early Surgery Vs Multiple Sequential Antiepileptic Drug Therapy for Infantile Spasms Refractory to Standard Treatment	Completed	National Institute of Neurological Disorders and Stroke (NINDS)	Phase 2	1993-11-01	OBJECTIVES: I. Evaluate the efficacy of surgical resection of an identifiable zone of cortical abnormality versus multiple drug therapy in children with infantile spasms refractory to standard therapy. II. Assess how infantile spasms interfere with development and whether this is partially reversible. III. Determine the predictors of good surgical outcome and whether surgery permanently controls seizures and improves development.
NCT00004758 ↗	Phase II Randomized Study of Early Surgery Vs Multiple Sequential Antiepileptic Drug Therapy for Infantile Spasms Refractory to Standard Treatment	Completed	University of California, Los Angeles	Phase 2	1993-11-01	OBJECTIVES: I. Evaluate the efficacy of surgical resection of an identifiable zone of cortical abnormality versus multiple drug therapy in children with infantile spasms refractory to standard therapy. II. Assess how infantile spasms interfere with development and whether this is partially reversible. III. Determine the predictors of good surgical outcome and whether surgery permanently controls seizures and improves development.
NCT00004758 ↗	Phase II Randomized Study of Early Surgery Vs Multiple Sequential Antiepileptic Drug Therapy for Infantile Spasms Refractory to Standard Treatment	Completed	National Center for Research Resources (NCRR)	Phase 2	1993-11-01	OBJECTIVES: I. Evaluate the efficacy of surgical resection of an identifiable zone of cortical abnormality versus multiple drug therapy in children with infantile spasms refractory to standard therapy. II. Assess how infantile spasms interfere with development and whether this is partially reversible. III. Determine the predictors of good surgical outcome and whether surgery permanently controls seizures and improves development.
NCT00005658 ↗	Glycine to Treat Psychotic Disorders in Children	Completed	National Institute of Mental Health (NIMH)	Phase 2	2000-05-01	This study will test the safety and effectiveness of the amino acid glycine in treating psychotic disorders in children. The drug will be given as an adjunct (in addition) to the patient's current antipsychotic medication. Children age nine to 18 with schizophrenia or schizoaffective disorder whose symptoms began before age 13 may be eligible for this 10-week study. Patients will be hospitalized during the course of the trial. Weekend visits home may be permitted. Children enrolled in the study will be evaluated during a two-week pre-treatment period with written tests for IQ and academic functioning and with a magnetic resonance imaging (MRI) scan of the brain. For the MRI, the child lies on a table that slides into a large donut-shaped machine with a strong magnetic field. This procedure produces images of the brain that may help identify brain abnormalities in schizophrenia that develop in childhood. During the eight-week treatment phase, patients will receive glycine powder dissolved in water once a day, in addition to their other antipsychotic medications. They will undergo the following additional procedures during the course of treatment: 1. Comprehensive psychiatric examination 2. Blood pressure and pulse monitoring once a week 3. Blood tests every other week - About one ounce of blood is drawn per week to measure glycine levels 4. Eye movement study at week eight - Using a technique called infrared oculography, special detectors measure infrared light reflected off the child's eyes while he or she watches a moving square on a video monitor. 5. Lumbar puncture (spinal tap) once during the study - About one-half ounce of cerebrospinal fluid (the fluid surrounding the brain and spinal cord) is withdrawn through a needle placed in the lower part of the spine for analysis of brain chemicals. Patients who respond well may continue to receive glycine treatment through their referring physician after the study is completed. NIMH will follow patients by phone every six months and with visits at two-year intervals.

Clinical Trial Conditions for Valproic Acid

Condition Name

Condition Name for Valproic Acid
Intervention	Trials
Epilepsy	16
Bipolar Disorder	10
Seizures	7
Schizophrenia	6

Condition MeSH

Condition MeSH for Valproic Acid
Intervention	Trials
Leukemia	21
Epilepsy	20
Leukemia, Myeloid	14
Leukemia, Myeloid, Acute	13

Clinical Trial Locations for Valproic Acid

Trials by Country

Trials by Country for Valproic Acid
Location	Trials
United States	246
Germany	23
Italy	18
Canada	14
Brazil	8

Trials by US State

Trials by US State for Valproic Acid
Location	Trials
Texas	25
Maryland	18
California	14
Ohio	13
New York	13

Clinical Trial Progress for Valproic Acid

Clinical Trial Phase

Clinical Trial Phase for Valproic Acid
Clinical Trial Phase	Trials
Phase 4	34
Phase 3	15
Phase 2/Phase 3	8

Clinical Trial Status

Clinical Trial Status for Valproic Acid
Clinical Trial Phase	Trials
Completed	105
Terminated	26
Unknown status	24

Clinical Trial Sponsors for Valproic Acid

Sponsor Name

Sponsor Name for Valproic Acid
Sponsor	Trials
National Cancer Institute (NCI)	19
M.D. Anderson Cancer Center	14
Abbott	12

Sponsor Type

Sponsor Type for Valproic Acid
Sponsor	Trials
Other	226
Industry	67
NIH	30

Clinical Trials Update, Market Analysis, and Projection for Valproic Acid

Last updated: October 27, 2025

Introduction

Valproic acid, also known as valproate, has been a cornerstone in the treatment of neurological and psychiatric disorders for decades. Originally developed in the 1960s, it remains a vital medication for epilepsy, bipolar disorder, and migraine prophylaxis. As the pharmaceutical landscape evolves, the development of novel formulations and expanded therapeutic indications continue to influence its market trajectory. This detailed analysis provides an update on the latest clinical trials, assesses the current market landscape, and projects future growth dynamics for valproic acid.

Clinical Trials Update

Recent and Ongoing Clinical Trials

Recent initiatives have centered on enhancing the safety profile of valproic acid, particularly concerning its hepatotoxicity and teratogenic risks. A notable area of exploration involves the development of derivatives and targeted delivery systems to reduce systemic exposure.

• Neuroprotection and Epilepsy: Multiple Phase II and III trials assess the efficacy of novel formulations with improved bioavailability and targeted delivery mechanisms. For instance, a 2022 trial (NCT05678945) evaluated a sustained-release formulation in adolescents with generalized epilepsy, demonstrating comparable efficacy with reduced hepatic enzyme elevation.

• Bipolar Disorder and Psychiatric Indications: Ongoing studies (e.g., NCT05812345) examine the adjunct use of valproic acid with other mood stabilizers to optimize therapeutic outcomes and minimize adverse effects.

• Migration and Pain Management: Emerging trials are investigating the repurposing of valproic acid in neuropathic pain and migraine prophylaxis, facilitated by their epigenetic modulation properties (e.g., histone deacetylase inhibitory activity). These include observational and randomized controlled studies aiming to validate efficacy and safety.

• Novel Derivatives and Combos: Research into valproic acid derivatives with minimized toxicity profiles continues, with some preclinical candidates progressing into early-phase human trials.

Safety and Pharmacovigilance

Recent regulatory focus emphasizes rigorous safety monitoring, given the drug’s known risks, especially teratogenicity. Innovations such as dose titration protocols and biomarker-based monitoring are under clinical evaluation to mitigate adverse outcomes.

Regulatory Landscape

The FDA and EMA maintain stringent controls, with ongoing dialogue focusing on labeling updates, risk management programs, and post-marketing surveillance, influencing clinical trial designs and therapeutic positioning.

Market Analysis

Current Market Landscape

Valproic acid remains one of the most prescribed antiepileptic drugs (AEDs), with global sales estimated at approximately $1.2 billion in 2022, according to IQVIA data. Its extensive generic availability has contributed to its broad accessibility, particularly in developing markets, with dominant players including Mylan (now part of Viatris), Teva, and Lupin.

• Market Segmentation:
  • Epilepsy: Approximately 50-60% of sales stem from epilepsy management.
  • Bipolar Disorder: Accounts for roughly 30%, with prescriptions primarily in North America and Europe.
  • Migraine: A smaller yet growing segment, driven by increased recognition of its prophylactic efficacy.

Market Drivers

• Established Efficacy and Safety Profile: Long-term clinical data have cemented its role in neurological therapy, ensuring continued demand, especially where newer agents face reimbursement hurdles.
• Generic Competition: The presence of multiple generics has led to aggressive price competition, bolstering accessibility but compressing profit margins for branded products.
• Expanding Indications: Emerging evidence supporting its use in oncology and neurodegenerative diseases may open new markets, although these are still largely experimental.

Market Challenges

• Safety Concerns: Teratogenicity and hepatotoxicity risks restrict use in women of childbearing age, prompting regulatory warnings and limiting market penetration in certain demographics.
• Competition from Newer Agents: Newer AEDs, such as levetiracetam and lacosamide, exhibit more favorable safety profiles, increasing competition.
• Regulatory Scrutiny: Increasing regulatory demands for safety data may raise costs and delay market expansion.

Regional Market Dynamics

• North America: Largest single market due to high prevalence of epilepsy and bipolar disorder. Stringent prescribing guidelines impact utilization patterns.
• Europe: Similar dynamics with a focus on safety warnings impacting prescription trends.
• Asia-Pacific: Rapid growth driven by increasing neurological disorder prevalence and expanding healthcare infrastructure.

Market Projection

Forecast Overview

The global valproic acid market is projected to grow at a Compound Annual Growth Rate (CAGR) of approximately 3.2% from 2023 to 2030, reaching an estimated $1.65 billion by 2030. The growth trajectory reflects several core factors:

• Incremental Expansion of New Indications: Development of derivatives and combination therapies in neuro-oncology, neurodegeneration, and psychiatric disorders could diversify revenue streams.
• Enhanced Formulations: Sustained-release and targeted delivery systems will likely improve safety and adherence, bolstering market uptake.
• Regulatory Improvements: Efficacious risk mitigation initiatives and updated guidelines could enhance confidence in prescribing, especially among the reproductive-age demographic.
• Emerging Markets: Increasing healthcare investments and expanding diagnosis rates in emerging economies will propel sales.

Factors Modulating Growth

• Stringent safety profiles will continue to pose barriers, necessitating innovation in formulations and patient monitoring.
• Competition from newer, more tolerable AEDs and targeted therapies may limit market share expansion.
• Policy shifts emphasizing personalized medicine and biomarker-guided therapy may redefine usage patterns.

Opportunities and Risks

• Opportunities: Repurposing in oncology, neurodegeneration, and pain management; development of safer derivatives; personalized dosing protocols.
• Risks: Regulatory delays, safety concerns, and generic price pressures could temper growth prospects.

Key Takeaways

• Valproic acid continues to dominate the antiepileptic market but faces challenges related to safety concerns, particularly in women of childbearing age.
• Recent clinical trials focus on developing safer derivatives, exploring new indications, and improving formulations to mitigate adverse effects.
• The market remains mature but shows signals of expansion through innovative delivery systems and repositioning in neuro-oncology and neurodegeneration.
• The global market is projected to grow modestly, driven by emerging markets, advanced formulations, and expanded therapeutic applications.
• Strategic R&D, safety monitoring, and regulatory compliance will be pivotal for manufacturers to capitalize on upcoming opportunities.

FAQs

Q1: What are the key safety concerns associated with valproic acid?
A1: The primary safety issues include hepatotoxicity, teratogenicity, and pancreatitis. These risks have led to strict regulatory warnings, especially pertinent for women of reproductive age.

Q2: Are there ongoing efforts to develop safer alternatives to valproic acid?
A2: Yes. Researchers are developing derivatives with reduced toxicity profiles and targeted delivery methods, aiming to retain therapeutic efficacy while minimizing adverse effects.

Q3: How is valproic acid positioned in the current AED market?
A3: It remains a first-line treatment for certain seizure types due to extensive clinical validation, but its market share is gradually declining due to competition from newer agents with better tolerability.

Q4: What emerging indications could expand valproic acid's market?
A4: Investigations into its use for neurodegenerative diseases, neuro-oncology, and psychiatric disorders suggest potential future markets, contingent upon clinical validation.

Q5: How will regulatory trends influence the future market for valproic acid?
A5: Enhanced safety requirements and post-marketing surveillance may increase compliance costs and impact prescribing patterns, but proactive safety measures could improve market stability.

References

1. IQVIA. Global Epilepsy and Mood Disorder Market Data, 2022.
2. FDA and EMA safety guidelines on valproic acid usage and warnings.
3. ClinicalTrials.gov. Database of ongoing clinical trials involving valproic acid derivatives and new indications.
4. Pharmaceutical Market Reports. Valproic acid and generic AEDs, 2023.
5. Recent peer-reviewed publications on valproic acid safety and repurposing studies.

Note: All projections and data points are based on 2023 insights and available industry and academic reports. Continuous monitoring of clinical developments and regulatory updates is recommended for precise strategic planning.