CLINICAL TRIALS PROFILE FOR EZOGABINE

All Clinical Trials for ezogabine

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT01332513 ↗	An Open Label, Randomised, Repeat Dose Study to Assess the Pharmacokinetic Performance of Five Ezogabine/Retigabine Modified Release (MR) Formulations at Steady State Compared to the Immediate Release (IR) Formulation.	Completed	GlaxoSmithKline	Phase 1	2011-02-10	This is an open-label, single centre, repeat dose, up- titration study in healthy male and female subjects to assess the pharmacokinetic (PK) performance of five prototypes of ezogabine modified release tablet formulations. The study will consist of a screening period, a treatment phase (consisting of a titration phase, bioavailability phase and food effect phase) and a post-treatment follow-up visit. The study duration from screening to follow up will be approximately 7 weeks. No study procedures will start before informed consent is obtained. Subjects will remain in the clinical unit for the duration of the treatment period (35 days). Subjects will receive repeat doses of ezogabine for up to 34 days starting at a dose of 100 mg IR TID (300mg TDD) with a standard meal (to be consumed 30 min prior to dosing) for Days 1-3, on days 4-6 subjects will receive 150mg IR TID (450mg TDD). On Day 7 through to the end of the study subjects will receive ezogabine (Mr or IR) at a dose of 600mgTDD. On Day 7 subjects will enter into a 6-way cross over period to investigate the 5 MR formulations being tested (each at 300mg BID) and the single IR formulation (at 200mg TID). Subjects will receive each formulaition for 4 days and blood samples for pharmacokinetic analysis will be collected up to 24 hours post dose on each 4th day (PK days). On Day 31 subjects will enter into a food effect phase to investigate the 5 MR formulations being tested (each at 600mg QD). Subjects in this period will have a PK day on Day 33 (following a standard breakfast), and on Day 34 (following a high fat breakfast) to investigate a food effect on the PK profile of ezogabine.
NCT01462656 ↗	Risk of Urinary Retention With Retigabine	Terminated	GlaxoSmithKline		2011-02-01	A prospective cohort study of antiepileptic drug (AED) polytherapy-treated epilepsy patients within the HealthCore Integrated Research Database (HIRD) will be conducted. Following the launch of Ezogabine (EZG), patients initiating a new AED polytherapy regimen will be followed until the earliest of an episode of urinary retention (UR), change in their AED regimen, end of follow-up, or end of study (when the specified sample size of EZG AED polytherapy users has been attained). After the end of study, the incidence of UR during exposures to EZG and non-EZG AED polytherapies will be compared. Polytherapy will be defined as treatment regimen containing at least two different AEDs. A prospective cohort study of patients who receive EZG under circumstances not indicated in the product label within the HIRD will also be conducted. Following the launch of EZG, epilepsy patients initiating AED monotherapy with EZG as well as non-epilepsy patients initiating EZG for another disease will be followed until the earliest of an episode of UR, change in their AED regimen (if applicable), end of follow-up, or end of study. The incidence of UR during exposure to EZG under circumstances not indicated in the product label will be described. A descriptive analysis of the patients will also be included. To meet the other secondary objective, non-EZG AED monotherapy users will be identified in the prospective cohort and incidence of UR will be calculated to determine if there is a difference in UR risk between monotherapy and polytherapy AED use.
NCT01462669 ↗	Crossover Study to Evaluate the Pharmacokinetics of Ezogabine/Retigabine in Taiwanese Subjects	Completed	GlaxoSmithKline	Phase 1	2012-04-10	The purpose of this study is to investigate the pharmacokinetics of single oral doses of ezogabine/retigabine and the primary metabolite (NAMR) in healthy male and female Taiwanese volunteers. Subjects will receive four separate doses of ezogabine/retigabine tablets: 50 mg, 100 mg, 200 mg and 400 mg administered once orally. Blood samples will be obtained at pre-defined timepoints over the duration of the study to determine the concentration of ezogabine/retigabine and NAMR. Safety assessments will include measurements of vital signs, collection of adverse events, clinical laboratory tests and the Columbia Suicide Severity Rating Scale.
NCT01480609 ↗	Effect of Haemodialysis on the Pharmacokinetics of Ezogabine/Retigabine and Its N-acetyl Metabolite	Completed	GlaxoSmithKline	Phase 1	2011-11-30	This in an open-label, single dose, fixed sequence, two treatment period study enrolling 8 patients (to obtain 6 evaluable) with end stage renal disease (ESRD) receiving haemodialysis. Patients will remain in the unit during each treatment period from admission to the collection of the final PK sample. The doses of ezogabine/retigabine in the two treatment periods will be separated by at least 7 days.
NCT01494584 ↗	Study in Pediatric Subjects With Epilepsy	Terminated	Bausch Health Americas, Inc.	Phase 2	2012-07-25	This is an open-label study to evaluate the pharmacokinetics, safety and tolerability of ezogabine/retigabine in subjects aged 12 years to less than 18 years with uncontrolled partial onset seizures or Lennos-Gastaut syndrome.
NCT01494584 ↗	Study in Pediatric Subjects With Epilepsy	Terminated	Valeant Pharmaceuticals International, Inc.	Phase 2	2012-07-25	This is an open-label study to evaluate the pharmacokinetics, safety and tolerability of ezogabine/retigabine in subjects aged 12 years to less than 18 years with uncontrolled partial onset seizures or Lennos-Gastaut syndrome.

Clinical Trial Conditions for ezogabine

Condition Name

Condition Name for ezogabine
Intervention	Trials
Epilepsy	12
Brain Diseases	2
Central Nervous System Diseases	2
Disease	2

Condition MeSH

Condition MeSH for ezogabine
Intervention	Trials
Epilepsy	11
Seizures	4
Depressive Disorder	2
Depression	2

Clinical Trial Locations for ezogabine

Trials by Country

Trials by Country for ezogabine
Location	Trials
United States	56
Australia	3
France	1
Belgium	1
Taiwan	1

Trials by US State

Trials by US State for ezogabine
Location	Trials
Maryland	6
Texas	5
Florida	5
California	5
New York	4

Clinical Trial Progress for ezogabine

Clinical Trial Phase

Clinical Trial Phase for ezogabine
Clinical Trial Phase	Trials
Phase 4	3
Phase 3	4
Phase 2	4

Clinical Trial Status

Clinical Trial Status for ezogabine
Clinical Trial Phase	Trials
Completed	8
Terminated	6
Recruiting	2

Clinical Trial Sponsors for ezogabine

Sponsor Name

Sponsor Name for ezogabine
Sponsor	Trials
GlaxoSmithKline	11
Valeant Pharmaceuticals International, Inc.	3
Bausch Health Americas, Inc.	3

Sponsor Type

Sponsor Type for ezogabine
Sponsor	Trials
Industry	20
Other	10
NIH	1

Ezogabine: Clinical Trials Update, Market Analysis, and Future Projections

Last updated: October 28, 2025

Introduction

Ezogabine, marketed as Potiga (or Trobalt in some regions), is an anticonvulsant drug primarily approved for the treatment of partial-onset seizures in adults. Developed by GlaxoSmithKline and later handed over to Valeant Pharmaceuticals (now Bausch Health Companies), Ezogabine represents a unique mechanism of action as a potassium channel opener. This positioning offers potential advantages and challenges in its commercial trajectory. This report provides an in-depth update on its clinical trial landscape, current market status, and forecasts future growth and challenges.

Clinical Trials Landscape

Regulatory Approval and Initial Clinical Trials

Ezogabine received FDA approval in 2016 for adjunctive treatment of partial-onset seizures in adults. The pivotal studies, including Phase III trials, demonstrated its efficacy in reducing seizure frequency. These studies primarily focused on its safety profile, especially regarding ocular and skin discoloration due to pigment deposition, and urinary symptoms.

Post-Approval Clinical Development

Post-approval, research efforts minimally expanded Ezogabine’s indications, primarily due to safety concerns leading to limited labeled uses. However, ongoing clinical investigations have explored its potential in treating Parkinson’s disease, particularly for dyskinesia, leveraging its potassium channel modulation mechanism. Notably:

• Parkinson’s Disease Trials: A Phase II trial (NCT Number: not publicly listed) evaluated Ezogabine’s efficacy in managing levodopa-induced dyskinesia. Results showed mixed outcomes, with some symptomatic improvements but concerns regarding side effects.

• Other Neurological Disorders: Limited investigational studies have probed Ezogabine's utility in neuropathic pain and neuroprotective roles, but none have advanced beyond early-phase trials.

Safety and Pharmacovigilance

While initially tolerated, post-marketing:

• Retinal discoloration was identified as a significant adverse event, with pigment deposits observed in the retina in long-term users.
• Urinary retention and skin discoloration remain concerns, influencing ongoing safety monitoring and limiting broader clinical exploration.

Current Trial Status

As of early 2023, there are no active Phase III trials involving Ezogabine for new indications. Most ongoing research is observational or post-marketing safety studies, suggesting limited clinical development momentum beyond existing approvals.

Market Analysis

Historical Market Performance

Ezogabine entered a niche anticonvulsant market characterized by multiple established therapeutics such as levetiracetam, carbamazepine, and lamotrigine. Its unique mechanism attracted consideration for patients refractory to standard treatments; however, its commercial uptake remained limited due to safety concerns and limited expanded indications.

Current Market Dynamics

• Sales Performance: Reports indicate modest sales post-approval, with figures roughly in the low hundreds of millions USD annually (approximate 2021-2022 data). The drug's revenue has been constrained by safety issues, market competition, and reluctance among physicians to prescribe Ezogabine widely.

• Competitive Landscape: Ezogabine faces stiff competition from newer antiepileptics with better safety profiles and broader indication approval, such as lamotrigine and levetiracetam.

• Regulatory Challenges: The safety warnings concerning retinal discoloration and urinary retention have restricted official recommendations, leading to conservative prescribing practices.

Market Opportunities and Challenges

• Potential in Rare or Specialist Markets: There remains a niche for Ezogabine in treatment-resistant epilepsy, especially if future formulations mitigate safety issues or if targeted biomarkers identify suitable patient subgroups.

• Challenges:

  • Safety profile concerns hindering wider adoption.
  • Limited pipeline or ongoing trials to revitalize drug positioning.
  • The emergence of gene therapy and other innovative therapeutics transforming epilepsy management.

Future Market Projections

Short-term Outlook (Next 2-3 Years)

Market forecast indicates stable but limited revenue, primarily driven by existing prescriptions for refractory epilepsy patients. The absence of new clinical trials or regulatory approvals limits significant growth. Pricing pressures and safety warnings are likely to restrain market expansion.

Long-term Outlook (3-10 Years)

• Potential revival through repositioning: Should new formulations or delivery methods reduce adverse effects, Ezogabine may regain interest. Exploring its neuroprotective properties or lighter formulations could open new markets.

• Emerging technologies and personalized medicine: Advances in genetic screening may identify patient subsets more responsive to Ezogabine, improving market acceptance. Simultaneously, competition from newer, safer drugs may further suppress sales unless significant advantages are demonstrated.

• Regulatory landscape: Vigilant pharmacovigilance and tailored safety management could facilitate future approvals for extended or new indications.

Strategic Recommendations

To capitalize on future market opportunities, stakeholders should:

• Invest in safety profile research to develop safer derivatives or formulations.
• Explore drug repositioning strategies for neurological disorders beyond epilepsy.
• Engage in post-marketing surveillance and real-world evidence collection to support regulatory and clinical decision-making.
• Foster partnerships with biotech firms working on targeted delivery systems.

Key Takeaways

• Clinical development for Ezogabine has largely plateaued post-initial approval, with no active Phase III trials underway. The safety concerns, particularly retinal discoloration and urinary effects, are central to its limited expansion.

• Market performance remains modest, constrained by safety profile issues and intense competition from newer therapies. Its niche remains primarily in treatment-resistant epilepsy for selected patient populations.

• Future growth hinges on safety improvements, targeted application, and possibly repositioning within neurotherapeutic indications. Without significant innovation or safety enhancements, Ezogabine’s market prospects appear limited.

• Regulatory vigilance and real-world evidence gathering are critical to explore potential new indications or to refine its safety profile.

• Stakeholders must weigh the high development and repositioning costs against potential benefits, with strategic focus on niche markets where Ezogabine’s unique mechanism may still offer advantages.

FAQs

1. Is Ezogabine still approved for epilepsy treatment?
Yes. Ezogabine is approved for adjunctive therapy for partial-onset seizures in adults, but its use is limited due to safety concerns and primarily in specialized settings.

2. Are there ongoing clinical trials exploring new indications for Ezogabine?
As of early 2023, no active Phase III trials are underway. Ongoing studies are mainly safety surveillance or exploratory investigations.

3. What are the main safety concerns associated with Ezogabine?
Retinal discoloration, skin pigmentation, urinary retention, and potential neurotoxicity are notable safety issues limiting widespread use.

4. Can Ezogabine be repositioned for other neurological conditions?
Potential exists, especially in neuroprotective roles or movement disorder management, but it requires robust clinical data and safety validation.

5. What are the key competitive disadvantages of Ezogabine?
Compared to newer anticonvulsants, Ezogabine faces challenges due to its safety profile, limited indications, and less favorable pharmacodynamics in the context of available therapies.

References

[1] U.S. Food and Drug Administration (FDA). Potiga (Ezogabine): Drug Approval Package. 2016.
[2] Dosing and safety data from product monographs and post-marketing surveillance reports.
[3] Market sales analyses from IQVIA and PharmaTrend report, 2022.
[4] ClinicalTrials.gov database: ongoing and completed studies related to Ezogabine.
[5] Peer-reviewed journal articles on Ezogabine’s safety and efficacy profile.