Study of the Pharmacokinetics, Safety, and Tolerability of ZONISADE in Children 1 Month to 17 Years of Age With Partial-onset Seizures

A Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Zonisamide Oral Suspension (100 mg/5 ml) to Determine a Dosing Regimen in Children 1 Month to 17 Years of Age With Partial-onset Seizures

The purpose of this research is to determine the optimal dose, safety and tolerability of zonisamide oral suspension in children ages 1 month to 17 years of age who have partial-onset (focal) seizures. The study consists of four periods: a Screening Period (about 14 days), a Titration Period (8 weeks), a Maintenance Period (4 weeks), and a Follow-Up Period (1 week).

Study Overview

• Status: Not yet recruiting
• Conditions: Epilepsy; Seizures; Epilepsies, Partial; Seizure Disorder, Partial; Seizures, Focal; Seizure, Partial Onset; Seizure, Partial
• Intervention / Treatment: Drug: Zonisamide Oral Product

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: David Sequeira, PhD; Phone Number: 1-800-461-7449; Email: david.sequeira@azurity.com
• Study Contact Backup: Name: Meredith Knaak; Email: meredith.knaak@azurity.com

Study Locations

• United States
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27101
      • Wake Forest University School of Medicine
      • Principal Investigator: Gautam Popli, MBBS
  • Tennessee
    • Memphis, Tennessee, United States, 38103
      • Le Bonheur Children's Hospital
      • Principal Investigator: James Wheless, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Pediatric participants (ages 1 month to 17 years of age, inclusive) will be considered eligible for the study based on the following criteria:

  1. Voluntarily obtained informed consent from parent/legal guardian of the participant and assent from the participant, when appropriate.
  2. Willing and able to follow protocol specific requirements.
  3. Participant of 1 month to 17 years of age, inclusive (at time of consent).
  4. Participant diagnosed with partial-onset (focal) seizures, with or without secondary generalization as per current International League Against Epilepsy (ILAE) classification of seizures. Participants with both focal-onset and generalized-onset seizures are eligible, but only focal-onset seizures count toward baseline seizure enrollment criteria. Tonic-clonic and tonic seizures with unknown onset are presumed to be focal-onset unless there are clear clinical and EEG data suggesting generalized-onset.

  5. Participant with seizure occurrence more than once in the past three (3) months and more than two (2) times in the past six (6) months.

     a. Participant who is 6 months of age and younger will have seizure profiling patterns assessed by the Investigator for appropriate consideration and inclusion in the study.

  6. Participant on a stable regimen of anti-epilepsy drugs (AEDs) for at least 30 days before screening

     a. Participant who is 6 months of age and younger will have regimen assessed for inclusion in the study at Investigator's discretion.

  7. Participant with acceptable laboratory investigations:

     1. Hemoglobin within normal range
     2. Alanine aminotransferase (ALT) within normal range
     3. Aspartate aminotransferase (AST) up to 1.5 x upper limit of normal (ULN)
     4. Bilirubin within normal range
     5. Creatinine clearance within normal range
  8. If male participant is able to father children must be willing to use a highly effective method of contraception for at least one month after the last dose of investigational product if at risk of pregnancy with her/his partner. If female participant has reached menarche, the participant is authorized to participate in this clinical study if additional criteria are met.

At screening:

1. (i) Participant reports sexual abstinence for the prior 3 months or reports use of at least 1 of the acceptable methods of contraception, including an intrauterine device, barrier methods (e.g., male or female condom), hormonal contraceptives (e.g., hormonal patches, vaginal devices, oral pills), levonorgestrel intrauterine system (e.g., Mirena®), or regular medroxyprogesterone injections (e.g., Depo-Provera®); or (ii) Participant agrees to initiate sexual abstinence from the time of screening until at least one month after end of treatment with study drug; and
2. Participant is advised to avoid conception from the time of screening until at least one month after last receipt of study drug and agrees not to attempt pregnancy from the time of screening until at least one month after end of treatment with study drug; and
3. Participant is provided guidelines regarding continuation of abstinence, initiation of abstinence, or about allowed contraception; and
4. Participant has a negative serum β-human chorionic gonadotropin (β-hCG) test just prior to study entry. Since serum tests may miss an early pregnancy, relevant menstrual history and sexual history, including methods of contraception, should be considered. Note: if the result of the serum β-hCG test cannot be obtained prior to dosing of investigational product, a participant may be enrolled on the basis of a negative urine pregnancy test, though a serum β-hCG test result must still be obtained.

Exclusion Criteria:

• Pediatric participant will be excluded from the study based on the following criteria:

  1. Known hypersensitivity to zonisamide or to any component of the investigational product or to sulfonamides.
  2. Participant who is pregnant or nursing.
  3. Participant with exclusively generalized-onset seizures.
  4. Participant with predisposition to nephrolithiasis or prior history of kidney stone(s).
  5. Participant who is underweight (weight-for-age <2 standard deviation (SD) from the median of the World Health Organization (WHO) Child Growth Standards) or have a decreased appetite.
  6. Participant currently on or scheduled to receive carbonic anhydrase inhibitors such as topiramate or acetazolamide.
  7. Participant currently on or are scheduled to receive drugs known to have pharmacokinetic (PK) interaction.
  8. Participant who has previously received zonisamide.
  9. Participant with positive serology for Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), or Human Immunodeficiency Virus (HIV).
  10. Participant who has degenerative or metabolic disease of the brain.
  11. Participant with history of psychiatric disorder (excluding stable attention deficit hyperactivity disorder (ADHD), mood disorder on adequate treatment).
  12. Participant has any condition which, in the Investigator's opinion, would make it unsafe for the participant to participate in this study.
  13. Participant who has participated in other clinical study 30 days prior to enrollment in this study or 4-5 half lives of investigational drug, whichever is longer.
  14. Participant who uses alcohol or is currently on or scheduled to receive other central nervous system (CNS) depressants.
  15. Participant has a positive COVID-19 polymerase chain reaction (PCR) test result; or has had exposure (within 2 weeks prior to screening) to someone who had a positive COVID-19 test result; or is suspected of having long COVID-19 by the Investigator or designee.
  16. Participant who is missing more than 15% of daily diary entries during the screening period.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Zonisamide Oral Suspension; Zonisamide Oral Suspension, 100 mg/5 ml administered orally twice daily; Titration Period: 1 mg/kg/day administered as a divided dose of 0.5 mg/kg twice daily for 2 weeks, then increased by 1 mg/kg/day (as divided doses) at weekly intervals in Weeks 3 to 8.; Maintenance Period: Up to 8 mg/kg/day given as a divided dose twice a day for 4 weeks (i.e., Weeks 9 to 12).

Drug: Zonisamide Oral Product; Zonisamide oral suspension; Other Names: ZONISADE; Zonisamide oral suspension

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentration of serum zonisamide	The concentration in serum of zonisamide following administration of zonisamide oral suspension, 100 mg/5 ml	Up to 15 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of treatment-emergent adverse events (TEAEs)	Incidence of treatment-emergent adverse events (TEAEs), serious and non-serious, reported throughout the study.	Up to 15 weeks
Number and/or percentage of participants who discontinued the study because of adverse events	Number and/or percentage of participants who discontinued the study because of adverse events	Up to 15 weeks
Number and/or percentage of participants who required zonisamide dose reduction because of TEAEs.	Number and/or percentage of participants who required zonisamide dose reduction because of TEAEs.	Up to 15 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in seizure frequency	Change from baseline in seizure frequency	Up to 15 weeks

Collaborators and Investigators

• Sponsor: Azurity Pharmaceuticals
• Investigators: Study Director: Evan Scullin, MD, Azurity Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: July 30, 2024
• First Submitted That Met QC Criteria: July 30, 2024
• First Posted (Actual): August 2, 2024

Study Record Updates

• Last Update Posted (Actual): March 27, 2026
• Last Update Submitted That Met QC Criteria: March 24, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Pediatrics; Zonisamide; Partial-onset (focal) seizures; ZONISADE
• Additional Relevant MeSH Terms: Neurologic Manifestations; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Epilepsy; Seizures; Epilepsies, Partial; Calcium-Regulating Hormones and Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Anticonvulsants; Calcium Channel Blockers; Zonisamide
• Other Study ID Numbers: AZ04.001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No