Therapy for Migraine Prevention in Children 6-11 Years of Age

A Randomized, Double-Blind, Placebo-Controlled, Multicenter, Parallel Group Study to Evaluate the Efficacy and Safety of SPN-538 as a Therapy for the Prevention of Migraine in Subjects Ages 6-11 Years

The aim of this study is to evaluate the effect of SPN-538 for the prophylaxis of migraine in pediatric patients 6 to 11 years old.

Study Overview

• Status: Terminated
• Conditions: Migraine Disorders; Headache Disorders
• Intervention / Treatment: Drug: Placebo; Drug: SPN-538

Detailed Description

The study is to assess the efficacy and safety of SPN-538 in reducing the monthly migraine headache frequency in pediatric patients with migraine.

This is a multicenter, randomized, double-blind, placebo-controlled, 2-arm, parallel group Phase 4 study in children 6 to 11 years of age to evaluate the efficacy and safety of SPN-538 for the prevention of migraine. SPN-538 (or matching placebo) will be administered as a single oral dose once a day (QD), starting at 25 mg/day and increasing every 2 weeks in 25 mg increments to a target dose of 2 to 3 mg/kg/day or the maximum tolerated dose (MTD), whichever is less. The total study duration is a maximum of 34 weeks including a Screening Period, Prospective Baseline Period of up to 8 weeks, a Treatment Phase of 20 weeks (8 weeks titration followed by 12 weeks of maintenance dosing), a Dose Tapering Period of 1 to 3 weeks, and a Safety Follow-up Period of 1 to 3 weeks

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • CNS Healthcare

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 11 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Otherwise, healthy male or female (6 to 11 years of age at the time of screening) with a history of migraine with or without aura for at least 6 months prior to screening, 3-12 migraine episodes and no more than 14 headache days (migraine and non-migraine) per month during the 3 months prior to Screening and during the 28-day Prospective Baseline Period, a PedMIDAS Disability score of ≥20 and ≤139 and weight at least 20 kg and no more than 60 kg.

Exclusion Criteria:

• Subjects with chronic migraine (>14 headache days per month), cluster headaches, or migraine aura without headache and who are unable to distinguish migraines from other headache types.
• Subjects with more than 14 headache days during the 28-day Prospective Baseline Period
• Have taken any disallowed migraine preventive medication including TPM within 14 days prior to the start of the Prospective Baseline Period; or used onabotulinumtoxinA (Botox®) within 3 months prior to Screening.
• Failure to respond to topiramate prophylaxis therapy (2 to 3 mg/kg/day) for a minimum of 3 months, or those who have previously discontinued TPM due to AEs within 6 months prior to Screening.
• Failure to more than 2 adequate clinical trials of an established prophylactic antimigraine regimen within 6 months prior to Screening.
• Current use of antipsychotics, antimanics, barbiturates, benzodiazepines amitriptyline, lithium, valproic acid, tricyclic antidepressants, AEDs, calcium channel blockers, sedatives, SSRIs, NSRIs, CGRP receptor antagonists, CBD oil, herbal preparations/supplements such as feverfew or St John's wort and/or any medications that could impair or decrease thinking and concentration.
• Overuse of analgesic or migraine-specific agents for acute treatment of migraine (>10 treatment days/month of ergot-containing medications or triptans; or >15 treatment days/month with simple analgesics (including non steroidal anti-inflammatory drugs [NSAIDs]), or use of narcotics.
• Use of non-pharmacologic complementary and alternative prophylactic approaches for migraine prevention, such as neuromodulation, acupuncture, behavioral interventions, spinal manipulation, occipital nerve block and neurofeedback.
• Diagnosis of psychiatric disorder (e.g., psychosis, bipolar disorder, major depression, generalized anxiety disorders), or documented developmental delays or impairments (e.g., autism, cerebral palsy, or mental retardation).
• Subjects with seizures or a history of seizure-like events.
• Known history of visual field defects, neurological disorder or structural disorder of the brain from birth; head trauma or previous CNS surgery.
• Evidence of active suicidal ideation and/or suicidal behaviors 6 months before screening, pregnancy, active liver disease or abnormal kidney function.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SPN-538 (Topiramate XR capsule); Participants will be treated with SPN-538	Drug: SPN-538; Participants will receive SPN-538
Placebo Comparator: Placebo; Participants will be treated with Placebo	Drug: Placebo; Participants will receive Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Monthly Migraine Days (MMDs) in Children 6 to 11 Years Old With Migraine.	The primary efficacy endpoint was the change in rate of the MMDs relative to the Prospective Baseline Period (PBP). The 28-day rate of MMDs was calculated as the ratio of the # days of migraine during the last 4 weeks of PBP and the # days with non-missing headache record in the electronic diary during the last 4 weeks of the 20-week double-blind Treatment Phase, x 28. The primary outcome measure was recorded on headache electronic diary uploaded on a Patient Reported Outcome (ePRO) application. The electronic diary will serve as the primary tool to collect daily headaches information.	Baseline, Titration Period 1 (Month 1), Titration Period 2 (Month 2), Maintenance Period 1 (Month 3), Maintenance Period 2 (Month 3), Maintenance Period 2 (Month 4) and Maintenance Period 3 (Month 5)

Collaborators and Investigators

• Sponsor: Supernus Pharmaceuticals, Inc.
• Investigators: Study Director: Gianpiera Ceresoli-Borroni, PhD, Employee of Supernus

Study record dates

Study Major Dates

• Study Start (Actual): July 14, 2020
• Primary Completion (Actual): March 1, 2023
• Study Completion (Actual): March 1, 2023

Study Registration Dates

• First Submitted: August 2, 2019
• First Submitted That Met QC Criteria: August 6, 2019
• First Posted (Actual): August 8, 2019

Study Record Updates

• Last Update Posted (Actual): January 22, 2026
• Last Update Submitted That Met QC Criteria: January 5, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Migraine Disorders; Headache Disorders
• Other Study ID Numbers: 538P401

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No