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.

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

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.