Headache Disorders, Migraine Disorders
Conditions
Brief summary
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.
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
Interventions
DRUGSPN-538
Participants will receive SPN-538
DRUGPlacebo
Participants will receive Placebo
Sponsors
Supernus Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Double-blind, randomized, placebo-controlled, 2-arm, parallel group study
Eligibility
Sex/Gender
ALL
Age
6 Years to 11 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Monthly Migraine Days (MMDs) in Children 6 to 11 Years Old With Migraine. | 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) | 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. |
Countries
United States
Contacts
STUDY_DIRECTORGianpiera Ceresoli-Borroni, PhD
Employee of Supernus
Participant flow
Pre-assignment details
Total of 60 participants were screened for eligibility; 26 participants randomized to receive double-blind treatment.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Patients received Placebo once a day. | 12 |
| SPN-538 Participants received SPN-538 once a day 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 maximal tolerated dose (MTD), whichever is less. | 14 |
| Total | 26 |
Baseline characteristics
| Characteristic | Total | SPN-538 | Placebo |
|---|---|---|---|
| Age, Categorical <=18 years | 26 Participants | 13 Participants | 13 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 8.2 years STANDARD_DEVIATION 1.6 | 8.2 years STANDARD_DEVIATION 1.68 | 8.2 years STANDARD_DEVIATION 1.59 |
| Baseline Migraine Frequency | 6.61 monthly migraine day STANDARD_DEVIATION 2.535 | 6.09 monthly migraine day STANDARD_DEVIATION 1.365 | 7.22 monthly migraine day STANDARD_DEVIATION 3.434 |
| Body Mass Index (BMI) | 20.93 kilograms per square meter STANDARD_DEVIATION 3.885 | 21.35 kilograms per square meter STANDARD_DEVIATION 4.285 | 20.51 kilograms per square meter STANDARD_DEVIATION 3.564 |
| Height | 135.6 centimeter STANDARD_DEVIATION 10.74 | 137.5 centimeter STANDARD_DEVIATION 10.97 | 133.6 centimeter STANDARD_DEVIATION 10.57 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 14 Participants | 7 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 12 Participants | 6 Participants | 6 Participants |
| Region of Enrollment United States | 26 participants | 13 participants | 13 participants |
| Sex: Female, Male Female | 15 Participants | 9 Participants | 6 Participants |
| Sex: Female, Male Male | 11 Participants | 4 Participants | 7 Participants |
| Weight | 39.4 Kilograms STANDARD_DEVIATION 11.67 | 41.6 Kilograms STANDARD_DEVIATION 13.29 | 37.2 Kilograms STANDARD_DEVIATION 9.81 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 13 |
| other Total, other adverse events | 4 / 13 | 4 / 13 |
| serious Total, serious adverse events | 0 / 13 | 0 / 13 |
Outcome results
Primary
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.
Time frame: 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)
Population: Full Analysis Set (FAS) included participants who received at least one dose of study medication and have a baseline and at least one valid post-baseline assessment of monthly migraine based on the headache diary data.~The number of participants in some rows differs from the overall number as some participants discontinued the study before the specific time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Monthly Migraine Days (MMDs) in Children 6 to 11 Years Old With Migraine. | Titration Period 2 (Month 2) | -3.52 monthly migraine days | Standard Deviation 2.211 |
| Placebo | Change From Baseline in Monthly Migraine Days (MMDs) in Children 6 to 11 Years Old With Migraine. | Maintenance Period 2 (Month 4) | -4.36 monthly migraine days | Standard Deviation 2.755 |
| Placebo | Change From Baseline in Monthly Migraine Days (MMDs) in Children 6 to 11 Years Old With Migraine. | Maintenance Period 1 (Month 3) | -3.28 monthly migraine days | Standard Deviation 2.317 |
| Placebo | Change From Baseline in Monthly Migraine Days (MMDs) in Children 6 to 11 Years Old With Migraine. | Maintenance Period 3 (Month 5) | -4.17 monthly migraine days | Standard Deviation 2.521 |
| Placebo | Change From Baseline in Monthly Migraine Days (MMDs) in Children 6 to 11 Years Old With Migraine. | Titration Period 1 (Month 1) | -2.68 monthly migraine days | Standard Deviation 1.678 |
| SPN-538 | Change From Baseline in Monthly Migraine Days (MMDs) in Children 6 to 11 Years Old With Migraine. | Maintenance Period 3 (Month 5) | -4.60 monthly migraine days | Standard Deviation 2.367 |
| SPN-538 | Change From Baseline in Monthly Migraine Days (MMDs) in Children 6 to 11 Years Old With Migraine. | Titration Period 1 (Month 1) | -3.22 monthly migraine days | Standard Deviation 1.185 |
| SPN-538 | Change From Baseline in Monthly Migraine Days (MMDs) in Children 6 to 11 Years Old With Migraine. | Titration Period 2 (Month 2) | -4.51 monthly migraine days | Standard Deviation 2.194 |
| SPN-538 | Change From Baseline in Monthly Migraine Days (MMDs) in Children 6 to 11 Years Old With Migraine. | Maintenance Period 1 (Month 3) | -5.02 monthly migraine days | Standard Deviation 2.234 |
| SPN-538 | Change From Baseline in Monthly Migraine Days (MMDs) in Children 6 to 11 Years Old With Migraine. | Maintenance Period 2 (Month 4) | -5.08 monthly migraine days | Standard Deviation 2.699 |