Trial Outcomes & Findings for Therapy for Migraine Prevention in Children 6-11 Years of Age (NCT NCT04050293)

Last Updated: 2026-01-22

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE4

Target enrollment

26 participants

Primary outcome timeframe

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)

Results posted on

2026-01-22

Participant Flow

Total of 60 participants were screened for eligibility; 26 participants randomized to receive double-blind treatment.

Participant milestones

Participant milestones
Measure	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.	Placebo Participants received Placebo once a day.
Overall Study STARTED	13	13
Overall Study COMPLETED	11	10
Overall Study NOT COMPLETED	2	3

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	Placebo Participants received Placebo once a day.
Overall Study Lost to Follow-up	2	1
Overall Study Withdrawal by Subject	0	2

Baseline Characteristics

The measure is the 28-day rate for the prospective baseline defined as the total number of migraine days during the last 4 weeks prior to randomization/total number of days with non-missing headache data during the 28 days prior to randomization \*28 in the FAS population. Number of participants is from the FAS: 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.

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=11 Participants Participants received Placebo once a day.	SPN-538 n=13 Participants 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.
Change From Baseline in Monthly Migraine Days (MMDs) in Children 6 to 11 Years Old With Migraine. Titration Period 1 (Month 1)	-2.89 monthly migraine days Standard Deviation 1.919	-3.08 monthly migraine days Standard Deviation 0.830
Change From Baseline in Monthly Migraine Days (MMDs) in Children 6 to 11 Years Old With Migraine. Titration Period 2 (Month 2)	-4.85 monthly migraine days Standard Deviation 2.199	-3.38 monthly migraine days Standard Deviation 2.057
Change From Baseline in Monthly Migraine Days (MMDs) in Children 6 to 11 Years Old With Migraine. Maintenance Period 1 (Month 3)	-4.25 monthly migraine days Standard Deviation 2.903	-4.35 monthly migraine days Standard Deviation 1.977
Change From Baseline in Monthly Migraine Days (MMDs) in Children 6 to 11 Years Old With Migraine. Maintenance Period 2 (Month 4)	-5.41 monthly migraine days Standard Deviation 3.049	-4.18 monthly migraine days Standard Deviation 2.279
Change From Baseline in Monthly Migraine Days (MMDs) in Children 6 to 11 Years Old With Migraine. Maintenance Period 3 (Month 5)	-4.32 monthly migraine days Standard Deviation 2.477	-4.50 monthly migraine days Standard Deviation 2.410

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

SPN-538

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Gianpiera Ceresoli-Borroni Director Clinical Research

Supernus Pharmaceuticals

Phone: 3018382521

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Placebo n=13 Participants Patients received Placebo once a day.	SPN-538 n=13 Participants 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.	Total n=26 Participants Total of all reporting groups
Sex: Female, Male Male	7 Participants n=13 Participants	4 Participants n=13 Participants	11 Participants n=26 Participants
Age, Categorical <=18 years	13 Participants n=13 Participants	13 Participants n=13 Participants	26 Participants n=26 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=13 Participants	0 Participants n=13 Participants	0 Participants n=26 Participants
Age, Categorical >=65 years	0 Participants n=13 Participants	0 Participants n=13 Participants	0 Participants n=26 Participants
Age, Continuous	8.2 years STANDARD_DEVIATION 1.59 • n=13 Participants	8.2 years STANDARD_DEVIATION 1.68 • n=13 Participants	8.2 years STANDARD_DEVIATION 1.60 • n=26 Participants
Sex: Female, Male Female	6 Participants n=13 Participants	9 Participants n=13 Participants	15 Participants n=26 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=13 Participants	0 Participants n=13 Participants	0 Participants n=26 Participants
Race (NIH/OMB) Asian	0 Participants n=13 Participants	0 Participants n=13 Participants	0 Participants n=26 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=13 Participants	0 Participants n=13 Participants	0 Participants n=26 Participants
Race (NIH/OMB) Black or African American	7 Participants n=13 Participants	7 Participants n=13 Participants	14 Participants n=26 Participants
Race (NIH/OMB) White	6 Participants n=13 Participants	6 Participants n=13 Participants	12 Participants n=26 Participants
Race (NIH/OMB) More than one race	0 Participants n=13 Participants	0 Participants n=13 Participants	0 Participants n=26 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=13 Participants	0 Participants n=13 Participants	0 Participants n=26 Participants
Region of Enrollment United States	13 participants n=13 Participants	13 participants n=13 Participants	26 participants n=26 Participants
Baseline Migraine Frequency	7.22 monthly migraine day STANDARD_DEVIATION 3.434 • n=11 Participants • The measure is the 28-day rate for the prospective baseline defined as the total number of migraine days during the last 4 weeks prior to randomization/total number of days with non-missing headache data during the 28 days prior to randomization \*28 in the FAS population. Number of participants is from the FAS: 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.	6.09 monthly migraine day STANDARD_DEVIATION 1.365 • n=13 Participants • The measure is the 28-day rate for the prospective baseline defined as the total number of migraine days during the last 4 weeks prior to randomization/total number of days with non-missing headache data during the 28 days prior to randomization \*28 in the FAS population. Number of participants is from the FAS: 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.	6.61 monthly migraine day STANDARD_DEVIATION 2.535 • n=24 Participants • The measure is the 28-day rate for the prospective baseline defined as the total number of migraine days during the last 4 weeks prior to randomization/total number of days with non-missing headache data during the 28 days prior to randomization \*28 in the FAS population. Number of participants is from the FAS: 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.
Height	133.6 centimeter STANDARD_DEVIATION 10.57 • n=13 Participants	137.5 centimeter STANDARD_DEVIATION 10.97 • n=13 Participants	135.6 centimeter STANDARD_DEVIATION 10.74 • n=26 Participants
Weight	37.2 Kilograms STANDARD_DEVIATION 9.81 • n=13 Participants	41.6 Kilograms STANDARD_DEVIATION 13.29 • n=13 Participants	39.4 Kilograms STANDARD_DEVIATION 11.67 • n=26 Participants
Body Mass Index (BMI)	20.51 kilograms per square meter STANDARD_DEVIATION 3.564 • n=13 Participants	21.35 kilograms per square meter STANDARD_DEVIATION 4.285 • n=13 Participants	20.93 kilograms per square meter STANDARD_DEVIATION 3.885 • n=26 Participants

Measure	Placebo n=13 participants at risk Participants received Placebo once a day.	SPN-538 n=13 participants at risk 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.
Gastrointestinal disorders Vomiting	0.00% 0/13 • Baseline (Day 1) to Week 26 Treatment Emergent Adverse Event (TEAE) is an adverse event (AE) with a start date on or after the first dose of study medication is taken, or that worsened following first administration of study medication.	7.7% 1/13 • Number of events 1 • Baseline (Day 1) to Week 26 Treatment Emergent Adverse Event (TEAE) is an adverse event (AE) with a start date on or after the first dose of study medication is taken, or that worsened following first administration of study medication.
Infections and infestations COVID-19	0.00% 0/13 • Baseline (Day 1) to Week 26 Treatment Emergent Adverse Event (TEAE) is an adverse event (AE) with a start date on or after the first dose of study medication is taken, or that worsened following first administration of study medication.	7.7% 1/13 • Number of events 1 • Baseline (Day 1) to Week 26 Treatment Emergent Adverse Event (TEAE) is an adverse event (AE) with a start date on or after the first dose of study medication is taken, or that worsened following first administration of study medication.
Infections and infestations Croup infectious	7.7% 1/13 • Number of events 1 • Baseline (Day 1) to Week 26 Treatment Emergent Adverse Event (TEAE) is an adverse event (AE) with a start date on or after the first dose of study medication is taken, or that worsened following first administration of study medication.	0.00% 0/13 • Baseline (Day 1) to Week 26 Treatment Emergent Adverse Event (TEAE) is an adverse event (AE) with a start date on or after the first dose of study medication is taken, or that worsened following first administration of study medication.
Respiratory, thoracic and mediastinal disorders Asthma	7.7% 1/13 • Number of events 1 • Baseline (Day 1) to Week 26 Treatment Emergent Adverse Event (TEAE) is an adverse event (AE) with a start date on or after the first dose of study medication is taken, or that worsened following first administration of study medication.	0.00% 0/13 • Baseline (Day 1) to Week 26 Treatment Emergent Adverse Event (TEAE) is an adverse event (AE) with a start date on or after the first dose of study medication is taken, or that worsened following first administration of study medication.
Respiratory, thoracic and mediastinal disorders Cough	7.7% 1/13 • Number of events 2 • Baseline (Day 1) to Week 26 Treatment Emergent Adverse Event (TEAE) is an adverse event (AE) with a start date on or after the first dose of study medication is taken, or that worsened following first administration of study medication.	7.7% 1/13 • Number of events 1 • Baseline (Day 1) to Week 26 Treatment Emergent Adverse Event (TEAE) is an adverse event (AE) with a start date on or after the first dose of study medication is taken, or that worsened following first administration of study medication.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	7.7% 1/13 • Number of events 1 • Baseline (Day 1) to Week 26 Treatment Emergent Adverse Event (TEAE) is an adverse event (AE) with a start date on or after the first dose of study medication is taken, or that worsened following first administration of study medication.	0.00% 0/13 • Baseline (Day 1) to Week 26 Treatment Emergent Adverse Event (TEAE) is an adverse event (AE) with a start date on or after the first dose of study medication is taken, or that worsened following first administration of study medication.
Gastrointestinal disorders Dyspepsia	0.00% 0/13 • Baseline (Day 1) to Week 26 Treatment Emergent Adverse Event (TEAE) is an adverse event (AE) with a start date on or after the first dose of study medication is taken, or that worsened following first administration of study medication.	7.7% 1/13 • Number of events 1 • Baseline (Day 1) to Week 26 Treatment Emergent Adverse Event (TEAE) is an adverse event (AE) with a start date on or after the first dose of study medication is taken, or that worsened following first administration of study medication.
Gastrointestinal disorders Nausea	23.1% 3/13 • Number of events 3 • Baseline (Day 1) to Week 26 Treatment Emergent Adverse Event (TEAE) is an adverse event (AE) with a start date on or after the first dose of study medication is taken, or that worsened following first administration of study medication.	0.00% 0/13 • Baseline (Day 1) to Week 26 Treatment Emergent Adverse Event (TEAE) is an adverse event (AE) with a start date on or after the first dose of study medication is taken, or that worsened following first administration of study medication.
Psychiatric disorders Depressed mood	0.00% 0/13 • Baseline (Day 1) to Week 26 Treatment Emergent Adverse Event (TEAE) is an adverse event (AE) with a start date on or after the first dose of study medication is taken, or that worsened following first administration of study medication.	7.7% 1/13 • Number of events 1 • Baseline (Day 1) to Week 26 Treatment Emergent Adverse Event (TEAE) is an adverse event (AE) with a start date on or after the first dose of study medication is taken, or that worsened following first administration of study medication.
Psychiatric disorders Mood altered	0.00% 0/13 • Baseline (Day 1) to Week 26 Treatment Emergent Adverse Event (TEAE) is an adverse event (AE) with a start date on or after the first dose of study medication is taken, or that worsened following first administration of study medication.	7.7% 1/13 • Number of events 1 • Baseline (Day 1) to Week 26 Treatment Emergent Adverse Event (TEAE) is an adverse event (AE) with a start date on or after the first dose of study medication is taken, or that worsened following first administration of study medication.
Immune system disorders Hypersensitivity	7.7% 1/13 • Number of events 1 • Baseline (Day 1) to Week 26 Treatment Emergent Adverse Event (TEAE) is an adverse event (AE) with a start date on or after the first dose of study medication is taken, or that worsened following first administration of study medication.	0.00% 0/13 • Baseline (Day 1) to Week 26 Treatment Emergent Adverse Event (TEAE) is an adverse event (AE) with a start date on or after the first dose of study medication is taken, or that worsened following first administration of study medication.
Immune system disorders Rhinitis allergic	7.7% 1/13 • Number of events 1 • Baseline (Day 1) to Week 26 Treatment Emergent Adverse Event (TEAE) is an adverse event (AE) with a start date on or after the first dose of study medication is taken, or that worsened following first administration of study medication.	0.00% 0/13 • Baseline (Day 1) to Week 26 Treatment Emergent Adverse Event (TEAE) is an adverse event (AE) with a start date on or after the first dose of study medication is taken, or that worsened following first administration of study medication.
Injury, poisoning and procedural complications Skin abrasion	0.00% 0/13 • Baseline (Day 1) to Week 26 Treatment Emergent Adverse Event (TEAE) is an adverse event (AE) with a start date on or after the first dose of study medication is taken, or that worsened following first administration of study medication.	7.7% 1/13 • Number of events 1 • Baseline (Day 1) to Week 26 Treatment Emergent Adverse Event (TEAE) is an adverse event (AE) with a start date on or after the first dose of study medication is taken, or that worsened following first administration of study medication.
General disorders Fatigue	7.7% 1/13 • Number of events 1 • Baseline (Day 1) to Week 26 Treatment Emergent Adverse Event (TEAE) is an adverse event (AE) with a start date on or after the first dose of study medication is taken, or that worsened following first administration of study medication.	0.00% 0/13 • Baseline (Day 1) to Week 26 Treatment Emergent Adverse Event (TEAE) is an adverse event (AE) with a start date on or after the first dose of study medication is taken, or that worsened following first administration of study medication.
Investigations Ammonia increased	0.00% 0/13 • Baseline (Day 1) to Week 26 Treatment Emergent Adverse Event (TEAE) is an adverse event (AE) with a start date on or after the first dose of study medication is taken, or that worsened following first administration of study medication.	7.7% 1/13 • Number of events 1 • Baseline (Day 1) to Week 26 Treatment Emergent Adverse Event (TEAE) is an adverse event (AE) with a start date on or after the first dose of study medication is taken, or that worsened following first administration of study medication.
Skin and subcutaneous tissue disorders Rash	7.7% 1/13 • Number of events 1 • Baseline (Day 1) to Week 26 Treatment Emergent Adverse Event (TEAE) is an adverse event (AE) with a start date on or after the first dose of study medication is taken, or that worsened following first administration of study medication.	0.00% 0/13 • Baseline (Day 1) to Week 26 Treatment Emergent Adverse Event (TEAE) is an adverse event (AE) with a start date on or after the first dose of study medication is taken, or that worsened following first administration of study medication.
Injury, poisoning and procedural complications Arthropod sting	7.7% 1/13 • Number of events 1 • Baseline (Day 1) to Week 26 Treatment Emergent Adverse Event (TEAE) is an adverse event (AE) with a start date on or after the first dose of study medication is taken, or that worsened following first administration of study medication.	0.00% 0/13 • Baseline (Day 1) to Week 26 Treatment Emergent Adverse Event (TEAE) is an adverse event (AE) with a start date on or after the first dose of study medication is taken, or that worsened following first administration of study medication.
Injury, poisoning and procedural complications Skin Laceration	0.00% 0/13 • Baseline (Day 1) to Week 26 Treatment Emergent Adverse Event (TEAE) is an adverse event (AE) with a start date on or after the first dose of study medication is taken, or that worsened following first administration of study medication.	7.7% 1/13 • Number of events 1 • Baseline (Day 1) to Week 26 Treatment Emergent Adverse Event (TEAE) is an adverse event (AE) with a start date on or after the first dose of study medication is taken, or that worsened following first administration of study medication.