Efficacy, Tolerability, and Safety of DFN-15

Percentage of subjects who are free from their Most Bothersome Symptom (MBS) among nausea, photophobia, and phonophobia (first double-blind treatment period)

Time frame: 2 hours postdose

Population: Full Analysis Set 1

The primary efficacy end point (for first treated DB1 attack only) were the percentage of subjects who were pain-free 2 hours postdose compared between DFN-15 and placebo (defined as a reduction from predose moderate \[Grade 2\] or severe \[Grade 3\] pain to none \[Grade 0\]

Time frame: 2 hours postdose

Population: Full Analysis Set 1

The percentage of subjects with their Screening MBS (Most Bothersome Symptom) absent at 15, 30, and 45 minutes and 1, 1.5, 2 (DB2 period), 4, and 24 hours postdose compared between DFN-15 and placebo.

Time frame: 15 minutes to 24 hours postdose

Change in functional disability score at 2, 4, and 24 hours postdose compared between DFN-15 and placebo. The values of the functional disability scale were: 0=no disability, able to function normally; 1=performance of daily activities mildly impaired, can still do everything but with difficulty; 2=performance of daily activities moderately impaired, unable to do some things; 3=performance of daily activities severely impaired, cannot do all or most things, bed rest may be necessary. A decrease in values indicates improvement from baseline.

Time frame: 2 to 24 hours postdose

The percentage of subjects who were free from nausea, photophobia, and phonophobia at 15, 30, and 45 minutes and 1, 1.5, 2, 4, and 24 hours postdose compared between DFN-15 and placebo

Time frame: 15 minutes to 24 hours postdose

The percentage of subjects who were pain-free at 2 and 4 hours postdose whose BMI was \< 30 kg/m2 vs. subjects whose BMI was ≥ 30 kg/m2, and whose BMI was \< 25 kg/m2 vs. subjects whose BMI was ≥ 25 kg/m2

Time frame: 2 and 4 hours postdose

Population: Subjects were stratified and data were evaluated by subject BMI, therefore the overall number analyzed differs from the participant numbers reported in the data table.

The percentage of subjects who were pain-free at 2 and 4 hours postdose compared between DFN-15 and placebo, among those reporting cutaneous allodynia predose

Time frame: 2 and 4 hours postdose

The percentage of subjects who were pain-free at 15, 30, and 45 minutes and 1, 1.5, 2 (DB2 period), 4, and 24 hours postdose compared between DFN-15 and placebo

Time frame: 15 minutes to 24 hours postdose

Population: data for 2 hours postdose were not collected for DB1 per protocol

The percentage of subjects who had pain recurrence between 2 to 24 hours (i.e., pain-free at 2 hours postdose, with pain \[mild, moderate, or severe\] reported at 24 hours postdose) compared between DFN-15 and placebo

Time frame: 2 to 24 hours postdose

Headache pain relief was defined for DB1 as a reduction from moderate or severe pain before dosing to mild or none postdose, and for DB2 as moderate or severe pain before dosing reduced to mild or none postdose, or mild pain before dosing reduced to none postdose. Data are reported by percentage reporting headache pain relief over time postdose.

Time frame: 15 minutes to 24 hours postdose

Patient Perception of Migraine Questionnaire-Revised had 30 questions assessing subject's satisfaction with migraine medication, including 3 global items & 4 subscales (i.e., efficacy, function, ease of use, tolerability). A 5-point scale (1-Not At All to 5-Extremely) was used for tolerability subscale questions; a 7-point scale (1-Very Satisfied to 7-Very Dissatisfied) was used for all other subscales and global items. Total score was average of efficacy/function/ease of use subscale scores. Each subscale & total scores were transformed to range from 0-100, with higher scores indicating better satisfaction or tolerability. Total raw score/global items were not transformed. The total raw score could range from 17 (min) to 119 (max), with lower scores indicating better satisfaction. Change from baseline scores at 24-hour-postdose for each subscale score, global item score, total score, & total raw score were summarized by treatment group below.

Time frame: 24 hours postdose

Subject-rated treatment overall satisfaction was based on a 7-point scale at 2 and 4 hours postdose during each DB treatment period. The difference between the subject-rated study drug treatment satisfaction score at 2 and 4 hours postdose and the baseline PPMQ-R (Patient Perception of Migraine Questionnaire) response for the same question were summarized by treatment group (global satisfaction item at baseline asked about the subject's usual migraine treatment). The possible values of the subject treatment satisfaction scale were: 1=very satisfied, 2=satisfied, 3=somewhat satisfied, 4=neither satisfied nor dissatisfied, 5=somewhat dissatisfied, 6=dissatisfied, 7=very dissatisfied. A decrease in values indicates improvement from baseline.

Time frame: 2 and 4 hours postdose

The percentage of subjects who had sustained pain freedom at 2 to 24 hours postdose compared between DFN-15 and placebo in each DB period. Sustained pain freedom at 2 to 24 hours postdose is defined as pain-free at 2 hours postdose, with no use of rescue medication, and no recurrence of headache pain within 2 to 24 hours postdose

Time frame: 2 to 24 hours postdose

The percentage of the population of subjects who reported headache pain relief between 2 and 24 hours postdose.

Time frame: 2 to 24 hours postdose

For DB1: TEAE that started or worsening of a pre-existing condition on or after the first dose of study drug (DFN-15 or placebo) in to taking DB2 study drug, whichever occurs first. For DB2: TEAE that started or worsened on or after the first dose of study drug in DB2 up to 5 days after the date of the last dose of study drug in DB2.

Time frame: Per protocol, the maximum dosing timeframe for DB2 was 10 weeks; therefore, the maximum AE collection window was 11 weeks total.

The time to headache pain freedom was defined as the time in minutes from when a subject took study drug until the time pain freedom was indicated by the subject in the eDiary within 2 hours postdose.

Time frame: 2 hours postdose

The time to headache pain relief was defined as the time in minutes from when a subject took study drug until the time pain relief was indicated by the subject in the eDiary within 2 hours postdose.

Time frame: 2 hours postdose

The percentage of subjects who used rescue medication after 2 hours (2 to 24 hours) postdose compared between DFN-15 and placebo in each DB period

Time frame: 2 to 24 hours postdose