An Efficacy and Safety Study of DFN-02 (Sumatriptan Nasal Spray 10 mg)

Study Overview
=================
Brief Summary
-----------------
A safety and efficacy study of DFN-02 (Sumatriptan Nasal Spray 10 mg), being conducted at multiple centers in the United States.

Detailed Description
-----------------
This was a randomized, two double-blind (DB) treatment period dosing study. Previously diagnosed subjects with a history of episodic migraine (as defined by International Classification of Headache Disorders (ICHD), 3rd edition [beta version] [ICHD 3]) who experienced an average of 2 to 8 migraine attacks per month for at least the prior 12 months, with no more than 14 headache days per month, and with 48 hours of headache free time between migraine, were randomized in a 1:1 ratio in both DB periods to receive either DFN-02 (sumatriptan nasal spray 10 mg) or a matching placebo. Subjects treated one moderate to severe migraine attack in the first double-blind treatment period (DB1) and, if eligible, were re-randomized into the second double-blind treatment period (DB2) to treat another migraine attack at any pain level. There was a screening period of up to 21 days to evaluate whether subjects fit the migraine inclusion criteria pursuant to ICHD-3, and did not have medication overuse. Subjects with at least a 12 month medical history of acute migraine were eligible for enrollment in the treatment period. Subjects continued to take their normal migraine medication during this screening period. If eligible and randomized, subjects in the DB1 treatment period were instructed to use the study medication in one migraine attack as soon as (and no more than within one hour after) experiencing moderate to severe migraine pain (defined as headache pain rating of Grade 2 [moderate] or Grade 3 [severe] on a pain severity scale of 0 to 3). If the subject was not able to use study medication for the first migraine after randomization, they were instructed to use the study medication for the next attack. Those subjects who did not experience a migraine attack, and/or did not treat any migraine attack with study medication or record diary data, were not allowed to continue into the DB2 treatment period, and were discontinued. After treating a migraine attack with study medication, subjects were instructed to contact the site within 24 hours of the treated migraine (or the next working day) to schedule their next visit. Subjects returned to the study site within 2 to 7 days in the DB1 treatment period and, if continuing to be eligible, were re-randomized into a DB2 treatment period to treat one migraine attack at any pain level, and return to the study site within 2 to 7 days of the second treatment. Once randomized, the total duration of each subject's participation in the study was up to 10 weeks.

Official Title
-----------------
A Multicenter, Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety Study of DFN-02 in Episodic Migraine With or Without Aura

Conditions
-----------------
Migraine Headaches

Intervention / Treatment
-----------------
* Drug: Sumatriptan 10 mg Nasal Spray
* Other: Sumatriptan Placebo Nasal Spray


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: A history of episodic migraine who experience an average of 2 to 8 migraine attacks per month for at least the past 12 months, with no more than 14 headache days per month, and with 48 hours of headache free time between migraine headaches Patients who have migraine with or without aura. If migraine with aura, the aura cannot last longer than 60 minutes. Patients who are willing and able to: Evaluate and record pain, migraine symptoms, and study medication effectiveness information in real-time using a diary for the duration of the study; Record each instance of the use of study medication and rescue medication in a patient diary in real-time for the duration of the study; Comply with all other study procedures and scheduling requirements. Exclusion Criteria: Minors, even if they are in the specified study age range Medication overuse: Opioids ≥ 10 days during the 90 days prior to screening Combination medications (e.g., Fiorinal®) ≥ 10 days during the 90 days prior to screening (only applies if combination medication contains an opioid and/or barbiturate) Nonsteroidal Anti-inflammatory Drugs or other simple medications ˃ 14 days a month during the 90 days prior to screening Triptans or ergots ≥ 10 days a month during the 90 days prior to screening Treated with onabotulinumtoxinA (Botox®) or other botulinum toxin treatment within 4 months prior to screening for migraine prophylaxis (patients who were treated with same for cosmetic purposes may be allowed on a case-by-case basis after approval from the Medical Monitor) A history of or current neurological or psychiatric impairment, or cognitive dysfunction that, in the opinion of the Investigator, would compromise data collection Use of antipsychotics at least 15 days prior to randomization Patients who received treatment with an investigational drug or device within 30 days prior to randomization, or within 3 months if associated with central nervous system Patients who participated in a central nervous system clinical trial within 3 months prior to randomization Patients who test positive for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) antibody serology testing Patients who are employees or immediate relatives of the employees of the Sponsor, any of its affiliates or partners, or of the clinical study research site

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DFN-02<br>Participants self-administered a single-dose of DFN-02 (sumatriptan 10-mg/100 μL nasal spray) intranasally within one hour of an acute migraine pain episode. | Drug: Sumatriptan 10 mg Nasal Spray<br>* 100 μL nasal spray once<br>* Other names: Sumatriptan;|
| Other: Placebo<br>Participants self-administered a single-dose of DFN-02 placebo nasal spray matching DFN-02 intranasally within one hour of an acute migraine pain episode. | Other: Sumatriptan Placebo Nasal Spray<br>* 100 μL nasal spray once<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Free From Headache Pain at 2 Hours After the First Dose of Study Medication Taken for a Migraine Attack With Moderate to Severe Headache Pain During the Double-blind Treatment Period 1 (DB1). | Freedom from headache pain at 2 hours after the first dose of study medication taken within one hour after experiencing a migraine attack of moderate to severe headache pain during the DB1 treatment period, e.g., headache pain rating of moderate [Grade 2] or severe [Grade 3] predose and reduced to none [Grade 0] postdose). Mild headache pain was recorded as Grade 1. If the subject was not able to use study medication for the first migraine after randomization, they were instructed to use the study medication for the next attack. If the subject experienced insufficient relief from the first dose of study medication, they were permitted to take a second dose of study medication or rescue medication 2 or more hours after the first dose, and only after completing the 2 hours' postdose assessments. If no relief was experienced from the first dose of study medication after 2 hours only rescue medication could be administered. Maximum 2 doses of study medication per 24 hours. | 2 hours after study medication administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Absence of Most Bothersome Symptom (MBS) Among Nausea, Photophobia and Phonophobia at 2 Hours (DB1) | Number of participants with their MBS among nausea, photophobia and phonophobia absent at 10, 15, 20, 30, 60, 90, and 120 minutes after the first dose of study medication taken for a migraine attack during DB1 treatment period are summarized by treatment group and time point for the full analysis set (FAS1). The corresponding p-values from Fisher's exact test were computed for the comparison between treatment groups. Subjects who reported a MBS predose and reported the status of the MBS at the particular postdose time point were analyzed. | 2 hours after study medication administration | 
| Number of Participants With Headache Pain Freedom at 2 Hours Postdose in the Double-blind Treatment Period 2 (DB2) | In Double-blind Treatment Period 2 (DB2), freedom from headache pain 2 hours after the first dose of study medication taken within one hour of experiencing a migraine attack for any headache pain level, e.g., mild [Grade 1], moderate [Grade 2], or severe [Grade 3] and reduced to none [Grade 0] after study medication administration. If the subject was not able to use study medication for the first migraine after randomization, they were instructed to use the study medication for the next attack. | 2 hours after study medication administration | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Aura