Efficacy, Tolerability, and Safety Study of DFN-15

Phase 3

Completed

Conditions: Migraine Headache

Interventions: Other: DFN-15 Placebo
Drug: DFN-15 Active

Registration Number: NCT03006276

Lead Sponsor: BioDelivery Sciences International

Brief Summary: Efficacy, Tolerability, and Safety of DFN-15 in episodic migraine with or without aura, being conducted at multiple centers in the United States.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 622

Inclusion Criteria

A history of episodic migraine, who experience 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 attacks.
Patients who have migraine with or without aura with onset before age 50 years
Report usual migraine pain of 2 (moderate) or 3 (severe) on headache pain severity scale without treatment.
Subjects who are willing and able to:
1. Evaluate and record pain, migraine symptoms, and study drug effectiveness information in real-time using a subject eDiary for the duration of the study;
2. Record each instance of the use of study drug and rescue medication in real-time using a subject eDiary for the duration of the study;
3. Comply with all other study procedures and scheduling requirements.

Exclusion Criteria

Minors, even if they are in the specified study age range
Medication overuse:
1. Opioids greater than or equal to 10 days during the 90 days prior to screening
2. Combination medications (e.g., Fiorinal®) greater than or equal to 10 days during the 90 days prior to screening (applies only if includes opioid and/or barbiturate)
3. Nonsteroidal Anti-inflammatory Drugs or other simple medications greater than 14 days a month during the 90 days prior to screening
4. Triptans or ergots greater than or equal to 10 days a month during the 90 days prior to screening
Treated with onabotulinumtoxin A (Botox®) for migraine within 4 months prior to screening. (If treated for cosmetic reasons, subjects may be included).
Current treatment with antipsychotics or use of antipsychotics within 30 days prior to randomization.
Patients who have received treatment with an investigational drug or device within 30 days of randomization, or participated in a central nervous system clinical trial within 2 months prior to randomization
Patients with positive screening test for human immunodeficiency virus [HIV], positive hepatitis B surface antigen (HBsAg), or positive hepatitis C virus [HCV] antibody
Subjects who are employees or immediate relatives of the employees of the Sponsor, any of its affiliates or partners, or of the clinical research study site.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
DFN-15 Placebo	DFN-15 Placebo	DFN-15 Placebo
DFN-15 Active	DFN-15 Active	DFN-15 Active

Primary Outcome Measures

Name	Time	Method
Percentage of Subjects Who Are Pain-free at 2 Hours Postdose (DB1)	2 hours post dose	Percentage of subjects who were pain-free 2 hours postdose compared between DFN-15 and placebo in the DB1 period (defined as a reduction from predose moderate \[Grade 2\] or severe \[Grade 3\] pain to none \[Grade 0\]) during DB1.
Percentage of Subjects Who Are Free From Their MBS at 2 Hours Postdose (DB1)	2 hours post dose	Percentage of subjects who are free from their most bothersome symptom (MBS) among nausea, photophobia, and phonophobia at 2 hours postdose during DB1.

Secondary Outcome Measures

Name	Time	Method
Freedom From Nausea, Photophobia, and Phonophobia Postdose (DB1 and DB2)	15 minutes through 24 hours	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 during each DB treatment period were summarized by symptom, treatment group, and time point.
Time to Headache Pain Relief Postdose (DB1 and DB2)	2 hours postdose
Headache Pain Freedom Among BMI Category (DB1 and DB2)	2 to 4 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 during each DB treatment period were summarized by treatment group and time point.
Change in Functional Disability Score Postdose (DB1 and DB2)	2 to 24 hours postdose	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.
Headache Pain Recurrence Postdose (DB1 and DB2)	2 to 24 hours postdose	Headache pain recurrence was defined as pain-free at 2 hours postdose with pain reported as mild, moderate, or severe at 24 hours postdose. This outcome measure shows percentage of subjects who reported pain-free status and 2 hours postdose but subsequently reported recurrent pain at 24 hours postdose.
Time to Headache Pain Freedom Postdose (DB1 and DB2)	2 hours postdose
Headache Pain Freedom Postdose (DB1 and DB2)	15 minutes to 24 hours postdose	The percentage of subjects who were pain-free at 15, 30, and 45 minutes and 1, 1.5, 2 (DB2), and 4, and 24 hours postdose during each DB treatment period were summarized by treatment group.
Sustained Headache Pain Relief Postdose (DB1 and DB2)	2 to 24 hours postdose	Sustained headache pain relief was defined as pain relief at 2 hours postdose with no use of rescue medication and no worsening of headache pain within 2 to 24 hours postdose. This outcome measure shows the percentage of subjects who reported pain relief at 2 hours postdose with no use of rescue medication or worsening of headache pain through 24 hours postdose.
Headache Pain Relief Postdose (DB1 and DB2)	15 minutes to 24 hours postdose	Headache pain relief during postdose in DB1 was defined as a reduction from moderate or severe pain at predose reduced to mild or none postdose, and for DB2 as moderate or severe pain at predose reduced to mild or none postdose, or mild pain at predose reduced to none postdose. Outcome measure shows percentage of subjects experiencing headache pain relief by time point.
Absence of Screening MBS at Time Points Postdose (DB1 and DB2)	15 minutes to 24 hours postdose	The percentage of subjects with their Screening MBS (most bothersome symptoms) among nausea, photophobia, and phonophobia (from eDiary data collection) absent at 15, 30, and 45 minutes and 1, 1.5, 2 (DB2 period), 4, and 24 hours postdose during each DB treatment period were summarized by treatment group and time point.
Headache Pain Freedom Among Subjects With Cutaneous Allodynia (DB1 and DB2)	2 to 4 hours postdose	The percentage of subjects who were pain-free at 2 and 4 hours postdose during each DB treatment period among those subjects reporting cutaneous allodynia before dosing were summarized by treatment group and time point.
Use of Rescue Medication Postdose (DB1 and DB2)	2 to 24 hours postdose	The percentage of subjects who used rescue mediation after 2 hours (2 to 24 hours) postdose compared between DFN-15 and placebo in each DB period.
Subject-Rated Treatment Satisfaction at 24 Hours Postdose - PPMQ-R (DB1 and DB2)	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.
Sustained Headache Pain Freedom Postdose (DB1 and DB2)	2 to 24 hours postdose	Sustained headache pain freedom was 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. This outcome measure shows percentage of subjects who were pain-free at 2 hours postdose without the use of rescue medication or recurrence of headache pain through 24 hours postdose.
Subject-Rated Treatment Satisfaction Postdose (DB1 and DB2)	2 to 4 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.

Trial Locations

Locations (45): Site 720
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Decatur, Georgia, United States
Site 735
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DeLand, Florida, United States
Site 727
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Phoenix, Arizona, United States
Site 726
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Colorado Springs, Colorado, United States
Site 736
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Hazelwood, Missouri, United States
Site 723
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Little Rock, Arkansas, United States
Site 737
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Springfield, Missouri, United States
Site 740
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Blue Ridge, Georgia, United States
Site 708
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Orange, California, United States
Site 734
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West Des Moines, Iowa, United States
Site 706
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Shreveport, Louisiana, United States
Site 711
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Hialeah, Florida, United States
Site 716
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Berlin, New Jersey, United States
Site 741
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Salem, Oregon, United States
Site 721
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Jacksonville, Florida, United States
Site 724
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Chattanooga, Tennessee, United States
Site 705
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Manhattan, New York, United States
Site 715
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Raleigh, North Carolina, United States
Site 709
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Los Angeles, California, United States
Site 729
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San Diego, California, United States
Site 703
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Boston, Massachusetts, United States
Site 745
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Las Vegas, Nevada, United States
Site 728
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Cincinnati, Ohio, United States
Site 713
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Wichita, Kansas, United States
Site 739
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Prairie Village, Kansas, United States
Site 704
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Minneapolis, Minnesota, United States
Site 701
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Oklahoma City, Oklahoma, United States
Site 738
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Simi Valley, California, United States
Site 733
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Upland, California, United States
Site 725
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Santa Monica, California, United States
Site 712
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Baltimore, Maryland, United States
Site 710
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Anderson, South Carolina, United States
Site 714
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Virginia Beach, Virginia, United States
Site 702
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Plano, Texas, United States
Site 744
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Birmingham, Alabama, United States
Site 731
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Philadelphia, Pennsylvania, United States
Site 707
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Dayton, Ohio, United States
Site 722
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Bellevue, Washington, United States
Site 730
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New Bedford, Massachusetts, United States
Site 743
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Williamsville, New York, United States
Site 746
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Amherst, New York, United States
Site 717
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Media, Pennsylvania, United States
Site 742
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Lincoln, Rhode Island, United States
Site 718
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Rogers, Arkansas, United States
Site 719
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Austin, Texas, United States