Migraine Headaches
Conditions
Keywords
Aura
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.
Interventions
DRUGSumatriptan 10 mg Nasal Spray
100 μL nasal spray once
OTHERSumatriptan Placebo Nasal Spray
100 μL nasal spray once
Sponsors
Upsher-Smith Laboratories
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. 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 2. Patients who have migraine with or without aura. If migraine with aura, the aura cannot last longer than 60 minutes. 3. Patients who are willing and able to: 1. Evaluate and record pain, migraine symptoms, and study medication effectiveness information in real-time using a diary for the duration of the study; 2. 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; 3. Comply with all other study procedures and scheduling requirements.
Exclusion criteria
1. Minors, even if they are in the specified study age range 2. Medication overuse: 1. Opioids ≥ 10 days during the 90 days prior to screening 2. 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) 3. Nonsteroidal Anti-inflammatory Drugs or other simple medications ˃ 14 days a month during the 90 days prior to screening 4. Triptans or ergots ≥ 10 days a month during the 90 days prior to screening 3. 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) 4. A history of or current neurological or psychiatric impairment, or cognitive dysfunction that, in the opinion of the Investigator, would compromise data collection 5. Use of antipsychotics at least 15 days prior to randomization 6. 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 7. Patients who participated in a central nervous system clinical trial within 3 months prior to randomization 8. Patients who test positive for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) antibody serology testing 9. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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). | 2 hours after study medication administration | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Absence of Most Bothersome Symptom (MBS) Among Nausea, Photophobia and Phonophobia at 2 Hours (DB1) | 2 hours after study medication administration | 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. |
| Number of Participants With Headache Pain Freedom at 2 Hours Postdose in the Double-blind Treatment Period 2 (DB2) | 2 hours after study medication administration | 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. |
Countries
United States
Participant flow
Recruitment details
The study was conducted in the United States. At least 1 subject was enrolled at 9 study centers.
Pre-assignment details
Subjects had to have 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.
Participants by arm
| Arm | Count |
|---|---|
| DFN-02 (Double-Blind Treatment Period 1) 50 of 54 randomized subjects started and were dosed; 2 subjects had no migraine attack, 1 subject withdrew and 1 subject was lost to follow-up. Per protocol these 4 subjects are excluded from analysis. | 50 |
| Placebo (Double-Blind Treatment Period 1) 43 of 53 randomized subjects started and were dosed; 6 subjects had no migraine attack, 3 subjects withdrew and 1 subject was terminated by the sponsor. Per protocol these 10 subjects are excluded from analysis. | 43 |
| Total | 93 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Double-Blind Treatment Period 1 | Lack of diary compliance | 0 | 2 |
| Double-Blind Treatment Period 1 | Lost to Follow-up | 1 | 0 |
| Double-Blind Treatment Period 1 | Protocol Violation | 0 | 1 |
| Double-Blind Treatment Period 1 | Sponsor terminated | 1 | 0 |
| Double-Blind Treatment Period 1 | Withdrawal by Subject | 0 | 2 |
| Double-Blind Treatment Period 2 | Lost to Follow-up | 1 | 0 |
Baseline characteristics
| Characteristic | DFN-02 (Double-Blind Treatment Period 1) | Placebo (Double-Blind Treatment Period 1) | Total |
|---|---|---|---|
| Age, Continuous | 43.4 years | 41.0 years | 42.3 years |
| BMI | 27.70 kg/m^2 STANDARD_DEVIATION 6.441 | 28.80 kg/m^2 STANDARD_DEVIATION 7.5 | 28.21 kg/m^2 STANDARD_DEVIATION 6.933 |
| Race/Ethnicity, Customized Asian | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Black or African American | 5 participants | 2 participants | 7 participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 1 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Other | 2 participants | 0 participants | 2 participants |
| Race/Ethnicity, Customized White | 42 participants | 40 participants | 82 participants |
| Region of Enrollment United States | 50 participants | 43 participants | 93 participants |
| Sex: Female, Male Female | 38 Participants | 37 Participants | 75 Participants |
| Sex: Female, Male Male | 12 Participants | 6 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 50 | 0 / 43 | 0 / 37 | 0 / 38 |
| other Total, other adverse events | 5 / 50 | 0 / 43 | 5 / 37 | 0 / 38 |
| serious Total, serious adverse events | 0 / 50 | 0 / 43 | 0 / 37 | 0 / 38 |
Outcome results
Primary
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.
Time frame: 2 hours after study medication administration
Population: Full Analysis Set (FAS) population. Last observation carried forward (LOCF) imputation method. The FAS included all randomized subjects who took at least one dose of study medication during the DB treatment period (1) and had at least one post-baseline efficacy time point assessment in DB treatment period (1).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| DFN-02 (DB1) | 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). | 21 Participants |
| Placebo (DB1) | 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). | 9 Participants |
Comparison: Statistical testing and confidence intervals (CIs) were 2 sided and performed using a significance (alpha) level of 0.05. All statistical analyses were conducted with the statistical analysis system (SAS)® software package (version 9.3).p-value: 0.04495% CI: [1.05, 6.83]Fisher Exact
Secondary
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.
Time frame: 2 hours after study medication administration
Population: Subjects who reported a MBS predose and reported the status of the MBS at the particular postdose time point were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| DFN-02 (DB1) | Number of Participants With Absence of Most Bothersome Symptom (MBS) Among Nausea, Photophobia and Phonophobia at 2 Hours (DB1) | 29 Participants |
| Placebo (DB1) | Number of Participants With Absence of Most Bothersome Symptom (MBS) Among Nausea, Photophobia and Phonophobia at 2 Hours (DB1) | 15 Participants |
p-value: 0.007Fisher Exact
Secondary
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.
Time frame: 2 hours after study medication administration
Population: Last observation carried forward (LOCF) imputation method. Analysis included all randomized subjects who took at least one dose of study medication during the second DB treatment period (2) and had at least one post-baseline efficacy time point assessment in DB treatment period (2).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| DFN-02 (DB1) | Number of Participants With Headache Pain Freedom at 2 Hours Postdose in the Double-blind Treatment Period 2 (DB2) | 19 Participants |
| Placebo (DB1) | Number of Participants With Headache Pain Freedom at 2 Hours Postdose in the Double-blind Treatment Period 2 (DB2) | 17 Participants |
Comparison: Statistical testing and confidence intervals (CIs) were 2 sided and performed using a significance (alpha) level of 0.05. All statistical analyses were conducted with the SAS® software package (version 9.3).p-value: 0.64295% CI: [0.52, 3.3]Fisher Exact