Episodic Migraine
Conditions
Brief summary
Safety and Efficacy of DFN-11 in patients with episodic migraines with or without aura.
Interventions
DRUGDFN-11
OTHERPlacebo
Sponsors
Dr. Reddy's Laboratories Limited
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. If female, a subject must have a negative serum pregnancy test at screening, does not plan to become pregnant during the study, and is not lactating 2. If female, a subject also must have a negative urine pregnancy test at all subsequent study visits after the Screening Visit, and agree to practice a reliable form of contraception or abstinence during the study. Acceptable forms of contraception include implants, injectables, combined oral contraceptives, an intrauterine device, a vasectomized partner, an exclusively female partner, and double-barrier methods. 3. If male (with female partner), a subject must agree to practice a reliable form of contraception or abstinence during the study. 4. A history of episodic migraine who experience 2 to 6 migraine attacks a month for at least the past 12 months with no more than 14 migraine headache days per month, and with 48 hours of headache free time between migraine headaches 5. Have migraine with or without aura; if with aura, the aura cannot last longer than 60 minutes
Exclusion criteria
1. Minors, even if they are in specified study age range 2. Medication overuse headache as defined by ICHD II: * Opioids ≥ 10 days a month during the 90 days prior to screening * Combination medications (e.g., Fiorinal®) ≥ 10 days a month during the 90 days prior to screening * Nonsteroidal anti-inflammatory drugs (NSAIDs) 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 3. Subjects treated with onabotulinumtoxin A (Botox®) or other botulinum toxin treatment; or history of receiving such treatment during the 180 days prior to screening 4. On unstable dosages of migraine prophylactic medications during the 30 days prior to and through screening 5. Taking mini-prophylaxis for menstrual migraine 6. Subjects with hemiplegic or basilar migraine or other forms of neurologically complicated migraine 7. Subjects who have prolonged aura (i.e., more than 1 hour) 8. Cerebrovascular disease including but not limited to a history of stroke or transient ischemic attack (TIA) 9. A history of migralepsy (seizure following a migraine) or a concurrent diagnosis of seizure disorder 10. Subjects who cannot differentiate between a migraine headache and tension-type or cluster headache or other types of headache 11. Subjects with a history of more than occasional (based on Investigator's judgment) tension-type headache (distinct from migraine headache days count). 12. Subjects with a history of cluster headaches 13. Subjects with the diagnosis of probable migraine (ICHD II) 14. Ischemic coronary artery disease (CAD): including but not limited to angina pectoris, history of myocardial infarction or documented silent ischemia or coronary artery vasospasm, including Prinzmetal's angina 15. Subjects with Wolff-Parkinson-White syndrome or arrhythmias associated with other cardiac accessory conduction pathway disorders 16. Subjects with a history of congenital heart disease 17. A history of uncontrolled hypertension or screening systolic/diastolic \> 140/90 mmHg 18. Have peripheral vascular disease including but not limited to ischemic bowel disease (IBD) and Raynaud's disease. 19. Any abnormal physiology and/or pathology which, in the opinion of the Investigator or Sponsor, which would be contraindicated for study participation and would not allow the objectives of the study to be met 20. Subjects who show any clinical laboratory or electrocardiogram (ECG) abnormality that in the opinion of the Investigator would endanger the subject or interfere with the study conduct. If the results of the clinical laboratory or ECG are outside of normal reference range the subject may still be enrolled but only if these findings are determined to be not clinically significant by the Investigator. This determination must be recorded in the subject's source document prior to enrolment. 21. Fridericia's corrected QT (QTcF) interval greater than 450 msec 22. Severe renal impairment (creatinine \> 2 mg/dl) 23. Serum total bilirubin \> 2.0 mg/dL 24. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), or alkaline phosphatase \> 2.5 times the upper limit of normal 25. Subjects with uncontrolled diabetes mellitus, or a glycosylated hemoglobin (HbA1c) \> 7.0%, or with diabetes mellitus requiring insulin 26. A history of alcohol or substance use disorder according to the Diagnostic and Statistical Manual of Mental Disorders, Edition V (DSM-V) (including marijuana) within 1 year prior to screening 27. Current treatment with antipsychotics or use of antipsychotics within 30 days of screening 28. A history of or current neurological or psychiatric impairment, including but not limited to psychosis, current major depression, bipolar disorder or cognitive dysfunction that, in the opinion of the Investigator, would compromise data collection 29. Subjects who have received treatment with an investigational drug or device within 30 days of the screening visit or participated in a central nervous system clinical trial in the 3 months prior to screening 30. Subjects with any other medical condition that, in the judgment of the Investigator and/or Medical Monitor, would confound the objectives of the study (e.g., positive screening test for human immunodeficiency virus \[HIV\], hepatitis B surface antigen positive or hepatitis C positive, a known history of systemic lupus erythematosis) 31. Subjects who plan to donate blood, sperm, or oocytes during the study and for 30 days after the last dose of study medication 32. Subjects who are employees or immediate relatives of the employees of the Sponsor, any of its affiliates or partners, or of the study center
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The Percentage of Subjects in the Double-blind Period Who Are Pain Free at 2 Hours After Dosing as Reported by the Subject in the eDiary | 2 hours |
Secondary
| Measure | Time frame |
|---|---|
| The Percentage of Subjects in the Double-blind Period Who Are Pain Free at 1 Hour After Dosing as Reported by the Subject in the eDiary | 1 hour |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| DFN-11 - Double-blind DFN-11 active injection upon occurrence of migraine
DFN-11 | 131 |
| Placebo - Double-blind Placebo injection upon occurrence of migraine
Placebo | 137 |
| Total | 268 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 |
| Overall Study | Did not experience migraine attack | 10 | 7 |
| Overall Study | Lost to Follow-up | 3 | 3 |
| Overall Study | Physician Decision | 1 | 1 |
| Overall Study | Protocol Violation | 1 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 2 |
Baseline characteristics
| Characteristic | DFN-11 - Double-blind | Total | Placebo - Double-blind |
|---|---|---|---|
| Age, Continuous | 41.9 years STANDARD_DEVIATION 12.47 | 41.0 years STANDARD_DEVIATION 12.38 | 40.2 years STANDARD_DEVIATION 12.28 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 4 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 29 Participants | 52 Participants | 23 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 7 Participants | 4 Participants |
| Race (NIH/OMB) White | 98 Participants | 203 Participants | 105 Participants |
| Region of Enrollment United States | 131 participants | 268 participants | 137 participants |
| Sex: Female, Male Female | 20 Participants | 39 Participants | 19 Participants |
| Sex: Female, Male Male | 111 Participants | 229 Participants | 118 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 131 | 0 / 137 |
| other Total, other adverse events | 37 / 131 | 16 / 137 |
| serious Total, serious adverse events | 0 / 131 | 0 / 137 |
Outcome results
Primary
The Percentage of Subjects in the Double-blind Period Who Are Pain Free at 2 Hours After Dosing as Reported by the Subject in the eDiary
Time frame: 2 hours
Population: Subjects analyzed had efficacy data at the time of specified assessment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DFN-11 - Double-Blind | The Percentage of Subjects in the Double-blind Period Who Are Pain Free at 2 Hours After Dosing as Reported by the Subject in the eDiary | 51.0 Percentage of responders |
| Placebo - Double-Blind | The Percentage of Subjects in the Double-blind Period Who Are Pain Free at 2 Hours After Dosing as Reported by the Subject in the eDiary | 30.8 Percentage of responders |
Secondary
The Percentage of Subjects in the Double-blind Period Who Are Pain Free at 1 Hour After Dosing as Reported by the Subject in the eDiary
Time frame: 1 hour
Population: Subjects analyzed had efficacy data at the time of specified assessment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DFN-11 - Double-Blind | The Percentage of Subjects in the Double-blind Period Who Are Pain Free at 1 Hour After Dosing as Reported by the Subject in the eDiary | 34.6 Percentage of responders |
| Placebo - Double-Blind | The Percentage of Subjects in the Double-blind Period Who Are Pain Free at 1 Hour After Dosing as Reported by the Subject in the eDiary | 19.8 Percentage of responders |