Migraine Disorders
Conditions
Brief summary
This study was a randomized, parallel group, double-blind, placebo controlled design to compare the efficacy and tolerability of NP101 to a placebo iontophoretic transdermal patch. The primary objective of this study was to assess the proportion of subjects who were headache pain free at two hours after patch activation. Key secondary objectives included: 1. The proportion of subjects who were nausea free at two hours after patch activation. 2. The proportion of subjects who were photophobia free at two hours after patch activation. 3. The proportion of subjects who were phonophobia free at two hours after patch activation.
Detailed description
Subjects stayed in the study until they had treated one migraine headache with a study patch or two months after randomization, whichever occurred first. During a migraine headache, subjects rated their baseline headache pain severity in a Migraine Study Diary using a 4-point scale (0 = none, 1 = mild, 2 = moderate, 3 = severe) and applied the study patch only if their score was 2 or 3 (i.e., qualifying migraine headache). In addition to headache pain severity, subjects also recorded the presence or absence of aura, nausea, phonophobia, and photophobia, as well as the location of their headache (unilateral or bilateral) and whether their headache increased with movement.
Interventions
DRUGNP101 - Sumatriptan iontophoretic transdermal patch
Sumatriptan iontophoretic transdermal patch
DRUGPlacebo
NP101 Placebo iontophoretic transdermal patch
Sponsors
NuPathe Inc.
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
* Subject is an adult male or female, age range 18 years to 65 years. * Subject has a diagnosis of migraine headache, with or without aura, as defined in the ICDH-II and the diagnosis was made before the age of 50. * Subject typically experiences moderate to severe headaches during a migraine attack. * Subject has at least a one year history of migraine. * Subject will be judged to be in good health, based on results of a medical history, physical examination, vital signs, ECG and laboratory profile. * Female subject of childbearing potential must have a negative pregnancy test at screening and prior to randomization. * Subject must have a negative drug screen. * Subject must be capable of reading and understanding either English or Spanish subject information materials. Be able to successfully apply a practice patch, carry-out all subject procedures, and be able to voluntarily sign and date an IRB approved IC agreement. * Subject has an acceptable patch application site (upper arm) that is relatively hair free and has no scars, tattoos, scratches, or bruises.
Exclusion criteria
* Subject has or plans to start, stop, or change treatment or dose with prophylactic anti-migraine treatment within 3 months prior to the subjects' study randomization date and through the final visit. * Subject has or plans to start, stop, or change treatment or dose of any of the following within 3 months prior to the subjects' study randomization date through final visit: anxiolytics, lithium and other mood stabilizers, hypnotics or antipsychotics. * Subject had less than one migraine per month or more than six migraines per month, or more than 15 headache days per month for any of the three months prior to randomization. * Subject has suspected or confirmed cardiovascular disease that contraindicates study participation. * Subject has a history of epilepsy or conditions associated with a lowered seizure threshold. * Subject has Raynaud's disease. * Subject has a history of basilar or hemiplegic migraines. * Subject has a current diagnosis of a major depressive disorder per the DSM IV R. * Subject has a history (within 1 year) or current evidence of drug or alcohol abuse or dependence. * Subject is unwilling to discontinue use of serotonin agonists (triptans), except for the study patch, through the Final Visit. * Subject has taken SSRI's, SNRI's, TCA's, MAOI's or preparations containing St. John's Wort within 1 month prior to screening and/or is planning to start any of these medications during the study. * Subject is unwilling to discontinue use of a PD-5 inhibitors through the Final Visit. * Subject has taken ergot medications within 7 days prior to Randomization and/or is unwilling to discontinue use through the Final Visit. * Subject has a history of a significant allergy or hypersensitivity to any component of the study patch. * Subject has any generalized skin irritation or disease including eczema, psoriasis, melanoma, or contact dermatitis. * Subject has clinically significant abnormal laboratory parameters, vital signs or ECG parameters. * Subject is known to be hepatitis B, hepatitis C or HIV positive. * Subject has hepatic dysfunction based on laboratory results or if in the opinion of the Investigator the subject's history, physical examination or other laboratory tests suggest hepatic dysfunction. * Female subject who is pregnant, breast feeding, or if of childbearing potential, is not using or is unwilling to use an effective form of contraception during the study and for a period of 30 days following dosing. * Subject has known history of failure to respond to sumatriptan. * Subject has participated in a clinical study within 30 days of screening or is planning to participate in another clinical study. * Subject has been previously enrolled in NP101-007 * Subject is electrically sensitive or who have electrically sensitive support systems (e.g., pacemaker).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pain Free at Two Hours | 2 hours post patch activation | Subjects whose headache severity score equaled zero (0) two hours post patch activation and who had not received any rescue medication before their two-hour assessment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Photophobia Free at Two Hours | 2 hours post patch activation | Subjects who were photophobia free and who had not received any rescue medication before their two-hour assessment. |
| Phonophobia Free at Two Hours | 2 hours post patch activation | Subjects who were phonophobia free and who had not received any rescue medication before their two-hour assessment. |
| Nausea Free at Two Hours | 2 hours post patch activation | Number of subjects who were nausea free and who had not received any rescue medication before their two-hour assessment. |
Countries
United States
Participant flow
Recruitment details
The study was initiated January 2009 and completed July 2009. Patients were enrolled from 38 investigative sites across the United States.
Participants by arm
| Arm | Count |
|---|---|
| NP101 Patch The NP101 patch contained 86 mg of sumatriptan and was designed to deliver approximately 6.5 mg of sumatriptan over 4 hours. Patients were asked to treat one migraine episode with moderate to severe headache pain. | 234 |
| Placebo Patch The study placebo patch contained sodium chloride instead of sumatriptan which was delivered over 4 hours. Patients were asked to treat one migraine episode with moderate to severe headache pain. | 235 |
| Total | 469 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 5 | 3 |
| Overall Study | Lost to Follow-up | 4 | 1 |
| Overall Study | Other Various | 3 | 5 |
| Overall Study | Randomized, not treated | 31 | 30 |
Baseline characteristics
| Characteristic | Placebo Patch | NP101 Patch | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 235 Participants | 233 Participants | 468 Participants |
| Age, Continuous | 41.2 years STANDARD_DEVIATION 11.06 | 40.5 years STANDARD_DEVIATION 11.2 | 40.8 years STANDARD_DEVIATION 11.12 |
| Region of Enrollment United States | 235 participants | 234 participants | 469 participants |
| Sex: Female, Male Female | 201 Participants | 197 Participants | 398 Participants |
| Sex: Female, Male Male | 34 Participants | 37 Participants | 71 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 114 / 234 | 100 / 235 |
| serious Total, serious adverse events | 0 / 234 | 0 / 235 |
Outcome results
Primary
Pain Free at Two Hours
Subjects whose headache severity score equaled zero (0) two hours post patch activation and who had not received any rescue medication before their two-hour assessment.
Time frame: 2 hours post patch activation
Population: Per protocol, the intent-to-treat population was assessed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NP101 Patch | Pain Free at Two Hours | 40 participants |
| Placebo Patch | Pain Free at Two Hours | 21 participants |
Secondary
Nausea Free at Two Hours
Number of subjects who were nausea free and who had not received any rescue medication before their two-hour assessment.
Time frame: 2 hours post patch activation
Population: Per protocol, the intent-to-treat population was assessed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NP101 Patch | Nausea Free at Two Hours | 189 participants |
| Placebo Patch | Nausea Free at Two Hours | 144 participants |
Secondary
Phonophobia Free at Two Hours
Subjects who were phonophobia free and who had not received any rescue medication before their two-hour assessment.
Time frame: 2 hours post patch activation
Population: Per protocol, the intent-to-treat population was assessed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NP101 Patch | Phonophobia Free at Two Hours | 125 participants |
| Placebo Patch | Phonophobia Free at Two Hours | 89 participants |
Secondary
Photophobia Free at Two Hours
Subjects who were photophobia free and who had not received any rescue medication before their two-hour assessment.
Time frame: 2 hours post patch activation
Population: Per protocol, the intent-to-treat population was assessed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NP101 Patch | Photophobia Free at Two Hours | 116 participants |
| Placebo Patch | Photophobia Free at Two Hours | 83 participants |