Migraine Headache
Conditions
Keywords
Migraine, Headache, Pain, Efficacy, Adolescents
Brief summary
The purpose of this study is to investigate if Zomig® Nasal Spray will help children (age 12-17 years) with migraine headaches feel better. This will be done by comparing 3 different doses of Zomig Nasal Spray with placebo nasal spray (inactive treatment).
Interventions
DRUGPlacebo
Placebo nasal spray
DRUGZolmitriptan
0.5 mg nasal spray
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Provision of written informed consent by parent or legal guardian, and written assent provided by patient prior to any study specific procedures. * Established diagnosis of migraine. * History of a minimum of 2 migraine attacks (moderately or severely disabling)per month.
Exclusion criteria
* Any medical condition that may put the patient at increased risk with exposure to zolmitriptan or that may interfere with the safety or efficacy assessments. * A history of basilar, ophthalmoplegic, or hemiplegic migraine headache or any potentially serious neurological condition that is associated with headache. * Have had an unacceptable adverse experience following previous use of any 5HT1B/1D agonist drug.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pain-free Status at 2 Hours Post-treatment | 2 hours post-treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pain-free Status at 24 Hours Post-treatment | 24 hours post-treatment | — |
| Headache Response at 2 Hours Post-treatment | 2 hours post-treatment | Headache response is a binary response variable derived from the headache intensities recorded in the patient diary. Headache response is defined as a reduction in headache pain intensity from severe or moderate to mild or none with no use of rescue medication prior to the assessment. |
| Headache Response at 24 Hours Post-treatment | 24 hours post-treatment | Headache response is a binary response variable derived from the headache intensities recorded in the patient diary. Headache response is defined as a reduction in headache pain intensity from severe or moderate to mild or none with no use of rescue medication prior to the assessment. |
| Sustained Headache Response at 2 Hours | Up to 2 hours post-treatment | Sustained headache response at 2 hours is a binary response variable derived from the headache intensities recorded in the patient diary. Sustained headache response is defined as a reduction in migraine headache pain intensity from severe or moderate to mild or none a 1 hr. which is then maintained (without a return to moderate or severe pain) at 2 hrs. with no use of rescue medication prior to the 2 hr. assessment. |
| Use of Rescue Medication During the First 24 Hours After Treatment | 24 hours post-treatment. | — |
Countries
Estonia, Finland, Hungary, Latvia, Poland, Serbia, Slovakia, United States
Participant flow
Recruitment details
This multicenter study was conducted between 7 October 2010 and 31 October 2013.
Pre-assignment details
The study had a 30 day run-in period and up to a 10-week double-blind treatment period. Patients were randomized to receive ZOMIG nasal spray 0.5, 2.5, 5.0 mg, or matching placebo spray to treat a migraine headache. 1653 patients were enrolled, 798 were randomized.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo to ZOMIG nasal spray | 296 |
| ZOMIG 0.5 mg ZOMIG nasal spray | 115 |
| ZOMIG 2.5 mg ZOMIG nasal spray | 99 |
| ZOMIG 5 mg ZOMIG nasal spray | 288 |
| Total | 798 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Eligibility criteria not fulfilled | 16 | 12 | 10 | 15 |
| Overall Study | Lost to Follow-up | 3 | 2 | 1 | 2 |
| Overall Study | Patient decision | 2 | 1 | 0 | 2 |
| Overall Study | Reason not specified | 3 | 2 | 2 | 1 |
| Overall Study | Severe noncompliance to protocol | 1 | 0 | 0 | 0 |
| Overall Study | Study-specific withdrawal criteria | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo | ZOMIG 0.5 mg | ZOMIG 2.5 mg | ZOMIG 5 mg | Total |
|---|---|---|---|---|---|
| Age, Continuous | 14.3 Years STANDARD_DEVIATION 1.67 | 14.5 Years STANDARD_DEVIATION 1.72 | 14.6 Years STANDARD_DEVIATION 1.77 | 14.5 Years STANDARD_DEVIATION 1.67 | 14.4 Years STANDARD_DEVIATION 1.69 |
| Sex: Female, Male Female | 188 Participants | 71 Participants | 62 Participants | 172 Participants | 493 Participants |
| Sex: Female, Male Male | 108 Participants | 44 Participants | 37 Participants | 116 Participants | 305 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 | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 25 / 253 | 14 / 92 | 9 / 81 | 59 / 231 |
| serious Total, serious adverse events | 0 / 253 | 0 / 92 | 0 / 81 | 0 / 231 |
Outcome results
Primary
Pain-free Status at 2 Hours Post-treatment
Time frame: 2 hours post-treatment.
Population: Full analysis set (last observation carried forward)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Pain-free Status at 2 Hours Post-treatment | No | 211 Participants |
| Placebo | Pain-free Status at 2 Hours Post-treatment | Yes | 42 Participants |
| ZOMIG 0.5 mg | Pain-free Status at 2 Hours Post-treatment | No | 71 Participants |
| ZOMIG 0.5 mg | Pain-free Status at 2 Hours Post-treatment | Yes | 20 Participants |
| ZOMIG 2.5 mg | Pain-free Status at 2 Hours Post-treatment | Yes | 20 Participants |
| ZOMIG 2.5 mg | Pain-free Status at 2 Hours Post-treatment | No | 61 Participants |
| ZOMIG 5 mg | Pain-free Status at 2 Hours Post-treatment | Yes | 68 Participants |
| ZOMIG 5 mg | Pain-free Status at 2 Hours Post-treatment | No | 161 Participants |
p-value: 0.31295% CI: [0.75, 2.5]Regression, Logistic
p-value: 0.07195% CI: [0.95, 3.26]Regression, Logistic
p-value: <0.00195% CI: [1.4, 3.39]Regression, Logistic
Secondary
Headache Response at 24 Hours Post-treatment
Headache response is a binary response variable derived from the headache intensities recorded in the patient diary. Headache response is defined as a reduction in headache pain intensity from severe or moderate to mild or none with no use of rescue medication prior to the assessment.
Time frame: 24 hours post-treatment
Population: Full analysis set (observed case)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Headache Response at 24 Hours Post-treatment | Yes | 170 Participants |
| Placebo | Headache Response at 24 Hours Post-treatment | No | 81 Participants |
| ZOMIG 0.5 mg | Headache Response at 24 Hours Post-treatment | No | 28 Participants |
| ZOMIG 0.5 mg | Headache Response at 24 Hours Post-treatment | Yes | 63 Participants |
| ZOMIG 2.5 mg | Headache Response at 24 Hours Post-treatment | Yes | 61 Participants |
| ZOMIG 2.5 mg | Headache Response at 24 Hours Post-treatment | No | 19 Participants |
| ZOMIG 5 mg | Headache Response at 24 Hours Post-treatment | Yes | 168 Participants |
| ZOMIG 5 mg | Headache Response at 24 Hours Post-treatment | No | 59 Participants |
p-value: 0.75395% CI: [0.64, 1.84]Regression, Logistic
p-value: 0.14595% CI: [0.86, 2.79]Regression, Logistic
p-value: 0.12795% CI: [0.91, 2.04]Regression, Logistic
Secondary
Headache Response at 2 Hours Post-treatment
Headache response is a binary response variable derived from the headache intensities recorded in the patient diary. Headache response is defined as a reduction in headache pain intensity from severe or moderate to mild or none with no use of rescue medication prior to the assessment.
Time frame: 2 hours post-treatment
Population: Full analysis set (last observation carried forward)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Headache Response at 2 Hours Post-treatment | Yes | 99 Participants |
| Placebo | Headache Response at 2 Hours Post-treatment | No | 154 Participants |
| ZOMIG 0.5 mg | Headache Response at 2 Hours Post-treatment | No | 51 Participants |
| ZOMIG 0.5 mg | Headache Response at 2 Hours Post-treatment | Yes | 40 Participants |
| ZOMIG 2.5 mg | Headache Response at 2 Hours Post-treatment | No | 38 Participants |
| ZOMIG 2.5 mg | Headache Response at 2 Hours Post-treatment | Yes | 43 Participants |
| ZOMIG 5 mg | Headache Response at 2 Hours Post-treatment | No | 113 Participants |
| ZOMIG 5 mg | Headache Response at 2 Hours Post-treatment | Yes | 116 Participants |
p-value: 0.45895% CI: [0.74, 1.96]Regression, Logistic
p-value: 0.02195% CI: [1.09, 3.03]Regression, Logistic
p-value: 0.0195% CI: [1.12, 2.32]Regression, Logistic
Secondary
Pain-free Status at 24 Hours Post-treatment
Time frame: 24 hours post-treatment
Population: Full analysis set (observed case)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Pain-free Status at 24 Hours Post-treatment | Yes | 155 Participants |
| Placebo | Pain-free Status at 24 Hours Post-treatment | No | 96 Participants |
| ZOMIG 0.5 mg | Pain-free Status at 24 Hours Post-treatment | No | 32 Participants |
| ZOMIG 0.5 mg | Pain-free Status at 24 Hours Post-treatment | Yes | 59 Participants |
| ZOMIG 2.5 mg | Pain-free Status at 24 Hours Post-treatment | Yes | 60 Participants |
| ZOMIG 2.5 mg | Pain-free Status at 24 Hours Post-treatment | No | 20 Participants |
| ZOMIG 5 mg | Pain-free Status at 24 Hours Post-treatment | Yes | 155 Participants |
| ZOMIG 5 mg | Pain-free Status at 24 Hours Post-treatment | No | 72 Participants |
p-value: 0.57595% CI: [0.7, 1.91]Regression, Logistic
p-value: 0.03295% CI: [1.06, 3.31]Regression, Logistic
p-value: 0.13795% CI: [0.91, 1.95]Regression, Logistic
Secondary
Sustained Headache Response at 2 Hours
Sustained headache response at 2 hours is a binary response variable derived from the headache intensities recorded in the patient diary. Sustained headache response is defined as a reduction in migraine headache pain intensity from severe or moderate to mild or none a 1 hr. which is then maintained (without a return to moderate or severe pain) at 2 hrs. with no use of rescue medication prior to the 2 hr. assessment.
Time frame: Up to 2 hours post-treatment
Population: Full analysis set (observed case)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Sustained Headache Response at 2 Hours | Yes | 59 Participants |
| Placebo | Sustained Headache Response at 2 Hours | No | 192 Participants |
| ZOMIG 0.5 mg | Sustained Headache Response at 2 Hours | No | 64 Participants |
| ZOMIG 0.5 mg | Sustained Headache Response at 2 Hours | Yes | 27 Participants |
| ZOMIG 2.5 mg | Sustained Headache Response at 2 Hours | Yes | 27 Participants |
| ZOMIG 2.5 mg | Sustained Headache Response at 2 Hours | No | 54 Participants |
| ZOMIG 5 mg | Sustained Headache Response at 2 Hours | Yes | 66 Participants |
| ZOMIG 5 mg | Sustained Headache Response at 2 Hours | No | 158 Participants |
p-value: 0.27495% CI: [0.79, 2.32]Regression, Logistic
p-value: 0.06795% CI: [0.96, 2.91]Regression, Logistic
p-value: 0.12795% CI: [0.91, 2.08]Regression, Logistic
Secondary
Use of Rescue Medication During the First 24 Hours After Treatment
Time frame: 24 hours post-treatment.
Population: Full analysis set (observed cases)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Use of Rescue Medication During the First 24 Hours After Treatment | Yes | 80 Participants |
| Placebo | Use of Rescue Medication During the First 24 Hours After Treatment | No | 173 Participants |
| ZOMIG 0.5 mg | Use of Rescue Medication During the First 24 Hours After Treatment | No | 69 Participants |
| ZOMIG 0.5 mg | Use of Rescue Medication During the First 24 Hours After Treatment | Yes | 22 Participants |
| ZOMIG 2.5 mg | Use of Rescue Medication During the First 24 Hours After Treatment | Yes | 18 Participants |
| ZOMIG 2.5 mg | Use of Rescue Medication During the First 24 Hours After Treatment | No | 63 Participants |
| ZOMIG 5 mg | Use of Rescue Medication During the First 24 Hours After Treatment | Yes | 47 Participants |
| ZOMIG 5 mg | Use of Rescue Medication During the First 24 Hours After Treatment | No | 184 Participants |
p-value: 0.15395% CI: [0.38, 1.16]Regression, Logistic
p-value: 0.08795% CI: [0.33, 1.08]Regression, Logistic
p-value: 0.00495% CI: [0.36, 0.83]Regression, Logistic