| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Acute Migraine Headache in Adolescents |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 15.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10066635 |
| E.1.2 | Term | Acute migraine |
| E.1.2 | System Organ Class | 100000004852 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| The primary objective of this study is to compare the efficacy of zolmitriptan nasal spray 0.5, 2.5, and 5 mg with placebo in the acute treatment of migraine headache in adolescents (aged 12 to 17 years), as measured by the primary endpoint (outcome variable) of pain-free status at 2 hours post treatment. |
|
| E.2.2 | Secondary objectives of the trial |
The secondary objectives are:
To evaluate the efficacy of zolmitriptan nasal spray 0.5, 2.5, and 5 mg as compared
with placebo in the acute treatment of migraine headache in adolescents (aged 12 to
17 years), as assessed by:
− pain-free status
− headache response
− sustained headache response
− presence and resolution of associated symptoms of photophobia, phonophobia,
or nausea
− incidence and time to use of rescue medication
− ability to perform normal activities
− headache recurrence
− bilateral headache (yes/no)
− intensity increased by movement (yes/no)
To assess safety and tolerability of zolmitriptan when used for the acute treatment of migraine headache in adolescents. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Parent or legal guardian is able to provide written informed consent and patient is
able to provide written assent.
2. Adolescents aged 12 to 17 years at the time of screening; patients must not be
enrolled if they will turn 18 years of age within 10 weeks after randomization
(Visit 2).
3. An established diagnosis of migraine (history indicating the presence of migraine
for at least 1 year) with or without aura as defined by the IHS or IHS-R criteria. Patients
with medical history of migraine for at least 1 year prior to screening as defined
by IHS or IHS-R criteria without a historic documentation of migraine may be
considered for entry after the history has been established and discussed with the
medical monitor.
4. A minimum of 2 migraines, considered to be moderately/severely disabling, per
month (by history);
5. A medical history of usual untreated migraine duration of ≥3 hours for any 3 month
period prior to screening (Visit 1);
6. A history of migraine attacks occurring at intervals of >24 hours apart, which is
confirmed by medical history;
8. Have the ability to differentiate between migraine and non-migraine headaches;
9. All females in a relationship capable of producing a pregnancy should use a highly
effective form of birth control. All females will have a pregnancy test. They must
have a negative urine pregnancy test and confirmed (by the investigator) use of a
highly effective form of birth control. The highly effective form of birth control
includes, but is not limited to, total sexual abstinence, a vasectomized male partner
with confirmation of azoospermia plus condom, female sterilization by tubal occlusion plus condom, intrauterine devices (IUD, ie, copper banded coils plus condom, intrauterine systems (IUS, ie, levonorgestrel [eg, Mirena] plus condom),
Depo-Provera plus condom, etonogestrel implants (eg, Implanon, NuvaRing) plus condom, Evra plus condom, normal and low-dose combined oral
contraceptives plus condom, norelgestromin/ethinyl estradiol (EE) transdermal
system plus condom, intravaginal device (eg, EE and etonogestrel) plus condom,
and Cerazette (desogestrel) – currently the only highly effective progesterone-based
pill – plus condom. A diaphragm and foam or condom or sponge and condom are
not acceptable. Females should be on a stable method of birth control for a
minimum of 3 months prior to study entry.
10. Absence of clinically significant abnormalities indicated from the medical history,
physical examination, laboratory assessments (clinical chemistry, hematology,
urinalysis), and urine drug screen results;
11. Clearly understands and is likely to comply with all study procedures and scheduled visits, as demonstrated during the run-in and placebo challenge period;
12. Ability to read and write and use the patient diary;
13. The investigator believes participation in the study will not be harmful to the
patient. |
|
| E.4 | Principal exclusion criteria |
1. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site);
2. Had previous randomization of treatment in this study;
3. Is currently participating or has participated in another clinical study within 30 days
prior to screening for this study;
4. 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 (in the
opinion of the investigator);
5. A history of basilar, ophthalmoplegic, or hemiplegic migraine headache or any
potentially serious neurological condition that is associated with headache;
6. Had an unacceptable adverse experience following previous use of any 5HT1B/1D
agonist drug (in the opinion of the investigator);
7. Evidence of ischemic heart disease, arrhythmia (eg, atrial fibrillation or flutter,
frequent premature ventricular contractions, atrioventricular block), accessory conduction pathway disorder (eg, Wolff-Parkinson-White syndrome) as determined
by central cardiologist using predetermined and agreed upon pediatric standards;
8. History, symptoms, or significant risk factors for ischemic heart (eg, silent
ischemia, angina, myocardial infarction) or other cardiovascular disease, including
coronary vasospasm, cardiac accessory conduction pathways, arrhythmias,
cerebrovascular syndromes (eg, stroke), or peripheral vascular disease;
9. Clinically significant abnormalities indicated from the medical history, physical
examination, clinical chemistry, hematology, and urine drug screen (eg, stable
diabetes mellitus would not qualify as a clinically significant abnormality for the
purposes of this study);
10. Had a diagnosis or suspicion of drug-induced or chronic daily headaches within
1 year;
11. Has 14 or more non-migraine headache days each month for 3 months before the
screening visit;
12. Has uncontrolled hypertension defined as systolic or diastolic BP that exceeds the
95th percentile for age and height (Appendix E; NHBPEP 2005);
13. Has used monoamine oxidase-A (MAO-A) inhibitor, methysergide,
methylergonovine, or cimetidine in the 2 weeks before randomization or an SSRI
4 weeks before randomization; if the patient has been on stable dose of SSRI for 8
weeks (2 months) prior to randomization, they may be included in the study.
14. Has any recent history of abuse (in the previous year) of alcohol or other drugs
including drugs for the acute treatment of headache;
15. Is a female who is pregnant or breast-feeding;
16. Has severe hepatic impairment or any serious condition which, in the opinion of the investigator, would present a risk to the patient participating in the study;
17. Has a clinically relevant abnormality on nasopharyngeal examination as determined by the investigator; nasopharyngeal examination means a standard physical examination to rule out gross abnormalities of the nasopharynx and does not imply specialist examination prior to enrolling a patient.
18. Has a positive urine test for drug abuse not explained by the use of appropriately
prescribed rescue medications.
19. Responds to the placebo challenge during the run-in period (i.e., migraine headache intensity is mild or none at 2 hours after the placebo challenge).
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
• Efficacy
Primary outcome variable: pain-free status at 2 hours post treatment.
Secondary outcome variables:
− Pain-free status at 15 minutes and at 1, 2, 3, 4, and 24 hours post treatment
− Headache response at 15 minutes and at 1, 2, 3, 4, and 24 hours post treatment
− Sustained headache response at 2 hours subsequent to a 1-hour headache
response
− Presence of associated symptoms of photophobia, phonophobia, or nausea at
15 minutes and at 1, 2, 3, 4, and 24 hours post treatment
− Resolution of associated symptoms of photophobia, phonophobia, or nausea at
15 minutes and at 1, 2, 3, 4, and 24 hours post treatment
− Incidence and time to use of rescue medication up to 24 hours post treatment
− Ability to perform normal activities at 15 minutes and at 1, 2, 3, 4, and 24 hours
post treatment
− Headache recurrence 2 to 24 hours post treatment
− Bilateral headache (yes/no) at 15 minutes and at 1, 2, 3, 4, and 24 hours post
treatment
− Intensity increased by movement (yes/no) at 15 minutes and at 1, 2, 3, 4, and
24 hours post treatment
• Safety
− Incidence, nature, and intensity of AEs; vital signs; physical examination
changes; laboratory assessments (ie, chemistry, hematology, and urinalysis);
electrocardiogram (ECG); and incidences of suicidal behavior and suicidal
ideation as measured by the Columbia-Suicide Severity Rating Scale (CSSRS). |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 4 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 11 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 60 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Argentina |
| Bulgaria |
| Estonia |
| Finland |
| Germany |
| Latvia |
| Poland |
| Serbia |
| Slovakia |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| Last visit of last subject. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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