Efficacy & Safety Of Zomig Nasal Spray For Acute Migraine Treatment In Subjects 6 To 11 Years, With OLE

Study Overview
=================
Brief Summary
-----------------
To evaluate the efficacy and safety of zolmitriptan nasal spray (ZNS) in the acute treatment of migraine headache in subjects ages 6 to 11 years. Part 1: Approximately 20 weeks (includes screening and double-blind treatment). Screening will be performed based on the inclusion exclusion criteria specified in the study protocol. Randomize approximately 288 subjects into the double-blind crossover phase. Part 2: Approximately 100 subjects who complete the double-blind crossover phase will enter part 2, a 6 month open-label safety extension (OLE). Efficacy will be evaluated in the double-blind part of the trial. Safety will be evaluated in both the double-blind and the OLE.

Official Title
-----------------
A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Crossover Study To Evaluate The Efficacy And Safety Of Zolmitriptan Nasal Spray For The Treatment Of Acute Migraine In Subjects Ages 6 To 11 Years, With An Open-Label Extension

Conditions
-----------------
Migraine

Intervention / Treatment
-----------------
* Drug: Placebo ZNS
* Drug: ZNS


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria Parent or legal guardian is able to provide written informed consent and subject is able to provide assent. Subjects ages 6 to 11 years throughout the double-blind portion of the studyAn established diagnosis of migraine By history, average migraine frequency of ≥ 2 attacks per month lasting on average ≥ 3 hours per attack By history, experiences at least 16 headache-free days per month on average Exclusion Criteria: History of ischemic or vasospastic heart disease, arrhythmias associated with accessory conduction pathways (eg, Wolff-Parkinson-White syndrome), cerebrovascular disease, hemiplegic or basilar artery migraine, peripheral vascular disease, ischemic bowel disease, uncontrolled hypertension, recent (within 24 hours) or use of another 5HT1 agonist, ergots or ergotamine-containing medications. Any medical condition, including severe hepatic impairment, which, in the opinion of the investigator, may put the subject at increased risk with exposure to zolmitriptan, or may interfere with the safety or efficacy assessments. Had an unacceptable adverse experience following previous use of any 5HT1B/1D agonist drug (in the opinion of the investigator). Had not experienced satisfactory relief from migraine pain during prior treatment with 2 or more adequate courses of triptans. Prior use of any nasal spray (triptan or dihydroergotamine [DHE]) for the acute treatment of migraine Disease or anatomic abnormalities of the nasal cavity precluding or complicating the use of ZNS.

Ages Eligible for Study
-----------------
Minimum Age: 6 Years
Maximum Age: 11 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: A Multicenter, Randomized, Double-blind, Placebo-controlled, Crossover Study
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Run-in - ZNS - Placebo - OLE<br>After Run-in period, subjects will be randomized to ZNS followed by placebo ZNS. Upon successful completion of Part 1, subjects may enroll into OLE (Part 2). | Drug: Placebo ZNS<br>* Placebo Zolmitriptan Nasal Spray<br>* Other names: Placebo;Drug: ZNS<br>* Zolmitriptan Nasal Spray<br>|
| Other: Run-in - Placebo - ZNS - OLE<br>After Run-in period, subjects will be randomized to placebo ZNS followed by ZNS. Upon successful completion of Part 1, subjects may enroll into OLE (Part 2). | Drug: Placebo ZNS<br>* Placebo Zolmitriptan Nasal Spray<br>* Other names: Placebo;Drug: ZNS<br>* Zolmitriptan Nasal Spray<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain-free status at 2 hours post treatment | Headache pain intensity is assessed by the subjects immediately prior to treatment and 2 hours post-dose using a 4-point headache pain intensity scale (severe = 3, moderate = 2, mild = 1, or none = 0). | 2 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects who achieve pain-free status at 24 hours post-dose | The headache pain intensity is assessed by the subjects using a 4-point headache pain intensity scale (severe = 3, moderate = 2, mild = 1, or none = 0). | 24 hours post-dose | 
| Headache response at 24 hours post-dose | The subject diary captures the headache severity using a 4-point headache pain intensity scale (severe = 3, moderate = 2, mild = 1, or none = 0). Headache response is defined as a reduction in moderate (2) or severe (3) pain to mild (1) or no (0) pain at 24 hour post-dose. | 24 hours post-dose | 
| Sustained headache response at 24 hours post-dose | Sustained headache response is defined as a reduction in migraine headache pain intensity from severe or moderate to mild or none at 2 hours which is then maintained (without a return to moderate or severe pain) at 24 hours with no use of rescue medication prior to the 24 hour assessment. | 24 hours post-dose | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Migraine, Headache, Pain, Efficacy, Pediatric