Efficacy and Tolerability of Zolmitriptan Nasal Spray for the Treatment of Acute Migraine in Adolescents

Results of a Randomized, Double-blind, Multi-center, Parallel-group Study (TEENZ)

Paul Winner, DO; Viktor Farkas, MD; Helena Štillová, MD; Brian Woodruff, MD; Charlie Liss, MS; Stefan Lillieborg, MD; Shane Raines, Ms

Disclosures

Headache. 2016;56(7):1107-1119. 

In This Article

Abstract and Introduction

Abstract

Objective. The primary objective of the TEENZ Study (NCT01211145) was to assess the efficacy of zolmitriptan nasal spray in the acute treatment of adolescent migraine patients (ages 12 to 17 years), as measured by the primary outcome variable of pain-free status at 2 hours post-treatment.

Methods. This randomized, double-blind, placebo-controlled, four-arm parallel group study compared zolmitriptan nasal spray with placebo in the treatment of a single episode of adolescent migraine. Patients completed a 30-day run-in period to treat a single migraine attack with single-blind placebo nasal spray. Eligible patients, who had not responded to placebo, were randomized to one of three zolmitriptan nasal spray doses (5, 2.5, or 0.5 mg) or placebo in a ratio of 5:3:3:5 according to a computer-generated randomization scheme. Patients completed diaries for 24 hours after treatment, recording headache pain scores, adverse events (AEs), and medications taken.

Results. In an interim futility analysis, zolmitriptan nasal spray doses of 0.5 and 2.5 mg were declared futile relative to placebo and further randomization to these treatment arms was discontinued. Of 1653 patients enrolled into the study, 855 patients failed to meet study eligibility criteria and were considered screen failures. The most common reason for screen failure was response to placebo challenge (325 patients [38.0%]). Of the 798 patients who were randomized to treatment, 721 (90.4%) completed the study period. Of these, 657 (82.3%) treated a migraine within the study period and contributed data for analysis. Zolmitriptan nasal spray 5 mg was significantly more effective than placebo in achieving pain-free status at 2 hours after treatment (P < .001), with 30% of patients achieving pain-free status at 2 hours vs 17% of placebo-treated patients (OR 2.18; 95% CI 1.40, 3.39). Zolmitriptan nasal spray 5 mg was also more effective than placebo in achieving pain-free status at 3 and 4 hours post-treatment (45 vs 24%, and 56 vs 39%; both P < .001). Zolmitriptan nasal spray 5 mg was also more effective than placebo in achieving headache response at 2, 3, and 4 hours after treatment (51 vs 39%, 61 vs 48%, and 69 vs 57%, respectively; all P ≤ .011). Zolmitriptan nasal spray was well-tolerated at all doses. Dysgeusia was the most frequently reported AE, with greater frequencies reported in active treatment groups versus placebo. No serious AEs or AEs leading to discontinuation were reported. Most AEs were mild or moderate in severity, and consistent with the known profile of zolmitriptan in adult and adolescent populations.

Conclusion. Zolmitriptan nasal spray was well-tolerated in the acute treatment of adolescent (ages 12 to 17 years) migraine. Zolmitriptan 5 mg nasal spray demonstrated superior efficacy compared with placebo for the primary efficacy endpoint of pain-free status 2 hours after treatment and the efficacy of the 5 mg dose was supported by the majority of secondary efficacy endpoints.

Introduction

Migraine is a common disabling neurological disorder, associated with headache, nausea, and occasionally vomiting. It is estimated that 10–15% of people worldwide suffer from migraine, with more than 80% of sufferers experiencing associated disability.[1,2]

As well as the suffering caused, migraine presents a considerable social and economic burden to society.[3] In the United States (US), an estimated $19.6 billion is lost each year in productive time due to headaches.[4]

Serotonin5HT1B/1D receptor agonists, or triptans, have demonstrated efficacy and are a well-tolerated acute therapy.[5] Zolmitriptan (ZOMIG®) is a second-generation serotonin 5HT1B/1D receptor agonist, with proven efficacy in the acute treatment of adult migraine. In adults, the nasal spray formulation provides onset of headache relief within 10 minutes for some patients and also abolishes other major migraine symptoms.[6]

Globally, between 6 and 10% of children and adolescents experience migraine attacks.[7] Compared with adults who suffer from migraine, however, the number of drugs studied and approved for the abortive treatment of adolescent or pediatric migraine attacks is limited.[8,9] In younger patients, the onset of migraine is more rapid than in adults, usually hindering the capability of tablet formulations.[10] The attacks are also of shorter duration than in adult migraine and are more frequently associated with vomiting, with the latter also limiting the use of tablet formulations.[10]

High placebo-response rates have been consistently reported in adolescent studies of triptan use and can contribute to a failure to demonstrate efficacy.[11,12] Novel trial designs that incorporate enrichment strategies to enhance the likelihood of demonstrating efficacy have been used in some adolescent migraine trials.[13–15] Among these, the inclusion of a placebo challenge prior to treatment with randomized medication[13] and the selection of patients with a history of protracted migraines[14] are two approaches that have been used.[13,14] Using such enrichment strategies, this study aimed to investigate the efficacy, safety, and tolerability of zolmitriptan nasal spray in the acute treatment of migraine headache in adolescent patients. Using the International Headache Society (IHS)-recommended endpoint of pain-free status, the primary null hypothesis to be tested was that the response rates at 2 hours post-treatment for zolmitriptan doses of 0.5, 2.5, and 5 mg are no different from that of placebo.

Comments

3090D553-9492-4563-8681-AD288FA52ACE

processing....