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` DEPARTMENT OF HEALTH & HUMAN SERVICES
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`Public Health Service
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`Food and Drug Administration
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`Rockville, MD 20857
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`NDA 21-450/S-005
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`Lynley K. Thinnes
`Director, Regulatory Affairs
`Neuroscience Emerging Products
`AstraZeneca
`1800 Concord Pike
`PO Box 8355
`Wilmington, DE 19803-8355
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`Dear Ms. Thinnes:
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`Please refer to your supplemental new drug application dated December 14, 2007, received
`December 14, 2007, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act for
`Zomig (zolmitriptan) nasal spray.
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`We acknowledge receipt of your submissions dated April 3, 2008, August 6, 2008 and
`September 15, 2008.
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`This supplemental new drug application provides for the use of Zomig (zolmitriptan) nasal spray
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`We completed our review of this application, as amended.
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`The pivotal efficacy trial (D1221C00005) in support of adolescent use was a multicenter, double-blind,
`randomized, placebo-controlled, 2-way crossover study with a single-blind placebo challenge. For each
`migraine attack, when migraine pain reached moderate-to-severe intensity, all subjects were initially
`challenged with a placebo nasal spray. Subjects who achieved reduction in headache pain to mild or
`none within 15 minutes were defined as early placebo responders and did not use randomized
`treatment for that attack. Subjects who did not respond within 15 minutes used randomized treatment
`with either zolmitriptan 5-mg nasal spray or placebo. The co-primary efficacy variables were 1-hour
`headache response and 2-hour sustained headache response.
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`(b)
`(4)
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`(b) (4)
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`(b) (4)
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`NDA 21-450/S-005
`Page 2
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`Despite the fact that
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`, the attached, agreed-upon labeling in PLR format, which includes a brief discussion of
`Study D1221C00005, is approved, effective on the date of this letter, with the minor editorial revisions
`indicated in the enclosed labeling.
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`Additionally, we note the following Changes Being Effected (CBE) labeling supplements have been
`submitted as described below, and have been superseded with the approval of this application. These
`CBE labeling supplements will be retained in our files.
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`1. CBE dated July 20, 2006 included prescribing information was revised to include Class
`Labeling changes as requested by the Agency in correspondence dated May 25, 2006. Changes
`appear in the WARNINGS, PRECAUTIONS and ADVERSE REACTIONS sections.
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`(b) (4)
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`(b) (4)
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`(b) (4)
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`NDA 21-450/S-005
`Page 3
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`2. CBE dated March 13, 2007 included Class Labeling changes as requested by the Agency in
`correspondence dated December 20, 2006. These labeling revisions pertain to the risk for
`serotonin syndrome with the use of triptans. Changes appear in the WARNINGS,
`PRECAUTIONS and PATIENT INFORMATION sections.
`We are waiving the requirements of 21 CFR 201.57(d)(8) regarding the length of Highlights of prescribing
`information. This waiver applies to all future supplements containing revised labeling unless we notify you
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`otherwise.
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`The final printed labeling (FPL) must be identical, and include the minor editorial revisions indicated,
`to the enclosed labeling (text for the package insert, text for the patient package insert) and submitted
`labeling (immediate container and carton labels submitted December 14, 2007). These revisions are
`terms of the approval of this application.
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`Please submit an electronic version of the FPL according to the guidance for industry titled Providing
`Regulatory Submissions in Electronic Format - NDA. Alternatively, you may submit 20 paper copies
`of the FPL as soon as it is available but no more than 30 days after it is printed. Individually mount 15
`of the copies on heavy-weight paper or similar material. For administrative purposes, designate this
`submission "FPL for approved supplement NDA 21-450/S-005.” Approval of this submission by
`FDA is not required before the labeling is used.
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`REQUIRED PEDIATRIC ASSESSMENTS
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`Under the Pediatric Research Equity Act (PREA) (21 U.S.C. 355c), all applications for new active
`ingredients, new indications, new dosage forms, new dosing regimens, or new routes of administration
`are required to contain an assessment of the safety and effectiveness of the product for the claimed
`indication in pediatric patients unless this requirement is waived, deferred, or inapplicable. We are
`waiving the pediatric study requirement for ages 0 to 5 years because necessary studies are impossible
`or highly impracticable. This is because the low prevalence of migraine and migraine presentation in
`that group would not allow to practically design a study and recruit the needed patient population.
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`As noted above,
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` you will need to design and conduct an additional study of ZOMIG in
`adolescents (ages 12-17 years).
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`In addition, you are required to study ZOMIG for treatment of acute migraine in pediatric patients ages
`6-11 years. However, we are deferring submission of this required pediatric study because it should be
`delayed until additional safety and effectiveness data are available from your study in adolescents.
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`Your deferred pediatric studies required by section 505B(a) of the Federal Food, Drug, and Cosmetic
`Act are required postmarketing studies. The status of these postmarketing studies must be reported
`annually according to 21 CFR 314.81 and section 505B(a)(3)(B) of the Federal Food, Drug, and
`Cosmetic Act. These required studies under NDA 21-450 N-000 are listed below.
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`1. Deferred pediatric study under PREA for the acute treatment of migraine in pediatric patients ages
`12 to 17 years.
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`Final Report Submission: October 14, 2011
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`(b) (4)
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`NDA 21-450/S-005
`Page 4
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`2. Deferred pediatric study under PREA for the acute treatment of migraine in pediatric patients ages
`6 to 11 years. Upon review of additional safety and effectiveness data in pediatric patients ages 12
`to 17 years, we will make a determination as to whether or not pediatric studies are practicable for
`this age range.
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`Final Report Submission: October 14, 2014
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`Submit final study reports to this NDA. For administrative purposes, all submissions related to these
`required pediatric postmarketing studies must be clearly designated “Required Pediatric
`Assessments”.
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`If you issue a letter communicating important information about this drug product (i.e., a “Dear Health
`Care Professional” letter), we request that you submit a copy of the letter to this NDA and a copy to
`the following address:
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`MEDWATCH
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`Food and Drug Administration
`Suite 12B05
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`5600 Fishers Lane
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`Rockville, MD 20857
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`We remind you that you must comply with reporting requirements for an approved NDA (21 CFR
`314.80 and 314.81).
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`If you have any questions, call Lana Chen, Regulatory Project Manager, at (301) 796-1056.
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`Sincerely,
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` {See appended electronic signature page}
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`Russell Katz, M.D.
`Director
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`Division of Neurology Products
`Office of Drug Evaluation I
`Center for Drug Evaluation and Research
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`Enclosure
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`This is a representation of an electronic record that was signed electronically and
`this page is the manifestation of the electronic signature.
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`/s/
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`Russell Katz
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`10/14/2008 03:43:13 PM
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