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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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` NDA 21-450/S-008
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`Food and Drug Administration
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`Silver Spring MD 20993
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`SUPPLEMENT APPROVAL
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`FULFILLMENT OF POSTMARKETING
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` REQUIREMENTS
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`RELEASE OF POSTMARKETING
`REQUIREMENT
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`NEW POSTMARKETING REQUIREMENTS
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`AstraZeneca Pharmaceuticals LP
`Attention: Mr. Robert Griffin
`Regulatory Affairs Director
`One MedImmune Way
`Gaithersburg, MD 21878
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`Dear Mr. Griffin:
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`Please refer to your Supplemental New Drug Application (sNDA) dated and received August 14,
`2014, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act (FDCA) for
`Zomig (zolmitriptan) nasal spray 0.5mg, 2.5mg, and 5mg.
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`We acknowledge receipt of your amendments dated the following:
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`December 17, 2014
`March 9, 2015
`April 14, 2015
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`May 19, 2015
`June 4, 2015
`June 5, 2015
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`This Prior Approval supplemental new drug application proposes zolmitriptan for the acute
`treatment of migraine with or without aura in adolescents 12 to 17 years old.
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`APPROVAL & LABELING
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`We have completed our review of this supplemental application, as amended. It is approved,
`effective on the date of this letter, for use as recommended in the enclosed, agreed-upon labeling
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`text.
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`Reference ID: 3778462
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`

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`NDA 21-450/S/008
`Page 2
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`LABELING
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`Submit final printed labeling, as soon as they are available, but no more than 30 days after they
`are printed. The final printed labeling (FPL) must be identical to the enclosed labeling (package
`insert,) and must be in the “Drug Facts” format (21 CFR 201.66), where applicable.
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`The final printed labeling should be submitted electronically according to the guidance for
`industry titled “Providing Regulatory Submissions in Electronic Format – Human
`Pharmaceutical Product Applications and Related Submissions Using the eCTD Specifications
`(June 2008).” Alternatively, you may submit 12 paper copies, with 6 of the copies individually
`mounted on heavy-weight paper or similar material. For administrative purposes, designate this
`submission “Final Printed Labeling for approved NDA 21-450/S-008.” Approval of this
`submission by FDA is not required before the labeling is used.
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`DRUG REGISTRATION AND LISTING
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`All drug establishment registration and drug listing information is to be submitted to FDA
`electronically, via the FDA automated system for processing structured product labeling (SPL)
`files (eLIST). At the time that you submit your final printed labeling (FPL), the content of
`labeling (Drug Facts) should be submitted in SPL format as described at
`http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm.
`Information on submitting SPL files using eLIST may be found in the guidance for industry
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`titled “SPL Standard for Content of Labeling Technical Qs and As” at
`http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/U
`CM072392.pdf. In addition, representative container or carton labeling, whichever includes
`Drug Facts, (where differences exist only in the quantity of contents statement) should be
`submitted as a JPG file.
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`FULFILLMENT OF POSTMARKETING REQUIREMENTS
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`We refer to the deferred pediatric study noted in our S-005 approval letter dated October 14,
`2008:
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`1. Deferred pediatric study under PREA for the acute treatment of migraine in pediatric
`patients ages 12 years to 17 years.
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`We have reviewed your supplemental application (S-008) and conclude that the above
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`requirement was fulfilled.
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`RELEASE OF POSTMARKETING REQUIREMENTS
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`We refer to the deferred pediatric study noted in our S-005 approval letter dated October 14,
`2008:
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`2.
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` 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
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`Reference ID: 3778462
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`

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`NDA 21-450/S/008
`Page 3
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`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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`Based on our review of the safety and efficacy data for zolmitriptan nasal spray for the treatment
`of migraine in children ages 12 years to 17 years that you have submitted in supplement S-008,
`and our review of other information, we have determined that pediatric studies to evaluate the
`safety and efficacy of zolmitriptan nasal spray in children ages 6 years to 11 years with migraine
`are practicable. Therefore, the above requirement is being released and replaced with PMR 2921-
`2 below.
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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(s) in pediatric patients unless this requirement is waived,
`deferred, or inapplicable.
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`We have waived the pediatric requirement for ages 0 months to up to 6 years because necessary
`studies are impossible or highly impracticable in that age group.
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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 FDCA. These
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`required studies are listed below.
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`PMR 2921-1 Conduct a juvenile rat toxicology study to identify the unexpected serious risk of
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`adverse effects of zolmitriptan on postnatal growth and development. The study
`should utilize animals of an age range and stage(s) of development that are
`comparable to the intended pediatric population; the duration of dosing should
`cover the intended length of treatment in the pediatric population. In addition to
`the usual toxicological parameters, this study must evaluate effects of zolmitriptan
`on growth, reproductive development, and neurological and neurobehavioral
`development.
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`Final Protocol Submission: November 2016
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`Study Completion: November 2017
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`Final Report Submission: May 2018
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`PMR 2921-2: Conduct a controlled efficacy and pharmacokinetics (PK) study in children ages
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`≥6 years to 11 years with migraine that includes sparse PK samples throughout
`the efficacy study. Conduct a long-term open-label safety study in pediatric
`patients with migraine ages ≥6 years to 11 years. The long-term safety study
`must provide a descriptive analysis of safety data in at least 50 pediatric patients
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`Reference ID: 3778462
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`

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`NDA 21-450/S/008
`Page 4
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`exposed for at least 6 months, treating on average at least one migraine attack per
`month, at doses evaluated in the efficacy study.
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`Final Protocol Submission: February 2016
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`Study Completion: November 2020
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`Final Report Submission: May 2021
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`Submit the protocols to your IND 53,848, with a cross-reference letter to this NDA 21-450.
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`Reports of these required pediatric postmarketing studies must be submitted as a new drug
`application (NDA) or as a supplement to your approved NDA with the proposed labeling
`changes you believe are warranted based on the data derived from these studies. When
`submitting the reports, please clearly mark your submission "SUBMISSION OF REQUIRED
`PEDIATRIC ASSESSMENTS" in large font, bolded type at the beginning of the cover letter of
`the submission.
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`REPORTING REQUIREMENTS
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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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`
` Eric Bastings, M.D.
`Deputy Director
`Division of Neurology Products
`Office of Drug Evaluation I
` Center for Drug Evaluation and Research
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`ENCLOSURE:
`Labeling
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`Reference ID: 3778462
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`

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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.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
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`ERIC P BASTINGS
`06/12/2015
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`Reference ID: 3778462
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