CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`APPLICATION NUMBER:
`022063Orig1s000
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`OTHER REVIEW(S)
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`

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`PMRIPMC Development Template I
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`NDA 022063
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`This template should be completed by the PMRJ'PMC Development Coordinator and included for each
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`PMRfPMC in the Action Package.
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`NDA/BLA #
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`Product Name:
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`NDA 022063
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`Mydayis (mixed salts of amphetamine product) 12.5 mg, 25 mg extended-
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`release capsules
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`PMR/PMC Description:
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`Pharmacokinetic study in 4 toS year olds
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`PMR/PMC Schedule Milestones: Final Protocol Submission:
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`Study/Trial Completion:
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`Final Report Submission:
`Other: N/A
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`09/01/2017
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`12/31/2018
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`06/30/2019
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`1. During application review, explain why this issue is appropriate for a PMR/PMC instead of a pre-approval
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`requirement. Cheek type below and describe.
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`I:I Unmet need
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`I:I Life—threatening condition
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`I:I Long-term data needed
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`I:I Only feasible to conduct post-approval
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`E] Prior clinical experience indicates safety
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`D Small subpopulation affected
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`1:] Theoretical concern
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`E Other
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`Per PeRC guidance, the Sponsor is being allowed to defer this study.
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`2. Describe the particular review issue and the goal of the study/clinical trial. Ifthe study/clinical trial is a
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`FDAAA PMR, describe the risk. If the FDAAA PMR is created post-approval, describe the “new safety
`information.”
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`The study will provide information on the PK profile of Mydayis in 4 toS year olds.
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`I PMR/PMC Development Template
`Reference ID: 4119537
`Reference ID: 4119537
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`Last Updated (SIB/ZONW Page 1 of 12
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`NDA 022063
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`3.
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`If the study/clinical trial is a PMR, check the applicable regulation.
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`13"not a PMR, skip to 4.
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`— Which regulation?
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`I:I Accelerated Approval (subpart I-I/E)
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`|:| Animal Efficacy Rule
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`IXI Pediatric Research Equity Act
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`I:I FDAAA required safety study/clinical trial
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`If the PMR is a FDAAA safety study/clinical trial, does it: (check all that apply)
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`E] Assess a known serious risk related to the use of the drug?
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`[I Assess signals of serious risk related to the use of the drug?
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`I:I Identify an unexpected serious risk when available data indicate the potential for a serious risk?
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`“
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`If the PMR is a FDAAA safety study/clinical trial, will it be conducted as:
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`El Analysis of spontaneous postmarketing adverse events?
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`Do not select the above study/clinical trial (me if such an analysis will not be sufficient to assess
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`or identify a serious risk
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`I:I Analysis using pharmacovigilance system?
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`Do not select the above study/clinical trial type if. the new pharmacovigilance system that the FDA
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`is required to establish under section 505(k)(3) has not yet been established and is thus not sufficient
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`to assess this known serious risk, or has been established but is nevertheless not sufficient to assess
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`or identify a serious risk
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`E] Study: all other investigations, such as investigations in humans that are not clinical trials as defined
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`below (e.g., observational epidemiologic studies), animal studies, and laboratory experiments?
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`Do not select the above study wpe if. a study will not be sufficient to identify or assess a serious
`risk
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`I] Clinical trial: any prospective investigation in which the sponsor or investigator determines the
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`method of assigning investigational product or other interventions to one or more human subjects?
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`4. What type of study or clinical trial is required or agreed upon (describe and check type below)? If the study
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`or trial will be performed in a subpopulation, list here.
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`A pharmacokinetic study in the preschool subpopulation is required for a new, lower (6.25mg)
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`dose than those studied for approval.
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`Required
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`I] Observational pharmacoepidemiologic study
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`I:I Registry studies
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`I:I Primary safety study or clinical trial
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`I:I Pharmacogenetic or pharmacogenomic study or clinical trial if required to further assess safety
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`I:I Thorough Q-T clinical trial
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`I:I Nonclinical (animal) safety study (e.g., carcinogenicity, reproductive toxicology)
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`I:I Nonclinical study (laboratory resistance, receptor affinity, quality study related to safety)
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`IX Pharmacokinetic studies or clinical trials
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`I:I Drug interaction or bioavailability studies or clinical trials
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`I:I Dosing trials
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`5. PMR/'PMC Development Template
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`Reference ID: 4119537
`Reference ID: 4119537
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`Last Updated 6/23/201769—34—201—762311-204—7
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`Page 2 of 12
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`Continuation o
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`n'on 4
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`El Additional data or analysis required for a previOusly submitted or expected study/clinical trial
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`(provide explanation)
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`NDA 022063
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`[I Meta—analysis or pooled analysis ofprevious studies/clinical trials
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`D Immunogenicity as a marker of safety
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`C] Other (provide explanation)
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`Agreed upon:
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`[:I Quality study-without a safety endpoint (e.g., manufacturing, stability)
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`[:I Pharmacoepidemiologic study not related to safe drug use (e.g., natural history of disease, background
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`rates of adverse events)
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`I:I Clinical trials primarily designed to fin’ther define efficacy (e.g., in another condition, different disease
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`severity, or subgroup) that are NOT required under Subpart HfE
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`I: Dose—response study or clinical trial performed for effectiveness
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`[:1 Nonclinical study, not safety-related (specify)
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`El Other
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`5.
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`Is the PMR/PMC clear, feasible, and appropriate?
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`E Does the study/clinical trial meet criteria for PMRs or PMCs?
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`E Are the objectives clear from the description of the PMRfPMC?
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`E Has the applicant adequately justified the choice of schedule milestone dates?
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`E Has the applicant had sufficient time to review the PMRs/PMCS, ask questions, determine feasibility,
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`and contribute to the development process?
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`El Check if this form describes a FDAAA PMR that is a randomized controlled clinical trial
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`Ifso, does the clinical trial meet thefollowing criteria?
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`[I There is a significant question about the public health risks of an approved drug
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`I] There is not enough existing information to assess these risks
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`E] Information cannot be gained through a different kind of investigation
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`[I The trial will be appropriately designed to answer question about a drug‘s efficacy and safety, and
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`I] The trial will emphasize risk minimization for participants as the protocol is developed
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`PMRIPMC Development Coordinator:
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`E This PWPMC has been reviewedfor clarity and consistency, and is necessary tofizrlher refine the
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`safety, efficacy, or optimal use ofa drug. or to ensure consistency and reliability ofdrug quality.
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`(signature line for BLAS)
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`I PMRJ'PMC Development Template
`Reference ID: 4119537
`Reference ID: 4119537
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`Last Updated 6/23,:‘20176f‘23429l36fi23429fi
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`Page 3 of 12
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`PMR/PMC Development Template II
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`
`
`NDA 022063
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`
`
`
`
`
`
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`
`
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`
`
`
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`
`
`This template should be completed by the PMR/PMC Development Coordinator and included for each
`
`
`
`
`
`PMR/PMC in the Action Package.
`
`
`
`
`NDA/BLA #
`
`Product Name:
`
`
`
`
`
`
`
`
`
`
`
`NDA 022063 Mydayis (mixed salts of amphetamine product) extended-
`
`
`release capsules
`
`
`PMR/PMC Description:
`
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`
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`
`
`
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`
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`Efficacy and safety study in 4 ms year olds
`
`
`
`PMR/PMC Schedule Milestones: Final Protocol Submission:
`
`
`
`
`
`
`
`Study/Trial Completion:
`
`
`Final Report Submission:
`Other: N/A
`
`
`
`
`
`
`
`09/01/2017
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`12/31/2018
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`06/30/2019
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`6. During application review, explain why this issue is appropriate for a PMR/PMC instead of a pre-approval
`
`
`
`
`
`
`requirement. Check type below and describe.
`
`
`
`
`
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`I] Unmet need
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`I:I Life-threatening condition
`
`
`
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`I:| Long-term data needed
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`D Only feasible to conduct post-approval
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`Prior clinical experience indicates safety
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`IX Small subpopulation affected
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`I:I Theoretical concern
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`C] Other
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`Per PeRC guidance, the Sponsor is being allowed to defer this study.
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`7. Describe the particular review issue and the goal of the study/clinical trial. If the study/clinical trial is a
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`FDAAA PMR, describe the risk. If the FDAAA PMR is created post-approval, describe the “new safety
`information.”
`
`
`
`
`
`
`
`
`
`
`
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`Drug use data demonstrates that 4 and 5 year old children are receiving XR and IR amphetamine products
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`simultaneously. Given that information, it is likely that Mydayis, a 16 hour dosage form, will be
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`prescribed for children who received the shorter dosage forms. The study will provide data to inform
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`clinicians about the safety and efficacy of a new lower dose of Mydayis in 4 ms year olds and help guide
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`them should they choose to prescribe the medication.
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`f PMR/PMC Development Template
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`
`Reference ID: 4119537
`Reference ID: 4119537
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`Last Updated 6/23/20176/23/20—1—16/2—3/20—1—1
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`Page 4 of 12
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`NDA 022063
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`8.
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`If the study/clinical trial is a PMR, check the applicable regulation.
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`Ifnot a PMR, skip to 4.
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`— Which regulation?
`
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`E] Accelerated Approval (subpart H/E)
`
`
`
`
`El Animal Efficacy Rule
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`
`E Pediatric Research Equity Act
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`
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`[I FDAAA required safety study/clinical trial
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`—
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`—
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`If the PMR is a FDAAA safety studylclinical trial, does it: (check all that apply)
`
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`
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`El Assess a known serious risk related to the use of the drug?
`
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`El Assess signals of serious risk related to the use of the drug?
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`
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`El Identify an unexpected serious risk when available data indicate the potential for a serious risk?
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`If the PMR is a FDAAA safety study/clinical trial, will it be conducted as:
`
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`
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`I] Analysis of spontaneous postmarketing adverse events?
`
`
`
`
`
`
`
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`
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`Do not select the above study/clinical trial type if such an analysis will not be sufficient to assess
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`or identify a serious risk
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`I:I Analysis using pharmacovigilance system?
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`Do not select the above study/clinical trial type if: the new pharrnacovigilance system that the FDA
`
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`
`
`
`
`
`
`
`
`
`
`
`
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`is required to establish under section 505(k)(3) has not yet been established and is thus not sufficient
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`
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`to assess this known serious risk, or has been established but is nevertheless not sufficient to assess
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`or identify a serious risk
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`I:] Study: all other investigations, such as investigations in humans that are not clinical trials as defined
`
`
`
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`
`
`
`
`
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`below (e.g., observational epidemiologic studies), animal studies, and laboratory experiments?
`
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`Do not select the above study type if: a study will not be sufficient to identify or assess a serious
`risk
`
`
`
`
`
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`I: Clinical trial: any prospective investigation in which the sponsor or investigator determines the
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`
`
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`
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`method of assigning investigational product or other interventions to one or more human subjects?
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`9. What type of study or clinical trial is required or agreed upon (describe and check type below)? If the study
`
`
`
`
`
`
`
`
`
`or trial will be performed in a subpopulation, list here.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
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`
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`A 4-week safety (and efficacy) trial evaluating Mydayis in 4 to 5 years old attention deficit
`
`
`
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`hyperactivity disorder patients
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`
`
`
`
`
`
`Required
`
`
`
`I:I Observational pharmacoepidemiologic study
`
`
`
`I:I Registry studies
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`
`
`
`
`
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`IZI Primary safety study or clinical trial
`
`
`
`
`
`
`
`
`
`
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`I] Pharmacogenetic or pharrnacogenomic study or clinical trial if required to further assess safety
`
`
`
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`I] Thorough Q-T clinical trial
`
`
`
`
`
`
`
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`[I Nonclinical (animal) safety study (e.g., carcinogenicity, reproductive toxicology)
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`I: Nonclinical study (laboratory resistance, receptor affinity, quality study related to safety)
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`I] Pharmacokinetic studies or clinical trials
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`I] Drug interaction or bioavailability studies or clinical trials
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`I: Dosing trials
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`I PMR/PMC Development Template
`Reference ID: 4119537
`Reference ID: 4119537
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`Last Updated 6/23/20176/23301—76231129l4
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`Page 5 of 12
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`@finuafion 0t destian 4
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`E] Additional data or analysis required for a previously submitted or expected study/clinical trial
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`(provide explanation)
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`[:I Meta-analysis or pooled analysis of previous studies/clinical trials
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`E] Immunogenicity as a marker of safety
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`C] Other (provide explanation)
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`NDA 022063
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`Agreed upon:
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`D Quality study without a safety endpoint (e.g., manufacturing, stability)
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`El Pharmaeoepiderniologic study not related to safe drug use (e.g., natural history of disease, background
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`rates of adverse events)
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`[I Clinical trials primarily designed to further define efficacy (e. g., in another condition, different disease
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`severity, or subgroup) that are NOT required under Subpart HE
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`E] Dose—response study or clinical trial performed for effectiveness
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`I:I Nonclinical study, not safety-related (specify)
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`D Other
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`10. Is the PMR/PMC clear, feasible, and appropriate?
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`E Does the study/clinical trial meet criteria for PMRs or PMUS?
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`IX Are the objectives clear from the description of the PMRJPMC?
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`12] Has the applicant adequately justified the choice of schedule milestone dates?
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`E Has the applicant had sufficient time to review the PMRSIPMCS, ask questions, determine feasibiIity,
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`and contribute to the development process?
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`E] Check if this form describes a FDAAA PMR that is a randomized controlled clinical trial
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`Ifso, does the clinical trial meet thefollowing criteria?
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`[I There is a significant question about the public health risks of an approved drug
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`1:] There is not enough existing information to assess these risks
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`D Information cannot be gained through a different kind of investigation
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`CI The trial will be appropriately designed to answer question about a drug’s efficacy and safety, and
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`E] The trial will emphasize risk minimization for participants as the protocol is developed
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`PMRIPMC Development Coordinator:
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`This PAIR/PMC has been reviewedfor clarity and consistency, and is necessary tofiirther refine the
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`safegi, eflieacy, or optimal use ofa drug, or to ensure consistency and reliability ofdrug quality.
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`(signature line for BLAs)
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`
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`
`I PMR/PMC Development Template
`Reference ID: 4119537
`Reference ID: 4119537
`
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`
`Last Updated @3/20176r'i23yQO-1—161-237L20-1—7
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`Page 6 of 12
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`PMR/PMC Development Template III
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`NDA 022063
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`This template should be completed by the PMR/PMC Development Coordinator and included for each
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`PMR/PMC in the Action Package.
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`NDA/BLA #
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`Product Name:
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`.
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`PMR/PMC Description:
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`NDA 022063 Mydayis (mixed salts of amphetamine product) extended-
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`release capsules
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`Efficacy and safety study of 6.25mg dose in 6 to 12 year olds
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`PMR/PMC Schedule Milestones: Final Protocol Submission:
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`Study/Trial Completion:
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`Final Report Submission:
`Other: N/A
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`09/01/2017
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`12/31/201 8
`06/30/2019
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`11. During application review, explain why this issue is appropriate for a PMR/PMC instead of a pre—approval
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`requirement. Check type below and describe.
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`[I Unmet need
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`[I Life-threatening condition
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`[I Long-term data needed
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`I] Only feasible to conduct post-approval
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`IE Prior clinical experience indicates safety
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`I] Small subpopulation affected
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`D Theoretical concern
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`El Other
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`Pro-approval review of Mydayis 12.5 and 25mg doses demonstrate high exposure levels and
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`adverse reactions of severe insomnia and decreased appetite in 6 to 12 year olds. Mydayis will be
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`approved with a limitation of use; use in less than 12 years is not recommended.
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`Therefore, safety of a new, lower 6.25mg dose should be evaluated in that age group.
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`12. Describe the particular review issue and the goal of the study/clinical trial. If the study/clinical trial is a
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`FDAAA PMR, describe the risk. Ifthe FDAAA PMR is created post-approval, describe the “new safety
`information.”
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`See question 11.
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`l PMR/PMC Development Template
`Reference ID: 4119537
`Reference ID: 4119537
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`Last Updated 6/23/20176/33QQJ46/23/29—1—2
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`Page 7 of 12
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`NDA 022063
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`13. If the study/clinical trial is a PMR, check the applicable regulation.
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`Ifnot a PMR, skip to 4'.
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`— Which regulation?
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`I:I Accelerated Approval (subpart HE)
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`D Animal Efficacy Rule
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`E Pediatric Research Equity Act
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`El FDAAA required safety study/clinical trial
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`—
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`—
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`If the PMR is a FDAAA safety study/clinical trial, does it: (check all that apply)
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`[:I Assess a lmown serious risk related to the use of the drug?
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`I:I Assess signals of serious risk related to the use of the drug?
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`[I Identify an unexpected serious risk when available data indicate the potential for a serious risk?
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`If the PMR is a FDAAA safety study/clinical trial, will it be conducted as:
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`[I Analysis of spontaneous postmarketing adverse events?
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`Do not select the above study/clinical trial,r type if: such an analysis will not be sufficient to assess
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`or identify a serious risk
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`[I Analysis using pharmacovigilance system?
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`Do not select the above study/clinical trial type if: the new pharmacovigilance system that the FDA
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`is required to establish under section 505 (k)(3) has not yet been established and is thus not sufficient
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`to assess this known serious risk, or has been established but is nevertheless not sufficient to assess
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`or identify a serious risk
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`[:I Study: all other investigations, such as investigations in humans that are not clinical trials as defined
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`below (e. g., observational epidemiologic studies), animal studies, and laboratory experiments?
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`Do not select the above study type if: a study will not be sufficient to identify or assess a serious
`risk
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`[I Clinical trial: any prospective investigation in which the sponsor or investigator determines the
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`method of assigning investigational product or other interventions to one or more human subjects?
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`14. What type of study or clinical trial is required or agreed upon (describe and check type below)? If the study
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`or trial will be performed in a subpopulation, list here.
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`' A 4-week safety (and efficacy) trial evaluating 6.25mg Mydayis in 6 to 12 years old attention
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`deficit hyperactivity disorder patients
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`Required
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`I:I Observational phannacoepidemiologic study
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`I:I Registry studies
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`IE Primary safety study or clinical trial
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`I:I Pharmacogenetic or pharrnacogenomic study or clinical trial if required to further assess safety
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`I: Thorough Q-T clinical trial
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`El Nonclinical (animal) safety study (e.g., carcinogenicity, reproductive toxicology)
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`I:I Nonclinical study (laboratory resistance, receptor affinity, quality study related to safety)
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`I:I Pharmacokinetic studies or clinical trials
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`I:I Drug interaction or bioavailability studies or clinical trials
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`I:I Dosing trials
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`
`I PMRJIPMC Development Template
`
`
`
`Reference ID: 4119537
`Reference ID: 4119537
`
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`
`Last Updated 6/23/2017'6i123i12Q4—716.123M-‘LlQ-l—il
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`Page 8 of 12
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`Continuation 0
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`esrion 4
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`El Additional data or analysis required for a previously submitted or expected study/clinical trial
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`(provide explanation)
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`NDA 022063
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`I] Meta-analysis or pooled analysis of previous studies/clinical trials
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`D Immunogenicity as a marker of safety
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`I:I Other (provide explanation)
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`Agreed upon:
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`I:] Quality study Without a safety endpoint (e.g., manufacturing, stability)
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`El Pharmacoepidemiologic study not related to safe drug use (e.g., natural history of disease, background
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`rates of adverse events)
`_
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`[I Clinical trials primarily designed to further define efficacy (e.g., in another condition, different disease
`
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`
`
`
`
`
`
`
`
`severity, or subgroup) that are NOT required under Subpart HfE
`
`
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`
`
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`
`I:I Dose-response study or clinical trial performed for effectiveness
`
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`I:I Nonclinical study, not safety-related (specify)
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`D Other
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`15. Is the PMR/PMC clear, feasible, and appropriate?
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`E Does the study/clinical trial meet criteria for PMRs or PMCs'!
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`E Are the objectives clear from the description of the PMRfPMC?
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`E Has the applicant adequately justified the choice of schedule milestone dates?
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`Has the applicant had sufficient time to review the PMRs/PMCS, ask questions, determine feasibility,
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`and contribute to the development process?
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`I:I Check if this form describes a FDAAA PMR that is a randomized controlled clinical trial
`
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`
`
`
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`
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`Ifso, does the clinical trial meet thefollowing criteria?
`
`
`
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`
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`
`
`
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`1:] There is a significant question about the public health risks ofan approved drug
`
`
`
`
`
`
`
`
`
`
`
`D There is not enough existing information to assess these risks
`
`
`
`
`
`
`
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`
`
`D Information cannot be gained through a different kind ofinvestigation
`
`
`
`
`
`
`
`
`
`
`
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`
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`
`D The trial will be appropriately designed to answer question about a drug’s efficacy and safety, and
`
`
`
`
`
`
`
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`
`
`
`
`
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`El The trial will emphasize risk minimization for participants as the protocol is developed
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`
`PMRJPMC Development Coordinator:
`
`
`
`
`
`
`
`
`
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`
`
`E This PWPMC has been reviewedfor clarity and consistency, and is necessary tofiirther refine the
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`safety. eflz‘cacy, or optimal use ofa drug or to ensure consistency and reliability ofdrug quality.
`
`
`
`
`
`
`(signature line for BLAS)
`
`
`
`
`
`
`
`] PMR/PMC Development Template
`Reference ID: 4119537
`Reference ID: 4119537
`
`
`
`
`
`
`
`Last Updated 6123/2017W Page 9 of 12
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`
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`

`

`
`
`
`PMR/PMC Development Template IV
`
`
`
`NDA 022063
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`This template should be completed by the PMR/PMC Development Coordinator and included for each
`
`
`
`
`
`PMR/PMC in the Action Package.
`
`
`
`
`NDA/BLA #
`
`Product Name:
`
`
`
`
`
`
`
`
`
`
`
`NDA 022063 Mydayis (mixed salts of amphetamine product) extended-
`
`
`release capsules
`
`
`PMR/PMC Description:
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Long-term safety study, at least 1 year in length, in 4 to 5 year olds
`
`
`
`
`
`
`
`
`PMR/PMC Schedule Milestones: Final Protocol Submission:
`
`
`Study/Trial Completion:
`
`
`
`Final Report Submission:
`Other:
`
`
`
`
`09/01/2018
`
`12/31/2019
`06/30/2020
`
`
`
`
`
`
`
`
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`16. During application review, explain why this issue is appropriate for a PMIUPMC instead of a pre-approval
`
`
`
`
`
`
`requirement. Check type below and describe.
`
`
`
`
`[:I Unmet need
`
`
`
`D Life—threatening condition
`
`
`
`
`1:] Long-term data needed
`
`
`
`
`
`
`[:I Only feasible to conduct post-approval
`
`
`
`
`
`El Prior clinical experience indicates safety
`
`
`
`
`Small subpopulation affected
`
`
`
`El Theoretical concern
`
`
`C] Other
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`Per PeRC guidance, the Sponsor is being allowed to defer this study.
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`17. Describe the particular review issue and the goal of the study/clinical trial. If the study/clinical trial is a
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`FDAAA PMR, describe the risk. If the FDAAA PMR is created post-approval, describe the “new safety
`information.”
`
`
`
`
`
`
`
`
`
`
`
`
`
`
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`
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`
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`
`
`It is unclear if the 6- month long-term open-label study (Study 308) will provide enough data to measure
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`
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`grovvth suppression (as assessed by change in height and weight) during 6 months time. The duration of the
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`long-term safety study needs to be of Sufficient length to assess effects on growth in the proposed
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`I PMR/PMC Development Template
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`Last Updated 6/23/20176R9/20—146/B/20H
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`Reference ID: 4119537
`Reference ID: 4119537
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`NDA 022063
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`18. If the study/clinical trial is a PIVIR, check the applicable regulation.
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`Ifnot 0 PAIR, skip to 4.
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`~ Which regulation?
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`[j Accelerated Approval (subpart HIE)
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`El Animal Efficacy Rule
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`Pediatric Research Equity Act
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`[I FDAAA required safety study/clinical trial
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`—
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`If the PMR is a FDAAA safety study/clinical trial, does it: (check all that apply)
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`[:I Assess a known serious risk related to the use of the drug?
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`I:I Assess signals of serious risk related to the use of the drug?
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`El Identify an unexpected serious risk When available data indicate the potential for a serious risk?
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`If the PMR is a FDAAA safety study/clinical trial, will it be conducted as:
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`D Analysis of smntaneous mstmarketing adverse events?
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`Do not select the above study/clinical trial {we if: such an analysis will not be sufficient to assess
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`or identify a serious risk
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`I:I Analysis using phannacovigilance system?
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`Do not select the above study/clinical trial type if the new pharmacovigilance system that the FDA
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`is required to establish under section 505(k)(3) has not yet been established and is thus not sufficient
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`to assess this known serious risk, or has been established but is nevertheless not sufficient to assess
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`or identify a serious risk
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`I] Study: all other investigations, such as investigations in humans that are not clinical trials as defined
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`below (e.g., observational epidemiologic studies), animal studies, and laboratory experiments?
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`Do not select the above study {me if: a study will not be sufficient to identify or asseSS a serious
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`[I Clinical trial: any prospective investigation in which the sponsor or investigator determines the
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`method of assigning investigational product or other interventions to one or more human subjects?
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`19. What type of study or clinical trial is required or agreed upon (describe and check type below)? Ifthe study
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`or trial will be performed in a subpopulation, list here.
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`A long—term open-label safety study to evaluate growth suppression.
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`Required
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`E] Observational pharmacoepidemiologic study
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`I] Registry studies
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`E Primary safety study or clinical trial
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`[:1 Pharmacogenetic or pharmacogenoruic study or clinical trial if required to firrther assess safety
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`E] Thorough Q—T clinical trial
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`[:I Nonclinical (animal) safety study (e.g., carcinogenicity, reproductive toxicology)
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`I:I Nonclinical study (laboratory resistance, receptor affinity, quality study related to safety)
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`[I Pharmacokinetic studies or clinical trials
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`E] Drug interaction or bioavailability studies or clinical trials
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`I:I Dosing trials
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`| PMR/PMC Development Template
`Reference ID: 4119537
`Reference ID: 4119537
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`Last Updated 6/23/2017me
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`Page 11 of 12
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`Continuation o
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`estion 4
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`El Additional data or analysis required for a previously submitted or expected study/clinical trial
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`(provide explanation)
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`NDA 022063
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`El Meta-analysis or pooled analysis of previous studies/clinical trials
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`El Immunogenicity as a marker of safety
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`D Other (provide explanation)
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`Agreed upon:
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`I:I Quality study without a safety endpoint (e.g., manufacturing, stability)
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`I:I Pharmacoepidemiologic study not related to safe drug use (e.g., natural history of disease, background
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`rates of adverse events)
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`I:I Clinical trials primarily designed to fiirther define efficacy (e.g., in another condition, different disease
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`severity, or subgroup) that are NOT required under Subpart I-L’E
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`I:I Dose-response study or clinical trial performed for effectiveness
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`[I Nonclinical study, not safety—related (specify)
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`I:I Other
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`20. Is the PMR/PMC clear, feasible, and appropriate?
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`[Z Does the study/clinical trial meet criteria for PMRs or PMCs?
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`IE Are the objectives clear from th