CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`APPLICATION NUMBER:
`
`022272Orig1s027
`
`
`OTHER REVIEW(S)
`
`

`

`PMR/PMC Development Template
`
`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:
`
`PMR/PMC Description:
`
`NDA 22272/S-027
`OxyContin
`2923-1: Postmarket Adverse Event and Medication Error Reporting
`
`To assess the serious risks of respiratory depression, accidental injury,
`overdose, misuse, accidental exposure, and medication errors
`associated with the use of OxyContin in opioid-tolerant pediatric
`patients aged 11-17, and to assess the serious risks of respiratory
`depression, accidental injury, overdose, misuse, accidental exposure,
`and medication errors associated with the use of the product in children
`who are either younger than the approved age range or who do not meet
`the labeled criteria for opioid tolerance, provide reports of all
`postmarket adverse events occurring in children aged 17 and younger
`related to respiratory depression, accidental injury, overdose, misuse,
`accidental exposure, and all medication errors, regardless of outcome.
`After three years of submitting reports, submit a comprehensive
`analysis of these adverse event and medication errors reports, and
`provide an explanation of how you have addressed them.
`
`PMR/PMC Schedule Milestones: Final Protocol Submission: 08/2015
`Interim Report Submission: 12/2015
`Interim Report Submission: 12/2016
`Interim Report Submission: 12/2017
`Interim Report Submission:
` 12/2018
` 04/2019
`Final Report Submission:
`
`1. During application review, explain why this issue is appropriate for a PMR/PMC instead of a pre-approval
`requirement. Check type below and describe.
`Unmet need
`Life-threatening condition
`Long-term data needed
`Only feasible to conduct post-approval
`Prior clinical experience indicates safety
`Small subpopulation affected
`Theoretical concern
`Other
`
`PMR/PMC Development Template
`
`Last Updated 8/13/2015
`
`Page 1 of 4
`
`Reference ID: 3805672
`
`

`

`OxyContin has been marketed for nearly 20 years.
`
`2. 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.”
`
`OxyContin has been studied in opioid-tolerant pediatric patients, mostly in the 11-17 year old age range.
`Additional safety data is needed in younger patients and those who are not opioid tolerant.
`
`3.
`
`If the study/clinical trial is a PMR, check the applicable regulation.
`If not a PMR, skip to 4.
`- Which regulation?
`Accelerated Approval (subpart H/E)
`Animal Efficacy Rule
`Pediatric Research Equity Act
`FDAAA required safety study/clinical trial
`- If the PMR is a FDAAA safety study/clinical trial, does it: (check all that apply)
`Assess a known serious risk related to the use of the drug?
`Assess signals of serious risk related to the use of the drug?
`Identify an unexpected serious risk when available data indicate the potential for a serious risk?
`- If the PMR is a FDAAA safety study/clinical trial, will it be conducted as:
`Analysis of spontaneous postmarketing adverse events?
`Do not select the above study/clinical trial type if: such an analysis will not be sufficient to assess
`or identify a serious risk
`
`Analysis using pharmacovigilance system?
`Do not select the above study/clinical trial type if: the new pharmacovigilance system that the FDA
`is required to establish under section 505(k)(3) has not yet been established and is thus not sufficient
`to assess this known serious risk, or has been established but is nevertheless not sufficient to assess
`or identify a serious risk
`
`Study: all other investigations, such as investigations in humans that are not clinical trials as defined
`below (e.g., observational epidemiologic studies), animal studies, and laboratory experiments?
`Do not select the above study type if: a study will not be sufficient to identify or assess a serious
`risk
`
`PMR/PMC Development Template
`
`Last Updated 8/13/2015
`
`Page 2 of 4
`
`Reference ID: 3805672
`
`

`

`Clinical trial: any prospective investigation in which the sponsor or investigator determines the
`method of assigning investigational product or other interventions to one or more human subjects?
`4. 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.
`Expedited reporting of adverse events related to respiratory depression, accidental injury,
`overdose, misuse, accidental exposure, and medication errors.
`
`Required
`Observational pharmacoepidemiologic study
`Registry studies
`Primary safety study or clinical trial
`Pharmacogenetic or pharmacogenomic study or clinical trial if required to further assess safety
`Thorough Q-T clinical trial
`Nonclinical (animal) safety study (e.g., carcinogenicity, reproductive toxicology)
`Nonclinical study (laboratory resistance, receptor affinity, quality study related to safety)
`Pharmacokinetic studies or clinical trials
`Drug interaction or bioavailability studies or clinical trials
`Dosing trials
`Continuation of Question 4
`
`Additional data or analysis required for a previously submitted or expected study/clinical trial
`(provide explanation)
`
`Meta-analysis or pooled analysis of previous studies/clinical trials
`Immunogenicity as a marker of safety
`Other (provide explanation)
`Expedited pharmacovigilance reporting
`
`Agreed upon:
`Quality study without a safety endpoint (e.g., manufacturing, stability)
`Pharmacoepidemiologic study not related to safe drug use (e.g., natural history of disease, background
`rates of adverse events)
`Clinical trials primarily designed to further define efficacy (e.g., in another condition, different disease
`severity, or subgroup) that are NOT required under Subpart H/E
`Dose-response study or clinical trial performed for effectiveness
`Nonclinical study, not safety-related (specify)
`
`Other
`
`5.
`
`Is the PMR/PMC clear, feasible, and appropriate?
`Does the study/clinical trial meet criteria for PMRs or PMCs?
`Are the objectives clear from the description of the PMR/PMC?
`Has the applicant adequately justified the choice of schedule milestone dates?
`Has the applicant had sufficient time to review the PMRs/PMCs, ask questions, determine feasibility,
`and contribute to the development process?
`
`PMR/PMC Development Template
`
`Last Updated 8/13/2015
`
`Page 3 of 4
`
`Reference ID: 3805672
`
`

`

`Check if this form describes a FDAAA PMR that is a randomized controlled clinical trial
`
`If so, does the clinical trial meet the following criteria?
`
`There is a significant question about the public health risks of an approved drug
`There is not enough existing information to assess these risks
`Information cannot be gained through a different kind of investigation
`The trial will be appropriately designed to answer question about a drug’s efficacy and safety, and
`The trial will emphasize risk minimization for participants as the protocol is developed
`
`PMR/PMC Development Coordinator:
`This PMR/PMC has been reviewed for clarity and consistency, and is necessary to further refine the
`safety, efficacy, or optimal use of a drug, or to ensure consistency and reliability of drug quality.
`_______________________________________
`(signature line for BLAs)
`
`PMR/PMC Development Template
`
`Last Updated 8/13/2015
`
`Page 4 of 4
`
`Reference ID: 3805672
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`DIANA L WALKER
`08/13/2015
`
`SHARON H HERTZ
`08/13/2015
`
`Reference ID: 3805672
`
`

`

`PMR/PMC Development Template
`
`This template should be completed by the PMR/PMC Development Coordinator and included for each
`PMR/PMC in the Action Package.
`NDA/BLA #
`NDA 22272/S-027
`Product Name:
`OxyContin
`2923-2: Drug utilization
`
`PMR/PMC Description:
`
`Conduct a nationally representative drug utilization study of sufficient
`detail to characterize use of OxyContin in children aged 17 years and
`younger. The data from this study will provide a denominator for the
`risks assessed in PMR #2923-1and any future safety studies and clinical
`trials used to assess those risks. The following analyses should be
`conducted with the data collected:
`
`1) Total number of prescriptions dispensed across all settings of care
`a.
`stratify by age group (0-1, 2-5, 6-10, 11-17), indication, setting
`of care, and prescriber specialty, and geographic location
`b. provide characteristics of dose dispensed (mean, median,
`range)
`
`2) Total number of unique patients receiving dispensed prescriptions
`across all settings of care
`a. stratify by age group (0-1, 2-5, 6-10, 11-17), indication, setting
`of care, and prescriber specialty
`i. provide unique incident users every quarter-year
`b. patient demographics of users of the product
`c. clinical characteristics of users of the product (including what
`percentage of patients are opioid tolerant at the time they get
`the OxyContin prescription)
`
`3) Duration of therapy (include definitions of allowable gaps in drug
`therapy in calculating duration of therapy)
`a. total and stratified by indication
`b. exploration of possible ‘intermittent’ use
`c. percentage of patients switching from immediate-release opioids
`to OxyContin
`d. percentage of patients switching from other extended-release
`opioids to OxyContin
`e. dose adjustments over time
`
`PMR/PMC Schedule Milestones: Final Protocol Submission:
`Interim Report Submission:
`Interim Report Submission:
`Interim Report Submission:
`
`10/2015
`01/2016
`12/2016
`12/2017
`
`PMR/PMC Development Template
`
`Last Updated 8/13/2015
`
`Page 1 of 4
`
`Reference ID: 3805679
`
`

`

`Final Report Submission:
`
`12/2108
`
`1. During application review, explain why this issue is appropriate for a PMR/PMC instead of a pre-approval
`requirement. Check type below and describe.
`Unmet need
`Life-threatening condition
`Long-term data needed
`Only feasible to conduct post-approval
`Prior clinical experience indicates safety
`Small subpopulation affected
`Theoretical concern
`Other
`
`OxyContin has been marketed for nearly 20 years.
`
`2. 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.”
`
`OxyContin has been studied in opioid-tolerant pediatric patients, mostly in the 11-17 year old age range.
`Additional safety data is needed in younger patients and those who are not opioid tolerant.
`
`3.
`
`If the study/clinical trial is a PMR, check the applicable regulation.
`If not a PMR, skip to 4.
`- Which regulation?
`Accelerated Approval (subpart H/E)
`Animal Efficacy Rule
`Pediatric Research Equity Act
`FDAAA required safety study/clinical trial
`- If the PMR is a FDAAA safety study/clinical trial, does it: (check all that apply)
`Assess a known serious risk related to the use of the drug?
`Assess signals of serious risk related to the use of the drug?
`Identify an unexpected serious risk when available data indicate the potential for a serious risk?
`
`PMR/PMC Development Template
`
`Last Updated 8/13/2015
`
`Page 2 of 4
`
`Reference ID: 3805679
`
`

`

`- If the PMR is a FDAAA safety study/clinical trial, will it be conducted as:
`Analysis of spontaneous postmarketing adverse events?
`Do not select the above study/clinical trial type if: such an analysis will not be sufficient to assess
`or identify a serious risk
`
`Analysis using pharmacovigilance system?
`Do not select the above study/clinical trial type if: the new pharmacovigilance system that the FDA
`is required to establish under section 505(k)(3) has not yet been established and is thus not sufficient
`to assess this known serious risk, or has been established but is nevertheless not sufficient to assess
`or identify a serious risk
`
`Study: all other investigations, such as investigations in humans that are not clinical trials as defined
`below (e.g., observational epidemiologic studies), animal studies, and laboratory experiments?
`Do not select the above study type if: a study will not be sufficient to identify or assess a serious
`risk
`
`Clinical trial: any prospective investigation in which the sponsor or investigator determines the
`method of assigning investigational product or other interventions to one or more human subjects?
`4. 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.
`Various data sources will be accessed to define the extent of OxyContin utilization in the pediatric
`population.
`
`Required
`Observational pharmacoepidemiologic study
`Registry studies
`Primary safety study or clinical trial
`Pharmacogenetic or pharmacogenomic study or clinical trial if required to further assess safety
`Thorough Q-T clinical trial
`Nonclinical (animal) safety study (e.g., carcinogenicity, reproductive toxicology)
`Nonclinical study (laboratory resistance, receptor affinity, quality study related to safety)
`Pharmacokinetic studies or clinical trials
`Drug interaction or bioavailability studies or clinical trials
`Dosing trials
`Continuation of Question 4
`
`Additional data or analysis required for a previously submitted or expected study/clinical trial
`(provide explanation)
`
`Meta-analysis or pooled analysis of previous studies/clinical trials
`Immunogenicity as a marker of safety
`Other (provide explanation)
`
`Agreed upon:
`Quality study without a safety endpoint (e.g., manufacturing, stability)
`Pharmacoepidemiologic study not related to safe drug use (e.g., natural history of disease, background
`rates of adverse events)
`
`PMR/PMC Development Template
`
`Last Updated 8/13/2015
`
`Page 3 of 4
`
`Reference ID: 3805679
`
`

`

`Clinical trials primarily designed to further define efficacy (e.g., in another condition, different disease
`severity, or subgroup) that are NOT required under Subpart H/E
`Dose-response study or clinical trial performed for effectiveness
`Nonclinical study, not safety-related (specify)
`
`Other
`
`5.
`
`Is the PMR/PMC clear, feasible, and appropriate?
`Does the study/clinical trial meet criteria for PMRs or PMCs?
`Are the objectives clear from the description of the PMR/PMC?
`Has the applicant adequately justified the choice of schedule milestone dates?
`Has the applicant had sufficient time to review the PMRs/PMCs, ask questions, determine feasibility,
`and contribute to the development process?
`
`Check if this form describes a FDAAA PMR that is a randomized controlled clinical trial
`
`If so, does the clinical trial meet the following criteria?
`
`There is a significant question about the public health risks of an approved drug
`There is not enough existing information to assess these risks
`Information cannot be gained through a different kind of investigation
`The trial will be appropriately designed to answer question about a drug’s efficacy and safety, and
`The trial will emphasize risk minimization for participants as the protocol is developed
`
`PMR/PMC Development Coordinator:
`This PMR/PMC has been reviewed for clarity and consistency, and is necessary to further refine the
`safety, efficacy, or optimal use of a drug, or to ensure consistency and reliability of drug quality.
`_______________________________________
`(signature line for BLAs)
`
`PMR/PMC Development Template
`
`Last Updated 8/13/2015
`
`Page 4 of 4
`
`Reference ID: 3805679
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`DIANA L WALKER
`08/13/2015
`
`SHARON H HERTZ
`08/13/2015
`
`Reference ID: 3805679
`
`

`

`OxyContin labeling Review @2015
`
`“ 5|”!!an
`*0»
`4'1
`5’
`DEPARTIWENT OF HEALTH & HURIAN SERVICES Public Health Service
`‘2
`‘9, —
`~I'Vam
`Food and Drug Administration
`Olfice ofNew Drugs/Ofliee ofDrug Evaluation IV
`Division of Pediatric and Matunal Health
`Silver Spring, MD 20993
`Telephone
`301-796-2200
`FAX
`301—796—9855
`
`MEMORANDUM TO FILE
`
`Pediatric Review
`
`From:
`
`Through:
`
`Amy M. Taylor. MD. MHS Medical Officer
`Division of Pediatric and Maternal Health
`
`Linda L. Lewis. MD Acting Deputy Director
`Division of Pediatric and Maternal Health
`
`NDA Number:
`
`22272/S—027
`
`Sponsor:
`
`Drug:
`
`Purdue Pharma
`
`OxyContin® (oxycodone hydrochloride)
`
`Dosage form and
`route of administration:
`
`extended-release tablets. oral
`
`Indication:
`
`Consult request:
`
`For the management of pain severe enough to require daily.
`around-the-clock. long-term opioid treatment and for which
`altemative treatment options are inadequate.
`
`The Division of Anesthesia. Analgesia and Addiction
`Products (DAAAP) requests DPMI-I‘s input on the
`proposed labeling changes for OxyContin®.
`
`Background
`OxyContin was original approved on April 5. 2010 for adults. On November 4. 1998 a
`Written Request (WR) was issued for pharmacokinetic and pharmacodynamic studies of
`immediate release and controlled-release oxycodone. On December 31. 2001 . a new WR
`was issued which added safety and efficacy studies in opioid naive and opioid tolerant
`patients. On May 13. 2009. A new WR was issued which changed the safety and
`eflicacy study of opioid tolerant patients to an open-label. safety and PK study. This WR
`was amended on November 18. 2010 and November 14. 2011. The studies requested in
`the final amended WR were:
`
`Reference ID: 3776755
`
`

`

`OxyContin Labeling Review 6-2015
`
`Study 1: Pharmacokinetic study of an age-appropriate formulation of oxycodone in
`opioid-naïve patients from birth up to < 4 years of age.
`
`Study 2: Efficacy, safety, and pharmacokinetic study of an age-appropriate formulation
`of immediate-release (IR) oxycodone in opioid-naïve patients from 5 years up to ≤ 16
`years of age.
`
`Study 3: Open-label, safety and pharmacokinetic study of an oxycodone extended-release
`tablet in opioid-tolerant patients from 6 years to ≤ 16 years of age with moderate to
`severe pain requiring around-the-clock opioid therapy for an extended period of time.
`
`Reviewer comment: The study conducted by the sponsor of opioid tolerant patients aged
`6 to 16 years included very few patients less than 11 years. Currently, the Division is
`considering approval only in patients 11 years and older.
`
`
`Sponsor’s proposed pediatric specific labeling with DPMH comments and edits
`Highlights
`Use in Specific Populations
`
`
`
`2
`
`Reference ID: 3776755
`
`(b) (4)
`
`

`

`OxyContin Labeling Review 6-2015
`
`
`
`
`
`
`Reference ID: 3776755
`
`3
`
`(b) (4)
`
`

`

`OxyContin Labeling Review 6-2015
`
`4
`
`
`
`
`
`Reference ID: 3776755
`
`(b) (4)
`
`

`

`OxyContin Labeling Review 6-2015
`
`
`
`5
`
`Reference ID: 3776755
`
`(b) (4)
`
`

`

`OxyContin Labeling Review 6-2015
`
`Reviewer comment: Labeling will continue to be negotiated with the sponsor and as a
`result the final labeling may be different.
`
`
`
`6
`
`Reference ID: 3776755
`
`(b) (4)
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`AMY M TAYLOR
`06/09/2015
`
`LINDA L LEWIS
`06/11/2015
`
`Reference ID: 3776755
`
`

`

`Department of Health and Human Services
`Public Health Service
`Food and Drug Administration
`Center for Drug Evaluation and Research
`Office of Medical Policy
`
`PATIENT LABELING REVIEW
`
`
`May 27, 2015
`
`Sharon Hertz, MD
`Acting Director
`Division of Anesthesia, Analgesia, and Addiction Products
`(DAAAP)
`
`LaShawn Griffiths, MSHS-PH, BSN, RN
`Associate Director for Patient Labeling
`Division of Medical Policy Programs (DMPP)
`
`Barbara Fuller, RN, MSN, CWOCN
`Team Leader, Patient Labeling
`Division of Medical Policy Programs (DMPP)
`
`Morgan Walker, PharmD
`Patient Labeling Reviewer
`Division of Medical Policy Programs (DMPP)
`
`Koung Lee, RPh, MSHS
`Regulatory Review Officer
`Office of Prescription Drug Promotion (OPDP)
`Review of Patient Labeling: Medication Guide (MG)
`
`OXYCONTIN (oxycodone hydrochloride extended-release
`tablets)
`
`for oral use
`NDA 022272/S-027
`
`Purdue Pharma L.P.
`
`
`Date:
`
`To:
`
`
`Through:
`
`
`From:
`
`Subject:
`
`Drug Name, Dosage
`Form (established
`name):
`Route:
`Application
`Type/Number:
`Applicant:
`
`
`
`
`
`
`
`Reference ID: 3765830
`
`
`
`

`

`
`
` 1
`
` 2
`
`INTRODUCTION
`On December 8, 2014, Purdue Pharma L.P. submitted for the Agency’s review a
`Prior Approval Supplement (S-027) to New Drug Application (NDA) 022272 for
`OXYCONTIN (oxycodone hydrochloride extended-release tablets). This labeling
`supplement provides proposed revisions to the Prescribing Information to include
`pediatric dosing, adverse reactions, and clinical study data.
`OXYCONTIN (oxycodone hydrochloride extended-release tablets) was originally
`approved on April 5, 2010 and is indicated for the management of pain severe
`enough to require daily, around-the-clock, long-term opioid treatment and for which
`alternative treatment options are inadequate.
`This collaborative review is written by the Division of Medical Policy Programs
`(DMPP) and the Office of Prescription Drug Promotion (OPDP) in response to a
`request by the Division of Anesthesia, Analgesia, and Addiction Products (DAAAP)
`on May 20, 2015, for DMPP and OPDP to review the Applicant’s proposed
`Medication Guide (MG) for OXYCONTIN (oxycodone hydrochloride extended-
`release tablets).
`
` MATERIAL REVIEWED
`• Draft OXYCONTIN (oxycodone hydrochloride extended-release tablets) MG
`received on December 8, 2014, and received by DMPP and OPDP on May 20,
`2015.
`• Draft OXYCONTIN (oxycodone hydrochloride extended-release tablets)
`Prescribing Information (PI) received on December 8, 2014, revised by the
`Review Division throughout the review cycle, and received by DMPP and OPDP
`on May 20, 2015.
`
`
`3 REVIEW METHODS
`To enhance patient comprehension, materials should be written at a 6th to 8th grade
`reading level, and have a reading ease score of at least 60%. A reading ease score of
`60% corresponds to an 8th grade reading level. In our review of the MG the target
`reading level is at or below an 8th grade level.
`Additionally, in 2008 the American Society of Consultant Pharmacists Foundation
`(ASCP) in collaboration with the American Foundation for the Blind (AFB)
`published Guidelines for Prescription Labeling and Consumer Medication
`Information for People with Vision Loss. The ASCP and AFB recommended using
`fonts such as Verdana, Arial or APHont to make medical information more
`accessible for patients with vision loss. We have reformatted the MG document
`using the Arial font, size 10.
`In our collaborative review of the MG we have:
`simplified wording and clarified concepts where possible
`•
`
`
`
`
`
`Reference ID: 3765830
`
`
`
`

`

`•
`•
`
`•
`•
`
`ensured that the MG is consistent with the Prescribing Information (PI)
`ensured that the MG is free of promotional language or suggested revisions to
`ensure that it is free of promotional language
`ensured that the MG meets the Regulations as specified in 21 CFR 208.20
`ensured that the MG meets the criteria as specified in FDA’s Guidance for
`Useful Written Consumer Medication Information (published July 2006)
`
` CONCLUSIONS
`The MG is acceptable with our recommended changes.
`
` RECOMMENDATIONS
`• Please send these comments to the Applicant and copy DMPP and OPDP on the
`correspondence.
`• Our collaborative review of the MG is appended to this memorandum. Consult
`DMPP and OPDP regarding any additional revisions made to the PI to determine
`if corresponding revisions need to be made to the MG.
` Please let us know if you have any questions.
`
` 4
`
` 5
`
`
`
`
`
`Reference ID: 3765830
`
`
`
`2 Page(s) of Draft Labeling have been Withheld in Full as b4 (CCI/TS) immediately following this page
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`MORGAN A WALKER
`05/27/2015
`
`KOUNG U LEE
`05/27/2015
`
`BARBARA A FULLER
`05/27/2015
`
`Reference ID: 3765830
`
`

`

`FOOD AND DRUG ADMINISTRATION
`Center for Drug Evaluation and Research
`Office of Prescription Drug Promotion
`
`
`****Pre-decisional Agency Information****
`
`
`
`Memorandum
`
`Date:
`May 21, 2015
`
`
`To:
`
`
`
`
`
`
`
`
`Diana Walker, Ph.D., RHPM
`
`Sharon Hertz, MD, Director
`Division of Anesthesia, Analgesia, and Addiction Products (DAAAP)
`
`
`
`
`From:
`
`Koung Lee, Regulatory Review Officer,
`Office of Prescription Drug Promotion (OPDP)
`
`Olga Salis, Senior Regulatory Project Manager - OPDP
`
`NDA 22272/S-027 OXYCONTIN Professional Labeling
`
`
`
`
`Through: Samuel M. Skariah, Team Leader - OPDP
`
`
`cc:
`
`
`
`Subject:
`
`
`
`
`As requested in the DAAAP’s consult dated April 29, 2015, OPDP has reviewed
`the Oxycontin prescribing information. As described in DAAAP’s consult request,
`this labeling supplement adds pediatric labeling revisions in response to a
`pediatric written request.
`
`OPDP has reviewed the proposed substantially complete version of the
`prescribing information emailed by DAAAP on May 15, 2015. OPDP’s comments
`are included in the attached document below.
`
`Thank you for your consult. OPDP appreciates the opportunity to provide
`comments. If you have any questions, please contact me at 240-402-8686 or by
`email, Koung.Lee@fda.hhs.gov.
`
`
`
`Reference ID: 3761857
`
`1
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`39 Page(s) of Draft Labeling have been Withheld in Full as b4 (CCI/TS) immediately following this page
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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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`KOUNG U LEE
`05/21/2015
`
`Reference ID: 3761857
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`

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`M E M O R A N D U M
`
` DEPARTMENT OF HEALTH AND HUMAN SERVICES
` PUBLIC HEALTH SERVICE
` FOOD AND DRUG ADMINISTRATION
` CENTER FOR DRUG EVALUATION AND RESEARCH
`______________________________________________________________________________________________________________________
`
`DATE:
`
`TO:
`
`FROM
`
`THROUGH:
`
`CLINICAL INSPECTION SUMMARY
`
`April 29, 2015
`
`Lisa Basham, Regulatory Project Manager
`Javier Muniz, M.D., Medical Officer
`John Feeney, M.D., Team Leader
`Division of Analgesia, Anesthesia, and Addiction Products (DAAAP)
`John Lee M.D., Medical Officer
`Good Clinical Practice Assessment Branch
`Division of Good Clinical Practice Compliance
`Office of Scientific Investigations (OSI)
`Janice Pohlman, M.D., M.P.H., Team Leader
`Kassa Ayalew, M.D., M.P.H., Branch Chief
`Good Clinical Practice Assessment Branch
`Division of Clinical Compliance Evaluation, OSI
`
`SUBJECT:
`APPLICATIONS:
`APPLICANT:
`DRUG:
`NME:
`INDICATION:
`
`Evaluation of Clinical Inspections
`NDA 22272 S-027
`Purdue Pharma, LP
`Oxycodone Hydrochloride (OxyContin®) Extended-Release Tablet
`No
`Management of pain severe enough to require daily, around-the-clock, long-term
`opioid treatment and for which alternative treatment options are inadequate
`(no new OxyContin® indication for use proposed in this NDA supplement)
`
`THERAPEUTIC CLASSIFICATION:
`CONSULTATION REQUEST DATE:
`INSPECTION SUMMARY GOAL DATE:
`REGULATORY ACTION GOAL DATE:
`PDUFA DUE DATE:
`
`Priority (Pediatric Written Request)
`January 26, 2015
`May 1, 2015
`June 8, 2015
`June 8, 2015
`
`
`
`Reference ID: 3742225
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`Page 2
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`Clinical Inspection Summary
`
`NDA 22272-27
`
`BACKGROUND
`I.
`In NDA 22272 S-027, Purdue Pharma, LP (Purdue) seeks to update the OxyContin® label to reflect the
`findings of three pediatric studies recently completed in response to FDA’s 2011 Pediatric Written Request
`(PWR). Purdue proposes no new proposed indication for use; OxyContin® is currently approved for the
`management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for
`which alternative treatment options are inadequate. Purdue requests priority review (granted) in seeking
`six months of pediatric exclusivity
`.
`According to PWRs 1 and 2, Studies OXP1005 and OXP3003 were conducted in hospitalized opioid-naive
`subjects. According to PWR 3, Study OTR3001 was conducted in opioid-tolerant subjects (hospitalized or
`out-patients) selected to assure ethnic diversity: 2034 patients were pre-screened worldwide (nine
`countries), of whom 155 were enrolled and treated (United Kingdom, Greece, Guatemala, Hungary, Israel,
`New Zealand, Spain, and United States). Two oxycodone formulations were used in the three studies,
`reformulated OxyContin and immediate-release oral solution.
`The three pediatric studies were audited at good clinical practice (GCP) inspections of three clinical
`investigator (CI) sites selected for large site subject enrollment. Four specific study-sites were audited in
`support of this NDA review; two studies were audited at inspection of one site (Studies OXP3003 and
`OXP1005 at Site 0033A), and two sites were inspected in auditing one study (Sites 1360A and 1863A in
`Study OTR3001). The three audited studies are described briefly below, with emphasis on study features
`relevant to the inspectional observations.
`Study OTR3001
`An Open-label, Multicenter Study of the Safety of Twice Daily Oxycodone Hydrochloride Controlled-
`Release Tablets in Opioid Experienced Children from Ages 6 to 16 Years Old, Inclusive, with Moderate to
`Severe Malignant and/or Nonmalignant Pain Requiring Opioid Analgesics
`This Phase 3, open-label, single-arm study was conducted between February 2011 and July 2014 at 101 CI
`sites worldwide in 173 opioid-tolerant subjects, of whom 155 were treated and 122 completed the study.
`The primary study objective was to characterize the safety of oxycodone controlled-release (CR) tablets in
`opioid-tolerant pediatric subjects (6-16 years of age) with moderate to severe (malignant or non-malignant)
`pain requiring opioid therapy. The study consisted of open-label treatment for up to four weeks, as either
`out-patient or in-patient.
`Subjects and Treatment
`The study treatment consisted of oral oxycodone CR every 12 hours (tablet strengths of 10, 15, 20, 30, or
`40 mg) for a total daily dose of 20-240 mg in subjects meeting the following eligibility criteria:
` Opioid-tolerant subjects of age 6-16 years expected to require on-going around-the-clock opioid
`treatment equivalent to 20-240 mg of oxycodone daily for at least two weeks for the management of
`moderate to severe malignant or nonmalignant pain
` Had tolerated opioid therapy for at least five consecutive days prior to study entry using 20-240 mg daily
`of oxycodone (or equivalent) for at least 48 hours
` Subjects excluded for any contraindication to opioid use; eligible opioid-tolerant post-operative subjects
`not dosed with oxycodone CR until at least five days after surgery
`Study Endpoints
` Efficacy assessment consisted of pain scores, Functional Disability Inventory (FDI), Parent/Caregiver-
`assessed Global Impression of Change (PGIC), and supplemental opioid analgesic use.
` In assessing pain and pain relief, subjects of age 6-12 years completed the Faces Pain Scale-Revised
`(FPS-R), and subjects of age12-16 years completed the visua