`CENTER FOR DRUG EVALUATION AND RESEARCH
`
`Approval Package for:
`
`
`APPLICATION NUMBER:
`
`203794Orig1s000
`
`Nucynta oral solution, 20 mg/mL.
`
`Trade Name:
`
`Generic Name:
`
`Sponsor:
`
`Approval Date:
`
`Indications:
`
`tapentadol
`
`Janssen Research & Development, L.L.C.
`on behalf of Janssen Pharmaceuticals, Inc.
`October 15, 2012
`
` Provides for the use of Nucynta (tapentadol) oral
`solution for the management of moderate to severe
`acute pain in adults.
`
`

`

`CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`203794Orig1s000
`
`CONTENTS
`
`Reviews / Information Included in this NDA Review.
`
`
`
`Approval Letter
`Other Action Letters
`Labeling
`REMS
`Summary Review
`Officer/Employee List
`Office Director Memo
`Cross Discipline Team Leader Review
`Medical Review(s)
`Chemistry Review(s)
`Environmental Assessment
`Pharmacology Review(s)
`Statistical Review(s)
`Microbiology Review(s)
`Clinical Pharmacology/Biopharmaceutics Review(s)
`Other Reviews
`Risk Assessment and Risk Mitigation Review(s)
`Proprietary Name Review(s)
`Administrative/Correspondence Document(s)
`
`
`X
`
`X
`
`X
`X
`
`
`
`X
`
`X
`
`X
`X
`X
`
`
`X
`
`

`

`
`
`
`
`
`
`CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`
`APPLICATION NUMBER:
`203794Orig1s000
`
`APPROVAL LETTER
`
`

`

`
`
`
`
`
`
`DEPARTMENT OF HEALTH AND HUMAN SERVICES
`
`
`
`
`
`
`NDA 203794
`
`
`
`
`
`
`Food and Drug Administration
`Silver Spring, MD 20993
`
`NDA APPROVAL
`
`
`
`
`Janssen Research & Development, L.L.C.
` on behalf of Janssen Pharmaceuticals, Inc.
`920 Route 202 PO Box 300
`Raritan, New Jersey 08869
`
`Attention: Peggy Ferrone
`
`Manager, Regulatory Affairs
`
`Dear Ms. Ferrone:
`
`Please refer to your New Drug Application (NDA) dated and received December 15, 2011,
`submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act, for Nucynta
`(tapentadol) oral solution, 20 mg/mL.
`
`We acknowledge receipt of your amendments dated February 7, March 13, April 3 and 10,
`May 7 (2), June 13 and 18, July 12, August 3, 10, and 29, and October 15, 2012.
`
`This new drug application provides for the use of Nucynta (tapentadol) oral solution for the
`management of moderate to severe acute pain in adults.
`
`We have completed our review of this application, as amended. It is approved, effective on the
`date of this letter, for use as recommended in the enclosed agreed-upon labeling text.
`
`We are waiving the requirements of 21 CFR 201.57(d)(8) regarding the length of Highlights of
`prescribing information. This waiver applies to all future supplements containing revised
`labeling unless we notify you otherwise.
`
`
`CONTENT OF LABELING
`
`As soon as possible, but no later than 14 days from the date of this letter, submit the content of
`labeling [21 CFR 314.50(l)] in structured product labeling (SPL) format using the FDA
`automated drug registration and listing system (eLIST), as described at
`http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm. Content
`of labeling must be identical to the enclosed labeling (text for the package insert, Medication
`Guide, and Instructions for Use). Information on submitting SPL files using eLIST may be
`
`
`
`Reference ID: 3203437
`
`

`

`NDA 203794
`Page 2
`
`
`found in the guidance for industry titled “SPL Standard for Content of Labeling Technical Qs
`and As” at
`http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/U
`CM072392.pdf.
`
`The SPL will be accessible via publicly available labeling repositories.
`
`
`CARTON AND IMMEDIATE CONTAINER LABELS
`
`Submit final printed carton and container labels that are identical to the enclosed carton and
`immediate container labels and carton and immediate container labels submitted on August 3,
`2012, as soon as they are available, but no more than 30 days after they are printed. Please
`submit these labels 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 Carton
`and Container Labels for approved NDA 203794.” Approval of this submission by FDA is
`not required before the labeling is used.
`
`Marketing the product(s) with FPL that is not identical to the approved labeling text may render
`the product misbranded and an unapproved new drug.
`
`
`REQUIRED PEDIATRIC ASSESSMENTS
`
`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.
`
`We are deferring submission of your pediatric studies in accordance with study report
`submission dates below because this product is ready for approval for use in adults and the
`pediatric studies have not been completed. We acknowledge that your pediatric program for
`PREA requirements under NDA 022304 for Nucynta (tapentadol) immediate-release tablets is
`ongoing and those studies are intended to also fulfill the PREA requirements for Nucynta oral
`solution specified below.
`
`Your deferred pediatric studies required under section 505B(a) of the Federal Food, Drug, and
`Cosmetic Act are required postmarketing studies. The status of these postmarketing studies must
`be reported annually according to 21 CFR 314.81 and section 505B(a)(3)(B) of the Federal Food,
`Drug, and Cosmetic Act. The required studies are listed below.
`
`
`
`
`
`Reference ID: 3203437
`
`

`

`NDA 203794
`Page 3
`
`
`1937-1
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`
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`
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`1937-2
`
`
`
`
`
`A pharmacokinetic, efficacy, and safety study of Nucynta for the management of
`moderate to severe acute pain in pediatric patients ages 6 to less than 17 years.
`
`Final Protocol Submission: May 31, 2014
`Study/Trial Completion:
`September 30, 2018
`Final Report Submission: March 31, 2019
`
`A pharmacokinetic, efficacy, and safety study of Nucynta for the management of
`moderate to severe acute pain in pediatric patients ages birth to 5 years.
`
`Final Protocol Submission: March 31, 2017
`Study/Trial Completion:
`July 31, 2021
`Final Report Submission: December 31, 2021
`
`
`Submit the protocol(s) to your IND 108134, with a cross-reference letter to this NDA.
`
`Reports of this/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.
`
`
`PROMOTIONAL MATERIALS
`
`You may request advisory comments on proposed introductory advertising and promotional
`labeling. To do so, submit, in triplicate, a cover letter requesting advisory comments, the
`proposed materials in draft or mock-up form with annotated references, and the package insert
`to:
`
`
`Food and Drug Administration
`Center for Drug Evaluation and Research
`Office of Prescription Drug Promotion
`5901-B Ammendale Road
`Beltsville, MD 20705-1266
`
`
`As required under 21 CFR 314.81(b)(3)(i), you must submit final promotional materials, and the
`package insert, at the time of initial dissemination or publication, accompanied by a Form FDA
`2253. For instruction on completing the Form FDA 2253, see page 2 of the Form. For more
`information about submission of promotional materials to the Office of Prescription Drug
`Promotion (OPDP), see http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm090142.htm.
`
`
`
`
`
`
`
`Reference ID: 3203437
`
`

`

`NDA 203794
`Page 4
`
`
`EXPIRY DATING PERIOD
`
` A
`
` 24-month expiry dating period is granted for Nucynta oral solution in 100 mL and 200 mL
`bottles when stored at 20° to 25°C (68° to 77°F) with excursions permitted from 15° to 30°C
`(59° to 86°F).
`
`
`REPORTING REQUIREMENTS
`
`We remind you that you must comply with reporting requirements for an approved NDA
`(21 CFR 314.80 and 314.81).
`
`If you have any questions, call Dominic Chiapperino, Ph.D., Regulatory Project Manager, at
`(301) 796-1183.
`
`
`
`Sincerely,
`
`{See appended electronic signature page}
`
`Sharon Hertz, M.D.
`Deputy Director
`Division of Anesthesia, Analgesia, and
` Addiction Products
`Office of Drug Evaluation II
`Center for Drug Evaluation and Research
`
`
`
`ENCLOSURE(S):
`Content of Labeling
`Carton and Container Labeling
`
`
`
`
`
`
`
`
`Reference ID: 3203437
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`SHARON H HERTZ
`10/15/2012
`
`Reference ID: 3203437
`
`