`
`
`
`DEPARTMENT OF HEALTH AND HUMAN SERVICES
`
`
`
`
`
`
`NDA 21436/S-038
`NDA 21713/S-030
`NDA 21729/S-022
`
`NDA 21866/S-023
`
`
`
`
`
`
`
`Food and Drug Administration
`
`Silver Spring MD 20993
`
`SUPPLEMENT APPROVAL
`
`
`Otsuka Pharmaceutical Development & Commercialization, Inc.
`Attention: David Goldberger, RPh, RAC
`Vice President, Global Regulatory Affairs
`2440 Research Blvd.
`Rockville, MD 20850
`
`Dear Mr. Goldberger:
`
`Please refer to your Supplemental New Drug Applications (sNDA) dated and received February
`12, 2014 (NDA 21436/S-038), and April 3, 2014 (NDAs 21713/S-030, 21729/S-022, 21866/S-
`023), submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act (FDCA) for
`Abilify (aripiprazole) tablets 2 mg, 5 mg, 10 mg, 15 mg, 20 mg, 30 mg (NDA 21436), oral
`solution 1 mg/ml (NDA 21713), orally disintegrating tablet 10 mg, 15 mg (NDA 21729), and
`injectable formulation 9.75 mg/1.3 mL single-dose vial (NDA 21866).
`
`We acknowledge receipt of your amendments dated March 7, 2014; March 26, 2014; April 30,
`2014; June 10, 2014; June 20, 2014; June 26, 2014; August 29, 2014; October 28, 2014;
`November 14, 2014; November 24, 2014; December 2, 2014, December 8, 2014, and December
`9, 2014.
`
`Please also refer to our approval letter dated December 12, 2014. That letter contained an error in
`the “indications” sentence as described below:
`
`Prior Statement: “These ‘Prior Approval’ supplemental new drug applications provide for
`labeling revisions based upon two adequate and well-controlled trials that demonstrate the
`efficacy for the new indication in pediatric patients with Tourette’s Disorder.”
`
`Corrected Statement: “These ‘Prior Approval’ supplemental new drug applications provide for
`labeling revisions based upon two adequate and well-controlled trials that demonstrate the
`efficacy for the new indication in patients with Tourette’s Disorder.”
`
`The effective approval date will remain December 12, 2014, the date of the original approval
`letter. The corrected labeling is unchanged.
`
`APPROVAL & LABELING
`
`
`
`Reference ID: 3706133
`
`

`

`NDAs 21436/S-038; 21713/S-030; 21729/S-022; 21866/S-023
`Page 2
`
`
`We have completed our review of these supplemental applications, as amended. They are
`approved, effective on the date of this letter, for use as recommended in the enclosed, agreed-
`upon labeling text.
`
`WAIVER OF HIGHLIGHTS SECTION
`
`
`Please note that we have previously granted a waiver of the requirements of 21 CFR
`201.57(d)(8) regarding the length of Highlights of prescribing information.
`
`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), with the addition of any labeling changes in pending “Changes Being Effected” (CBE)
`supplements, as well as annual reportable changes not included in the enclosed labeling.
`
`Information on submitting SPL files using eList may be found in the guidance for industry titled
`“SPL Standard for Content of Labeling Technical Qs and As at
`http://www.fda.gov/downloads/DrugsGuidanceComplianceRegulatoryInformation/Guidances/U
`CM072392.pdf
`
`
`The SPL will be accessible from publicly available labeling repositories.
`
`
`Also within 14 days, amend all pending supplemental applications that includes labeling changes
`for this NDA, including CBE supplements for which FDA has not yet issued an action letter,
`with the content of labeling [21 CFR 314.50(l)(1)(i)] in MS Word format, that includes the
`changes approved in this supplemental application, as well as annual reportable changes and
`annotate each change. To facilitate review of your submission, provide a highlighted or marked-
`up copy that shows all changes, as well as a clean Microsoft Word version. The marked-up copy
`should provide appropriate annotations, including supplement number(s) and annual report
`date(s).
`
` 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.
`
`Because this drug product for this indication has an orphan drug designation, you are exempt
`from this requirement.
`
`
`
`Reference ID: 3706133
`
`

`

`
`
`
`
`
`
`Final Protocol Submission: 01/31/2016
`
`Trial Completion: 07/31/2021
`Final Report Submission: 07/31/2022
`
`
`A controlled trial to evaluate the longer-term (i.e., maintenance) efficacy of
`aripiprazole in the treatment of pediatric patients (6-17 years) Tourette’s
`
`Disorder. This trial must include a placebo group and more than one fixed dose
`and must utilize a randomized withdrawal design, following an adequate period of
`
`stabilization with open-label treatment of aripiprazole. Because it is important to
`
`establish the dose-response for maintenance, this trial should randomize patients
`on stable doses of aripiprazole and different doses of aripiprazole (and to placebo)
`
`during the maintenance phase.
`
`
`NDAs 21436/S-038; 21713/S-030; 21729/S-022; 21866/S-023
`Page 3
`
`
`
` POSTMARKETING COMMITMENTS SUBJECT TO REPORTING REQUIREMENTS
`UNDER SECTION 506B
`
`
`We remind you of your postmarketing commitment agreed upon in your communication dated
`November 14, 2014:
` 
`2837-1
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`The timetable you submitted on November 25, 2014, states that you will conduct this study
`according to the following schedule:
`
`
`
`
`
`Submit clinical protocols to your IND 116003 for this product. Submit nonclinical and
`chemistry, manufacturing, and controls protocols and all postmarketing final reports to this
`NDA. In addition, under 21 CFR 314.81(b)(2)(vii) and 314.81(b)(2)(viii) you should include a
`status summary of each commitment in your annual report to this NDA. The status summary
`should include expected summary completion and final report submission dates, any changes in
`plans since the last annual report, and, for clinical studies/trials, number of patients entered into
`each study/trial. All submissions, including supplements, relating to this postmarketing
`commitment should be prominently labeled “Postmarketing Commitment Protocol,”
`
`“Postmarketing Commitment Final Report,” or “Postmarketing Commitment
`Correspondence.”
`
`PROMOTIONAL MATERIALS
`
`You may request advisory comments on proposed introductory advertising and promotional
`labeling. To do so, submit the following, in triplicate, (1) a cover letter requesting advisory
`comments, (2) the proposed materials in draft or mock-up form with annotated references, and
`(3) the package insert(s) to:
`
`
`Food and Drug Administration
`
`Center for Drug Evaluation and Research
`
`Office of Prescription Drug Promotion (OPDP)
`
`
`5901-B Ammendale Road
`
`
`Beltsville, MD 20705-1266
`
`
`Reference ID: 3706133
`
`
`
`

`

`NDAs 21436/S-038; 21713/S-030; 21729/S-022; 21866/S-023
`Page 4
`
`
`
` You must submit final promotional materials and package insert(s), accompanied by a Form
`
` FDA 2253, at the time of initial dissemination or publication [21 CFR 314.81(b)(3)(i)]. Form
`
`FDA 2253 is available at
`http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM083570.pdf.
`Information and Instructions for completing the form can be found at
`http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM375154.pdf. 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.
`
`
`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, please call CAPT William Bender, Senior Regulatory Project
`Manager, at (301) 796-2145 or via email at william.bender@fda.hhs.gov.
`
`
`
`
`Sincerely,
`
`{See appended electronic signature page}
`
`
`Mitchell V. Mathis, M.D.
`CAPT, USPHS
`Director
`
`Division of Psychiatry Products
`Office of Drug Evaluation I
`Center for Drug Evaluation and Research
`
`
`ENCLOSURE:
`Content of Labeling
`
`
`Reference ID: 3706133
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`MITCHELL V Mathis
`12/12/2014
`
`Reference ID: 3706133
`
`