`
` DEPARTMENT OF HEALTH & HUMAN SERVICES
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`Public Health Service
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`
`
` Food and Drug Administration
`Rockville, MD 20857
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`NDA 21-436 S-019, S-020, S-022
`NDA 21-713 S-014, S-015, S-017
`NDA 21-729 S-006, S-007, S-009
`NDA 21-866 S-006, S-007, S-009
`
`
`Otsuka Pharmaceutical Development & Commercialization, Inc.
`Attn: Kusuma Mallikaarjun, Ph.D.
`Senior Director, Regulatory Affairs
`2440 Research Boulevard
`Rockville, MD 20850
`
`Dear Dr. Mallikaarjun:
`
`Please refer to your supplemental new drug applications [sNDAs] submitted and received on
`July 11, 2007 [NDA 21-436 S-019, S-020] under section 505(b) of the Federal Food, Drug, and
`
`Cosmetic Act for Abilify (aripiprazole) Tablets.
`
`Please also refer to your supplemental new drug applications [sNDAs] submitted August 28,
`2007 and received on August 29, 2007 [NDA 21-713 S-014, S-015; NDA 21-729 S-006, S-007;
`and NDA 21-866 S-006, S-007] under section 505(b) of the Federal Food, Drug, and Cosmetic
`Act for Abilify (aripiprazole) Oral Solution, Orally Disintegrating Tablet, and Injection for
`Intramuscular Use, respectively.
`
`Please also refer to your labeling supplements NDA 21-436 S-022, NDA 21-713 S-017, NDA
`21-729 S-009, and NDA 21-866 S-009, submitted December 27, 2007 and received December
`28, 2007.
`
`
`Please also refer to your amendments to NDA 21-436 S-019 and S-020, NDA 21-713 S-014 and
`S-015; NDA 21-729 S-006 and S-007; and NDA 21-866 S-006 and S-007, submitted on
`September 4, 2007, September 6, 2007, October 18, 2007, January 18, 2008, and March 19,
`2008.
`
`Your supplemental NDAs 21-436 S-019, 21-713 S-014, 21-729 S-006, and 21-866 S-006
`provide for the use of Abilify as monotherapy in the acute treatment of bipolar disorder, manic or
`mixed, at a starting dose of 15 mg/day.
`
`Your supplemental NDAs 21-436 S-020, 21-713 S-015, 21-729 S-007, and 21-866 S-007
`provide for the use of Abilify as adjunctive therapy added to lithium or valproate in the short-
`term treatment of bipolar disorder, manic or mixed, again at a starting dose of 15 mg/day.
`
`Your labeling supplements NDA 21-436 S-022, NDA 21-713 S-017, NDA 21-729 S-009, and
`NDA 21-866 S-009 provide for revision of the "Drug Interactions" section of labeling to state
`that aripiprazole has no clinically meaningful effect on the pharmacokinetics of lamotrigine.
`
`

`

`
`
`2
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`NDA 21-436 S-019, S-020, S-022
`NDA 21-713 S-014, S-015, S-017
`NDA 21-729 S-006, S-007, S-009
`NDA 21-866 S-006, S-007, S-009
`
`We have completed our review of these applications as amended. They are approved, effective
`on the date of this letter, for use as recommended in the enclosed agreed-upon labeling text.
`
`Content of Labeling: Structured Product Labeling [SPL]. the final printed labeling (FPL) must
`be identical to the enclosed labeling [package insert], and must be formatted in accordance with
`the requirements of 21 CFR 201.66.
`
`As soon as possible, but no later than 14 days from the date of this letter, please submit the
`content of labeling [21 CFR 314.50(l)] in structured Product Labeling (SPL) format, as described
`at http://www.fda.gov/oc/datacouncil/spl.html , that is identical to the enclosed agreed-upon
`labeling text. Upon receipt, we will transmit that version to the National Library of Medicine for
`public dissemination. For administrative purposes, please designate this submission "SPL for
`approved NDA labeling under NDA 21-436 S-019, NDA 21-436 S-020, NDA 21-713 S-014,
`NDA 21-713 S-015, NDA 21-729 S-006, NDA 21-729 S-007, NDA 21-866 S-006, and NDA 21-
`866 S-007".
`
`Pediatric Research Equity Act (PREA) Requirements: Phase 4 Commitments.
`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.
`
`With reference to NDA 21-436 S-019, NDA 21-713 S-014, NDA 21-729 S-006, and NDA 21-
`866 S-006, we are waiving the requirement for pediatric studies in all age groups, because:
`A) necessary studies are impossible or highly impracticable. The pediatric starting dose
`of aripiprazole is 2 mg/day; this is titrated to 5 mg/day after 2 days and 10 mg/day after 2
`more days. The target dose for pediatric patients is 10 mg/day. Therefore, study of a 15
`mg starting dose in pediatric patients is not feasible.
`
`
`With reference to NDA 21-436 S-020, NDA 21-713 S-015, NDA 21-729 S-007, and NDA 21-
`866 S-007, this product is now appropriately labeled for use in all relevant pediatric populations.
`Therefore, no additional pediatric studies are needed at this time.
`
`There are no other Phase 4 commitments or Phase 4 requirements for any of these submissions.
`
`"Dear Healthcare Professional" Letters.
`If you issue a letter communicating important information about this product (i.e., a “Dear
`Health Care Professional” letter), we request that you submit a copy of the letter to all four
`NDAs referenced above, with a copy to the following address:
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`MEDWATCH, HFD-410
`Food and Drug Administration
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`5901-B Ammendale Road
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`Beltsville, MD 20705-1266
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`

`

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`
`NDA 21-436 S-019, S-020, S-022
`NDA 21-713 S-014, S-015, S-017
`NDA 21-729 S-006, S-007, S-009
`NDA 21-866 S-006, S-007, S-009
`
`Introductory Promotional Materials.
`In addition, submit three copies of the introductory promotional materials that you propose to use
`for these products. Submit all proposed materials in draft or mock-up form, not final print. Send
`one copy to this Division and two copies of both the promotional materials and the package
`insert directly to:
`
`
`3
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`Food and Drug Administration
`Center for Drug Evaluation and Research
`Division of Drug Marketing, Advertising, and Communications
`5901-B Ammendale Road
`Beltsville, MD 20705-1266
`
`
`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 Doris J. Bates, Ph.D., Regulatory Project Manager, at 301-
`796-1040.
`
`
`Sincerely,
`
`{See appended electronic signature page}
`
`
`Thomas P. Laughren, M.D.
`Director
`
`Division of Psychiatry Products
`Office of Drug Evaluation I
`Center for Drug Evaluation and Research
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`
`
`Enclosure: agreed-upon labeling.
`
`

`

`---------------------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed electronically and
`this page is the manifestation of the electronic signature.
`---------------------------------------------------------------------------------------------------------------------
`/s/
`
`---------------------
`Thomas Laughren
`
`5/6/2008 10:47:15 AM
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`