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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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`NDA 201281
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`Food and Drug Administration
`Silver Spring MD 20993
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`NDA APPROVAL
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`Boehringer Ingelheim Pharmaceuticals, Inc.
`Attention: Dawn Collette
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`Associate Director, Drug Regulatory Affairs
`900 Ridgebury Rd/ P.O. Box 368
`Ridgefield, CT 06877-0368
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`Dear Ms. Collette:
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`Please refer to your New Drug Application (NDA) dated and received January 19, 2011,
`submitted pursuant to section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act, for
`linagliptin and metformin tablets (2.5 mg/500 mg, 2.5 mg/850 mg and 2.5 mg/1000 mg).
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`We acknowledge receipt of your amendments dated January 28, March 11, April 12, 19 and 27,
`May 19, June 1 and 13, July 1 and 27, August 3, 17 and 26, September 1, 15 and 21, November 1
`(2), 3, 7, 8 and 30, 2011, and January 17, 2012. The November 30, 2011, submission constituted
`a complete response to our action letter dated November 16, 2011. We also acknowledge receipt
`of your email dated January 27, 2012, that includes the agreed-upon labeling.
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`This new drug application provides for the use of Jentadueto (linagliptin and metformin fixed-
`dose combination) tablets as an adjunct to diet and exercise to improve glycemic control in
`adults with type 2 diabetes mellitus.
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`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.
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`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.
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`Reference ID: 3079250
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`NDA 201281
`Page 2
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` CONTENT OF LABELING
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`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 and the patient
`package insert). Information on submitting SPL files using eLIST may be found in the guidance
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`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.
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`The SPL will be accessible via publicly available labeling repositories.
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`CARTON AND IMMEDIATE CONTAINER LABELS
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`Submit final printed carton and container labels that are identical to the enclosed carton and
`immediate container labels submitted on November 8, 2011, 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
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`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
`201281”. Approval of this submission by FDA is not required before the labeling is used.
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`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.
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`REQUIRED PEDIATRIC ASSESSMENTS
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`We remind you of your requirements under the Pediatric Research Equity Act (PREA) as stated
`in the approval letter for NDA 201280 for Tradjenta (linagliptin), dated May 2, 2011:
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`PMR 1766-1: A randomized, placebo-controlled, dose-finding study under PREA evaluating at
`least two doses of linagliptin as monotherapy in pediatric patients ages 10 to 16 years (inclusive).
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`Final Protocol Submission: by November 30, 2011
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`Trial Completion: by February 28, 2014
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`Final Report Submission: by August 31, 2014
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`Reference ID: 3079250
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`NDA 201281
`Page 3
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`PMR 1766-2: Deferred randomized and controlled pediatric study under PREA to evaluate
`efficacy, safety, and pharmacokinetics of linagliptin for the treatment of type 2 diabetes mellitus
`in pediatric patients ages 10 to 16 years (inclusive) as monotherapy and when added to
`metformin therapy.
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`Final Protocol Submission: by June 30, 2014
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`Trial Completion: by March 31, 2017
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`Final Report Submission: by September 30, 2017
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`Please cross-reference this NDA when you submit your final study reports.
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`PROMOTIONAL MATERIALS
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`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:
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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
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`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
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`information about submission of promotional materials to the Division of Drug Marketing,
`Advertising, and Communications (DDMAC), see
`http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm090142.htm.
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`REPORTING REQUIREMENTS
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`We remind you that you must comply with reporting requirements for an approved NDA
`(21 CFR 314.80 and 314.81).
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`Reference ID: 3079250
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`NDA 201281
`Page 4
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`If you have any questions, please contact Mehreen Hai, Ph.D., Regulatory Project Manager, at
`(301) 796-5073.
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`Sincerely,
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`{See appended electronic signature page}
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`Mary H. Parks, M.D.
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` Director
`Division of Metabolism and Endocrinology Products
`Office of Drug Evaluation II
`Center for Drug Evaluation and Research
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`ENCLOSURES:
`Package Insert
`Patient Package Insert
`Professional sample label 2.5 mg/500 mg - 14 tablets
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`Trade bottle label 2.5 mg/500 mg - 60 tablets
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`Trade bottle label 2.5 mg/500 mg - 180 tablets
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`Trade bottle label 2.5 mg/500 mg - 2000 tablets
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`Professional sample label 2.5 mg/850 mg - 14 tablets
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`Trade bottle label 2.5 mg/850 mg - 60 tablets
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`Trade bottle label 2.5 mg/850 mg - 180 tablets
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`Trade bottle label 2.5 mg/850 mg - 2000 tablets
` Professional sample label 2.5 mg/1000 mg - 14 tablets
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` Trade bottle label 2.5 mg/1000 mg - 60 tablets
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` Trade bottle label 2.5 mg/1000 mg - 180 tablets
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` Trade bottle label 2.5 mg/1000 mg - 2000 tablets
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`Reference ID: 3079250
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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.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
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`MARY H PARKS
`01/30/2012
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`Reference ID: 3079250
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