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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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`NDA 201280/S-002
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`Food and Drug Administration
`Silver Spring MD 20993
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`SUPPLEMENT APPROVAL
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`Boehringer Ingelheim Pharmaceuticals, Inc.
`Attention: Chung Lee-Sogaard, Ph.D.
`Associate Director, Drug Regulatory Affairs
`900 Ridgebury Road, P.O. Box 368
`Ridgefield, CT 06877
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`Dear Dr. Lee-Sogaard:
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`Please refer to your Supplemental New Drug Application (sNDA) dated and received on July 22,
`2011, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act (FDCA) for
`Tradjenta (linagliptin) tablets, 5 mg.
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`We acknowledge receipt of your amendments dated September 21, and 22, and November 16,
`2011, and March 9, and April 19, 2012. We also acknowledge receipt of your email dated May
`21, 2012, that includes the agreed-upon labeling.
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`This “Prior Approval” supplemental new drug application provides for modifications to the
`Patient Package Insert (PPI), changes to the ADVERSE REACTIONS section of the Highlights
`of Prescribing Information section and changes to the ADVERSE REACTIONS, USE IN
`SPECIFIC POPULATIONS, OVERDOSAGE, CLINICAL PHARMACOLOGY, AND
`CLINICAL STUDIES of the Full Prescribing Information sections of the Tradjenta package
`insert (PI).
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`These changes are based on the safety and efficacy results from trial 1218.46, entitled “A Phase
`3, randomized, double-blind, placebo-controlled parallel group study to compare the efficacy and
`safety of twice daily administration of the free combination of linagliptin 2.5 mg + metformin
`500 mg or of linagliptin 2.5 mg + metformin 1000 mg, with the individual components of
`metformin (500 mg or 1000 mg, twice daily) and linagliptin (5 mg, once daily) over 24 weeks in
`drug naive or previously treated (4 weeks washout and 2 weeks placebo run-in) type 2 diabetic
`patients with insufficient glycemic control.” The efficacy and safety of trial 1218.46 was fully
`reviewed under the Jentadueto (linagliptin/metformin fixed-dose combination) NDA (201281).
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`Reference ID: 3133899
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` NDA 201280/S-002
`Page 2
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`We have completed our review of the 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.
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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
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`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 patient
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`package insert), 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.
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`Information on submitting SPL files using eLIST may be found in the guidance for industry
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`titled “SPL Standard for Content of Labeling Technical Qs and As” at
`http://www.fda.gov/downloads/DrugsGuidanceComplianceRegulatoryInformation/Guidances/U
`CM072392.pdf.
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`The SPL will be accessible from publicly available labeling repositories.
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`Also within 14 days, amend all pending supplemental applications 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).
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`REQUIRED PEDIATRIC ASSESSMENTS
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`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.
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`Because none of these criteria apply to your application, you are exempt from this requirement.
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`Reference ID: 3133899
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` NDA 201280/S-002
`Page 3
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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 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:
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`Food and Drug Administration
`Center for Drug Evaluation and Research
`Office of Prescription Drug Promotion (OPDP)
`5901-B Ammendale Road
`Beltsville, MD 20705-1266
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`You must submit final promotional materials and package insert(s), accompanied by a Form
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`FDA 2253, at the time of initial dissemination or publication [21 CFR 314.81(b)(3)(i)]. Form
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`FDA 2253 is available at http://www.fda.gov/opacom/morechoices/fdaforms/cder.html;
`instructions are provided on 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.
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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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`If you have any questions, call Raymond Chiang, Regulatory Project Manager, at (301) 796-
`1940.
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`Sincerely,
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`{See appended electronic signature page}
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`Mary H. Parks, M.D.
`Director
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`Division of Metabolism and Endocrinology Products
`Office of Drug Evaluation II
`Center for Drug Evaluation and Research
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`ENCLOSURES:
`Package Insert (PI)
`Patient Package Insert (PPI)
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`Reference ID: 3133899
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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
`05/22/2012
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`Reference ID: 3133899
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