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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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`Food and Drug Administration
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` Silver Spring MD 20993
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` NDA APPROVAL
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` NDA 208026
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`Boehringer Ingelheim Pharmaceuticals, Inc.
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`Attention: Renee Zindell, M.S., RAC
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`Associate Director, Regulatory Affairs
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`900 Ridgebury Road, P.O. Box 368
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`Ridgefield, CT 06877
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`Dear Ms. Zindell:
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`Please refer to your New Drug Application (NDA) dated and received July 27, 2015, and your
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`amendments, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act
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`(FDCA) for Jentadueto XR (linagliptin and metformin hydrochloride extended-release) tablets.
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`This new drug application provides for the use of Jentadueto XR (linagliptin and metformin
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`hydrochloride extended-release) tablets as an adjunct to diet and exercise to improve glycemic
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`control in adults with type 2 diabetes mellitus when treatment with both linagliptin and
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`metformin is appropriate.
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`We have completed our review of this application, as amended. It is approved, effective on the
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`date of this letter, for use as recommended in the enclosed agreed-upon labeling text.
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`WAIVER OF HIGHLIGHTS SECTION
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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
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`labeling unless we notify you otherwise.
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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
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`automated drug registration and listing system (eLIST), as described at
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`http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm. Content
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` of labeling must be identical to the enclosed labeling (text for the package insert, text for the
` patient package insert, Medication Guide). Information on submitting SPL files using eLIST
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` may be found in the guidance for industry SPL Standard for Content of Labeling Technical Qs
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` and As, available at
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`http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/U
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`CM072392.pdf.
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`Reference ID: 3938100
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` NDA 208026
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` Page 2
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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 immediate container labels that are identical to the enclosed
` carton and immediate container labels and submitted on April 6, 2016, as soon as they are
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` available, but no more than 30 days after they are printed. Please submit these labels
` electronically according to the guidance for industry Providing Regulatory Submissions in
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` Electronic Format – Human Pharmaceutical Product Applications and Related Submissions
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` Using the eCTD Specifications (June 2008). Alternatively, you may submit 12 paper copies,
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` with 6 of the copies individually mounted on heavy-weight paper or similar material. For
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` administrative purposes, designate this submission “Final Printed Carton and Container
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` Labels for approved NDA 208026.” Approval of this submission by FDA is not required
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` 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
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` the product misbranded and an unapproved new drug.
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`ADVISORY COMMITTEE
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`Your application for Jentadueto XR was not referred to an FDA advisory committee because this
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`drug is not the first in its class.
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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
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`active ingredients, new indications, new dosage forms, new dosing regimens, or new routes of
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`administration are required to contain an assessment of the safety and effectiveness of the
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`product for the claimed indication(s) in pediatric patients unless this requirement is waived,
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`deferred, or inapplicable.
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`We are waiving the pediatric studies requirement for ages 0 to 9 years (inclusive) because
`necessary studies are impossible or highly impracticable. This is because there are too few
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`children in this age range with type 2 diabetes mellitus to study.
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`We are deferring submission of your pediatric studies for ages 10 to 16 years (inclusive) for this
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`application because this product is ready for approval for use in adults and the pediatric studies
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`have not been completed.
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`Your deferred pediatric studies required by section 505B(a) of the Federal Food, Drug, and
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`Cosmetic Act/FDCA are required postmarketing studies. The status of these postmarketing
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`studies must be reported annually according to 21 CFR 314.81 and section 505B(a)(3)(C) of the
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`FDCA. These required studies are listed below.
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`Reference ID: 3938100
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` NDA 208026
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` Page 3
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` Your requirements under the PREA (PMRs 1766-1 and 1766-2) as stated in the approval letter
` for NDA 201280 for Tradjenta (linagliptin) tablets, dated May 2, 2011, also apply to
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` NDA 208026. We refer to our May 18, 2015, letter granting deferral extension of PMR 1766-1,
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` and denying deferral extension for PMR 1766-2. Accordingly, your requirements under the
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` PREA are as follows:
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`1766-1 A randomized, placebo-controlled, dose-finding study under PREA evaluating
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`at least two doses of linagliptin as monotherapy in pediatric patients ages 10
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`to 16 years (inclusive).
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`Final Report Submission:
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`September 30, 2016
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`1766-2 Deferred randomized and controlled pediatric study under PREA to evaluate
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`efficacy, safety, and pharmacokinetics of linagliptin for the treatment of
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`type 2 diabetes mellitus in pediatric patients ages 10 to 16 years (inclusive) as
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`monotherapy and when added to metformin therapy.
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`Study Completion:
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`Final Report Submission:
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`March 31, 2017
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`July 31, 2018
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`Submit the protocols to your IND 070963, with a cross-reference letter to NDA 201280 and to
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`this NDA.
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`Reports of these required pediatric postmarketing studies must be submitted as a new drug
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`application (NDA) or as a supplement to your approved NDA with the proposed labeling
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`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
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`the submission.
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`Please cross-reference this NDA when you submit your final reports for requirements 1766-1
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`and 1766-2 to NDA 201280.
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`PROMOTIONAL MATERIALS
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`You may request advisory comments on proposed introductory advertising and promotional
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`labeling. To do so, submit, in triplicate, a cover letter requesting advisory comments, the
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`proposed materials in draft or mock-up form with annotated references, and the package insert,
`Medication Guide, and patient PI (as applicable) to:
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`OPDP Regulatory Project Manager
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`Food and Drug Administration
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`Center for Drug Evaluation and Research
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`Office of Prescription Drug Promotion
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`5901-B Ammendale Road
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`Beltsville, MD 20705-1266
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`Reference ID: 3938100
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` NDA 208026
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` Page 4
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` Alternatively, you may submit a request for advisory comments electronically in eCTD format.
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`For more information about submitting promotional materials in eCTD format, see the draft
`Guidance for Industry (available at:
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`http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/
`UCM443702.pdf ).
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`As required under 21 CFR 314.81(b)(3)(i), you must submit final promotional materials, and the
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`package insert, at the time of initial dissemination or publication, accompanied by a Form FDA
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`2253. Form FDA 2253 is available at
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`http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM083570.pdf.
`Information and Instructions for completing the form can be found at
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`http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM375154.pdf. For
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`more information about submission of promotional materials to the Office of Prescription Drug
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`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
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`(21 CFR 314.80 and 314.81).
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`If you have any questions, call Richard Whitehead, M.S., Regulatory Project Manager, at (301)
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`796-4945.
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`Enclosures:
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`Content of Labeling
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`Carton and Container Labeling
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`Reference ID: 3938100
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`Sincerely,
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` {See appended electronic signature page}
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`Jean-Marc Guettier, M.D.
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`Director
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`Division of Metabolism and Endocrinology Products
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`Office of Drug Evaluation II
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`Center for Drug Evaluation and Research
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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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`JEAN-MARC P GUETTIER
`05/27/2016
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`Reference ID: 3938100
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`(
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