DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Silver Spring MD 20993 NDA 208026 NDA APPROVAL Boehringer Ingelheim Pharmaceuticals, Inc. Attention: Renee Zindell, M.S., RAC Associate Director, Regulatory Affairs 900 Ridgebury Road, P.O. Box 368 Ridgefield, CT 06877 Dear Ms. Zindell: Please refer to your New Drug Application (NDA) dated and received July 27, 2015, and your amendments, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act (FDCA) for Jentadueto XR (linagliptin and metformin hydrochloride extended-release) tablets. This new drug application provides for the use of Jentadueto XR (linagliptin and metformin hydrochloride extended-release) tablets as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus when treatment with both linagliptin and metformin is appropriate. 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. WAIVER OF HIGHLIGHTS SECTION 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. 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, text for the patient package insert, Medication Guide). Information on submitting SPL files using eLIST may be found in the guidance for industry SPL Standard for Content of Labeling Technical Qs and As, available at http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/U CM072392.pdf. Reference ID: 3938100 NDA 208026 Page 2 The SPL will be accessible via publicly available labeling repositories. CARTON AND IMMEDIATE CONTAINER LABELS 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 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 Electronic Format – Human Pharmaceutical Product Applications and Related Submissions Using the eCTD 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 208026.” Approval of this submission by FDA is not required before the labeling is used. 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. ADVISORY COMMITTEE Your application for Jentadueto XR was not referred to an FDA advisory committee because this drug is not the first in its class. 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. 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 children in this age range with type 2 diabetes mellitus to study. We are deferring submission of your pediatric studies for ages 10 to 16 years (inclusive) for this application because this product is ready for approval for use in adults and the pediatric studies have not been completed. Your deferred pediatric studies required by section 505B(a) of the Federal Food, Drug, and Cosmetic Act/FDCA are required postmarketing studies. The status of these postmarketing studies must be reported annually according to 21 CFR 314.81 and section 505B(a)(3)(C) of the FDCA. These required studies are listed below. Reference ID: 3938100 NDA 208026 Page 3 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 NDA 208026. We refer to our May 18, 2015, letter granting deferral extension of PMR 1766-1, and denying deferral extension for PMR 1766-2. Accordingly, your requirements under the PREA are as follows: 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). Final Report Submission: 1766-2 September 30, 2016 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. Study Completion: Final Report Submission: March 31, 2017 July 31, 2018 Submit the protocols to your IND 070963, with a cross-reference letter to NDA 201280 and to this NDA. Reports of these required pediatric postmarketing studies must be submitted as a new drug application (NDA) or as a supplement to your approved NDA with the proposed labeling 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 the submission. Please cross-reference this NDA when you submit your final reports for requirements 1766-1 and 1766-2 to NDA 201280. PROMOTIONAL MATERIALS 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, Medication Guide, and patient PI (as applicable) to: OPDP Regulatory Project Manager Food and Drug Administration Center for Drug Evaluation and Research Office of Prescription Drug Promotion 5901-B Ammendale Road Beltsville, MD 20705-1266 Reference ID: 3938100 NDA 208026 Page 4 Alternatively, you may submit a request for advisory comments electronically in eCTD format. For more information about submitting promotional materials in eCTD format, see the draft Guidance for Industry (available at: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ UCM443702.pdf ). 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. 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, call Richard Whitehead, M.S., Regulatory Project Manager, at (301) 796-4945. Sincerely, {See appended electronic signature page} Jean-Marc Guettier, M.D. Director Division of Metabolism and Endocrinology Products Office of Drug Evaluation II Center for Drug Evaluation and Research Enclosures: Content of Labeling Carton and Container Labeling Reference ID: 3938100 --------------------------------------------------------------------------------------------------------This is a representation of an electronic record that was signed electronically and this page is the manifestation of the electronic signature. --------------------------------------------------------------------------------------------------------/s/ ---------------------------------------------------JEAN-MARC P GUETTIER 05/27/2016 Reference ID: 3938100 (