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`( ~ rffl.l U.S. FOOD & DRUG
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`ADMINISTRAT I ON
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` NDA 201280/S-027
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`SUPPLEMENT APPROVAL
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` Boehringer Ingelheim Pharmaceuticals, Inc.
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` Attention: Addison Nguyen, Pharm.D.
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` Associate Director, Regulatory Affairs
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` 900 Ridgebury Road, PO Box 368
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` Ridgefield, CT 06877
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` Dear Dr. Nguyen:
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` Please refer to your supplemental new drug application (sNDA) dated and received on
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` December 20, 2022, and your amendments, submitted under section 505(b) of the
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` Federal Food, Drug, and Cosmetic Act (FDCA) for Tradjenta (linagliptin) tablets.
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` This Prior Approval sNDA provides for revisions to section 8.4 Pediatric Use of the
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` Tradjenta Prescribing Information based on results from Protocol 1218-0091 titled, A
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`double-blind, randomised, placebo-controlled, parallel group trial to evaluate the efficacy
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` and safety of empagliflozin and linagliptin over 26 weeks, with a double-blind active
` treatment safety extension period up to 52 weeks, in children and adolescents with type
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` 2 diabetes mellitus.
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` This study was conducted to address the following Postmarketing Requirement that was
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` established under the Pediatric Research Equity Act.
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` 3300-1 Conduct a 26-week randomized, double-blind, placebo-controlled study
` to evaluate the efficacy and safety of linagliptin and empagliflozin for the
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`treatment of pediatric patients ages 10 to < 18 years with type 2 diabetes
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` mellitus, followed by a 26-week site- and subject-blinded safety
` extension period (weeks 26 to 52). Background therapy will consist of
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` metformin, insulin, or metformin plus insulin. A second randomization will
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` take place at week 12, with uptitration of empagliflozin dose (from 10 mg
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`to 25 mg) for approximately half of the subjects with a hemoglobin A1C
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` greater than or equal to 7%.
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` APPROVAL & LABELING
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` We have completed our review of this application, as amended. It is approved, effective
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` on the date of this letter, for use as recommended in the enclosed agreed-upon
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` labeling.
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` WAIVER OF ½ PAGE LENGTH REQUIREMENT FOR HIGHLIGHTS
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` Please note that we have previously granted a waiver of the requirements of 21 CFR
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`Reference ID: 5193739
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` NDA 201280/S-027
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` Page 2
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` 201.57(d)(8) regarding the length of Highlights of Prescribing Information.
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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
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` the FDA automated drug registration and listing system (eLIST), as described at
` FDA.gov.1 Content of labeling must be identical to the enclosed labeling (text for the
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` Prescribing Information and Medication Guide), with the addition of any labeling
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`changes in pending “Changes Being Effected” (CBE) supplements, as well as annual
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` 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
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` industry SPL Standard for Content of Labeling Technical Qs and As.2
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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 that include labeling
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` changes for this NDA, including CBE supplements for which FDA has not yet issued an
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` action letter, with the content of labeling [21 CFR 314.50(l)(1)(i)] in Microsoft Word
`format, that includes the changes approved in this supplemental application, as well as
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` annual reportable changes. To facilitate review of your submission(s), provide a
` highlighted or marked-up copy that shows all changes, as well as a clean Microsoft
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` Word version. The marked-up copy should provide appropriate annotations, including
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` 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
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`new active ingredients (which includes new salts and new fixed combinations), new
` indications, new dosage forms, new dosing regimens, or new routes of administration
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` are required to contain an assessment of the safety and effectiveness of the product for
`the claimed indication in pediatric patients unless this requirement is waived, deferred,
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` or inapplicable.
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` Because none of these criteria apply to your application, you are exempt from this
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` requirement.
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` PROMOTIONAL MATERIALS
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` You may request advisory comments on proposed introductory advertising and
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` promotional labeling. For information about submitting promotional materials, see the
`final guidance for industry Providing Regulatory Submissions in Electronic and Non-
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` 1 http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm
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` 2 We update guidances periodically. For the most recent version of a guidance, check the FDA Guidance
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` Documents Database https://www.fda.gov/RegulatoryInformation/Guidances/default.htm.
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` U.S. Food and Drug Administration
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` Silver Spring, MD 20993
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` www.fda.gov
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`Reference ID: 5193739
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` NDA 201280/S-027
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` Page 3
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` Electronic Format-Promotional Labeling and Advertising Materials for Human
`Prescription Drugs. 3
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` You must submit final promotional materials and Prescribing Information, accompanied
` by a Form FDA 2253, at the time of initial dissemination or publication
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` [21 CFR 314.81(b)(3)(i)]. Form FDA 2253 is available at FDA.gov.4 Information and
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` Instructions for completing the form can be found at FDA.gov.5
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` PATENT LISTING REQUIREMENTS
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` Pursuant to 21 CFR 314.53(d)(2) and 314.70(f), certain changes to an approved NDA
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` submitted in a supplement require you to submit patent information for listing in the
` Orange Book upon approval of the supplement. You must submit the patent information
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` required by 21 CFR 314.53(d)(2)(i)(A) through (C) and 314.53(d)(2)(ii)(A) and (C), as
` applicable, to FDA on Form FDA 3542 within 30 days after the date of approval of the
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` supplement for the patent information to be timely filed (see 21 CFR
` 314.53(c)(2)(ii)). You also must ensure that any changes to your approved NDA that
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` require the submission of a request to remove patent information from the Orange Book
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` are submitted to FDA at the time of approval of the supplement pursuant to 21 CFR
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` 314.53(d)(2)(ii)(B) and 314.53(f)(2)(iv).
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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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` 3 For the most recent version of a guidance, check the FDA guidance web page at
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` https://www.fda.gov/media/128163/download.
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` 4 http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM083570.pdf
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` 5 http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM375154.pdf
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` U.S. Food and Drug Administration
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` Silver Spring, MD 20993
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` www.fda.gov
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`Reference ID: 5193739
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` NDA 201280/S-027
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` Page 4
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` If you have any questions, call Michael Oyewole, Regulatory Project Manager, at
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` (301) 796-3897.
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` Sincerely,
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` {See appended electronic signature page}
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` Michelle Carey, M.D., M.P.H.
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` Associate Director for Therapeutics
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` Division of Diabetes, Lipid Disorders, and Obesity
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`Office of Cardiology, Hematology, Endocrinology,
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` and Nephrology
` Office of New Drugs
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` Center for Drug Evaluation and Research
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` ENCLOSURES:
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`• Content of Labeling
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`o Prescribing Information
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`o Medication Guide
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` U.S. Food and Drug Administration
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` Silver Spring, MD 20993
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` www.fda.gov
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`Reference ID: 5193739
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`Signature Page 1 of 1
`--------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically. Following this are manifestations of any and all
`electronic signatures for this electronic record.
`--------------------------------------------------------------------------------------------
`/s/
`------------------------------------------------------------
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`MICHELLE CAREY
`06/20/2023 02:35:51 PM
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`Reference ID: 5193739
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