` NDA 021995/S-047
`
` NDA 022044/S-048
`
` NDA 202270/S-022
`
`
`
`
`
` SUPPLEMENT APPROVAL
`
`FULFILLMENT OF POSTMARKETING
`REQUIREMENTS
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`
` Merck Sharp & Dohme Corp.
`
`
`
` Attention: Lou Ann Eader, Ph.D.
` Director, Global Regulatory Affairs
` 351 N. Sumneytown Pike
`
`
`
` P. O. Box 1000, UG2D-44
` North Wales, PA 19454-1099
`
`
`
` Dear Dr. Eader:
`
` Please refer to your supplemental new drug applications (sNDAs) dated June 4, 2020,
`
`
`
`
`
` received June 4, 2020, and your amendments, submitted under section 505(b) and
` pursuant to section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act (FDCA) for
`
`
`
` Januvia (sitagliptin) tablets, Janumet (sitagliptin and metformin HCl) tablets, and
` Janumet XR (sitagliptin and metformin HCl extended-release) tablets.
`
`
`
` These Prior Approval supplemental new drug applications provide for:
`
`
`
` NDA 21995/S-047 for Januvia
`
`
`
` Changes to the Prescribing Information and Medication Guide based on the results of
`
`
` Protocol 083, entitled “A Phase III, Multicenter, Double-Blind, Randomized, Placebo-
`
`
` Controlled Clinical Trial to Evaluate the Safety and Efficacy of Sitagliptin in Pediatric
`
` Patients with Type 2 Diabetes Mellitus with Inadequate Glycemic Control.”
`
`
`
`
`
` NDA 022044/S-048 for Janumet
`
`
`
` Changes to the Prescribing Information and Medication Guide based on the results of
`
`
` Protocol 170, entitled “A Phase III, Multicenter, Double-blind, Randomized, Placebo-
`
`
`
`
` Controlled Clinical Trial to Evaluate the Safety and Efficacy of MK-0431A (A Fixed-Dose
`
` Combination Tablet of Sitagliptin and Metformin) in Pediatric Patients with Type 2
`
`
` Diabetes Mellitus with Inadequate Glycemic Control on Metformin Therapy (Alone or in
`
`
`
` Combination with Insulin).”
`
`
`
` NDA 202270/S-022 for Janumet XR
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`
`
` Changes to the Prescribing Information and Medication Guide based on the results of
`
`
` Protocol 289, entitled “A Phase III Multicenter, Double-blind, Randomized, Placebo-
`
`
` controlled Clinical Trial to Evaluate the Safety and Efficacy of MK-0431A XR (a Fixed-
`
`
`
` Dose Combination Tablet of Sitagliptin and Extended-Release Metformin) in Pediatric
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`Reference ID: 4712165
`
`

`

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` NDA 021995/S-047
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` NDA 022044/S-048
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` NDA 202270/S-022
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` Page 2
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`
`
` Patients with Type 2 Diabetes Mellitus with Inadequate Glycemic Control on Metformin
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` Therapy (Alone or in Combination with Insulin).”
`
`
`
`
` APPROVAL & LABELING
`
` We have completed our review of these applications, as amended. They are approved,
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`
`
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`
`
` effective on the date of this letter, for use as recommended in the enclosed agreed-
`
`upon labeling.
`
` WAIVER OF ½ PAGE LENGTH REQUIREMENT FOR HIGHLIGHTS
`
` Please note that we have previously granted a waiver of the requirements of 21 CFR
`
`
`
`
` 201.57(d)(8) regarding the length of Highlights of Prescribing Information.
`
` 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
`
` FDA.gov.1 Content of labeling must be identical to the enclosed labeling (text for the
`
`
` Prescribing Information and Medication Guide), 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
`
`
`
` 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.2
`
`
`
` The SPL will be accessible from publicly available labeling repositories.
`
` Also within 14 days, amend all pending supplemental applications that include labeling
`
`
`
`
`
` changes 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 Microsoft Word
`
`
`
`format, that includes the changes approved in this supplemental application, as well as
`
` annual reportable changes. To facilitate review of your submission(s), provide a
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` 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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` 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
`
`
`
` Documents Database https://www.fda.gov/RegulatoryInformation/Guidances/default.htm.
`
`
`
` U.S. Food and Drug Administration
`
`
` Silver Spring, MD 20993
`
` www.fda.gov
`
`
`
`
`
`Reference ID: 4712165
`
`

`

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` NDA 021995/S-047
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` NDA 022044/S-048
`
` NDA 202270/S-022
`
` Page 3
`
`
`
` REQUIRED PEDIATRIC ASSESSMENTS
`
`Under the Pediatric Research Equity Act (PREA) (21 U.S.C. 355c), all applications for
`
` new active ingredients (which includes new salts and new fixed combinations), 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 in pediatric patients unless this requirement is waived, deferred,
`
` or inapplicable.
`
` Because none of these criteria apply to these supplemental applications, you are
`
`
` exempt from this requirement.
`
`
` FULFILLMENT OF POSTMARKETING REQUIREMENTS
`
` The supplemental application for NDA 021995 contained the final report for the
`
`
`
` following postmarketing requirement listed in the October 16, 2006, approval letter for
`
` NDA 021995.
`
`
`
`
`
`
`PMR 224-1 Deferred pediatric study under PREA for the treatment of type 2
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`
`
` diabetes in pediatric patients ages 11 to 16, inclusive.
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`
`
`
` The supplemental application for NDA 022044 contained the final report for the
`
`
` following postmarketing requirement listed in the March 30, 2007, approval letter for
`
` NDA 022044.
`
`
`PMR 856-1 Deferred pediatric study under PREA for the treatment of type 2
`
`
`
` diabetes in pediatric patients ages 11 to 16, inclusive.
`
`
`
`
` The supplemental application for NDA 202270 contained the final report for the
`
`
` following postmarketing requirement listed in the February 2, 2012, approval letter for
`
` NDA 202270.
`
`
`
`
` PMR 1802-4 A 54-week, randomized, double-blind, placebo-controlled trial to
` evaluate the efficacy and safety of JANUMET XR versus metformin
`
`
` extended-release in pediatric patients who are inadequately
` controlled on metformin immediate release.
`
`
`
`
`
` We have reviewed your submissions and conclude that the above requirements were
`
`
` fulfilled.
`
`
`
`
` U.S. Food and Drug Administration
`
`
` Silver Spring, MD 20993
`
` www.fda.gov
`
`
`
`Reference ID: 4712165
`
`

`

`
` NDA 021995/S-047
`
` NDA 022044/S-048
`
` NDA 202270/S-022
`
` Page 4
`
`
` This completes all of your postmarketing requirements and postmarketing commitments
`
`
` acknowledged in our October 16, 2006, March 30, 2007, and February 2, 2012,
`
` approval letters.
`
` PROMOTIONAL MATERIALS
`
` You may request advisory comments on proposed introductory advertising and
`
`
`
`
` promotional labeling. For information about submitting promotional materials, see the
`final guidance for industry Providing Regulatory Submissions in Electronic and Non-
`
`
`
` Electronic Format-Promotional Labeling and Advertising Materials for Human
`Prescription Drugs. 3
`
`
` You must submit final promotional materials and Prescribing Information, accompanied
`
`
`
`
`
` by a Form FDA 2253, at the time of initial dissemination or publication
` [21 CFR 314.81(b)(3)(i)]. Form FDA 2253 is available at FDA.gov.4 Information and
`
`
`
`
`
`
` Instructions for completing the form can be found at FDA.gov.5
`
`
` 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, contact Michael Oyewole, Regulatory Project Manager, at
`
` (301) 796-3897.
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`
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`
` Sincerely,
`
` {See appended electronic signature page}
`
` Patrick Archdeacon, M.D.
`
`
`
` Associate Director for Therapeutics
`
`
`
` Division of Diabetes, Lipid Disorders, and Obesity
`
`
` Office of Cardiology, Hematology, Endocrinology,
`
` and Nephrology
` Center for Drug Evaluation and Research
`
`
`
`
`
`
`
`
`
`
` 3 For the most recent version of a guidance, check the FDA guidance web page at
` https://www.fda.gov/media/128163/download.
`
`4 http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM083570.pdf
`
`
`5 http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM375154.pdf
`
`
`
`
` U.S. Food and Drug Administration
` Silver Spring, MD 20993
`
`
` www.fda.gov
`
`
`
`
`
`Reference ID: 4712165
`
`

`

`
` NDA 021995/S-047
`
` NDA 022044/S-048
`
` NDA 202270/S-022
`
` Page 5
`
`
` ENCLOSURES:
`
`• Content of Labeling for Januvia (sitagliptin) tablets
`
`
`
`o Prescribing Information
`
`
`o Medication Guide
`
`
`• Content of Labeling for Janumet (sitagliptin and metformin HCl) tablets
`
`
`
`
`o Prescribing Information
`
`
`o Medication Guide
`
`
`• Content of Labeling for Janumet XR (sitagliptin and metformin HCl extended-
`
`
`
` release) tablets
`
`o Prescribing Information
`
`
`o Medication Guide
`
`
`
`
`
`
`
`
` U.S. Food and Drug Administration
`
`
` Silver Spring, MD 20993
`
` www.fda.gov
`
`
`
`Reference ID: 4712165
`
`

`

`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/
`------------------------------------------------------------
`
`PATRICK ARCHDEACON
`12/04/2020 02:25:48 PM
`
`Reference ID: 4712165
`
`