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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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`NDA 202270
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`Food and Drug Administration
`Silver Spring MD 20993
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`NDA APPROVAL
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`Merck Sharp & Dohme Corp.
`Attention: Richard J. Swanson, Ph.D.
`Senior Director, Regulatory Affairs
`P.O. Box 1000, UG2C-50
`North Wales, PA 19454-1099
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`Dear Dr. Swanson:
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`Please refer to your New Drug Application (NDA) dated September 23, 2010, received
`September 23, 2010, submitted pursuant to section 505(b) of the Federal Food, Drug, and
`Cosmetic Act (FDCA) for JANUMET XR (sitagliptin/metformin hydrochloride extended-
`release) fixed-dose combination tablets, 100 mg/1000 mg, 50 mg/500 mg, and 50 mg/1000 mg.
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`We acknowledge receipt of your amendments dated September 30, November 11 and 12,
`December 16 and 23, 2010, and January 10 (2), January 21, March 25, April 11, 13, 27, and 29,
`May 6 (2), 18, 27, and 31, June 3, 22, and 30, July 1 (2), 11, 12 (2), 18, and 21 (2), August 3 and
`16, and September 7, 2011, and January 26 and 31, 2012. The August 3, 2011, submission
`constituted a complete response to our July 22, 2011, action letter.
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`This new drug application provides for the use of JANUMET XR as an adjunct to diet and
`exercise to improve glycemic control in adults with type 2 diabetes mellitus when treatment with
`both sitagliptin and metformin extended-release is appropriate.
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`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.
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`Reference ID: 3080889
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`NDA 202270
`Page 2
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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
`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
`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 text for the
`Medication Guide). Information on submitting SPL files using eLIST may be found in the
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`guidance for industry titled “SPL Standard for Content of Labeling Technical Qs and As” at
`http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/U
`CM072392.pdf.
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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 container labels that are identical to the enclosed carton and
`immediate container labels, 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 titled
`“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 202270.” Approval of this
`submission by FDA is not required before the labeling is used.
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`Marketing the product with FPL that is not identical to the approved labeling text may render the
`product misbranded and an unapproved new drug.
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`Reference ID: 3080889
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`NDA 202270
`Page 3
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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 in pediatric patients unless this requirement is waived,
`deferred, or inapplicable.
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`We are waiving the pediatric study requirement for ages 0 to 9 years (inclusive) because the
`necessary studies are impossible or highly impractical. This is because there are too few children
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`in this age range with type 2 diabetes mellitus to study.
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`We are deferring submission of your pediatric study for ages 10 to 17 years (inclusive) for this
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`application because the product is ready for approval for use in adults and pediatric studies have
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`not been completed.
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`Your deferred pediatric studies required by section 505B(a) of the 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)(B) of the FDCA. These required studies are
`listed below.
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`PMR 1802-1: A pharmacokinetic study of JANUMET XR in pediatric patients 10 through
`17 years of age (inclusive) with type 2 diabetes mellitus.
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`Final Protocol Submission:
`Trial Completion:
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`Final Report Submission:
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`by June 1, 2012
`by December 1, 2013
`by June 1, 2014
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`PMR 1802-2: A 54-week, randomized, double-blind placebo-controlled trial to evaluate
`the efficacy and safety of JANUMET XR vs. metformin in pediatric patients who are
`inadequately controlled on diet and exercise. You must also evaluate whether pediatric
`patients can safely swallow JANUMET XR over the course of the trial.
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`Final Protocol Submission: by June 1, 2012
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`Trial Completion:
`by September 1, 2016
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`Final Report Submission:
`by March 1, 2017
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`Submit the protocols to your IND 101964, with a cross-reference letter 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
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`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.
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`Reference ID: 3080889
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`NDA 202270
`Page 4
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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, in triplicate, a cover letter requesting advisory comments, the
`proposed materials in draft or mock-up form with annotated references, and the package insert
`to:
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`Food and Drug Administration
`Center for Drug Evaluation and Research
`Division of Drug Marketing, Advertising, and Communications
`5901-B Ammendale Road
`Beltsville, MD 20705-1266
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`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. For instruction on completing the Form FDA 2253, see page 2 of the Form. For more
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`information about submission of promotional materials to the Division of Drug Marketing,
`Advertising, and Communications (DDMAC), 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.
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` Director
`Division of Metabolism and Endocrinology
`Office of Drug Evaluation II
`Center for Drug Evaluation and Research
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`ENCLOSURES:
`Package Insert
`Medication Guide
`Container Label – 50 mg/500 mg, 14 tablet bottle (sample)
`Container Label - 50 mg/500 mg, 60 tablet bottle
`Container Label – 50 mg/500 mg, 180 tablet bottle
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`Reference ID: 3080889
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`NDA 202270
`Page 5
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`Container Label – 50 mg/500 mg, 1000 tablet bottle
`Container Label – 50 mg/1000 mg, 60 tablet bottle
`Container Label – 50 mg/1000 mg, 14 tablet bottle (sample)
`Container Label – 50 mg/1000 mg, 180 tablet bottle
`Container Label – 50 mg/1000 mg, 1000 tablet bottle
`Container Label – 100 mg/1000 mg, 30 tablet bottle
`Container Label – 100 mg/1000 mg, 7 tablet bottle (sample)
`Container Label – 100 mg/1000 mg, 90 tablet bottle
`Container Label – 100 mg/1000 mg, 1000 tablet bottle
`Carton Label – 50 mg/500 mg tablets (sample)
`Carton Label – 50 mg/1000 mg tablets (sample)
`Carton Label – 100 mg/1000 mg tablets (sample)
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`Reference ID: 3080889
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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
`02/02/2012
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`Reference ID: 3080889
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