`CENTER FOR DRUG EVALUATION AND RESEARCH
`
`Approval Package for:
`
`
`APPLICATION NUMBER:
`
`202270Orig1s000
`
`
`Janumet XR
`
`Trade Name:
`
`Generic Name:
`
`
`Sponsor:
`
`Approval Date:
`
`Indications:
`
`
`
`Sitagliptin/Metformin Hydrochloride
`extended release
`
`Merck Sharp & Dohme Corp
`
`2/2/2012
`
`Indicated 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
`
`

`

`CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`202270Orig1s000
`
`CONTENTS
`
`Reviews / Information Included in this NDA Review.
`
`
`X
`X
`X
`
`X
`X
`
`
`X
`X
`
`X
`
`
`X
`X
`X
`X
`X
`
`
`
`
`Approval Letter
`Other Action Letters
`Labeling
`REMS
`Summary Review
`Officer/Employee List
`Office Director Memo
`Cross Discipline Team Leader Review
`Medical Review(s)
`Chemistry Review(s)
`Environmental Assessment
`Pharmacology Review(s)
`Statistical Review(s)
`Microbiology Review(s)
`Clinical Pharmacology/Biopharmaceutics Review(s)
`Other Reviews
`Risk Assessment and Risk Mitigation Review(s)
`Proprietary Name Review(s)
`Administrative/Correspondence Document(s)
`
`
`

`

`CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`
`APPLICATION NUMBER:
`202270Orig1s000
`
`APPROVAL LETTER
`
`
`
`
`

`

`
`
`
`
`
`
`DEPARTMENT OF HEALTH AND HUMAN SERVICES
`
`
`
`
`
`NDA 202270
`
`
`
`
`
`
`Food and Drug Administration
`Silver Spring MD 20993
`
`NDA APPROVAL
`
`
`
`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
`
`
`Dear Dr. Swanson:
`
`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.
`
`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.
`
`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.
`
`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.
`
`
`Reference ID: 3080889
`
`

`

`NDA 202270
`Page 2
`
`
`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 and text for the
`Medication Guide). Information on submitting SPL files using eLIST may be found in the
`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.
`
`The SPL will be accessible via publicly available labeling repositories.
`
`CARTON AND IMMEDIATE CONTAINER LABELS
`
`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.
`
`Marketing the product with FPL that is not identical to the approved labeling text may render the
`product misbranded and an unapproved new drug.
`
`Reference ID: 3080889
`
`

`

`NDA 202270
`Page 3
`
`
`
`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 in pediatric patients unless this requirement is waived,
`deferred, or inapplicable.
`
`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
`in this age range with type 2 diabetes mellitus to study.
`
`We are deferring submission of your pediatric study for ages 10 to 17 years (inclusive) for this
`application because the product is ready for approval for use in adults and pediatric studies have
`not been completed.
`
`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.
`
`
`PMR 1802-1: A pharmacokinetic study of JANUMET XR in pediatric patients 10 through
`17 years of age (inclusive) with type 2 diabetes mellitus.
`
`Final Protocol Submission:
`Trial Completion:
`
`Final Report Submission:
`
`by June 1, 2012
`by December 1, 2013
`by June 1, 2014
`
`
`
`
`
`
`
`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.
`
`Final Protocol Submission: by June 1, 2012
`Trial Completion:
`
`by September 1, 2016
`Final Report Submission:
`by March 1, 2017
`
`
`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
`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.
`
`
`Reference ID: 3080889
`
`

`

`NDA 202270
`Page 4
`
`
`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
`to:
`
`
`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
`
`
`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
`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.
`
`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 Raymond Chiang, Regulatory Project Manager, at (301) 796-
`1940.
`
`
`
`Sincerely,
`
`{See appended electronic signature page}
`
`Mary H. Parks, M.D.
`Director
`Division of Metabolism and Endocrinology
`Office of Drug Evaluation II
`Center for Drug Evaluation and Research
`
`
`
`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
`
`Reference ID: 3080889
`
`

`

`NDA 202270
`Page 5
`
`
`
`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)
`
`
`
`Reference ID: 3080889
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`MARY H PARKS
`02/02/2012
`
`Reference ID: 3080889
`
`