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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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`NDA 202343/S-001, S-002, and S-004
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`Food and Drug Administration
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`Silver Spring MD 20993
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`SUPPLEMENT APPROVAL
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`Merck Sharp & Dohme Corp.
`Attention: Lou Ann Eader, Ph.D.
`Director, Regulatory Affairs
`P.O. Box 1000, UG2C-50
`North Wales, PA 19454-1099
`
`
`Dear Dr. Eader:
`
`Please refer to your Supplemental New Drug Applications (sNDAs) dated and received on
`November 22, 2011 (S-001) and March 7 (S-002) and April 27, 2012 (S-004), submitted under
`section 505(b) of the Federal Food, Drug, and Cosmetic Act (FDCA) for Juvisync
`(sitagliptin/simvastatin) Tablets, 100mg/10mg, 100 mg/20 mg, 100mg/40mg, 50mg/10mg,
`50 mg/20 mg, and 50mg/40mg.
`
`We acknowledge receipt of your amendments dated February 9 (S-001), March 13 (S-001), May
`8 (S-004), May 29 (S-002), July 16 (S-001), and August 23 (S-001), 2012.
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`We also acknowledge receipt of your email dated August 23, 2012, that includes the agreed-upon
`labeling.
`
`These “Changes Being Effected” (S-002 and S-004) and “Prior Approval” (S-001) supplemental
`new drug applications provide for modifications to the Medication Guide, changes to the
`RECENT MAJOR CHANGES, DOSAGE AND ADMINISTRATION, DOSAGE FORMS
`AND STRENGTHS and DRUG INTERACTIONS sections of the Highlights of Prescribing
`Information section and changes to the INDICATIONS AND USAGE, DOSAGE AND
`ADMINISTRATION, DOSAGE FORMS AND STRENGTHS, CONTRAINDICATIONS,
`WARNINGS AND PRECAUTIONS, ADVERSE REACTIONS, USE IN SPECIFIC
`POPULATIONS, CLINICAL PHARMACOLOGY, and HOW SUPPLIED/STORAGE
`AND HANDLING of the Full Prescribing Information sections of the Juvisync package insert.
`In addition, revisions were made to the container labels for Juvisync.
`
`The changes for S-001 are based on new chemistry, manufacturing and controls information, and
`data to support a bioavailability and bioequivalence waiver request for the three new dose
`strengths. S-002 provides for the addition of boceprevir and telaprevir to the list of drugs
`contraindicated for concomitant use with Juvisync. S-004 provides for the addition of arthralgia,
`myalgia, pain in extremity, and back pain to the listing of adverse reactions.
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`Reference ID: 3190889
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`

`

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` NDA 202343/S-001; S-002; S-004
`Page 2
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`We have completed our review of the supplemental applications, as amended. They are
`approved, effective on the date of this letter, for use as recommended in the enclosed, agreed-
`upon labeling text.
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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 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.
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`Information on submitting SPL files using eLIST may be found in the guidance for industry
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`titled “SPL Standard for Content of Labeling Technical Qs and As” at
`http://www.fda.gov/downloads/DrugsGuidanceComplianceRegulatoryInformation/Guidances/U
`CM072392.pdf.
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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 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 MS Word format, that includes the changes approved in this
`supplemental application, as well as annual reportable changes and annotate each change. To
`facilitate review of your submission, provide a 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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`CARTON AND IMMEDIATE CONTAINER LABELS
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`Submit final printed carton and container labels that are identical to the carton and immediate
`container labels submitted on July 16, 2012, as soon as they are available, but no more than 30
`days after they are printed.
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`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 “Product
`Correspondence – Final Printed Carton and Container Labels for approved NDA
`202343/S-001.” Approval of this submission by FDA is not required before the labeling is used.
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`Reference ID: 3190889
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`

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` NDA 202343/S-001; S-002; S-004
`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(s) in pediatric patients unless this requirement is waived,
`deferred, or inapplicable.
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`We are waiving the pediatric study requirement for this application because this product does not
`represent a meaningful therapeutic benefit over existing therapies for pediatric patients and is
`not likely to be used in a substantial number of pediatric patients. We also note that pediatric
`studies with the sitagliptin component of Juvisync are ongoing.
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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 the following, in triplicate, (1) a cover letter requesting advisory
`comments, (2) the proposed materials in draft or mock-up form with annotated references, and
`(3) the package insert(s) to:
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`
`Food and Drug Administration
`Center for Drug Evaluation and Research
`Office of Prescription Drug Promotion (OPDP)
`5901-B Ammendale Road
`Beltsville, MD 20705-1266
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`You must submit final promotional materials and package insert(s), accompanied by a Form
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`FDA 2253, at the time of initial dissemination or publication [21 CFR 314.81(b)(3)(i)]. Form
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`FDA 2253 is available at http://www.fda.gov/opacom/morechoices/fdaforms/cder.html;
`instructions are provided on page 2 of the form. 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.
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`All promotional materials that include representations about your drug product must be promptly
`revised to be consistent with the labeling changes approved in this supplement, including any
`new safety information [21 CFR 314.70(a)(4)]. The revisions in your promotional materials
`should include prominent disclosure of the important new safety information that appears in the
`revised package labeling. Within 7 days of receipt of this letter, submit your statement of intent
`to comply with 21 CFR 314.70(a)(4) to the address above or by fax to 301-847-8444.
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`All promotional materials that include representations about your drug product must be promptly
`revised to be consistent with the labeling changes approved in this supplement, including any
`new safety information [21 CFR 314.70(a)(4)]. The revisions in your promotional materials
`should include prominent disclosure of the important new safety information that appears in the
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`Reference ID: 3190889
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`

`

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` NDA 202343/S-001; S-002; S-004
`Page 4
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`revised package labeling. Within 7 days of receipt of this letter, submit your statement of intent
`to comply with 21 CFR 314.70(a)(4) to the address above or by fax to 301-847-8444.
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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}
`
`Mary H. Parks, M.D.
`Director
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`Division of Metabolism and Endocrinology Products
`Office of Drug Evaluation II
`Center for Drug Evaluation and Research
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`ENCLOSURES:
`Package Insert
`Medication Guide
`Container Label – 50mg/10mg, 30 tablets
`Container Label – 50mg/10mg, 90 tablets
`Container Label – 50mg/20mg, 30 tablets
`Container Label – 50mg/20mg, 90 tablets
`Container Label – 50mg/40mg, 30 tablets
`Container Label – 50mg/40mg, 90 tablets
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`Reference ID: 3190889
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`

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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
`09/18/2012
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`Reference ID: 3190889
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