CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`
`
`
`APPLICATION NUMBER:
`202343Orig1s000
`
`
`ADMINISTRATIVE and CORRESPONDENCE
`DOCUMENTS
`
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`

`

`a) Is it a 505(b)(1), 505(b)(2) or efficacy supplement?
`
`
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` YES
`
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`NO
`
`
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`EXCLUSIVITY SUMMARY
`
`
`NDA # 202343
`
`
`
`
`
`SUPPL # N/A
`
`
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`HFD # 510
`
`Trade Name Juvisync
`
`Generic Name sitagliptin and simvastatin fixed-dose combination tablets
`
`
`
`
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`Applicant Name Merck Sharp & Dohme Corp.
`
`Approval Date, If Known October 7, 2011
`
`PART I
`
`1. An exclusivity determination will be made for all original applications, and all efficacy
`supplements. Complete PARTS II and III of this Exclusivity Summary only if you answer "yes" to
`one or more of the following questions about the submission.
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`IS AN EXCLUSIVITY DETERMINATION NEEDED?
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`If yes, what type? Specify 505(b)(1), 505(b)(2), SE1, SE2, SE3,SE4, SE5, SE6, SE7, SE8
`
`
`
`505(b)(1)
`
`c) Did it require the review of clinical data other than to support a safety claim or change in
`labeling related to safety? (If it required review only of bioavailability or bioequivalence
`data, answer "no.")
`
`
`
`
`
` YES
`
`
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`NO
`
`
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`
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`If your answer is "no" because you believe the study is a bioavailability study and, therefore,
`not eligible for exclusivity, EXPLAIN why it is a bioavailability study, including your
`reasons for disagreeing with any arguments made by the applicant that the study was not
`simply a bioavailability study.
`
`
`
`Merck conducted eight clinical pharmacology studies in support of the sitagliptin/simvastatin FDC
`NDA, as follows:
`• Two bioequivalence studies - one using the lowest strength (Study P255: sitagliptin 100 mg /
`simvastatin 10 mg) and the other one using the highest strength (Study P153 Part I and Part II:
`sitagliptin 100 mg / simvastatin 80 mg)
`• One study for the food effect on sitagliptin 100 mg / simvastatin 80 mg
`• One study for the food effect on sitagliptin 100 mg/ simvastatin 80 mg
`• Two relative bioavailability studies to explore preliminary formulations
`• Two studies for assessment of drug-drug interaction
`
`
`
`
`Reference ID: 3025433
`
`Page 1
`
`

`

`
`If it is a supplement requiring the review of clinical data but it is not an effectiveness
`supplement, describe the change or claim that is supported by the clinical data:
`
`Not a supplement. This is a new fixed- dose combination of sitagliptin and
`simvastatin.
`
`
`
`d) Did the applicant request exclusivity?
`
`N/A
`
`
`If the answer to (d) is "yes," how many years of exclusivity did the applicant request?
`
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`
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` YES
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`NO
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`e) Has pediatric exclusivity been granted for this Active Moiety?
`
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` YES
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`NO
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`N/A
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` YES
`
`
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`NO
`
`
`
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`IF THE ANSWER TO QUESTION 2 IS "YES," GO DIRECTLY TO THE SIGNATURE BLOCKS
`ON PAGE 8 (even if a study was required for the upgrade).
`
`
`FIVE-YEAR EXCLUSIVITY FOR NEW CHEMICAL ENTITIES
`PART II
`(Answer either #1 or #2 as appropriate)
`
`1. Single active ingredient product.
`
`Has FDA previously approved under section 505 of the Act any drug product containing the same
`active moiety as the drug under consideration? Answer "yes" if the active moiety (including other
`esterified forms, salts, complexes, chelates or clathrates) has been previously approved, but this
`particular form of the active moiety, e.g., this particular ester or salt (including salts with hydrogen
`or coordination bonding) or other non-covalent derivative (such as a complex, chelate, or clathrate)
`has not been approved. Answer "no" if the compound requires metabolic conversion (other than
`
`
` If the answer to the above question in YES, is this approval a result of the studies submitted in
`response to the Pediatric Written Request?
`
`
`
`IF YOU HAVE ANSWERED "NO" TO ALL OF THE ABOVE QUESTIONS, GO DIRECTLY TO
`THE SIGNATURE BLOCKS AT THE END OF THIS DOCUMENT.
`
`
`2. Is this drug product or indication a DESI upgrade?
`
`
`
`
`
`
`
`Reference ID: 3025433
`
`Page 2
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`

`

`deesterification of an esterified form of the drug) to produce an already approved active moiety.
`
`
`N/A
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` YES
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`NO
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`If "yes," identify the approved drug product(s) containing the active moiety, and, if known, the NDA
`#(s).
`
`
`NDA# N/A
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`NDA#
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`NDA#
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`2. Combination product.
`
`If the product contains more than one active moiety(as defined in Part II, #1), has FDA previously
`approved an application under section 505 containing any one of the active moieties in the drug
`product? If, for example, the combination contains one never-before-approved active moiety and
`one previously approved active moiety, answer "yes." (An active moiety that is marketed under an
`OTC monograph, but that was never approved under an NDA, is considered not previously
`approved.)
`
`
`
`
`
`YES
`
`
`
`NO
`
`
`
`
`If "yes," identify the approved drug product(s) containing the active moiety, and, if known, the NDA
`#(s).
`
`NDA# 21995
`NDA# 22044
`
`Januvia (sitagliptin) tablets
`Janumet (sitagliptin and metformin fixed-dose combination)
`tablets
`Zocor (simvastatin) tablets
`Vytorin (ezetimibe/simvastatin fixed-dose combination) tablets
`Simvastatin orally disintegrating tablets
`Simcor (niacin ER/simvastatin fixed-dose combination) tablets
`
`NDA# 19766
`NDA# 21687
`NDA# 21961
`NDA# 22078
`
`
`IF THE ANSWER TO QUESTION 1 OR 2 UNDER PART II IS "NO," GO DIRECTLY TO THE
`SIGNATURE BLOCKS ON PAGE 8. (Caution: The questions in part II of the summary should
`only be answered “NO” for original approvals of new molecular entities.)
`IF “YES,” GO TO PART III.
`
`
`
`
`Reference ID: 3025433
`
`Page 3
`
`

`

`THREE-YEAR EXCLUSIVITY FOR NDAs AND SUPPLEMENTS
`
`
`
`
`
`YES
`
`
`
`NO
`
`
`
`
`IF "NO," GO DIRECTLY TO THE SIGNATURE BLOCKS ON PAGE 8.
`
`2. A clinical investigation is "essential to the approval" if the Agency could not have approved the
`application or supplement without relying on that investigation. Thus, the investigation is not
`essential to the approval if 1) no clinical investigation is necessary to support the supplement or
`application in light of previously approved applications (i.e., information other than clinical trials,
`such as bioavailability data, would be sufficient to provide a basis for approval as an ANDA or
`505(b)(2) application because of what is already known about a previously approved product), or 2)
`there are published reports of studies (other than those conducted or sponsored by the applicant) or
`other publicly available data that independently would have been sufficient to support approval of
`the application, without reference to the clinical investigation submitted in the application.
`
`
`
`PART III
`
`To qualify for three years of exclusivity, an application or supplement must contain "reports of new
`clinical investigations (other than bioavailability studies) essential to the approval of the application
`and conducted or sponsored by the applicant." This section should be completed only if the answer
`to PART II, Question 1 or 2 was "yes."
`
`
`1. Does the application contain reports of clinical investigations? (The Agency interprets "clinical
`investigations" to mean investigations conducted on humans other than bioavailability studies.) If
`the application contains clinical investigations only by virtue of a right of reference to clinical
`investigations in another application, answer "yes," then skip to question 3(a). If the answer to 3(a)
`is "yes" for any investigation referred to in another application, do not complete remainder of
`summary for that investigation.
`
`(a) In light of previously approved applications, is a clinical investigation (either conducted
`by the applicant or available from some other source, including the published literature)
`necessary to support approval of the application or supplement?
`
`
` YES
`
`
`If "no," state the basis for your conclusion that a clinical trial is not necessary for approval
`AND GO DIRECTLY TO SIGNATURE BLOCK ON PAGE 8:
`
`
`
`NO
`
`
`
`
`
`
`
`(b) Did the applicant submit a list of published studies relevant to the safety and
`effectiveness of this drug product and a statement that the publicly available data would not
`independently support approval of the application?
`
`
` YES
`
`
`
`NO
`
`
`
`
`
`
`(1) If the answer to 2(b) is "yes," do you personally know of any reason to disagree
`with the applicant's conclusion? If not applicable, answer NO.
`
`
`
`Reference ID: 3025433
`
`Page 4
`
`

`

`
`
` If yes, explain:
`
`
`
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`
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`
`
`
` YES
`
`
`
`NO
`
`
`
`
`
`
`(2) If the answer to 2(b) is "no," are you aware of published studies not conducted or
`sponsored by the applicant or other publicly available data that could independently
`demonstrate the safety and effectiveness of this drug product?
`
`
`
`
`
`
` YES
`
`
`
`NO
`
`
`
`
`
`
`
`
` If yes, explain:
`
`
`
`
`
`
`Studies comparing two products with the same ingredient(s) are considered to be bioavailability
`studies for the purpose of this section.
`
`
`3. In addition to being essential, investigations must be "new" to support exclusivity. The agency
`interprets "new clinical investigation" to mean an investigation that 1) has not been relied on by the
`agency to demonstrate the effectiveness of a previously approved drug for any indication and 2) does
`not duplicate the results of another investigation that was relied on by the agency to demonstrate the
`effectiveness of a previously approved drug product, i.e., does not redemonstrate something the
`agency considers to have been demonstrated in an already approved application.
`
`
`(c)
`
`If the answers to (b)(1) and (b)(2) were both "no," identify the clinical
`investigations submitted in the application that are essential to the approval:
`
`
`
`a) For each investigation identified as "essential to the approval," has the investigation been
`relied on by the agency to demonstrate the effectiveness of a previously approved drug
`product? (If the investigation was relied on only to support the safety of a previously
`approved drug, answer "no.")
`
`Investigation #1
`
`Investigation #2
`
`
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`
`
`YES
`
`YES
`
`
`
`
`
`NO
`
`NO
`
`
`
`
`
`If you have answered "yes" for one or more investigations, identify each such investigation
`and the NDA in which each was relied upon:
`
`
`
`
`
`
`
`
`
`
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`
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`
`
`Reference ID: 3025433
`
`Page 5
`
`

`

`
`
`Investigation #1
`
`Investigation #2
`
`
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`
`
`
`
`YES
`
`YES
`
`
`
`
`
`NO
`
`NO
`
`
`
`
`
`
`b) For each investigation identified as "essential to the approval", does the investigation
`duplicate the results of another investigation that was relied on by the agency to support the
`effectiveness of a previously approved drug product?
`
`
`
`
`
`
`
`
`If you have answered "yes" for one or more investigation, identify the NDA in which a
`similar investigation was relied on:
`
`
`
`c) If the answers to 3(a) and 3(b) are no, identify each "new" investigation in the application
`or supplement that is essential to the approval (i.e., the investigations listed in #2(c), less any
`that are not "new"):
`
`
`
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`
`
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`
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`
`
`4. To be eligible for exclusivity, a new investigation that is essential to approval must also have
`been conducted or sponsored by the applicant. An investigation was "conducted or sponsored by"
`the applicant if, before or during the conduct of the investigation, 1) the applicant was the sponsor of
`the IND named in the form FDA 1571 filed with the Agency, or 2) the applicant (or its predecessor
`in interest) provided substantial support for the study. Ordinarily, substantial support will mean
`providing 50 percent or more of the cost of the study.
`
`
`a) For each investigation identified in response to question 3(c): if the investigation was
`carried out under an IND, was the applicant identified on the FDA 1571 as the sponsor?
`
`!
`!
`
`! NO
`! Explain:
`
`
`
`!
`!
`
`! NO
`! Explain:
`
`Investigation #1
`
`
`
`IND #
`
`
`
`
`
`
`
`
`
`YES
`
`
`Investigation #2
`
`
`
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`
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`IND #
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`YES
`
`
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`Reference ID: 3025433
`
`Page 6
`
`

`

`
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`(b) For each investigation not carried out under an IND or for which the applicant was not
`identified as the sponsor, did the applicant certify that it or the applicant's predecessor in
`interest provided substantial support for the study?
`
`
`
`
`
`
`Investigation #1
`
`
`
`
`
`YES
`Explain:
`
`
`
`Investigation #2
`
`
`YES
`Explain:
`
`
`
`
`
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`
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`
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`
`
`
`
`
`
`
`
`
`
`!
`!
`
`! NO
`! Explain:
`
`
`
`!
`!
`
`! NO
`! Explain:
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`(c) Notwithstanding an answer of "yes" to (a) or (b), are there other reasons to believe that
`the applicant should not be credited with having "conducted or sponsored" the study?
`(Purchased studies may not be used as the basis for exclusivity. However, if all rights to the
`drug are purchased (not just studies on the drug), the applicant may be considered to have
`sponsored or conducted the studies sponsored or conducted by its predecessor in interest.)
`
`
`
`
`
`
`YES
`
`
`
`NO
`
`
`
`If yes, explain:
`
`
`
`
`
`
`
`
`=================================================================
`
`Name of person completing form: Raymond Chiang
`Title: Regulatory Project Manager
`Date: 10.6.11
`
`
`Name of Office/Division Director signing form: Dr. Ilan Irony signing on behalf of Dr. Mary Parks
`
`
`
`Reference ID: 3025433
`
`Page 7
`
`

`

`Title: Cross- Discipline Team Leader
`
`
`
`Form OGD-011347; Revised 05/10/2004; formatted 2/15/05
`
`
`
`
`Reference ID: 3025433
`
`Page 8
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`RAYMOND S CHIANG
`10/06/2011
`
`ILAN IRONY
`10/06/2011
`
`Reference ID: 3025433
`
`

`

`
`MK-0431D Tablets
`
`Debarment Certification
`
`As required by §306(k)(1) of 21 U.S.C. 335a(k)(l), we hereby certify‘that, in connection
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
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`
`
`with this application, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
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`(Merck), did not and will not use in any capacity the services of any person debarred '
`
`under subsections 306(a) or (b) ofthe Act.
`
`
`
`
`
`g:
`
`J. Swanson, Ph.D.
`Ric
`
`Senior Director
`
`
`Worldwide Regulatory Afl'airs
`
`Date
`
`
`
`7'} OH |0
`
`
`
`
`MK-O431D Tablets
`
`
`
`
`Restricted 9 Confidential — Limited Access
`
`.
`
`27-Oct-2010
`
`Reference ID: 3028282
`Reference ID: 3028282
`
`

`

`
`
`
`
`
`
`
`
`
`
`
`DEPARTMENT OF HEALTH & HUMAN SERVICES
`
`Public Health Service
`
`Food and Drug Administration
`CDER, Office of New Drug Quality Assessment
`Mail Room 2562
`10903 New Hampshire Ave.
`Silver Spring, Maryland 20993
`(301) 796-1679
`(301) 796-9747 (FAX)
`
`04-OCT-2011
`
`John C. Hill, Ph.D., CMC Reviewer
`
`
`
`Khushboo Sharma, NDA 202-343 file
`
`
`
`MEMORANDUM
`
`DATE:
`
`FROM:
`
`THROUGH: Ali Al-Hakim, Ph.D., Chief, DNDQA III/Branch VII
`
`TO:
`
`SUBJECT: Acceptable EES Inspection status for NDA 20-343
`
`
`
`This memo serves to update the CMC review for NDA 202-343, noting that a final
`overall recommendation of “acceptable” was issued by Compliance (OMPQ) on 04-
`OCT-2011.
`
`Reference ID: 3024647
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`JOHN C HILL
`10/04/2011
`
`ALI H AL HAKIM
`10/04/2011
`
`Reference ID: 3024647
`
`

`

`From:
`To:
`
`cc:
`
`Subject:
`
`Date:
`
`Chiangl Raymond
`
`"Swanson Richard John"'
`
`"carl sparrow@merck.com"; Simoneau, Margaret A;
`
`RE: NDA 19766/5—083 (Zocor), NDA 21687IS-
`041 (Vytorin), and NDA 202343 (Juvisync) labeling comment:
`Thursday, September 29, 2011 2:19:55 PM
`
`Hello Dr. Swanson and Dr. Sparrow,
`
`As per our phone conversation, see the Division's comments below (in black
`font) regarding proposed labeling for NDA 19766/8—083 (Zocor), NDA 21687/8—
`041 (Vytorin), and NDA 202343 (Juvisync).
`
`We disagree with your modification under 5 Warnings and Precautions, 5.1
`
`Myopathlehabdomyolysis.
`
`We agree with your deletion of "including other lipid-lowering medications (other
`fibrates or >= 1 g/day of niacin)" from the HIGHLIGHTS OF PRESCRIBING
`INFORMATION, WARNINGS AND PRECAUTIONS section.
`
`We disagree with your modification to the language under HIGHLIGHTS OF
`PRESCRIBING INFORMATION, DRUG INTERACTIONS section- We will
`
`consider modification of this section upon review of the final study report for
`HPSZ—THRIVE.
`
`If you have any questions, please do not hesitate to call or email.
`
`thanks,
`
`ray and margaret
`
`Reference ID: 3022571
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`RAYMOND S CHIANG
`09/29/2011
`
`Reference ID: 3022571
`
`

`

`-----Original Message-----
`From: Hill, John
`Sent: Wednesday, September 28, 2011 8:17 AM
`To: Chiang, Raymond
`Subject: RE: Revised Carton and Container labeling-- nda202343 SDN17--
`Juvisync (sita + simva FDC)
`
` Ray:
`
`Looks OK to me.
`
`
`John
`-----Original Message-----
`From: Skariah, Sam
`Sent: Monday, September 26, 2011 8:59 PM
`To: Chiang, Raymond
`Cc: Jones, Kendra
`Subject: RE: Revised Carton and Container labeling-- nda202343 SDN17--
`Juvisync (sita + simva FDC)
`
`
`Hi Ray-
`
`No comments from DDMAC.
`
`Thanks!
`
`Sam
`-----Original Message-----
`From: Tobenkin, Anne
`Sent: Monday, September 26, 2011 4:03 PM
`To: Chiang, Raymond; Hill, John; Skariah, Sam; Jones, Kendra
`Cc: Tran, Suong T; Sharma, Khushboo; Merchant, Lubna; Tossa, Margarita;
`Marchick, Julie
`Subject: RE: Revised Carton and Container labeling-- nda202343 SDN17--
`Juvisync (sita + simva FDC)
`
`The revised Juvisync labels have incorporated all our recommendations,
`therefore DMEPA finds them acceptable.
`
`Thanks for sending the revised labels for review prior to approval.
`
`Anne
`
`~~~~~~~~~~~~~~~~~
`Anne Crandall Tobenkin, PharmD
`Safety Evaluator
`DMEPA
`-----Original Message-----
`From: Chiang, Raymond
`Sent: Monday, September 26, 2011 2:23 PM
`To: Tobenkin, Anne; Hill, John; Skariah, Sam; Jones, Kendra
`Cc: Tran, Suong T; Sharma, Khushboo; Merchant, Lubna; Tossa, Margarita;
`Marchick, Julie
`Subject: RE: Revised Carton and Container labeling-- nda202343 SDN17--
`Juvisync (sita + simva FDC)
`
`Reference ID: 3023417
`
`

`

`
`Hi Anne, John, Sam, and Kendra,
`
`See attached pdf file with the carton and container labels for the
`soon-to-be approved Juvisync NDA. This pdf file will be attached to
`the approval letter. As a FYI, these carton and container labels were
`officially submitted by Merck on September 2 and September 20, 2011.
`
`Please review the carton and container labels in the pdf file and
`confirm that they are acceptable.
`Please do not hesitate to contact me if you have any questions.
`
`thanks!
`ray
`
`
`
`Raymond S. Chiang, MPT, MS, MS
`Regulatory Project Manager
`Division of Metabolism & Endocrinology Products
`Center for Drug Evaluation and Research
`Food and Drug Administration
`
`Email: Raymond.Chiang@fda.hhs.gov
`phone: 301-796-1940
`
`
`
`
`
`
`
`
`
`
`
`
`
`_______________________________________________________________________
`_________________________________________________
`
`-----Original Message-----
`From: Chiang, Raymond
`Sent: Monday, September 19, 2011 10:57 AM
`To: Hill, John; Tossa, Margarita; Tobenkin, Anne; Merchant, Lubna
`Cc: Skariah, Sam; Jones, Kendra; Sharma, Khushboo
`Subject: RE: Revised Carton and Container labeling-- nda202343 SDN17--
`Juvisync (sita + simva FDC)
`
`Hi John,
`Thanks for that observation!
`I will relay that to the sponsor.
`Do you have any other comments?
`
`Hello Sam, Anne, and Kendra,
`Before I send this information request, do you have any comments
`regarding these carton and container labels, or do the carton and
`
`Reference ID: 3023417
`
`

`

`container labels look okay. Anne, as a FYI, most of the initial
`comments/information requests regarding these carton and container
`labels, came from your initial labeling review.
`
`thanks,
`ray
`
`
`
`-----Original Message-----
`From: Hill, John
`Sent: Thursday, September 08, 2011 9:00 AM
`To: Chiang, Raymond; Tossa, Margarita; Tobenkin, Anne; Merchant, Lubna
`Cc: Skariah, Sam; Jones, Kendra; Sharma, Khushboo
`Subject: RE: Revised Carton and Container labeling-- nda202343 SDN17--
`Juvisync (sita + simva FDC)
` was looking at the proposed container labeling. It appears that the
`top line of the storage conditions on all of the 30 and 90 count labels
`has been clipped off at the top. I'm not sure if this is an artifact
`or a real issue.
` just wanted to call your attention to this.
`
`John
`
`
`John C. Hill, Ph.D., CAPT. USPHS
`
`
`-----Original Message-----
`From: Chiang, Raymond
`Sent: Thursday, September 08, 2011 8:40 AM
`To: Tossa, Margarita; Tobenkin, Anne; Merchant, Lubna
`Cc: Hill, John; Skariah, Sam; Jones, Kendra; Sharma, Khushboo
`Subject: Revised Carton and Container labeling-- nda202343 SDN17--
`Juvisync (sita + simva FDC)
`
`Hi Rita and Anne,
`
`See revised carton and container labeling incorporating responses to
`requests as per your labeling review dated June 21, 2011. They have
`also incorporated the pending trade name, JUVISYNC.
`
`Please review and advise whether or not Merck has adequately revised
`the carton and container labels, assuming the proprietary tradename
`JUVISYNC is approved of course.
` have also requested Merck submit the revised carton and container
`labels with the established name, in case this NDA is approved... but
`the proprietary trade name is found to be not acceptable.
`
`thanks,
`ray
`
`
`
`
` I
`
` I
`
` I
`
`Reference ID: 3023417
`
`

`

`-----Original Message-----
`From: asr-dontreply@fda.hhs.gov [mailto:asr-dontreply@fda.hhs.gov]
`Sent: Friday, September 02, 2011 5:35 PM
`To: Chiang, Raymond; CDER-OND-DMEP-EDRNOTIFY; CDER-
`EDR_ASR_Document_Coordinators; CDER-EDRSTAFF; CDER-EDRADMIN; CDER ESUB;
`Khalsa, Gurminders J; Livermore, Russell J; Thompson, Douglas L. *;
`CDER-EDRSTAFF
`Subject: Successfully Processed eCTD: nda202343 in DARRTS
`
`Successfully Processed eCTD: nda202343 in DARRTS. Details below:
`
`
`EDR Location: \\CDSESUB1\EVSPROD\NDA202343\202343.enx
`
`For Document Room Staff Use:
` Application Type/Number: nda202343
` Incoming Document Category/Sub Category: Electronic_Gateway
` Supporting Document Number: 17
` eCTD Sequence Number: 0017
` Letter Date: 09/02/2011
` Stamp Date: 9/2/2011
`
` Receipt Date/Time from Notification: 09-02-2011, 15:37:19
` Origination Date/Time from Notification: 09-02-2011, 15:34:02
` DOCUMENT ID: 4924216
`
` 356H Form: \\CDSESUB1\EVSPROD\NDA202343\0017\m1\us\form-356h.pdf
`
` Cover Letter: \\CDSESUB1\EVSPROD\NDA202343\0017\m1\us\cover-
`letter.pdf
`
` 3397 Form: NOT FOUND
`
` 3674 Form: NOT FOUND
`
`
`For EDR Staff Use:
` The submission has already been processed. The following information
` is provided if verification is required. No additional action is
` required on your part
`
` EDR Location: \\CDSESUB1\EVSPROD\NDA202343\0017
` Submission Size: 1789522
` Gateway Location:
`\\chdc9681\cderesub\inbound\ectd\ci1314992041526.243547@llnap22 te
`
`Copy to EDR Status: Good-1
`
`For CDER Project Manager Use:
` The following submission received through the Electronic Submission
`Gateway
` has been processed using the following information. This information
`will be
` updated once Document Room personnel have been able to verify the
`content of the submission.
`
` Application Type/Number: nda202343
`
`Reference ID: 3023417
`
`

`

` Incoming Document Category/Sub Category: Electronic_Gateway
` Supporting Document Number: 17
` eCTD Sequence Number: 0017
` Letter Date: 09/02/2011
`
`
`
`
`
`
`
`Reference ID: 3023417
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`RAYMOND S CHIANG
`09/30/2011
`
`Reference ID: 3023417
`
`

`

`
`
`DEPARTMENT OF HEALTH & HUMAN SERVICES
`
`
`
`
`Public Health Service
`Food and Drug Administration
`Silver Spring, MD 20993
`
`
`
`
`
`
`
`
`
`NDA 202343
`
`PROPRIETARY NAME REQUEST
`CONDITIONALLY ACCEPTABLE
`
`
`Richard J. Swanson, Ph.D.
`Senior Director, Worldwide Regulatory Affairs
`
`Merck Sharp & Dohme Corp.
`P.O. Box 1000, UG2C-50
`Upper Gwynedd, PA 19454-1099
`
`Attention:
`
`
`
`Dear Dr. Swanson:
`
`Please refer to your New Drug Application (NDA) dated December 6, 2010, received December
`7, 2010, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act for
`Sitagliptin and Simvastatin Tablets, 100 mg/10 mg, 100 mg/20 mg and 100 mg/40 mg.
`
`We also refer to your September 2, 2011, correspondence, received September 2, 2011,
`requesting review of your proposed proprietary name, Juvisync. We have completed our review
`of the proposed proprietary name, Juvisync, and have concluded that it is acceptable.
`
`The proposed proprietary name, Juvisync, will be re-reviewed 90 days prior to the approval of
`the NDA. If we find the name unacceptable following the re-review, we will notify you.
`
`If any of the proposed product characteristics as stated in your September 2, 2011, submission
`are altered prior to approval of the marketing application, the proprietary name should be
`resubmitted for review.
`
`If you have any questions regarding the contents of this letter or any other aspects of the
`proprietary name review process, contact Margarita Tossa, Safety Regulatory Project Manager in
`the Office of Surveillance and Epidemiology, at (301) 796-4053. For any other information
`regarding this application contact the Office of New Drugs (OND) Regulatory Project Manager
`Raymond Chiang at (301) 796-1940.
`
`
`Sincerely,
`{See appended electronic signature page}
`
`
`
`
`Carol Holquist, RPh
`Director
`Division of Medication Error Prevention and Analysis
`Office of Medication Error Prevention and Risk Management
`Office of Surveillance and Epidemiology
`
`Reference ID: 3020216
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`CAROL A HOLQUIST
`09/26/2011
`
`Reference ID: 3020216
`
`

`

`From:
`To:
`Subject:
`Date:
`
`Chiang, Raymond
`"Swanson, Richard John";
`RE: NDA 202343 (sitagliptin/simvastatin XR FDC tablets)-- Label
`Monday, September 19, 2011 1:57:26 PM
`
`Hello Dr. Swanson,
`As per our phone conversation, regarding your Medication Guide submitted on
`September 14, 2011, for ease of internal FDA review, please email me your
`revised Medication Guide only (minus the package insert). As a FYI, we will not
`be reviewing your September 14, 2011 MedGuide submission.
`
`thanks,
`ray
`
`
`
`Reference ID: 3016951
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`RAYMOND S CHIANG
`09/19/2011
`
`Reference ID: 3016951
`
`

`

`From:
`To:
`Subject:
`Date:
`
`Chiang, Raymond
`"Swanson, Richard John";
`RE: 202343 labeling response
`Monday, September 19, 2011 8:36:44 AM
`
`Hello Dr. Swanson,
`Regarding your most recent NDA 202343 labeling revisions to the package insert/
`MedGuide. Below (in black font) is our response to your revisions and
`comments.
`
`1. The HbA1c language is class labeling for the statins and is based on the
`results of 2 large meta-analyses - both of which implicate simvastatin.
`
`2. We can consider the use of the term angioedema, rather than serious
`hypersensitivity, for the last paragraph under W and P 5.6, regarding occurrence
`of such events with another DPP-4 inhibitor.
`
`Because of the fast approaching PDUFA date, please provide a response to
`these comments ASAP.
`
`thanks,
`
`ray
`
`Reference ID: 3016629
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`RAYMOND S CHIANG
`09/19/2011
`
`Reference ID: 3016629
`
`

`

`
`
`
`
`
`
`
`
`
`
`
`
`Date:
`From:
`Subject:
`
`
`
`DEPARTMENT OF HEALTH AND HUMAN SERVICES
`Public Health Service
`Food and Drug Administration
`Center for Drug Evaluation and Research
`Memorandum
`
`
`September 12, 2011
`
`Raymond Chiang, Regulatory Project Manager
`
`Tcon: NDA 202343 labeling request to incorporate Supplement Request letter
`of August 11, 2011 for Zocor
`
`
`
`
`
`Dr. Swanson of Merck was told that DMEP discussed further this issue whether or not the Zocor
`label changes (as per our Supplement Request letter of August 11, 2011 for Zocor) should be
`incorporated into the sita + simva FDC PI/MedGuide. DMEP came to the conclusion that these
`label changes should be incorporated into the sita + simva FDC PI/MedGuide for the next round
`of labeling negotiations.
`
`Reference ID: 3013966
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`RAYMOND S CHIANG
`09/13/2011
`
`Reference ID: 3013966
`
`

`

`
`
`
`
`
`
`DEPARTMENT OF HEALTH AND HUMAN SERVICES
`
`
`
`
`
`
`
`Food and Drug Administration
`Silver Spring MD 20993
`
`INFORMATION REQUEST
`
`
`
`NDA 202343
`
`CERTIFIED MAIL
`RETURN RECEIPT REQUESTED
`
`Merck Sharp & Dohme Corp.
`Attention: Richard J. Swanson, Ph.D.
`Senior Director, Regulatory Affairs
`P. O. Box 1000, UG2C-50
`Upper Gwynedd, PA 19454-1099
`
`
`Dear Dr. Swanson:
`
`Please refer to your New Drug Application (NDA) submitted under section 505(b) of the Federal
`Food, Drug, and Cosmetic Act for
` (sitagliptin/simvastatin) Tablets, 100 mg/10 mg, 100
`mg/20 mg, 100 mg/40 mg.
`
`FDA investigators have identified significant violations to the bioavailability and bioequivalence
`requirements of Title 21, Code of Federal Regulation, Part 320 in bioanalytical studies conducted
`by Cetero Research in Houston, Texas (Cetero).1 The pervasiveness and egregious nature of the
`violative practices by Cet