`
`
`
`DEPARTMENT OF HEALTH & HUMAN SERVICES
`
`
`
`
`
`Public Health Service
`Food and Drug Administration
`Rockville, MD 20857
`
`
`
`NDA 21-995/S-002, S-003, S-004, S-006
`
`
`Merck & Co., Inc.
`Attention: Steven A. Aurecchia, M.D.
`Director, Regulatory Affairs
`UG2CD-48, P.O. Box 1000
`North Wales, PA 19454-1099
`
`Dear Dr. Aurecchia:
`
`Please refer to your supplemental new drug applications dated December 11, 2006, received
`December 12, 2007 (S-002); dated December 14, 2006, received December 15, 2007 (S-003); dated
`April 18, 2007, received April 19, 2007 (S-004); and dated September 19, 2007, received September
`19, 2007 (S-006), submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act for
`Januvia (sitagliptin) Tablets.
`
`We acknowledge receipt of your submissions dated March 8, April 11, July 31, September 25, and
`October 12, 2007 to S-002, April 13, July 31, and October 12, 2007 to S-003, May 4 and 11, and
`October 12, 2007 to S-004, and October 12, 2007 to S-006.
`
`These supplemental new drug applications provide for:
`
`S-002: Additions to the Package Insert (PI) describing the results of (1) a study of combination therapy
`with a sulfonylurea when the single agent alone does not provide adequate glycemic control and in
`combination therapy with a sulfonylurea plus metformin when dual therapy does not provide adequate
`glycemic control, and (2) a non-inferiority study comparing Januvia to glipizide in patients without
`adequate glycemic control on metformin.
`
`S-003: Additions to the PI describing the results of a study of initial therapy in combination with
`metformin when diet and exercise do not provide adequate glycemic control.
`
`S-004: Additions to the PI and Patient Package Insert (PPI) to include hypersensitivity post-marketing
`adverse reaction data.
`
`S-006: Additions to the PI and PPI to include hypersensitivity as a contraindication.
`
`We have completed our review of these applications, as amended. These applications are approved,
`effective on the date of this letter, for use as recommended in the agreed-upon labeling text and with
`the following minor editorial revisions: (1) removal of the blank line within the Highlights of
`Prescribing Information, and (2) removal of the comma after Warnings and Precautions in the Recent
`Major Changes section of the Highlights of Prescribing Information.
`
`
`

`

`NDA 21-995/S-002, S-003, S-004, S-006
`Page 2
`
`We waive the requirements of 21 CRF 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.
`
`As soon as possible, but no later than 14 days from the date of this letter, please submit the content of
`labeling [21 CFR 314.50(l)] in structured product labeling (SPL) format as described at
`http://www.fda.gov/oc/datacouncil/spl.html that is identical in content to the enclosed labeling (text for
`package insert and text for patient package insert submitted on October 12, 2007. Upon receipt, we
`will transmit that version to the National Library of Medicine for public dissemination. For
`administrative purposes, please designate this submission, “SPL for approved NDA 21-995/S-002, S-
`003, S-004, S-006.”
`
`In addition, submit three copies of the introductory promotional materials that you propose to use for
`this product. Submit all proposed materials in draft or mock-up form, not final print. Send one copy to
`this Division and two copies of both the promotional materials and the package insert directly 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
`
`
`
`
`
`
`
`
`If you issue a letter communicating important information about this drug product (i.e., a “Dear Health
`Care Professional” letter), we request that you submit a copy of the letter to this NDA and a copy to
`the following address:
`
`
`
`
`
`
`
`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 Julie Marchick, Regulatory Project Manager, at (301) 796-1280.
`
`
`MEDWATCH
`Food and Drug Administration
`5515 Security Lane
`HFD-001, Suite 5100
`Rockville, MD 20852
`
`Sincerely,
`
`{See appended electronic signature page}
`
`Mary H. Parks, M.D.
`Director
`Division of Metabolism and Endocrinology Products
`Office of Drug Evaluation
`Center for Drug Evaluation and Research
`
`
`Enclosures: Package Insert, Patient Package Insert
`
`

`

`---------------------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed electronically and
`this page is the manifestation of the electronic signature.
`---------------------------------------------------------------------------------------------------------------------
` /s/
`---------------------
`Mary Parks
`10/12/2007 04:27:06 PM
`
`