`
`
`
`DEPARTMENT OF HEALTH & HUMAN SERVICES
`
`
`
`
`
`Public Health Service
`Food and Drug Administration
`Rockville, MD 20857
`
`
`
`NDA 22-044/S-003 and S-004
`
`
`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 April 27, 2007, received April 27, 2007
`(S-003); and dated May 11, 2007, received May 11, 2008 (S-004), submitted under section 505(b) of
`the Federal Food, Drug, and Cosmetic Act for Janumet (sitagliptin/metformin hydrochloride fixed-
`dose combination) Tablets.
`
`We acknowledge receipt of your submissions dated August 24, 2007, January 22, and February 25,
`2008, to S-003 and dated August 27, 2007, January 22, and February 25, 2008 to S-004.
`
`These supplemental new drug applications provide for:
`
`S-003: Additions to the Package Insert (PI) describing the results of a study of sitagliptin and
`metformin co-administration in patients with inadequate glycemic control on diet and exercise alone.
`
`S-004: Additions to the PI describing the results of (1) a study of sitagliptin add-on therapy in patients
`with inadequate glycemic control on metformin and glimepiride, and (2) a non-inferiority study
`comparing sitagliptin add-on therapy to glipizide add-on therapy in patients with inadequate glycemic
`control on metformin.
`
`Also, in response to our supplement request letter dated November 21, 2007, changes were made to the
`Indications and Usage section, and a statement regarding macrovascular outcome data was added to
`the Warning and Precautions section of the PI. Revisions were made to the Patient Package Insert
`(PPI).
`
`We 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) changing the dates in the Highlights section of the PI from
`“XX/200X” to “2/2008” and (2) revising the date at the end of the PPI from “Month 200X” to
`“February 2008”.
`
`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 February 25, 2008. Upon receipt, we
`
`

`

`NDA 22-044/S-003 and S-004
`Page 2
`
`will transmit that version to the National Library of Medicine for public dissemination. For
`administrative purposes, please designate this submission, “SPL for approved NDA 22-044/S-003, S-
`004.”
`
`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
`
`MEDWATCH
`Food and Drug Administration
`5515 Security Lane
`
`
`HFD-001, Suite 5100
`Rockville, MD 20852
`
`
`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.
`
`
`
`
`
`
`
`
`
`
`
`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
`2/26/2008 04:35:45 PM
`
`