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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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`NDA 022350/S-001 & S-002
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`Food and Drug Administration
`Silver Spring MD 20993
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`SUPPLEMENT APPROVAL
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`Bristol-Myers Squibb Company
`Attention: Pamela J. Smith, M.D.
`Group Director, GRS
`P.O. Box 4000
`Princeton, NJ 08543-4000
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`Dear Dr. Smith:
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`Please refer to your supplemental New Drug Applications (NDAs) dated and received April 19,
`2010, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act (FDCA) for
`Onglyza (saxagliptin) tablets, 2.5 mg and 5 mg.
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`We acknowledge receipt of your amendments dated July 21, August 10, 20, and 24 (2),
`September 16, December 6 and 29, 2010, and January 25, and February 9, 2011.
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`S-001: This “Prior Approval” supplemental new drug application provides for the following
`changes:
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`1. Amends the package insert with results from Study D1680C00001/CV181054 entitled,
`“Double-blind, Active-controlled, Phase III Study with a 52-Week Extension Period to Evaluate
`the Safety and Efficacy of Saxagliptin in Combination with Metformin Compared with
`Sulphonylurea in Combination with Metformin in Adult Patients with Type 2 Diabetes who have
`Inadequate Glycemic Control on Metformin Therapy Alone.”
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`2. Adds a description to the Pharmacokinetics section of the package insert with results from
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`Study CV181067 entitled, “Effect of Saxagliptin on the Pharmacokinetics of the Active Moieties
`of a Combined Oral Contraceptive (COC) Containing Ethinyl Estradiol and Norgestimate in
`Healthy Female Subjects.”
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`3. Amends the Pregnancy section of the package insert based on the results of two nonclinical
`embryofetal studies entitled, “Saxagliptin … and Metformin … : Oral Combination Study of
`Embryo-fetal Development in Rats (II)” and “Saxagliptin … and Metformin … Oral Combination
`Study of Embryo-fetal Development in Rabbits.”
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`S-002: This “Prior Approval” supplemental new drug application amends the package insert with
`results from Study D1680C00007/CV181062 entitled, “A Short-term 12-Week, Multi-centre,
`Randomized, Parallel-group, Double-blind, Placebo-controlled Study to Evaluate the Treatment
`Effect of Saxagliptin compared with Placebo in Adult Patients with Type 2 Diabetes and Renal
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`Reference ID: 2907737
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`

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`NDA 022350/S-001 & S-002
`Page 2
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` Impairment (Moderate, Severe, and End-Stage) with an Additional 40-week, Randomized,
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`Parallel-group, Double-blind, Placebo-controlled Long-term Observational Period (Short-term
`Clinical Study Report).”
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`We have completed our review of these supplemental applications, as amended. They are
`approved, effective on the date of this letter, for use as recommended in the enclosed, agreed-
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`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, 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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`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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`Because none of these criteria apply to your application, you are exempt from this requirement.
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`Reference ID: 2907737
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`

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`NDA 022350/S-001 & S-002
`Page 3
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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
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`Center for Drug Evaluation and Research
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`Division of Drug Marketing, Advertising, and Communications
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`5901-B Ammendale Road
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`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 Division of Drug Marketing, Advertising, and Communications
`(DDMAC), see http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm090142.htm.
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`LETTERS TO HEALTH CARE PROFESSIONALS
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`If you decide to issue a letter communicating important safety-related information about this
`drug product (i.e., a “Dear Health Care Professional” letter), we request that you submit, at least
`24 hours prior to issuing the letter, an electronic copy of the letter to this NDA to the following
`address:
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`MedWatch Program
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`Office of Special Health Issues
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`Food and Drug Administration
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`10903 New Hampshire Ave
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`Building 32, Mail Stop 5353
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`Silver Spring, MD 20993
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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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`Reference ID: 2907737
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`

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`NDA 022350/S-001 & S-002
`Page 4
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`If you have any questions, call Rachel Hartford, Regulatory Project Manager, at (301) 796-0331.
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`Sincerely,
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`{See appended electronic signature page}
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`Mary H. Parks, M.D.
`Director
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`Office of Drug Evaluation II
`Center for Drug Evaluation and Research
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`ENCLOSURE:
`Package Insert
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`Reference ID: 2907737
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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
`02/18/2011
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`Reference ID: 2907737
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