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`DEPARTMENT OF HEALTH & HUMAN SERVICES
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`Public Health Service
`Food and Drug Administration
`Rockville, MD 20857
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`NDA 21-928
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`Pfizer Inc
`50 Pequot Avenue
`New London, CT 06320
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`Attention: Michael J. Page, B.Sc.
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`Director, Worldwide Regulatory Strategy
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`Worldwide Regulatory Affairs and Quality Assurance
`
`Dear Mr. Page:
`
`Please refer to your new drug application (NDA) dated November 9, 2005, received November 10,
`2005, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act for Chantix®
`(varenicline) 0.5 mg and 1 mg Tablets.
`
`We acknowledge receipt of your submissions dated January 13, February 3, 7, 9, and 13, March 3,
`8, 10, 14(2), 15, 23, 24, 27, 29, and 31, April 7, 11, and 20, and May 1, 4, and 10, 2006.
`
`This new drug application provides for the use of Chantix® (varenicline) 0.5 mg and 1 mg Tablets
`as an aid to smoking cessation treatment.
`
`We have completed our review of this application, as amended, and it is approved, effective on the
`date of this letter, for use as recommended in the agreed-upon labeling text.
`
`The final printed labeling (FPL) must be identical to the enclosed labeling text for the package
`insert and the patient package insert submitted May 10, 2006, and further modified as agreed upon
`in our conversations of that date, and to the immediate container and carton labeling submitted
`April 11, 2006, and modified as documented in your submission of May 10, 2006. Marketing the
`product with FPL that is not identical to the approved labeling text may render the product
`misbranded and an unapproved new drug.
`
`Please submit an electronic version of the FPL according to the guidance for industry titled
`Providing Regulatory Submissions in Electronic Format - NDA. Alternatively, you may submit 20
`paper copies of the FPL as soon as it is available but no more than 30 days after it is printed.
`Individually mount 15 of the copies on heavy-weight paper or similar material. For administrative
`purposes, designate this submission “FPL for approved NDA 21-928.” Approval of this
`submission by FDA is not required before the labeling is used.
`
`All applications for new active ingredients, new dosage forms, new indications, new routes of
`administration, and new dosing regimens are required to contain an assessment of the safety and
`
`

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`NDA 21-928
`Page 2
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`effectiveness of the product in pediatric patients unless this requirement is waived or deferred. We
`are waiving the pediatric study requirement for ages 0 to 11 years and deferring pediatric studies for
`ages 12 through 16 years, inclusive, for this application.
`
`Your deferred pediatric studies required under section 2 of the Pediatric Research Equity Act
`(PREA) are considered required postmarketing study commitments. The status of these
`postmarketing studies shall be reported annually according to 21 CFR 314.81. These commitments
`are listed below.
`
`
`1. To conduct a study to determine the multiple-dose pharmacokinetics of varenicline in
`pediatric patients in order to determine the appropriate doses for efficacy and safety
`evaluations in adolescent smokers, ages 12 through 16, inclusive, to determine the adverse
`event profile in adolescent patients, and to establish whether there is any age group (or
`weight group) for whom varenicline is so poorly tolerated that its utility as an aid to
`smoking cessation treatment should not be evaluated in that group.
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`Final Report Submission:
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`
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`2. To conduct a study to determine whether varenicline, as part of an overall smoking cessation
`program, is effective in achieving and maintaining smoking cessation in tobacco-addicted
`adolescents, ages 12 through 16, inclusive, to determine a safe and effective dose, and to
`document the ability of treating physicians to select appropriate patients. You will need to
`develop a means for determining reliable criteria for appropriate patient selection of
`tobacco-addicted teens so that teenage smokers who are not addicted will not be recruited,
`and so that labeling can convey these criteria to physicians who may wish to use the drug in
`adolescents.
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`by November 10, 2007
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`Final Report Submission:
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`by May 10, 2011
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`We remind you of your postmarketing study commitment in your submission dated May 10, 2006.
`This commitment is listed below.
`
`3. To conduct a prospective epidemiologic cohort study in pregnant women who are
`smokers and who are exposed to varenicline at the time of conception or any time
`during pregnancy. This information will be used to assess the potential risk to the fetus
`and/or live born infant.
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`
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`Protocol Submission:
`Study Start:
`
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`Final Report Submission:
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`by November 10, 2006
`by May 10, 2007
`by May 10, 2011
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`Submit final study reports to this NDA. For administrative purposes, all submissions related to these
`pediatric postmarketing study commitments must be clearly designated “Required Pediatric Study
`Commitments.”
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`

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`NDA 21-928
`Page 3
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`Submit clinical protocols to your IND for this product. Submit all study final reports to this NDA.
`In addition, under 21 CFR 314.81(b)(2)(vii) and 314.81(b)(2)(viii), you should include a status
`summary of each commitment in your annual report to this NDA. The status summary should
`include expected summary completion and final report submission dates, any changes in plans since
`the last annual report, and, for clinical studies, number of patients entered into each study. All
`submissions, including supplements, relating to these postmarketing study commitments must be
`prominently labeled “Postmarketing Study Commitment Protocol,” “Postmarketing Study
`Commitment Final Report,” or “Postmarketing Study Commitment Correspondence.”
`
`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 the Division of Anesthesia, Analgesia, and Rheumatology Products and two copies of both
`the promotional materials and the package inserts 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
`
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`Please submit one market package of the drug product when it is available.
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`---------------------------- - --------- ----------- - --- ---- ---- -------------- ------- --- - - ----- - -- - -- --------
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`------(b)(4)
`---------------------------- ------------ ------- -------------- ------ -------------- ------ ------------------- - - ----- -
`-- ------- - -- - ------- - - - - --- --- -- - - -- - - - --- - ---- - --------- - - ---------- --- --- ---------- ----- ------ -
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`--------------------- --------- - ---- ------ --- - - ---------- ----- - ----- ----------------- - --------------------- ------
`------------------- -------------------------
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` ____________
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` _ ___
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` A
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`____
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` shelf life of 24 months is granted for this drug product packaged in ------ -----------------------------
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`------(b)(4)
` ____
` _ _ _____
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` _____
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` _ ______
` _ _ _ stored at room
`(b)(4)
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`__________
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`We have not completed validation of the regulatory methods. However, we expect your continued
`cooperation to resolve any problems that may be identified.
`
`We remind you that you must comply with reporting requirements for an approved NDA (21 CFR
`314.80 and 314.81).
`
`The MedWatch-to-Manufacturer Program provides manufacturers with copies of serious adverse
`event reports that are received directly by the FDA. New molecular entities and important new
`biologics qualify for inclusion for three years after approval. Your firm is eligible to receive copies
`of reports for this product. To participate in the program, please see the enrollment instructions and
`program description details at www.fda.gov/medwatch/report/mmp.htm.
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`

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`NDA 21-928
`Page 4
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`If you have any questions, call Dominic Chiapperino, Regulatory Project Manager, at (301) 796-
`1183.
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`
`
`Sincerely,
`
`{See appended electronic signature page}
`
`Curtis Rosebraugh, M.D., M.P.H.
`Deputy Director
`Office of Drug Evaluation II
`Center for Drug Evaluation and Research
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`
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`Enclosures
` Package Insert
` Patient Package Insert
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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/
`---------------------
`Curtis Rosebraugh
`5/10/2006 08:57:37 PM
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