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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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`Food and Drug Administration
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`Silver Spring MD 20993
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` NDA 021992/S-031
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`SUPPLEMENT APPROVAL
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`Pfizer Inc.
`Attention: Maria A. Pias
`Associate Director, Worldwide Regulatory Strategy
`445 Eastern Point Road
`Groton, CT 06340
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`Dear Ms. Pias:
`
`Please refer to the following Supplemental New Drug Application (sNDA) submitted under
`section 505(b) of the Federal Food, Drug, and Cosmetic Act (FDCA) for Pristiq (desvenlafaxine)
`50 mg, 100 mg Extended-Release Tablets:
`
`
` S-031, dated and received November 15, 2011, a “Prior Approval” supplemental new drug
`application that proposes to update Section 7.7 Potential for Desvenlafaxine to Affect Other
`Drugs, i.e., midazolam, aripiprazole, tamoxifen and organize pharmacokinetic data in forest
`plots, in response to our request dated April 16, 2012.
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`November 2, 2012
`November 30, 2012
`December 5, 2012
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`February 28, 2013
`October 29, 2013
`December 6, 2013
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`We acknowledge receipt of your amendments dated:
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`April 19, 2012
`May 8, 2012
`May 25, 2012
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`We have completed our review of this supplemental application, as amended. It is approved,
`effective on the date of this letter, for use as recommended in the enclosed, agreed-upon labeling
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`text.
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`We note that your May 25, 2012 submission includes final printed labeling (FPL) for your
`package insert and Medication Guide. We have not reviewed this FPL. You are responsible for
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`assuring that the wording in this printed labeling is identical to that of the approved content of
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`labeling in the structured product labeling (SPL) format.
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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
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`Reference ID: 3418879
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`

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`NDA 021992/S-031
`Page 2
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`of labeling must be identical to the enclosed labeling (package insert and Medication Guide),
`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
`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 that includes labeling changes
`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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`FULFILLMENT OF POSTMARKETING REQUIREMENT(S)/COMMITMENT(S)
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`We have received your submission dated August 19, 2013, containing the final report for the
`following postmarketing commitment listed in the February 29, 2008 approval letter.
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`1229-4
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`While it is clear that desvenlafaxine has a qualitatively negative effect on sexual
`function from the adverse events collected during your earlier trials, we do not
`have quantified sexual dysfunction data. You have agreed to assess sexual
`dysfunction in your planned lower dose study. If the lower dose study establishes
`that 50 mg/day is the lowest effective dose, you have agreed to conduct another
`acute, randomized controlled trial with placebo, 50, and 100 mg/day, and employ
`a validated and reliable outcome measure to assess for sexual dysfunction. This
`study could be conducted in parallel with the longer-term efficacy trial, and the
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`results could be submitted approximately 5.5 years from the date of approval for
`this NDA.
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`We have reviewed your submission and conclude that the above commitment was fulfilled.
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`We remind you that the following postmarketing requirements listed in the February 29, 2008,
`and February 14, 2013, approval letters are still open.
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`1229-1
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`Deferred Pediatric Studies Under PREA You have agreed to conduct studies to
`assess the safety and effectiveness of desvenlafaxine succinate as a treatment for
`Major Depressive Disorder in pediatric patients ages 7 to 17 (children and
`adolescents). Both children (ages 7 to 11 years) and adolescents (ages 12 to 17
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`Reference ID: 3418879
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`NDA 021992/S-031
`Page 3
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`years) will be equally represented in the samples, and there will be a reasonable
`distribution of both sexes in these age strata.
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`In reference to the Pediatric Deferral Extension Granted letter, dated March 15,
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`2013, you are reminded that the Final Report Submission is December 29, 2017.
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`Your NDA for desvenlafaxine succinate (DVS) demonstrates the effectiveness of
`doses as low as 50 mg as a treatment for Major Depressive Disorder (MDD),
`however, the available data for effectiveness for this drug in MDD suggests a flat
`dose response curve for efficacy between 50 and 400 mg/day. On the other hand,
`there is a clear dose response for adverse events as the dose increases from 50 to
`400 mg/day. Therefore, there is a need to better understand the lower end of the
`dose response curve to determine if efficacy might be achieved at doses even
`lower than 50 mg/day. You have agreed to conduct and submit the results of a
`randomized controlled study including placebo and DVS doses of 10, 25, and 50
`mg/day as a Postmarketing commitment. This study will assess efficacy in this
`dose range and will also include a validated and reliable outcome measure to
`assess for sexual dysfunction. You have agreed to submit the results of this trial
`no later than 3 years after the date of the approval for this NDA.
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`Deferred pediatric study under PREA for the maintenance treatment of Major
`Depressive Disorder (MDD) in subjects age 7 to 17 years. You have agreed to
`meeting the following milestones:
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`Protocol Submission Date: June 30, 2018
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`Study Completion Date: December 31, 2024
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`Final Report Submission: June 25, 2025
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`Submit final study reports to this NDA. For administrative purposes, all submissions related to
`this pediatric postmarketing study commitment must be clearly designated “Required Pediatric
`Study Commitments”.
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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
`Center for Drug Evaluation and Research
`Office of Prescription Drug Promotion (OPDP)
`5901-B Ammendale Road
`Beltsville, MD 20705-1266
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`1229-2
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`2053-1
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`Reference ID: 3418879
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`

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`NDA 021992/S-031
`Page 4
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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 Office of Prescription Drug Promotion (OPDP), see
`http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm090142.htm.
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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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`If you have any questions, email Juliette Touré, PharmD, Senior Regulatory Project Manager, at
`Juliette.Toure@fda.hhs.gov.
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`Sincerely,
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`{See appended electronic signature page}
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`
`Mitchell V. Mathis, M.D.
`CAPT, USPHS
`Director (acting)
`Division of Psychiatry Products
`Office of Drug Evaluation I
`Center for Drug Evaluation and Research
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`ENCLOSURE:
`Content of Labeling
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`Reference ID: 3418879
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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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`MITCHELL V Mathis
`12/10/2013
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`Reference ID: 3418879
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