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` DEPARTMENT OF HEALTH & HUMAN SERVICES
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`Public Health Service
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`Food and Drug Administration
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`Rockville, MD 20857
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`NDA 21-976/S-009
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`Tibotec, Incorporated
`Attention: Susan Fiordeliso
`Manager, Global Regulatory Affairs
`1020 Stony Hill Road, Suite 300
`Yardley, PA 19067
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`Dear Ms Fiordeliso:
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`Please refer to your supplemental new drug application dated and received June 20, 2008, submitted
`under section 505(b) of the Federal Food, Drug, and Cosmetic Act for PREZISTA (darunavir) 75 mg
`and 150 mg tablets.
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`We acknowledge receipt of your submissions dated July 18, 2008, August 8, 2008, August 11, 2008,
`September 12, 2008, September 18, 2008, October 8, 2008, October 15, 2008, November 6, 2008,
`November 10, 2008, November 21, 2008, and December 17, 2008.
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`This supplemental new drug application was submitted to provide dosing recommendations for human
`immunodeficiency virus (HIV-1) infected pediatric patients 6 to less than 18 years of age and to
`include two new dosage strengths, 75 mg and 150 mg tablets.
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`We completed our review of this application, as amended. This application is approved, effective on
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`the date of this letter, for use as recommended in the agreed-upon labeling text.
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`Approval of this supplement fulfills the following postmarketing commitment as numbered in the
`June 23, 2006, approval letter. This commitment is listed below:
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`3.
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`Please assess the pharmacokinetics, safety, tolerability and antiviral activity of two alternative
`doses of a suitable pediatric formulation in combination with ritonavir, in treatment-
`experienced pediatric children and adolescents between 6 and 17 years of age.
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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 in pediatric patients unless this requirement is waived, deferred, or inapplicable.
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`We are waiving the pediatric study requirement for ages 0 to below 3 years of age because of evidence
`strongly suggesting the drug would be unsafe in this pediatric age group. This decision is based on the
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`(b) (4)
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`NDA 21-976/S-009
`Page 2
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`results of juvenile rat toxicology studies that provide evidence of a potential safety risk as a result of
`overt toxicity in this age group and evidence of potential drug accumulation in brain tissue.
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`Your deferred pediatric studies required by section 505B(a) of the Federal Food and Drug and
`Cosmetic Act (FDCA) are required postmarketing studies. The status of these postmarketing studies
`must be reported annually according to 21 CFR 314.81 and section 505B(a)(3)(B) of the FDCA. We
`remind you of the deferred pediatric studies as listed in the October 21, 2008, approval letters for NDA
`21-976/006 and NDA 21-976/007, respectively.
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`1.
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`Deferred pediatric study under PREA for the treatment of HIV-1 infection in pediatric
`subjects 3 to 6 years of age. Please evaluate dose requirements and safety in treatment-
`experienced pediatric patients 3 to 6 years of age with HIV-1 infection after preliminary review
`of data from the 6 to 17 year olds in trial TMC114-C212 with the Division of Antiviral
`Products (DAVP).
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`Protocol Submission:
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`Final Report Submission:
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`December 31, 2008
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`June 30, 2011
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`Deferred pediatric study under PREA for the treatment of HIV-1 infection in treatment-naïve
`pediatric subjects from 12 to <18 years of age. Conduct a pediatric safety and activity study of
`darunavir, in combination with ritonavir, in the treatment-naïve population with activity based
`on the results of virologic response over at least 24 weeks of dosing and safety monitored over
`48 weeks.
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`Submission of final protocol:
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`Submission of final study report:
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`June, 2009
`July, 2012
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`Deferred pediatric study under PREA for the treatment of HIV-1 infection in treatment-naïve
`pediatric subjects from 3 to <12 years of age. Conduct a pediatric safety and activity study of
`darunavir, in combination with ritonavir, in the treatment-naïve population with activity based
`on the results of virologic response over at least 24 weeks of dosing and safety over 48 weeks.
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`1.
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`2.
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`Submission of final protocol:
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`Submission of final study report:
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`March, 2011
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`March, 2015
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`Submit final study reports to this NDA. For administrative purposes, all submissions related to this
`required pediatric postmarketing study must be clearly designated “Required Pediatric
`Assessment(s)”.
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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, please submit the content of
`labeling [21 CFR 314.50(1)] in structured product labeling (SPL) format as described at
`http://www.fda.gov/oc/datacouncil/spl/html that is identical to the enclosed labeling (text for the
`package insert and text for the patient package insert). 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 21-976/S-009.”
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`NDA 21-976/S-009
`Page 3
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`In addition, within 21 days of the date of this letter, amend any pending applications for this NDA with
`content of labeling in structures product labeling (SPL) format to include the changes approved in this
`application.
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`Marketing the product with FPL that is not identical to the approved labeling text and in the required
`format may render the product misbranded and an unapproved new drug.
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`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 Antiviral Products and two copies of both the promotional materials and the package
`insert directly to:
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`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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`LETTERS TO HEALTH CARE PROFESSIONALS
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`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:
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`MEDWATCH
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`Food and Drug Administration
`Suite 12B05
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`5600 Fishers Lane
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`Rockville, MD 20857
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`Please submit one market package of the drug product when it is available.
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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, call Stacy Powers Newalu M.P.H., Regulatory Project Manager, at (301)
`796-3978.
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`Sincerely,
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`{See appended electronic signature page}
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`Debra Birnkrant, M.D.
`Director
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`Division of Antiviral Products
`Office of Antimicrobial Products
`Center for Drug Evaluation and Research
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`Enclosure (clean copy of approved labels)
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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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`---------------------
`Jeffrey Murray
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`12/18/2008 04:22:54 PM
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