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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-007
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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 December 20, 2007, received
`December 21, 2007, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act for
`PREZISTA (darunavir) 400 mg tablets.
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`We acknowledge receipt of your submissions dated February 28, 2008, March 28, 2008, April 30,
`2008, May 14, 2008, June 13, 2008, July 2, 2008, July 21, 2008, July 31, 2008 and October 15, 2008.
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`This supplemental new drug application was submitted to expand the indication to include the
`treatment of human immunodeficiency virus (HIV) in antiretroviral treatment-naïve adults and to
`include a new dosing regimen, two 400 mg tablets of PREZISTA once a day, co-administered with 100
`mg of ritonavir.
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`We completed our review of this application, as amended. This application is approved, effective on
`the date of this letter, for use as recommended in the agreed-upon labeling text and patient labeling.
`Approval of this supplement and NDA 21-976, supplement 006 fulfills the commitment made under 21
`CFR 314.510, listed as PMC 2 in the June 23, 2006, approval letter:
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`2.
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`By December 31, 2007, submit the final study reports and datasets of the 48 week data for the
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`ongoing Phase 3 studies TMC114-C211 and TMC114-C214.
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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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`We are waiving the pediatric study requirement for ages 0 to below 3 years because of evidence
`strongly suggesting the drug would be unsafe in this pediatric age group. This decision was based on
`the results of juvenile rat toxicology studies that provide evidence of a potential safety risk as a result
`of the drug-brain accumulation.
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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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`June, 2009
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`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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`NDA 21-976/S-007
`Page 2
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`We are deferring submission of your pediatric studies for antiretroviral treatment-naïve pediatric
`subjects 3 to less than 18 years of age for this application because this product is ready for approval for
`use in adults and the pediatric studies have not been completed.
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`Your deferred pediatric studies required by section 505B(2) of the Federal Food and Drug and
`Cosmetic Act 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 Federal Food and
`Drug, and Cosmetic Act. These required studies are listed below.
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`1.
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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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`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 these
`required pediatric postmarketing studies must be clearly designated “Required Pediatric
`Assessments”.
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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-007.”
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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
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`NDA 21-976/S-007
`Page 3
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`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 Newalu, 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.
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`/s/
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`---------------------
`Jeffrey Murray
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`10/21/2008 06:29:52 PM
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