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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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`March 11, 2003
`July 28, 2003
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`April 18, 2003
`September 11, 2003
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`NDA 20-717/S-005; S-008
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`Cephalon, Inc.
`Attention: Paul Kirsch
`Senior Director, Regulatory Affairs
`145 Brandywine Parkway
`West Chester, PA 19380
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`Dear Mr. Kirsh:
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`Please refer to your supplemental new drug applications, (S-005 dated August 22, 2001, received
`August 23, 2001; S-008 dated and received on December 20, 2002), submitted under section
`505(b) of the Federal Food, Drug, and Cosmetic Act for Provigil® (modafinil) Tablets, 100 mg
`and 200 mg.
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`We acknowledge receipt of your additional submissions dated:
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`February 26, 2003
`May 14, 2003
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`Your submission of November 21, 2003, constituted a complete response to our October 20,
`2003 action letter.
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`Supplemental new drug application S-005 provides changes to the package insert to clarify
`previously described data and to provide data received from post-marketing studies. The
`following sections are involved: CLINICAL PHARMACOLOGY, CLINICAL TRIALS,
`PRECAUTIONS, ADVERSE REACTIONS, OVERDOSAGE AND HOW SUPPLIED.
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`Supplemental new drug application S-008 provides the use of Provigil (modafinil) Tablets to
`improve wakefulness in two new patient populations with excessive sleepiness: those with
`obstructive sleep apnea/hypopnea syndrome and those with shift work sleep disorder.
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`We have completed our review of these applications, as amended. These applications are
`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).
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`Please submit the FPL electronically 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, in no case more than 30 days after it is printed.
`Please individually mount 15 of the copies on heavy-weight paper or similar material. For
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`NDA 20-717/S-005; S-008
`Page 2
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`administrative purposes, this submission should be designated “FPL for approved supplements
`NDA 20-717/S-005 and S-008.” Approval of this submission by FDA is not required before the
`labeling is used.
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`Pediatric Post Marketing Commitment
`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
`effectiveness of the product in pediatric patients unless this requirement is waived or deferred.
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`For this application, the patient study requirements are listed below by indication:
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`• Shift Work Sleep Disorder
`We are waiving the pediatric study requirement for the treatment of excessive sleepiness
`(ES) associated with shift work sleep disorder.
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`• Obstruction Sleep Apnea/Hypopnea Syndrome (OSAHS)
`We are waiving the pediatric study requirement for the treatment of ES associated with
`OSAHS in pediatric patients less than 3 years of age.
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`We are deferring the pediatric study requirement for the treatment of ES associated with
`OSAHS in pediatric patients, ages 3 years and older, who continue with ES despite
`receiving standard treatment(s) for the underlying obstruction.
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`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
`commitment(s) are listed below.
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`1. Deferred pediatric study under PREA for the treatment of ES associated with OSAHS
`in pediatric patients, ages 3 years and older, who continue with ES despite receiving
`standard treatment(s) for the underlying obstruction.
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`Final Report Submission: February 2009
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`Submit final study reports to this NDA. For administrative purposes, all submissions related to
`this pediatric postmarketing study commitment(s) must be clearly designated “Required Pediatric
`Study Commitments”.
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`Promotional Materials
`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 this division, Division of Neuropharmacological Drug Products, and two copies of
`both the promotional materials and the package insert s directly to:
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`MEDWATCH, HFD-410
`FDA
`5600 Fishers Lane
`Rockville, MD 20857
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`Division of Drug Marketing, Advertising, and Communications, HFD-42
`Food and Drug Administration
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`5600 Fishers Lane
`Rockville, MD 20857
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`NDA 20-717/S-005; S-008
`Page 3
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`“Dear Health Care Professional” Letters
`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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`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 Merril J. Mille, Consumer Safety Officer, at (301) 594-5528.
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`Sincerely,
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`{See appended electronic signature page}
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`Russell G. Katz, M.D.
`Director
`Division of Neuropharmacological Drug Products
`Office of Drug Evaluation I
`Center for Drug Evaluation and Research
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`Enclosure
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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/
`---------------------
`Russell Katz
`1/23/04 06:30:26 PM
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