Public Health Service
`Food and Drug Administration
`Rockville, MD 20857
`
`
`
`DEPARTMENT OF HEALTH & HUMAN SERVICES
`
`
`
`
`
`
`NDA 21-368
`
`
`
`Lilly ICOS LLC
`Attention: Catherine Melfi, Ph.D.
`U.S. Regulatory Affairs
`Lilly Research Laboratories
`Lilly Corporate Center
`Indianapolis, IN 46285
`
`
`
`Dear Dr. Melfi:
`
`Please refer to your new drug application dated June 28, 2001, received June 29, 2001, submitted
`under section 505(b) of the Federal Food, Drug, and Cosmetic Act for Cialis® (tadalafil), tablets 5mg,
`10mg and 20mg.
`
`We acknowledge receipt of your submissions dated June 28, July 24, August 27, September 10, 17, 18,
`and 25, October 1, 22, 25, and 30, November 5, and December 6, 2001; January 14 and 23, February 1,
`6, 26, and 28, March 4, 6, 12, 18, 20, 22, and 25, April 1, 4, 5, and 16, May 10 (2), 14, 16, 24, and 30,
`June 6, 13, and 28, August 6, 8, 22, and 26, September 5, 12, 24, and 30, November 15 and 27, 2002,
`February 13, April 16 and 24, May 16, 27, and 30, June 5, 17, 24, and 26, July 15 and 22, August 7,
`11, 19, and 29, September 11, October 9, 14, 15, 20 (2), and 24 (2), and November 5, 11, 12, 17, 19,
`and 20, 2003.
`
`The May 27, 2003 submission constituted a complete response to our April 29, 2002 action letter.
`
`This new drug application provides for the use of Cialis® (tadalafil) tablets for the treatment of erectile
`dysfunction.
`
`We completed our review of this application, as amended. 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,
`text for the patient package insert). 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 21-368.” Approval of this submission by FDA is not required
`before the labeling is used.
`
`
`INTELGENX 1039, pg. 1
`
`

`
`NDA 21-368
`Page 2
`
`We remind you of the postmarketing study commitment you made in a letter dated November 19,
`2003. The commitment is listed below:
`
`
`1. To conduct a randomized, placebo-controlled study investigating the effects of Cialis®
`(tadalafil) tablets on color vision and retinal physiology (electroretinography) following
`multiple daily doses. The timeline is as follows:
`
`
`
`
`Protocol Submission
`
`Study Initiation
`
`Final Report Submission
`
`within 3 months of the date of this letter
`within 10 months of the date of this letter
`within 18 months of the date of this letter
`
`
`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 and two copies of both the promotional materials and the package inserts directly to:
`
`
`
`
`
`
`
`
`
`
`
`Division of Drug Marketing, Advertising,
`and Communications, HFD-42
`Food and Drug Administration
`5600 Fishers Lane
`Rockville, MD 20857
`
`
`
`
`
`
`
`
`
`
`
`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.
`
`If you have any questions, please call Eufrecina DeGuia, Regulatory Health Project Manager at
`(301) 827-4260.
`
`Sincerely,
`
`{See appended electronic signature page}
`
`Florence Houn, M.D., M.P.H.
`Director
`Office of Drug Evaluation III
`Center for Drug Evaluation and Research
`
`
`
`
`
`Enclosures:
` Physician Insert
` Patient Package Insert
`
`INTELGENX 1039, pg. 2
`
`

`
`---------------------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed electronically and
`this page is the manifestation of the electronic signature.
`---------------------------------------------------------------------------------------------------------------------
` /s/
`---------------------
`Florence Houn
`11/21/03 10:33:13 AM
`
`INTELGENX 1039, pg. 3