DEPARTMENT OF HEALTH & HUMAN SERVICES
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`Public Health Service
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`Food and Drug Administration
`Rockville MD 20857
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`NDA 21-688
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`Amgen Inc.
`Attention: Pamela Danagher
`Manager, Regulatory Affairs
`One Amgen Center Drive
`Thousand Oaks, CA 91320-1799
`
`Dear Ms. Danagher:
`
`Please refer to your new drug application (NDA) dated September 5, 2003, received
`September 8, 2003, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act
`for Sensipar (cinacalcet HCl) Tablets.
`
`We acknowledge receipt of your submissions dated August 14, October 8, and December 1, 3, 12,
`and 24, 2003, and January 12, 21, and 22, February 3, 5, 6, 11, 13, 20, and 26, and
`March 3 and 5, 2004.
`
`This new drug application provides for the use of Sensipar (cinacalcet HCl) Tablets for the
`treatment of secondary hyperparathyroidism in patients with chronic kidney disease on dialysis, and
`the treatment of hypercalcemia in patients with parathyroid carcinoma.
`
`This new drug application also provides for the use of Sensipar (cinacalcet HCl) Tablets for the
`(b)(4)----------------------------------------------------------------------------------------------------------------
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`(b)(4)- These two indications have been administratively unbundled from the original NDA. The
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`-W
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`e have completed the review of this application, as amended, and have concluded that adequate
`information has been presented to demonstrate that the drug product is safe and effective for use as
`recommended in the agreed-upon labeling text. Accordingly, the application is approved effective
`on the date of this letter. However,(b)(4)------------------------------------------------are approvable,
`and the deficiencies will be address---------------------------
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`Sufficient stability data have been submitted to support a 18-month expiration date for tablets
`packaged in blister packages, and a 24-month expiration date for tablets packaged in bottles.
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`The final printed labeling (FPL) must be identical to the submitted draft labeling (package insert
`submitted March 5, 2004, carton and container label submitted February 26, 2004). Marketing
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`NDA 21-688
`Page 2
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`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 copies of final printed labeling (FPL) electronically according to the guidance for
`industry titled Providing Regulatory Submissions in Electronic Format - NDA (January 1999).
`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. Please individually mount ten of the copies on heavy-weight
`paper or similar material. For administrative purposes, this submission should be designated
`"FPL for approved NDA 21-688." Approval of this submission by FDA is not required before
`the labeling is used.
`
`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.
`We are waiving the pediatric study requirement for this application.
`
`We remind you of your postmarketing study commitments in your submission dated
`March 3, 2004. These commitments are listed below.
`
`
`1. To conduct a drug interaction study in healthy volunteers with a preferred CYP2D6
`substrate such as desipramine (J Clin Pharmacol 2003;43:443) to address cinacalcet’s inhibition
`potential on CYP2D6.
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`
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`Protocol Submission:
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`Study Start:
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`Final Report Submission:
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`By July 2004
`By August 2004
`By March 2005
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`2. To conduct an in vitro drug metabolic enzymes induction study for cinacalcet in human
`liver cells.
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`
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`Protocol Submission:
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`Study Start:
`
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`Final Report Submission:
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`By April 2004
`By May 2004
`By September 2004
`
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`Submit clinical protocols to your IND for this product. Submit nonclinical and chemistry,
`manufacturing, and controls protocols and all study reports to this NDA. In addition, under 21
`CFR 314.81(b)(2)(vii) and 314.81(b)(2)(viii), you should include a status summary of each
`commitment in your annual report to this NDA. The status summary should include expected
`summary completion and final report submission dates, any changes in plans since the last
`annual report, and, for clinical studies, the number of patients entered into each study. All
`submissions, including supplements, relating to these postmarketing study commitments should
`be prominently labeled "Postmarketing Study Protocol," "Postmarketing Study Final
`Report," or "Postmarketing Study Correspondence."
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`NDA 21-688
`Page 3
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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 Metabolic and Endocrine Drug Products and two copies of both
`the promotional materials and the package insert directly to:
`
`
`Division of Drug Marketing, Advertising, and Communications, HFD-42
`Food and Drug Administration
`5600 Fishers Lane
`Rockville, Maryland 20857
`
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`We have not completed validation of the regulatory methods. However, we expect your
`continued cooperation to resolve any problems that may be identified.
`
`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.
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`If you have any questions, call Randy Hedin, R.Ph., Senior Regulatory Management Officer, at
`(301) 827-6392.
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`Enclosure
`
`
`Sincerely,
`
`{See appended electronic signature page}
`
`Robert Meyer, M.D.
`Director
`Office of Drug Evaluation II
`Center for Drug Evaluation and Research
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`

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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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`Robert Meyer
`3/8/04 03:46:30 PM
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