`
`CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`APPLICATION NUMBER:
`204654Orig1s000
`
`STATISTICAL REVIEW(S)
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`U.S. Department of Health and Human Services
`Food and Drug Administration
`Center for Drug Evaluation and Research
`Office of Translational Sciences
`Office of Biostatistics
`
`
`S T A T I S T I C A L R E V I E W A N D E VA L U A T I O N
`CLINICAL STUDIES
`
`NDA#:
`Drug Name:
`
`Indication(s):
`Applicant:
`Date(s):
`
`204654/N0000
`
` (norethindrone acetate and ethinyl estradiol chewable tablets, ethinyl
`estradiol chewable tablets and ferrous fumarate tablets)
`Prevention of pregnancy
`
`Warner Chilcott (US),
`
`Submission Date: 09/28/2012
`PDUFA Due Date: 07/28/2013
`Standard
`
`
`
`Division of Biometrics 3
`
`Review Priority:
`
`Biometrics Division:
`Statistical Reviewer:
`Xin Fang, Ph.D., Statistical Reviewer
`Concurring Reviewers: Mahboob Sobhan, Ph.D., Statistical Team Leader
`
`
`Medical Division:
`Clinical Team:
`
`Division of Bone, Reproductive and Urologic Drug Products
`
`Daniel Davis, MD., Clinical Reviewer
`Lisa Soule, MD., Clinical Team Leader
`Pamela Lucarelli
`
`Project Manager:
`
`
`Keywords: Bioavailability, NDA, Review, Clinical Studies
`
`
`Reference ID: 3314704
`
`(b) (4)
`
`

`

`BACKGROUND
`
`The Applicant, Warner Chilcott (US) LLC, submitted a 505(b)(1) NDA application for
` in the prevention of pregnancy. The efficacy and safety data were referred to the
`Applicant’s NDA 022501 for
`
`
`
`The Applicant has developed a new method of administration for low dose oral contraception
`consisting of one mint-flavored, chewable tablet (1 mg norethindrone acetate (NA) and 10 mcg
`ethinyl estradiol (EE)) daily for 24 days followed by one tablet containing 10 mcg EE alone
`daily for 2 days, and one ferrous fumarate tablet daily for 2 days, for a total of 28 days. The
`chewable tablets can be swallowed with liquid.
`
`The Applicant provided comparative bioavailability data and an oral irritation safety report in
`support of this application.
`
`
`CONCLUSION
`
`There were no new efficacy data submitted in support of this submission. Therefore, no
`statistical review was necessary.
`
`
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`
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`Reference ID: 3314704
`
`2
`
`(b) (4)
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`(b
`)
`(4
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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.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`XIN FANG
`05/28/2013
`
`MAHBOOB SOBHAN
`06/04/2013
`
`Reference ID: 3314704
`
`

`

`STATISTICS FILING CHECKLIST FOR A NEW NDA/BLA
`
`
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`NDA Number: 204-654/0000
`
`Applicant: Warner Chilcott (US),
`LLC
`NDA/BLA Type: Original/Standard Indication: Contraceptive
`
`Stamp Date: 09/28/2012
`
`
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`Drug Name:
`
`On initial overview of the NDA/BLA application for RTF:
`
`
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`Content Parameter
`
`1A Paper Submission: Index is sufficient to locate necessary
`reports, tables, data, etc.
`1B Electronic Submission: Indexing and reference links within
`the electronic submission are sufficient to permit navigation
`through the submission, including access to reports, tables,
`data, etc.
`ISS, ISE, and complete study reports are available
`(including original protocols, subsequent amendments, etc.)
`Safety and efficacy were investigated for gender, racial, and
`geriatric subgroups investigated.
`4 Data sets in EDR are accessible and conform to applicable
`guidances (e.g., existence of define.pdf file for data sets).
`
`2
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`3
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`Comments
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`Yes No NA
`X
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`X
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`X
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`X
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`X
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`505(b)(1)
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`Yes No
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`NA Comment
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`IS THE STATISTICAL SECTION OF THE APPLICATION FILEABLE? ___YES_____
`
`Content Parameter (possible review concerns for 74-day
`letter)
`Designs utilized are appropriate for the indications requested.
`Endpoints and methods of analysis are specified in the
`protocols/statistical analysis plans.
`Interim analyses (if present) were pre-specified in the protocol
`and appropriate adjustments in significance level made. DSMB
`meeting minutes and data are available.
`Appropriate references for novel statistical methodology (if
`present) are included.
`Safety data organized to permit analyses across clinical trials in
`the NDA/BLA.
`Investigation of effect of dropouts on statistical analyses as
`described by applicant appears adequate.
`
`Information requests for the Applicant: None at this time.
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`X
`X
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`X
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`X
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`X
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`X
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`File name: 5_Statistics Filing Checklist for a New NDA_204654
`
`Reference ID: 3214291
`
`(b) (4)
`
`

`

`STATISTICS FILING CHECKLIST FOR A NEW NDA/BLA
`
`
`
`
`
`
`
`
`
`
`
`
`
`11/05/2012
`Date
`
`11/05/2012
`Date
`
`
`Background:
`
`The sponsor, Warner Chilcott (US) LLC, submitted a 505(b)(1) NDA application for
`in the treatment of prevention of pregnancy. The efficacy and safety are
`referred to the sponsor’s NDA 022501 for
`
`
`
`The sponsor has developed a new method of administration for low dose oral
`contraception consisting of one mint-flavored, chewable tablet (1 mg norethindrone
`acetate (NA) and 10 mcg ethinyl estradiol (EE)) daily for 24 days followed by one tablet
`containing 10 mcg EE alone daily for 2 days, and one ferrous fumarate tablet daily for 2
`days, for a total of 28 days. The chewable tablets can be swallowed with liquid.
`
`In this submission, the sponsor provides comparative bioavailability data in support of
`this application. No new efficacy data were submitted. Statistical review is not needed at
`this time.
`
`
`
`
`Xin Fang, Ph.D.
`Reviewing Statistician
`
`Mahboob Sobhan, Ph.D.
`Supervisor/Team Leader
`
`
`
`
`
`
`
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`
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`File name: 5_Statistics Filing Checklist for a New NDA_204654
`
`Reference ID: 3214291
`
`(b) (4)
`
`(b
`)
`(4
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`XIN FANG
`11/08/2012
`
`MAHBOOB SOBHAN
`11/09/2012
`
`Reference ID: 3214291
`
`