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`CENTER FOR DRUG EVALUATION AND
`RESEARCH
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`APPLICATION NUMBER:
`203752Orig1s000
`
`
`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
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`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):
`
`203752/N0000
`
`Minivelle (estradiol transdermal system)
`
`Moderate to Severe Vasomotor Symptoms associated with Menopause
`
`Noven Pharmaceuticals Inc.
`
`Submission Date: 12/29/2011
`PDUFA Due Date: 10/29/2011
`Standard
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`
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`Division of Biometrics 3
`
`Division of Reproductive and Urological Drug Products
`
`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:
`
`Phill H. Price, MD., Clinical Reviewer
`Shelley R. Slaughter, MD., Clinical Team Leader
`Samantha S. Bell
`
`Project Manager:
`
`
`Keywords: NDA review, Bioequivalent
`
`
`
`Reference ID: 3191525
`
`

`

`BACKGROUND
`
`This submission is a 505(b)(1) NDA application in support of Minivelle for the treatment of
`moderate to severe vasomotor symptoms associated with menopause. The sponsor, Noven
`Pharmaceuticals Inc, has the right of reference to Novartis’s Vivelle and Vivelle-Dot approved
`by the Agency under NDA 20-323 and NDA 20-538, respectively.
`
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`
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`According to the meeting minutes dated Oct. 5, 2007 under IND 76,647, the sponsor needed to
`show in vivo bioequivalent (BE) comparing the highest strength of Minivelle and Vivelle.
`
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`CONCLUSION
`
`There was 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: 3191525
`
`2
`
`(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
`09/19/2012
`
`MAHBOOB SOBHAN
`09/21/2012
`
`Reference ID: 3191525
`
`

`

`STATISTICS FILING CHECKLIST FOR A NEW NDA/BLA
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`
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`NDA Number: 203-752/0000
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`Drug Name:
`
`
`
`Stamp Date: 12/29/2011
`
`Applicant: Noven Pharmaceuticals
`Inc.
`NDA/BLA Type: Original/Standard Indication: Moderate to Severe
`Vasomotor Symptoms associated
`with Menopause
`
`
`On initial overview of the NDA/BLA application for RTF:
`
`
`
`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.)
`
`2
`
`3
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`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).
`
`Comments
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`Yes No NA
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`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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`Efficacy and safety
`are referred to
`approved
`Novartis’s Vivelle
`and Vivelle-Dot.
`
`
`
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`Yes No
`
`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: No information is requested at this time.
`
`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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`X
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`File name: 5_Statistics Filing Checklist for a New NDA_203752
`
`Reference ID: 3087314
`
`(b) (4)
`
`

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`STATISTICS FILING CHECKLIST FOR A NEW NDA/BLA
`
`Background:
`
`mm for the treatment of moderate to severe vasomotor
`The sponsor developed
`.
`.
`.
`symptoms assocrated w1th menopause in women.
`
`om)
`
`Therefore, according to the meeting minutes dated Oct. 5, 2007, the
`sponsor only needs to show the following for the approval of
`(am)
`0
`bioequivalent (BE) comparing the highest strength of Vivelle and
`o
`proportional pharmacokinetics of
`(ma) over the dose range of 0.025 to
`0.1 mg/day
`
`lb) (4)
`
`Sponsor’s Efficacy Results: Efficacy and safety are referred to approved Novartis’s
`Vivelle (NDA 20-323) and Vivelle-Dot (NDA 20-538). No efficacy data were provided
`in this submission.
`
`Xin Fang, Ph.D.
`
`Reviewing Statistician
`
`Mahboob Sobhan, Ph.D.
`
`Supervisor/Team Leader
`
`02/14/2012
`
`Date
`
`02/ 14/2012
`
`Date
`
`File name: 5_Statistics Filing Checklist for a New NDA_203752
`
`Reference ID: 3087314
`
`

`

`---------------------------------------------------------------------------------------------------------
`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
`02/14/2012
`
`MAHBOOB SOBHAN
`03/16/2012
`
`Reference ID: 3087314
`
`