CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`
`APPLICATION NUMBER:
`
`201281Orig1s000
`
`
`SUMMARY REVIEW
`
`
`
`

`

`Cross Discipline Team Leader Review
`
`Cross-Discipline Team Leader Review
`
`
`Date
`January 26, 2012
`From
`Jean-Marc Guettier, M.D.
`m_ Cross-Disci line Team Leader Review
`NDA/BLA #
`201281/ Resubmission-Class 1
`
`Su lement#
`
`Boehrin . er In . elheim Phalmaceuticals, Inc.
`
`November 19", 2011
`Date of Submission
`Janua
`30 , 2012
`PDUFA Goal Date
`——
`Jentadueto®l
`Proprietary Name /
`Established (USAN) names
`
`Linagliptin and metformin hydrochloride fixed dose
`combination
`
`diabetes mellitus
`
`Dosage forms / Strength
`
`Oral tablets with the following dosage strengths:
`Linagliptin 2.5 mg / metformin 500 mg
`Linagliptin 2.5 mg / metformin 850 mg
`
`Linagliptin 2.5 mg / metformin 1000 mg
`To improve glycemic control in adults patients with type 2
`
`Proposed Indication(s)
`
`Page 1 of 3
`
`Reference ID: 3077349
`
`

`

`Cross Discipline Team Leader Review
`
`1. Introduction
`
`Boehringer Ingelheim Pharmaceuticals, Inc. is resubmitting (class-1 resubmission) the New
`Drug Application #201281 under section 505(b)(2) of the Federal Food, Drug and Cosmetic
`Act for the fixed-dose combination product linagliptin /metformin hydrochloride. The
`reference listed drug is the US approved Glucophage (metformin). The applicant was issued a
`complete response on November 16th 2011 due to deficiencies noted at a facility
`
` used for the testing of metformin hydrochloride and excipients
`contained in the final drug product. The applicant was informed that satisfactory resolution of
`these deficiencies would be needed before the product could be approved. To resolve this
`deficiency the applicant notifies the Agency that the
`
`testing facility has been removed, that the testing of metformin hydrochloride will be
`performed by Boehringer Ingelheim Pharma GmbH & Co. KG (Ingelheim, Germany) and that
`the testing of excipients will be performed by
`
`
`
`for
`information
`limited new safety
`that only
`the applicant states
`In addition,
`linagliptin/metformin FDC has been received since submission of the four-month safety
`update data and that these new data do not reveal significant changes or findings relevant to
`the safety profile of the product. The product is not currently marketed outside of the US.
`There are no clinical data in this resubmission.
`2. Background
`
`All disciplines, with the exception of CMC, involved in the first review cycle (January 19th
`2011-November 19th 2011) recommended approval of the NDA. Refer to Dr. Irony’s October
`15th 2011 CDTL memo for details.
`3. CMC/Device
`
`The Office of Manufacturing & Product Quality (OMPQ) has determined that the new
`facilities employed to manufacture and test the drug substances and drug product are
`acceptable. Chemistry and OMPQ recommend approval.
`4. Nonclinical Pharmacology/Toxicology
`No new information. Refer to Dr. Irony’s CDTL memo.
`5. Clinical Pharmacology/Biopharmaceutics
`No new information. Refer to Dr. Irony’s CDTL memo.
`6. Clinical Microbiology
`No new information. Refer to Dr. Irony’s CDTL memo.
`
`Page 2 of 3
`
`Reference ID: 3077349
`
`2
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`

`

`Cross Discipline Team Leader Review
`
`7. Clinical/Statistical- Efficacy
`No new information. Refer to Dr. Irony’s CDTL memo.
`8. Safety
`No new information. Refer to Dr. Irony’s CDTL memo.
`9. Advisory Committee Meeting
`No new information. Refer to Dr. Irony’s CDTL memo.
`10.
`Pediatrics
`No new information. Refer to Dr. Irony’s CDTL memo.
`11.
`Other Relevant Regulatory Issues
`No new information. Refer to Dr. Irony’s CDTL memo.
`12.
`Labeling
`Jentadueto has been conditionally approved as the proprietary trade name by the Division of
`Medication Error Prevention and Analysis. Labeling discussion around the pregnancy
`category for metformin occurred during the last review cycle. From these discussions and
`review of the clinical experience with metformin published in the literature it was determined
`that metformin should be designated as a Pregnancy Category B drug and that language to
`summarize the nonclinical findings be included in section 8.1 of the label. This pregnancy
`category is consistent with other approved metformin labels. Refer to Dr. Irony’s CDTL
`memo for details. Minor editing changes to the label were sent to the sponsor at the time this
`memorandum was written.
`13.
`Recommendations/Risk Benefit Assessment
`
`• Recommended Regulatory Action
`APPROVAL
`• Risk Benefit Assessment
`Refer to Dr. Irony’s CDTL memo.
`• Recommendation for Postmarketing Risk Evaluation and Management Strategies
`No new safety findings to trigger the need for REMS
`• Recommendation for other Postmarketing Requirements and Commitments
`No new safety findings to trigger the need for Postmarketing Requirements and
`Commitments
`• Recommended Comments to Applicant
`None
`
`Page 3 of 3
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`Reference ID: 3077349
`
`3
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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/
`----------------------------------------------------
`JEAN-MARC P GUETTIER
`01/26/2012
`
`MARY H PARKS
`01/26/2012
`concur
`
`Reference ID: 3077349
`
`