CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`
`
`
`APPLICATION NUMBER:
`
`ADMINISTRATIVE and CORRESPONDENCE
`DOCUMENTS
`
`
`
`
`
`
`
`
` 22-024
`
`

`

`Department of Health and Human Services
`Food and Drug Administration
`
`PATENT INFORMATION SUBMITTED UPON AND
`AFTER APPROVAL OF AN NDA OR SUPPLEMENT
`
`Form Approved: OMB No. 0910-0513
`Expiration Date: 7/31/10
`See OMB Statement on Page 3.
`
`NDA NUMBER
`
`For Each Patent That Claims a Drug Substance
`(Active Ingredient), Drug Product (FormulafiOn Ol’
`Composition) and/or Method of Use
`
`NAME OF APPLICANT/NDA HOLDER
`Takeda Global Research & Development Center, Inc.
`
`The following is provided'In accordance with Section 505(b) and (c) of the Federal Food, Drug, and Cosmetic Act.
`TRADE NAME
`
`ACTIVE INGREDIENT(S
`
`Pioglitazone Hydrochlo)ride/Metformin Hydrochloride
`
`STRENGTH(S
`
`15 mg/iOOO)mg and 30 mg/lOOOmg
`
`DOSAGE FORM
`
`APPROVAL DATE OF NDA OR SUPPLEMENT
`
`Fixed dose combination extended release tablets
`
`5/12/2009
`
`This patent declaration form is required to be submitted to the Food and Drug Administration (FDA) within thirty (30) days after
`approval Of an NDA or supplement or within thirty (30) days Of issuance of a patent as required by 21 CFR 314.53(c)(2)(ii) at the
`address provided in 21 CFR 314.53(d)(4). TO expedite review Of this patent declaration form, you may submit an additional copy of
`this declaration form to the Center for Drug Evaluation and Research "Orange Book" staff.
`
`For hand-written or typewriter versions of this report: If additional space is required for any narrative answer (i.e., one that does
`not require a "Yes" or "No" response), please attach an additional page referencing the question number.
`
`FDA will not list patent information if you file an incomplete patent declaration or the patent declaration indicates the patent
`is not eligible for listing.
`
`For each patent submitted for the approved NDA or supplement referenced above, you must submit all the information
`described below. If you are not submitting any patents for this NDA or supplement, complete above section and sections 5
`and 6.
`
`b. Issue Date of Patent
`8/18/1987
`
`0. Expiration Date of Patent
`1/17/2011
`
`Address (of Patent Owner)
`
`1'1 Doshomachi 4-Chome
`City/State
`
`ChuO-Ku, Osaka, 540-8645 Japan
`
`
`
`‘ FAX Number (ifavailable)
`
`ZIP Code
`
`Telephone Number
`
`E-Mail Address (if available)
`Tel. no. 81 6 6204 2111
`
`
`
`1. GENERAL
`
`a. United States Patent Number
`4,687,777
`
`d. Name of Patent Owner
`
`Takeda Pharmaceutical Company Limited
`
`e. Name of agent or representative who resides or main-
`tains a place Of business within theUnited States author-
`Ized to recere name of patent certIfIcatIon under sectlon
`505(b)(3) and (j)(2)(B) of the Federal Food, Drug, and
`Cosmetic Act and 21 CFR 314.52 and 314.95 (if patent
`owner or NDA applicant/holder does not reside or have a
`place of business within the United States)
`I}? Takeda Global Research & Development Center, Inc.
`
`f.
`
`
`
`Address (ofagent or representative named in 1.e.)
`One Takeda Parkway
`
`,
`CIty/State
`Deerfield, IlinOiS
`ZIP Code
`60015
`Telephone Number
`(847) 582-5780
`Is the patent referenced above a patent that has been submitted previously for the
`approved NDA or supplement referenced above?
`
`
`
`FAX Number (ifavai/able)
`(224) 554-7870
`E-Mail Address (if available)
`
`g.
`
`If the patent referenced above has been submitted previously for listing, is the expiration
`date a new expiration date?
`
`FORM FDA 3542 (7/07)
`
`Page 1
`l’SC Graplucs (101) 443—1090
`131’
`
`

`

`For the patent referenced above, provide the following information on each patent that claims the drug substance, drug
`product, or method of use that is the subject of the approved MBA or supplement. FDA will not list patent information if
`you file an incomplete patent declaration or the patent declaration indicates the patent is not eligible for listing. FDA will
`consider an incomplete patent declaration to be a declaration that does not include a response to all the questions
`contained within each section below applicable to the patent referenced above.
`
`2. Drug Substance (Active Ingredient)
`2.1 Does the patent claim the drug substance that is the active ingredient in the drug product
`described in the approved NDA or supplement?
`
`'
`
`2.2 Does the patent claim a drug substance that is a different polymorph of the active
`ingredient described in the NBA?
`
`m Yes
`
`E] No
`
`[:1 Yes
`
`[2] No
`
`2.3 If the answer to question 2.2 is "Yes," do you certify that, as of the date of this declaration, you have test data
`demonstrating that a drug product containing the polymorph will perform the same as the drug product
`described in the NDA? The type of test data required is described at 21 CFR 314.53(b).
`
`I: Yes
`
`[:1 No
`
`2.4 Specify the polymorphic form(s) claimed by the patent for which you have the test results described in 2.3.
`
`2.5 Does the patent claim only a metabolite of the approved active ingredient? (Complete the information in
`section 4 below if the patent claims an approved method of using the approved drug product to administer the
`metabolite.)
`
`I] Yes
`
`[2| No
`
`2.6 Does the patent claim only an intermediate?
`
`
`
`2.7 If the patent referenced in 2.1 is a product-by-process patent, is the product claimed in the
`patent novel? (An answer is required only if the patent is a product-by-process patent.)
`
`FDA will not list the patent in the Orange Book as claiming the drug substance if:
`0 the answers to 2.1 and 2.2 are "No," or,
`the answer to 2.2 is "Yes" and the answer to 2.3 is "No," or,
`the answer to 2.3 is "Yes" and there is no response to 2.4, or,
`the answer to 2.5 or 2.6 is "Yes."
`the answer to 2.7 is "No."
`
`3. Drug Product (Composition/Formulation)
`3.1 Does the patent claim the approved drug product as defined in 21 CFR 314.3?
`
`'
`
`3.2 Does the patent claim only an intermediate?
`
`3.3 If the patent referenced in 3.1 is a product-by-process patent, is the product claimed in the
`patent novel? (An answer is required only if the patent is a product-by-process patent.)
`
`FDA will not list the patent in the Orange Book as claiming the drug product if:
`0 the answer to question 3.1 is "No," or,
`0 the answer to question 3.2 is "Yes," or,
`0 the answer to question 3.3 is "No."
`
`4. Method of Use
`
`[:I Yes
`
`No
`
`[I Yes
`
`M No
`
`Sponsors must submit the information in section 4 for each approved method of using the approved drug product claimed by the patent.
`For each approved method of use claimed by the patent, provide the following information:
`
`4.1 Does the patent claim one or more approved methods of using the approved drug product?
`
`CI Yes
`
`No
`
`4.2 Patent Claim Number(s) (as listed in the patent)
`
`Does (Do) the patent claim(s) referenced in 4.2 claim an
`approved method of use of the approved drug product?
`
`[I Yes
`
`El No
`
`4.2a If the answer to 4.2 is
`"Yes," identify the use
`with specific reference to
`the approved labeling for
`the drug product.
`
`Use: (Submit indication or method of use information as identified specifically in the approved labeling.)
`
`FORM FDA 3542 (7/07)
`
`Page 2
`
`

`

`4.2b If the answer to 4.2 is
`"Yes," also provide the
`information on the
`indication or method of
`use for the Orange Book
`"Use Code" description.
`
`Use: (Submit the description of the approved indication or method of use that you propose FDA include as
`the "Use Code" in the Orange Book, using no more than 240 total characters including spaces.)
`
`FDA will not list the patent in the Orange Book as claiming the method of use if:
`0 the answer to question 4.1 or 4.2 is "No," or
`
`0 if the answer to 4.2 is "Yes" and the information requested in 4.2a and 4.2b is not provided in full.
`
`5. No Relevant Patents
`
`For this NDA or supplement, there are no relevant patents that claim the approved drug substance (active
`ingredient) or the approved drug product (formulation or composition) or approved method(s) of use with
`respect to which a claim of patent infringement could reasonably be asserted if a person not licensed by the
`owner of the patent engaged in the manufacture, use, or sale of the drug product.
`
`
`
`6. Declaration Certification
`
`,
`
`,
`
`5-1 The undersigned declares that this is an accurate and complete submission of patent information for the NDA or
`supplement approved under section 505 of the Federal Food, Drug, and Cosmetic Act. This time-sensitive patent
`information is submitted pursuant to 21 CFR 314.53. I attest that I am familiar with 21 CFR 314.53 and this submission
`complies with the requirements of the regulation. I verify under penalty of perjury that the foregoing is true and
`correct.
`
`Warning: A willfully and knowingly false statement is a criminal offense under 18 U.S. C. 1001.
`
`6.2 Authorized Signature of NDA Applicant/Holder or Patent Owner (Attorney, Agent, Representative or
`
`Date Signed
`
`ial) (Provide Informationbelow)
`otherAuthorized I
`/ <3" fliZe/j/D >WZM
`
`{/fl? 6’7
`
`NOTE: Only an NDA applicant/holder may submit this declaration directly to the FDA. A patent owner who is not the NDA applicant] holder
`is authorized to sign the declaration but may not submit it directly to FDA. 21 CFR 314. 53(c)(4) and (d)(4).
`
`Check applicable box and provide information below.
`
` 3 Patent Owner
`
`
`
`
`
`Patent Owner's Attorney, Agent (Representative) or Other Authorized
`Official
`
`information unless it displays a currently valid OMB control number.
`
`
`
`
`7NDA Applicant's/Holder's Attorney, Agent (Representative) or other
`:] NDA Applicant/Holder
`Authorized Official
`
`
`Name
`Dean Sundberg
`
`Address
`675 North Field Drive
`
`ZIP Code
`
`FAX Number (ifavailable)
`(224) 554-7870
`
`City/State
`Lake Forest, Illinois
`
`Telephone Number
`
`E—M ail Address (if available)
`
`including the time for reviewing
`The public reporting burden for this collection of information has been estimated to average 5 hours per response,
`instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing the collection of information. Send
`comments regarding this burden estimate or any other aspect ofthis collection ofinformation, including suggestions for reducing this burden to:
`
`Food and Drug Administration
`CDER (HFD«007)
`5600 Fishers Lane
`Rockville, MD 20857
`
`An agency may not conduct or sponsor, and a person is not required to respond to, a collection of
`
`FORM FDA 3542 (7/07)
`
`Page 3
`
`

`

`EXCLUSIVITY SUMMARY
`
`
`NDA # 22-024
`
`
`
`
`
`SUPPL #
`
`
`
`
`
`HFD # 510
`
`Trade Name ActoPlus Met XR
`
`Generic Name pioglitazone and metformin hydrochloride extended-release tablets
`
`
`
`
`
`Applicant Name Takeda Global Research & Development Center, Inc
`
`Approval Date, If Known December 2008
`
`PART I
`
`1. An exclusivity determination will be made for all original applications, and all efficacy
`supplements. Complete PARTS II and III of this Exclusivity Summary only if you answer "yes" to
`one or more of the following questions about the submission.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`IS AN EXCLUSIVITY DETERMINATION NEEDED?
`
`a) Is it a 505(b)(1), 505(b)(2) or efficacy supplement?
`
`
`
`
`
` YES
`
`
`
`NO
`
`
`
`
`
`If yes, what type? Specify 505(b)(1), 505(b)(2), SE1, SE2, SE3,SE4, SE5, SE6, SE7, SE8
`
`
`
`505(b)(2)
`
`c) Did it require the review of clinical data other than to support a safety claim or change in
`labeling related to safety? (If it required review only of bioavailability or bioequivalence
`data, answer "no.")
`
`
`
`
`
` YES
`
`
`
`NO
`
`
`
`If your answer is "no" because you believe the study is a bioavailability study and, therefore,
`not eligible for exclusivity, EXPLAIN why it is a bioavailability study, including your
`reasons for disagreeing with any arguments made by the applicant that the study was not
`simply a bioavailability study.
`
`
`2 BE studies and 1 food effect study submitted
`
`
`If it is a supplement requiring the review of clinical data but it is not an effectiveness
`supplement, describe the change or claim that is supported by the clinical data:
`
`
`
`
`
`
`Page 1
`
`
`
`
`
`
`
`
`
`
`
`
`

`

`d) Did the applicant request exclusivity?
`
`
`
`
`
` YES
`
`
`
`NO
`
`
`
`
`If the answer to (d) is "yes," how many years of exclusivity did the applicant request?
`
`
`
`
`
`
`e) Has pediatric exclusivity been granted for this Active Moiety?
`
`
` YES
`
`
`
`NO
`
`
`
`
`
`
` If the answer to the above question in YES, is this approval a result of the studies submitted in
`response to the Pediatric Written Request?
`
`
`
`IF YOU HAVE ANSWERED "NO" TO ALL OF THE ABOVE QUESTIONS, GO DIRECTLY TO
`THE SIGNATURE BLOCKS AT THE END OF THIS DOCUMENT.
`
`
`2. Is this drug product or indication a DESI upgrade?
`
`
`
`
`
` YES
`
`
`
`NO
`
`
`
`
`
`If "yes," identify the approved drug product(s) containing the active moiety, and, if known, the NDA
`#(s).
`
`
`IF THE ANSWER TO QUESTION 2 IS "YES," GO DIRECTLY TO THE SIGNATURE BLOCKS
`ON PAGE 8 (even if a study was required for the upgrade).
`
`
`FIVE-YEAR EXCLUSIVITY FOR NEW CHEMICAL ENTITIES
`PART II
`(Answer either #1 or #2 as appropriate)
`
`1. Single active ingredient product.
`
`Has FDA previously approved under section 505 of the Act any drug product containing the same
`active moiety as the drug under consideration? Answer "yes" if the active moiety (including other
`esterified forms, salts, complexes, chelates or clathrates) has been previously approved, but this
`particular form of the active moiety, e.g., this particular ester or salt (including salts with hydrogen or
`coordination bonding) or other non-covalent derivative (such as a complex, chelate, or clathrate) has
`not been approved. Answer "no" if the compound requires metabolic conversion (other than
`deesterification of an esterified form of the drug) to produce an already approved active moiety.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` YES
`
`
`
`NO
`
`
`
`
`
`
`
`
`
`
`Page 2
`
`

`

`NDA#
`
`
`
`NDA#
`
`
`
`NDA#
`
`
`
`
`
`
`
`
`
`
`
`
`
`Actos (pioglitazone HCl)
`Fortamet (metformin HCl extended-release) tablets
`
`
`THREE-YEAR EXCLUSIVITY FOR NDAs AND SUPPLEMENTS
`
`
`
`
`Page 3
`
`
`
`
`
`2. Combination product.
`
`If the product contains more than one active moiety(as defined in Part II, #1), has FDA previously
`approved an application under section 505 containing any one of the active moieties in the drug
`product? If, for example, the combination contains one never-before-approved active moiety and
`one previously approved active moiety, answer "yes." (An active moiety that is marketed under an
`OTC monograph, but that was never approved under an NDA, is considered not previously
`approved.)
`
`YES
`
`
`
`NO
`
`
`
`
`If "yes," identify the approved drug product(s) containing the active moiety, and, if known, the NDA
`#(s).
`
`NDA# 21-073
`NDA# 21-574
`NDA#
`
`
`
`IF THE ANSWER TO QUESTION 1 OR 2 UNDER PART II IS "NO," GO DIRECTLY TO THE
`SIGNATURE BLOCKS ON PAGE 8. (Caution: The questions in part II of the summary should
`only be answered “NO” for original approvals of new molecular entities.)
`IF “YES,” GO TO PART III.
`
`
`PART III
`
`To qualify for three years of exclusivity, an application or supplement must contain "reports of new
`clinical investigations (other than bioavailability studies) essential to the approval of the application
`and conducted or sponsored by the applicant." This section should be completed only if the answer
`to PART II, Question 1 or 2 was "yes."
`
`
`1. Does the application contain reports of clinical investigations? (The Agency interprets "clinical
`investigations" to mean investigations conducted on humans other than bioavailability studies.) If
`the application contains clinical investigations only by virtue of a right of reference to clinical
`investigations in another application, answer "yes," then skip to question 3(a). If the answer to 3(a)
`is "yes" for any investigation referred to in another application, do not complete remainder of
`
`

`

`summary for that investigation.
`
`
`
`
`
`YES
`
`
`
`NO
`
`
`
`
`IF "NO," GO DIRECTLY TO THE SIGNATURE BLOCKS ON PAGE 8.
`
`2. A clinical investigation is "essential to the approval" if the Agency could not have approved the
`application or supplement without relying on that investigation. Thus, the investigation is not
`essential to the approval if 1) no clinical investigation is necessary to support the supplement or
`application in light of previously approved applications (i.e., information other than clinical trials,
`such as bioavailability data, would be sufficient to provide a basis for approval as an ANDA or
`505(b)(2) application because of what is already known about a previously approved product), or 2)
`there are published reports of studies (other than those conducted or sponsored by the applicant) or
`other publicly available data that independently would have been sufficient to support approval of
`the application, without reference to the clinical investigation submitted in the application.
`
`
`(a) In light of previously approved applications, is a clinical investigation (either conducted
`by the applicant or available from some other source, including the published literature)
`necessary to support approval of the application or supplement?
`
`
` YES
`
`
`If "no," state the basis for your conclusion that a clinical trial is not necessary for approval
`AND GO DIRECTLY TO SIGNATURE BLOCK ON PAGE 8:
`
`
`
`NO
`
`
`
`
`
`
`
`BE studies & food effect study
`
`(b) Did the applicant submit a list of published studies relevant to the safety and effectiveness
`of this drug product and a statement that the publicly available data would not independently
`support approval of the application?
`
`
`(1) If the answer to 2(b) is "yes," do you personally know of any reason to disagree
`with the applicant's conclusion? If not applicable, answer NO.
`
`
`
`
`
` YES
`
`
`
`NO
`
`
`
`
`
`
`
`
`
`
`
`
` YES
`
`
`
`NO
`
`
`
` If yes, explain:
`
`
`
`
`
`(2) If the answer to 2(b) is "no," are you aware of published studies not conducted or
`sponsored by the applicant or other publicly available data that could independently
`demonstrate the safety and effectiveness of this drug product?
`
`
`
`
`
`
` YES
`
`
`
`NO
`
`
`
`
`
`Page 4
`
`
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`
`

`

` If yes, explain:
`
`
`
`
`(c)
`
`If the answers to (b)(1) and (b)(2) were both "no," identify the clinical investigations
`submitted in the application that are essential to the approval:
`
`None, BE studies & food effect study
`
`
`
`Studies comparing two products with the same ingredient(s) are considered to be bioavailability
`studies for the purpose of this section.
`
`
`3. In addition to being essential, investigations must be "new" to support exclusivity. The agency
`interprets "new clinical investigation" to mean an investigation that 1) has not been relied on by the
`agency to demonstrate the effectiveness of a previously approved drug for any indication and 2) does
`not duplicate the results of another investigation that was relied on by the agency to demonstrate the
`effectiveness of a previously approved drug product, i.e., does not redemonstrate something the
`agency considers to have been demonstrated in an already approved application.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`a) For each investigation identified as "essential to the approval," has the investigation been
`relied on by the agency to demonstrate the effectiveness of a previously approved drug
`product? (If the investigation was relied on only to support the safety of a previously
`approved drug, answer "no.")
`
`Investigation #1
`
`Investigation #2
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`YES
`
`YES
`
`
`
`
`
`NO
`
`NO
`
`
`
`
`
`If you have answered "yes" for one or more investigations, identify each such investigation
`and the NDA in which each was relied upon:
`
`
`
`
`b) For each investigation identified as "essential to the approval", does the investigation
`duplicate the results of another investigation that was relied on by the agency to support the
`effectiveness of a previously approved drug product?
`
`
`
`
`
`
`
`
`Investigation #1
`
`Investigation #2
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`YES
`
`YES
`
`
`
`
`
`NO
`
`NO
`
`
`
`
`
`Page 5
`
`

`

`
`If you have answered "yes" for one or more investigation, identify the NDA in which a
`similar investigation was relied on:
`
`N/A
`
`c) If the answers to 3(a) and 3(b) are no, identify each "new" investigation in the application
`or supplement that is essential to the approval (i.e., the investigations listed in #2(c), less any
`that are not "new"):
`
`
`
`BE Study OPIXT-002 and OPIXT-003
`
`
`
`
`
`
`
`
`
`4. To be eligible for exclusivity, a new investigation that is essential to approval must also have
`been conducted or sponsored by the applicant. An investigation was "conducted or sponsored by"
`the applicant if, before or during the conduct of the investigation, 1) the applicant was the sponsor of
`the IND named in the form FDA 1571 filed with the Agency, or 2) the applicant (or its predecessor
`in interest) provided substantial support for the study. Ordinarily, substantial support will mean
`providing 50 percent or more of the cost of the study.
`
`
`
`Investigation #1
`
`
`
`
`IND # 33,729 and 68,462
`
`
`
`
`
`
`
`
`Investigation #2
`
`
`
`
`
`
`
`
`
`
`! NO
`
`
`
`
`
`
`a) For each investigation identified in response to question 3(c): if the investigation was
`carried out under an IND, was the applicant identified on the FDA 1571 as the sponsor?
`
`!
`!
`YES
`
`! Explain:
`
`
`
`!
`!
`
`YES
`! Explain:
`
`
`! NO
`
`
`
`IND # 33,729 and 68,462
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`(b) For each investigation not carried out under an IND or for which the applicant was not
`identified as the sponsor, did the applicant certify that it or the applicant's predecessor in
`interest provided substantial support for the study?
`
`
`
`
`
`
`
`
`
`
`
`
`
`Page 6
`
`

`

`Investigation #1
`
`
`
`
`YES
`
`Explain:
`N/A
`
`
`Investigation #2
`
`YES
`
`Explain:
`N/A
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`!
`!
`
`! NO
`! Explain:
`
`
`
`!
`!
`
`! NO
`! Explain:
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`(c) Notwithstanding an answer of "yes" to (a) or (b), are there other reasons to believe that
`the applicant should not be credited with having "conducted or sponsored" the study?
`(Purchased studies may not be used as the basis for exclusivity. However, if all rights to the
`drug are purchased (not just studies on the drug), the applicant may be considered to have
`sponsored or conducted the studies sponsored or conducted by its predecessor in interest.)
`
`
`
`
`
`
`YES
`
`
`
`NO
`
`
`
`If yes, explain:
`
`
`
`
`No clinical studies performed, BE (2) & food effect only
`
`
`
`=================================================================
`
`Name of person completing form: Jena Weber
`Title: Project Manager
`Date: 12/01/08
`
`
`Name of Office/Division Director signing form: Mary Parks, M.D.
`Title: Division Director, DMEP
`
`
`
`Form OGD-011347; Revised 05/10/2004; formatted 2/15/05
`
`
`
`
`
`Page 7
`
`

`

`---------------------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed electronically and
`this page is the manifestation of the electronic signature.
`---------------------------------------------------------------------------------------------------------------------
` /s/
`---------------------
`Mary Parks
`12/1/2008 08:58:51 AM
`
`

`

`PEDIATRIC PAGE
`(Complete for all filed original applications and efficacy supplements)
`NDA/BLA#: 22-024
`Supplement Number: NDA Supplement Type (e.g. SE5): 3S
`Division Name:DMEP
`PDUFA Goal Date: 11/01/08 Stamp Date: 5/1/2008
`Proprietary Name: Actoplus Met XR
`Established/Generic Name: pioglitazone HCl + metformin HCl extended-release
`Dosage Form:
`Tablets
`Applicant/Sponsor: Takeda Global R&D Center
`Indication(s) previously approved (please complete this question for supplements and Type 6 NDAs only):
`(1)
`(2)
`(3)
`(4)
`Pediatric use for each pediatric subpopulation must be addressed for each indication covered by current
`application under review. A Pediatric Page must be completed for each indication.
`Number of indications for this pending application(s):1
`(Attach a completed Pediatric Page for each indication in current application.)
`Indication: This new drug application provides for the use of Actoplus Met XR as an adjunct to diet and
`exercise to improve glycemic control in patients with type 2 diabetes who are already treated with a
`combination of pioglitazone and metformin or whose diabetes is not adequately controlled with metformin
`alone, or for those patients who have initially responded to pioglitazone alone and require additional glycemic
`control. Actoplus Met was approved on August 29, 2005, under NDA 21-842, as an adjunct to diet and
`exercise to improve glycemic control in patients with type 2 diabetes who are already treated with a
`combination of pioglitazone and metformin or whose diabetes is not adequately controlled with metformin
`alone, or for those patients who have initially responded to pioglitazone alone and require additional glycemic
`control. The metformin component (Fortamet) was approved on April 27, 2004, under NDA 21-574.
`Q1: Is this application in response to a PREA PMR?
`Yes
` Continue
` Please proceed to Question 2.
`
`
`
`
`
`
`
`
`No
`If Yes, NDA/BLA#:
`Supplement #:
`PMR #:
`
`
`Does the division agree that this is a complete response to the PMR?
` Yes. Please proceed to Section D.
`
` No. Please proceed to Question 2 and complete the Pediatric Page, as applicable.
`Q2: Does this application provide for (If yes, please check all categories that apply and proceed to the next
`question):
` active ingredient(s) (includes new combination);
`(a) NEW
` route of administration?*
`regimen; or
` No. PREA does not apply. Skip to signature block.
`(b)
`* Note for CDER: SE5, SE6, and SE7 submissions may also trigger PREA.
`Q3: Does this indication have orphan designation?
` Yes. PREA does not apply. Skip to signature block.
`
` No. Please proceed to the next question.
`
`
` dosage form;
`
` indication(s);
`
` dosing
`
`IF THERE ARE QUESTIONS, PLEASE CONTACT THE CDER PMHS VIA EMAIL (cderpmhs@fda.hhs.gov) OR AT 301-796-0700.
`
`
`

`

`
`
`Page 2
`
`
`
`NDA/BLA# 22-02422-02422-02422-02422-024
`Q4: Is there a full waiver for all pediatric age groups for this indication (check one)?
` Yes: (Complete Section A.)
`
` No: Please check all that apply:
`
` Partial Waiver for selected pediatric subpopulations (Complete Sections B)
`
` Deferred for some or all pediatric subpopulations (Complete Sections C)
`
`
` Completed for some or all pediatric subpopulations (Complete Sections D)
` Appropriately Labeled for some or all pediatric subpopulations (Complete Sections E)
`
` Extrapolation in One or More Pediatric Age Groups (Complete Section F)
`
`
`(Please note that Section F may be used alone or in addition to Sections C, D, and/or E.)
`Section A: Fully Waived Studies (for all pediatric age groups)
`Reason(s) for full waiver: (check, and attach a brief justification for the reason(s) selected)
` Necessary studies would be impossible or highly impracticable because:
`
` Disease/condition does not exist in children
` Too few children with disease/condition to study
` Other (e.g., patients geographically dispersed):
` Product does not represent a meaningful therapeutic benefit over existing therapies for pediatric
`patients AND is not likely to be used in a substantial number of pediatric patients.
` Evidence strongly suggests that product would be unsafe in all pediatric subpopulations (Note: if
`studies are fully waived on this ground, this information must be included in the labeling.)
` Evidence strongly suggests that product would be ineffective in all pediatric subpopulations (Note: if
`studies are fully waived on this ground, this information must be included in the labeling.)
` Evidence strongly suggests that product would be ineffective and unsafe in all pediatric
`subpopulations (Note: if studies are fully waived on this ground, this information must be included in
`the labeling.)
` Justification attached.
`If studies are fully waived, then pediatric information is complete for this indication. If there is another
`indication, please complete another Pediatric Page for each indication. Otherwise, this Pediatric Page is
`complete and should be signed.
`
`IF THERE ARE QUESTIONS, PLEASE CONTACT THE CDER PMHS VIA EMAIL (cderpmhs@fda.hhs.gov) OR AT 301-796-0700.
`
`
`
`

`

`NDA/BLA# 22-02422-02422-02422-02422-024
`
`
`
`
`
`Page 3
`
`
`
`minimum
`
`maximum
`
`Not
`feasible#
`
`Ineffective or
`unsafe†
`
`Formulation
`failed∆
`
`
`
`
`
`
`
`
`
`
`
`
`
`Section B: Partially Waived Studies (for selected pediatric subpopulations)
`Check subpopulation(s) and reason for which studies are being partially waived (fill in applicable criteria below):
`Note: If Neonate includes premature infants, list minimum and maximum age in “gestational age” (in weeks).
`
`
`Reason (see below for further detail):
`Not meaningful
`therapeutic
`benefit*
`
`
` wk. mo.
` wk. mo.
` Neonate
`
`
` yr. mo.
` yr. mo.
` Other
`
`
` yr. mo.
` yr. mo.
` Other
`
`
` yr. mo.
` yr. mo.
` Other
`
`
` yr. mo.
` yr. mo.
` Other
` Yes.
` No;
`Are the indicated age ranges (above) based on weight (kg)?
` Yes.
` No;
`Are the indicated age ranges (above) based on Tanner Stage?
`Reason(s) for partial waiver (check reason corresponding to the category checked above, and attach a brief
`justification):
`# Not feasible:
` Necessary studies would be impossible or highly impracticable because:
`
`Disease/condition does not exist in children
`
`Too few children with disease/condition to study
`
`Other (e.g., patients geographically dispersed):
`* Not meaningful therapeutic benefit:
` Product does not represent a meaningful therapeutic benefit over existing therapies for pediatric
`patients in this/these pediatric subpopulation(s) AND is not likely to be used in a substantial number of
`pediatric patients in this/these pediatric subpopulation(s).
`† Ineffective or unsafe:
` Evidence strongly suggests that product would be unsafe in all pediatric subpopulations (Note: if studies
`are partially waived on this ground, this information must be included in the labeling.)
` Evidence strongly suggests that product would be ineffective in all pediatric subpopulations (Note: if
`studies are partially waived on this ground, this information must be included in the labeling.)
` Evidence strongly suggests that product would be ineffective and unsafe in all pediatric subpopulations
`(Note: if studies are partially waived on this ground, this information must be included in the labeling.)
`∆ Formulation failed:
` Applicant can demonstrate that reasonable attempts to produce a pediatric formulation necessary for
`this/these pediatric subpopulation(s) have failed. (Note: A partial waiver on this ground may only cover
`the pediatric subpopulation(s) requiring that formulation. An applicant seeking a partial waiver on this
`ground must submit documentation detailing why a pediatric formulation cannot be developed. This
`submission will be posted on FDA's website if waiver is granted.)
` Justification attached.
`For those pediatric subpopulations for which studies have not been waived, there must be (1) corresponding
`study plans that have been deferred (if so, proceed to Sections C and complete the PeRC Pediatric Plan
`Template); (2) submitted studies that have been completed (if so, proceed to Section D and complete the
`PeRC Pediatric Assessment form); (3) additional studies in other age groups that are not needed because the
`drug is appropriately labeled in one or more pediatric subpopulations (if so, proceed to Section E); and/or (4)
`additional studies in other age groups that are not needed because efficacy is being extrapolated (if so,
`proceed to Section F). Note that more than one of these options may apply for this indication to cover all of the
`IF THERE ARE QUESTIONS, PLEASE C