111111
`
`1111111111111111111111111111111111111111111111111111111111111
`US008329216B2
`
`c12) United States Patent
`Kao et al.
`
`(10) Patent No.:
`(45) Date of Patent:
`
`US 8,329,216 B2
`*Dec. 11, 2012
`
`(54) OXYMORPHONE CONTROLLED RELEASE
`FORMULATIONS
`
`(58) Field of Classification Search ........................ None
`See application file for complete search history.
`
`(75)
`
`Inventors: Haui-Hung Kao, Syosset, NY (US);
`Anand R. Baichwal, Wappingers Falls,
`NY (US); Troy McCall, Smyrna, GA
`(US); David Lee, Chadds, PA (US)
`
`(73) Assignee: Endo Pharmaceuticals Inc., Chadds
`Ford, PA (US)
`
`( *) Notice:
`
`Subject to any disclaimer, the term of this
`patent is extended or adjusted under 35
`U.S.C. 154(b) by 1192 days.
`
`This patent is subject to a terminal dis(cid:173)
`claimer.
`
`(21) Appl. No.: 11/427,438
`
`(22) Filed:
`
`Jun.29,2006
`
`(65)
`
`Prior Publication Data
`
`US 2007/0098794 AI
`
`May 3, 2007
`
`Related U.S. Application Data
`
`(63) Continuation of application No. 10/190,192, filed on
`Jul. 3, 2002.
`
`(60) Provisional application No. 60/329,445, filed on Oct.
`15, 2001, provisional application No. 60/329,432,
`filed on Oct. 15, 2001, provisional application No.
`60/303,357, filed on Jul. 6, 2001, provisional
`application No. 60/329,444, filed on Oct. 15, 2001.
`
`(51)
`
`Int. Cl.
`A61K 9122
`(2006.01)
`(2006.01)
`A61K 9/34
`(2006.01)
`A61K 9/36
`(52) U.S. Cl. ........ 424/464; 424/468; 424/470; 424/479;
`424/481; 424/482; 424/486
`
`(56)
`
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`Primary Examiner- Lakshmi Channavajjala
`(74) Attorney, Agent, or Firm- Mayer Brown LLP
`
`ABSTRACT
`(57)
`The invention pertains to a method of relieving pain by
`administering a controlled release pharmaceutical tablet con(cid:173)
`taining oxymorphone which produces a mean minimum
`blood plasma level12 to 24 hours after dosing, as well as the
`tablet producing the sustained pain relief.
`
`82 Claims, 10 Drawing Sheets
`
`PK Profile for 6-0H-Oxymorphone with PID Scores
`20,_----------------------------------------. 1.0
`
`\~~\
`
`!
`!
`/ 4
`
`......................
`·---
`
`',,
`'•-.....
`
`-~~---~-------·-------
`
`r~ .80
`
`02
`
`0.1
`
`OD
`
`0"
`
`0.7
`
`0.6
`
`0.8 ~
`..s ..,
`1:1
`0
`,..<:1
`0.5 e-
`0.4 ~ X
`03 9 ::r:
`
`0
`
`0
`J::,
`
`* Pain Intensity Difference
`
`6
`Time (Hour)
`• 6-0H-Oxymorphone Plasma Concentrations
`
`12
`
`1
`
`

`

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`
`5
`
`

`

`PK Profile for 6-0H-Oxymorphone with PID Scores
`
`~ 1.0
`
`1- 0.9
`
`.-...
`,__...
`
`0.8 ~
`
`0.7 ~
`""--"
`(\)
`~
`0
`..q
`
`0
`
`I
`
`e-
`~
`X
`0
`::r:
`0
`I
`\0
`
`0.6
`
`0.5
`
`0.4
`
`0.3
`
`0.2
`
`0.1
`
`0.0
`
`-.._.._
`
`'~,
`
`·---
`
`.........
`....
`
`'...._
`'~~,__
`~~--~-
`
`---~---~
`--~
`
`r= .80
`
`~
`\
`
`.---- ................
`
`'
`
`I
`I
`
`f
`I
`I
`I
`I
`I
`cj
`
`'
`
`20 I
`
`_,......,_
`
`t/j <
`c 15
`
`<I)
`u
`t:l
`<I)
`I-<
`~
`. .,.....
`tH
`0
`.??
`. ....
`(/)
`Q
`11.>
`..j...)
`
`10
`
`..... -- 5
`
`~
`•.-I
`cd
`P-t
`
`0~
`0
`
`2
`
`* Pain Intensity Difference
`
`4
`
`8
`
`10
`
`12
`
`6
`Time (Hour)
`• 6-0H-Oxyn1orphone Plasn1a Concentrations
`Ft&. I
`
`~
`00
`•
`~
`~
`~
`
`~ = ~
`
`c ('D
`~ ....
`.... ~
`0 ....
`
`N
`
`N
`
`('D
`('D
`
`rFJ =(cid:173)
`.....
`....
`0 .....
`....
`0
`
`d
`rJl
`00 w
`N
`\C
`'N
`
`""""' 0'1 = N
`
`6
`
`

`

`PK Profile for Oxymorphone with PID Scores
`
`r--......._,
`....
`'
`" '
`'
`
`f
`I
`J
`I
`I
`I
`I
`I
`f
`(
`I
`I
`~ ......
`..
`
`·----.....:
`
`'
`
`....
`.....
`.....
`'
`·-~----- .......
`.....
`.........
`'
`
`.........
`.....