11/18/2015
`
`American College of Rheumatology
`
`.
`
`.
`
`.
`
`Arthritis 8: Rheumatism 3:ia'ii§..:li7l.tT‘::i..Lc.L(:f
`
`‘_'.
`
`‘C’
`
`;
`
`munmou . ruumuun . unuutu hi-l1W| LEY- BLACKWELL
`
`
`Arthritis & Rheumatism, Volume 60,
`
`October 2009 Abstract Supplement
`The 2009 ACR/ARHP Annual Scientific Meeting
`Philadelphia October 16-21, 2009.
`
`Am“; 3 Rhwmm
`
`PN400 Significantly Reduces The Incidence Of Gastric Ulcers Compared
`With Enteric-Coated Naproxen In Patients Requiring Chronic NSAID
`Therapy Regardless Of Low-Dose Aspirin Use: Results From Two
`Prospective, Randomized Controlled Trials
`
`Goldstein‘, Jay L., Hochberg2, Marc C., Fort3, John G., Zhang3, Ying,
`Sostek4, Mark
`
`University of Illinois at Chicago, Chicago, IL
`University of Maryland School of Medicine, Baltimore, MD
`POZEN lnc., Chapel Hill, NC
`Astraleneca, Wilmington, DE
`
`Purpose:
`Co—therapy with proton pump inhibitors reduces the risk of NSAID-
`associated ulcers but, in practice, adherence is often sub—optimal,
`leading to poor |ong—term clinical outcomes (Van Soest et al. Aliment
`Pharmacol Ther 2007;26:265—275). Two Phase 3 studies evaluated the
`upper gastrointestinal (UGI) efficacy and safety of PN400, a fixed—dose
`combination tablet designed to provide sequential delivery of
`immediate—release (IR) esomeprazole (20 mg) and enteric—coated (EC)
`naproxen (500 mg), compared with EC naproxen (500 mg) alone in at—risk
`patients.
`Method:
`
`Two randomized, double-blind, controlled, multicenter studies enrolled H.
`pylori—negative patients with OA, RA, or any other condition requiring
`chronic NSAID therapy at risk of ulcers (age >=5O yrs or 18-49 yrs with a
`history of gastric ulcer [GU] or duodenal ulcer [DU] within the past 5 yrs).
`Patients were randomized to PN400 BID or EC naproxen 500 mg BID for 6
`months. The primary endpoint was the cumulative incidence of GUs (>=3
`mm diameter with depth) observed by endoscopy at 1, 3, and 6 months.
`A planned pooled analysis to assess the effect of low—dose aspirin use
`(LDA <=325 mg) on GU incidence, and an analysis of pre—specified
`NSAlD—associated UGI AEs (including DU) were also conducted.
`Results:
`
`Study A: 438 patients were randomized, 434 were treated: Study B: 423
`patients were randomized, 420 were treated. Baseline demographics
`were similar between groups in both studies. Approximately 82% of
`patients had OA and 6% had RA. In both studies, the incidence of GUs
`over 6 months was significantly lower in the PN400 groups vs the EC
`naproxen groups (Table). The pooled incidence of GUS was significantly
`lower in the PN400 group vs the EC naproxen group in LDA users (n=201)
`(3.0% vs 28.4%, p<0.001) and non-users (n=653) (6.4% vs 22.2%, p<0.001).
`The previously described pre—specified secondary endpoint was
`significantly lower in the PN400 groups (Table).
`
`Study A
`
`EC
`
`Study B
`
`EC
`
`PN400
`(n=218)
`GU, n (%) 9 (4.1)
`DU, n (%)
`1 (0.5)
`UGI
`114
`AE/DU, n (52.3)
`http://www.b|ackwelIpublishing.com/acrmeeting/abstract.asp?M eeting|D=761&id=80472
`
`naproxen
`(n=216)
`50 (23.1)
`11 (5.1)
`149 (69.0)
`
`PN400 naproxen
`(n=210) (n=210)
`p
`<0.001 15 (7.1) 51 (24.3)
`0.003 2 (1.0)
`12 (5.7)
`<0.00l 114
`151 (71.9)
`(54.3)
`
`p
`<0.001
`0.007
`<0.00l
`
`patent owner EX_ 2007
`CFAD v. Pozen
`IPRZO1 501718
`
`1/2
`
`Patent Owner Ex. 2007
`CFAD v. Pozen
`IPR2015-01718
`
`

`
`11/18/2015
`
`American College ct Rheumatology
`
`(%)
`Conc:luslon:
`PN400 significantly reduces the incidence of Gus, regardless of
`concomitant LDA use, and DUs in at-risk. patients. PN400, a f1Xed-dose
`combination of EC naproxen 500 mg and IR esomeprazole 20 mg,
`provides built-in gastroprotection and offers a treatment option for
`decreasing NSAID-ulcer occurrence in an appropriate target patient
`population.
`
`To cite this abstract, please use the following lnformaHon:
`Goldstein, Jay L., Hochberg, Marc C., Fort, John G., Zhang, Ying,
`SOJtek. Marte; PN400 SlgnlftcanHy Reduces the Incidence of Gastric Ulcers
`Compared with Enterlc-Coated Naproxen In Patients Requiring Chronic
`NSAID Therapy Regardless of Low-Dose Aspirin Use: Results From Two
`PraspecHve, Randomized Controlled Trials labstractl. ArthrHls Rheum
`2009;60 Suppl 10 :842
`DOI: 10.1002/art.25922
`
`Home I MeeHng Index I Search I ACR Annual MeeHng Page I Onnne Journal I
`Privacy Policy
`
`Copyright© 2013 American College of Rheumatology
`
`http://www.blackwel lpublishi ng.can/acrmeeli ng/abstract.asp?MeelinglD=761&id=80472
`
`212
`
`Patent Owner Ex. 2007
`CFAD v. Pozen
`IPR2015-01718