The American journal of
`gastroenterology : offici
`publication of the Nation
`Gastroenterological
`Association
`BML Annex
`UC
`Diego
`
`DRL EXHIBIT 1042 PAGE 1
`
`

`

`AJG - October, Suppl., 2004
`
`Abstracts
`
`S39
`
`Median Gastric pH with OME-IR(SUSP) 20 mg b.l.d.
`Day 8
`Meal Dose
`
`Dose Meal Meal
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`0900
`1300
`1700
`2100
`0100
`0500
`0900
`Hours
`
`117
`
`OMEPRAZOLE IMMEDIATE-RELEASE ORAL SUSPENSION IS
`MORE EFFECTlVE THAN PANTOPRAZOLE
`DELAYED-RELEASE CAPSULES IN REDUCING NIGHTTIME
`GASTRIC ACIDITY IN GERO PATIENTS
`Donald Castell, M.D.. Barry Gold/us/, Ph.D. , Gaetano Morelli, M.D.,
`Jacqueline Major, M.S., Theresa Gautille, R.N. , Bonnie Hepburn , M.D. •.
`Med. U of S. Carolina, Charleston, South Carolina; Santarus, Inc., San
`Diego, California and MDS Pharma Services, Montreal, Quebec, Canada.
`
`Purpose: The present trial was conducted to evaluate nighttime dosing of
`orneprazole irnediate-release oral suspension (OME-!R[SUSP)) in once- and
`twice-daily regimens, comparing the effect of OME-IR on nocturnal gastric
`acidity to that ofpantoprazole (P), the only PPI with FDA-approved labeling
`for reduction in rate of nighttime heartburn symptoms.
`Methods: Thirty-two patients with nocturnal GERO symptoms were en(cid:173)
`rolled in a crossover trial with 40-rng doses of P (Protonix®, Wyeth-Ayers!,
`Philadelphia) given at 2200 hrs (bedtime) on Day I and prior to dinner on
`Days 2--6 and 40-rng OME-IR(SUSP) (Santarus, San Diego) given at 2200
`hrs on Days 1--6. On Day 7, both PP!s were given I hr prior to breakfast and
`at 2200 hrs: P 40 mg (n = 32); OME-IR 40 mg (n = 17) and 20 mg (n =
`15). Continuous 24-hr gastric pH monitoring (Medtronic) was performed on
`Days I, 6, and 7. Median gastric pH,% time pH was > 4, and the proportion
`of patients with "nocturnal acid breakthrough" (NAB) ( > I hr of continuous
`pH < 4) were determined for the nighttime period (2200--0600 hrs).
`
`Nighttime Median Gastric pH After Once-daily Dosing
`with OME-IR and Pantoprazole (2200 • 0600 hours)
`Day6
`a..--------------------,
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`
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`
`u :s .. Cl c.,
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`
`affords superior intragastric pH control compared to other available proton
`pump inhibitors given twice daily.
`Methods: A retrospective review of patients in the database of our
`esophageal laboratory between 1990 and 2003 were identified. All stud(cid:173)
`ies in which PP!s were given bid were included for review. Data analyzed
`fo r percentage time intragastric pH greater than 4, total, upright, recumbent.
`Statistics: Bootstrap analysis (unequal sample size) used to compare es(cid:173)
`omeprazole against each proton pump inhibitor. Results: Three hundred and
`th irty-three studies identified, 29 excluded due to less than 16 hours worth of
`pH data or inadequate documentation of optimal or correct dosing regimen.
`Three hundred and four total studies were reviewed. Orne 20 bid (N = 194),
`Lanso 30 bid (N = 67) Rab 20 bid (N = 11), Panto 40 bid (N = 8), Eso 40
`bid (N = 24). Mean total time intragastric pH greater than 4 was superior
`for esorneprazole (76.4%, 18.3 hrs) compared to lansoprazole (64%, 15.4
`hr) and pantoprazole (56%, 15.4 hr), p < 0.03 and 0.0 I respectively, with no
`difference compared to orneprazole (27%, 17.5 hr) and rabeprazole (2 1 %,
`J 9 hrs). Though not specifically evaluated nocturnal breakthrough of gastric
`pH was seen with all five PPls.
`Results: Eso 40 mg twice daily may afford greater time intragastric pH
`greater than 4 than other PP!s.
`Conclusions: I. These retrospective results require validation in prospec(cid:173)
`tively designed clinical studies. 2. The clinical importance of this increase
`in acid control is unclear. 3. Twice daily proton pump inhibitors appear to
`afford approximately five additional hours of pH control when twice daily
`dosing is used.
`
`116
`
`NIGHTTIME DOSING OF OMEPRAZOLE
`IMMEDIATE-RELEASE ORAL SUSPENSION RAPIDLY
`DECREASES NOCTURNAL GASTRIC ACIDITY
`Barry Gold/ust, Ph.D., Bonnie Hepburn, M.D.*, Yzm Hardiman, M.S.
`Santarus, Inc .. San Diego, California.
`
`Purpose: Proton pump inhibitors (PP!s) suppress gastric acid secretion suf(cid:173)
`ficiently to treat most symptoms of GERO. However, in some patients, PP ls
`fail to control nighttime gastric acid secretion and also fa! I to control night(cid:173)
`time GERD symptoms. The PP!s used to treat these symptoms have all
`been d.elayed-release formulations with enteric coatings. A new orneprazole
`immediate-release suspension (OME-!R[SUSP]) has been developed, using
`sodium bicarbonate to protect the acid-labile PP!, rather than the traditional
`delayed-release enteric coating. The present trial was conducted to evaluate
`the effectiveness ofOME-IR(SUSP) in controlling nighttime gastric acidity
`after twice-daily (b.i.d.) dosing.
`Methods: Seventeen healthy subjects were enrolled in this open-label tria~.
`Single 20-mg doses of OME-!R(SUSP) (Santarus, San Diego) were given
`J hr prior to breakfast ( qAM) for 7 days. On Day 8, the 20-rng suspension
`was given b.i.d.: at 0830 hrs ( I hr prior to a standardized high-fat break(cid:173)
`fast) and at 2200 hrs (bedtime). On Days 7 and 8, standardized lunch and
`dinner were given at 1300 and 1800 hrs. Gastric pH was continuously mon(cid:173)
`itored (Medtronic) for 24 hrs following the morning doses on Days 7 and
`8. The percent time pH was > 4 was assessed for the 8-hr nighttime period
`(2200--0600 hrs) and for the 24-hr period following the morning dose. The
`proportion ~f subjects with "nocturnal acid breakthrough" (NAB) ( > I hr
`of continuous pH < 4) was assessed for the 8-hr nighttime period.
`Results: The figure below displays the 24-hr median gastric pH profile at
`steady state for b.i .d. dosing of OME-IR 20 mg. After the bedtime dose,
`OME- IR 20 mg abrupt ly raised the gastric pH and sustained this effect for
`approximately 8 hrs. The median% time pH was > 4 was greater for b.Ld
`dosing (87%) than for qAM dosing (39%) (p < 0.001). NAB occurred m
`fewe r subjects dosed b.i.d. (5/17 [29%]) than dosed qAM (13/ 17 [76%])
`(p = 0.005).[figure I]
`.
`.
`Conclusions: Twice-daily dosing (before breakfast and at bedtime) with
`OME-IR(SUSP) is effective in controlling nighttime acidity. Nighttime ad(cid:173)
`ministration ofOME-IR(SUSP) may be more effective in controlling night(cid:173)
`time GERD symptoms than delayed-release PPls.
`
`0 \ . - - - - - - - - - - . . - - - - - - , - - - - - - l
`0400
`0600
`
`2200
`
`2400
`
`1---oME-IR(SUSP) 40 mg &-<ttlPantoprazole 40 mg i
`
`Note: The pH data points correspond to the end of each 15-minute recording interval.
`In =321
`
`0200
`Hours
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`DRL EXHIBIT 1042 PAGE 2
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