ESOMEPRAZOLE MAGNESIUM: Package Insert and Label Information (Page 7 of 8)

14.2 Maintenance of Healing of EE in Adults

Two multicenter, randomized, double-blind placebo-controlled 4-arm trials were conducted in adult patients with endoscopically confirmed, healed EE to evaluate esomeprazole magnesium delayed-release capsules 40 mg (n=174), 20 mg (n=180), 10 mg (n=168) or placebo (n=171) once daily over six months of treatment.

No additional clinical benefit was seen with esomeprazole magnesium delayed-release capsules 40 mg over esomeprazole magnesium delayed-release capsules 20 mg. esomeprazole magnesium delayed-release capsules 40 mg once daily is not a recommended regimen for the maintenance of healing of EE in adults.

The percentages of patients that maintained healing of EE at the various time points are shown in the Figures 2 and 3:

Figure 2: Maintenance of Healing Rates by Month (Study 177)

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Figure 3:Maintenance of Healing Rates by Month (Study 178)

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Patients remained in remission significantly longer and the number of recurrences of EE was significantly less in patients treated with esomeprazole magnesium delayed-release capsules compared to placebo.

In both studies, the proportion of patients on esomeprazole magnesium delayed-release capsules who remained in remission and were free of heartburn and other GERD symptoms was well differentiated from placebo.

In a third multicenter open label study of 808 patients treated for 12 months with esomeprazole magnesium delayed-release capsules 40 mg, the percentage of patients that maintained healing of EE was 93.7% for six months and 89.4% for one year.

14.3 Symptomatic GERD in Adults

Two multicenter, randomized, double-blind, placebo-controlled studies were conducted in a total of 717 adult patients comparing four weeks of treatment with esomeprazole magnesium delayed-release capsules 20 mg or 40 mg once daily versus placebo for resolution of GERD symptoms. Patients had at least 6-month history of heartburn episodes, no EE by endoscopy, and heartburn on at least four of the seven days immediately preceding randomization.

The percentage of patients that were symptom-free of heartburn was significantly higher in the esomeprazole magnesium delayed-release capsules groups compared to placebo at all follow-up visits (Weeks 1, 2, and 4).

No additional clinical benefit was seen with esomeprazole magnesium delayed-release capsules 40 mg over esomeprazole magnesium delayed-release capsules 20 mg.

The percent of patients symptom-free of heartburn by day are shown in the Figures 4 and 5:

Figure 4: Percent of Patients Symptom-Free of Heartburn by Day (Study 225)

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Figure 5: Percent of Patients Symptom-Free of Heartburn by Day (Study 226)

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In three European symptomatic GERD trials, esomeprazole magnesium delayed-release capsules 20 mg and 40 mg and omeprazole 20 mg were evaluated. No significant treatment related differences were seen.

14.4 Pediatric GERD

12 Years to 17 Years of Age

In a multicenter, randomized, double-blind, parallel-group study, 149 adolescent patients (12 to 17 years of age; 89 female; 124 Caucasian, 15 Black, 10 Other) with clinically diagnosed GERD were treated with either esomeprazole magnesium delayed-release capsules 20 mg or esomeprazole magnesium delayed-release capsules 40 mg once daily for up to 8 weeks to evaluate safety and tolerability. Patients were not endoscopically characterized as to the presence or absence of EE.

14.5 Risk Reduction of NSAID-Associated Gastric Ulcer

Two multicenter, double-blind, placebo-controlled studies were conducted in adult patients at risk of developing gastric and/or duodenal ulcers associated with continuous use of non-selective and COX-2 selective NSAIDs. A total of 1,429 patients were randomized across the 2 studies. Patients ranged in age from 19 to 89 (median age 66 years) with 71% female, 29% male, 83% Caucasian, 5% Black, 4% Asian, and 8% Others. At baseline, the patients in these studies were endoscopically confirmed not to have ulcers but were determined to be at risk for ulcer occurrence due to their age (at least 60 years) and/or history of a documented gastric or duodenal ulcer within the past 5 years. Patients receiving NSAIDs and treated with esomeprazole magnesium delayed-release capsules 20 mg or 40 mg once daily experienced significant reduction in gastric ulcer occurrences relative to placebo treatment at 26 weeks. See Table 13. No additional benefit was seen with esomeprazole magnesium delayed-release capsules 40 mg over esomeprazole magnesium delayed-release capsules 20 mg. These studies did not demonstrate significant reduction in the development of NSAID-associated duodenal ulcer due to the low incidence.

1. %= Life Table Estimate. Significant difference from placebo (p<0.01).

Table 13: H. pylori Eradication Rates at 4 Weeks after 10 Day Treatment Regimen % of Adult Patients Cured [95% Confidence Interval] (Number of Patients)
Study No. of Patients Treatment Group % of Patients Remaining Gastric Ulcer Free 1
1 191 194 184 Esomeprazole Magnesium Delayed-Release Capsules 20 mg Esomeprazole Magnesium Delayed-Release Capsules 40 mg Placebo 95.4 96.7 88.2
2 267 271 257 Esomeprazole Magnesium Delayed-Release Capsules 20 mg Esomeprazole Magnesium Delayed-Release Capsules 40 mg Placebo 94.7 95.3 83.3

14.6 H. pylori Eradication in Adult Patients with Duodenal Ulcer Disease

Two multicenter, randomized, double-blind studies were conducted in adult patients using a 10-day treatment regimen ofTriple Therapy (Esomeprazole magnesium delayed-release capsules, amoxicillin and clarithromycin): The first study (191) compared Esomeprazole magnesium delayed-release capsules 40 mg once daily in combination with amoxicillin 1,000 mg twice daily and clarithromycin 500 mg twice daily to Esomeprazole magnesium delayed-release capsules 40 mg once daily plus clarithromycin 500 mg twice daily. The second study (193) compared Esomeprazole magnesium delayed-release capsules 40 mg once daily in combination with amoxicillin 1,000 mg twice daily and clarithromycin 500 mg twice daily to esomeprazole magnesium delayed-release capsules 40 mg once daily. H. pylori eradication rates, defined as at least two negative tests and no positive tests from CLOtest ® , histology and/or culture, at 4 weeks post-therapy were significantly higher in the esomeprazole magnesium delayed-release capsules plus amoxicillin and clarithromycin group than in the esomeprazole magnesium delayed-release capsules plus clarithromycin or esomeprazole magnesium delayed-release capsules alone group. The results are shown in Table 14:

1. Patients were included in the analysis if they had H. pylori infection documented at baseline, had at least one endoscopically verified duodenal ulcer ≥ 0.5 cm in diameter at baseline or had a documented history of duodenal ulcer disease within the past 5 years, and were not protocol violators. Patients who dropped out of the study due to an adverse reaction related to the study drug were included in the analysis as not H. pylori eradicated.

2. Patients were included in the analysis if they had documented H. pylori infection at baseline, had at least one documented duodenal ulcer at baseline, or had a documented history of duodenal ulcer disease, and took at least one dose of study medication. All dropouts were included as not H. pylori eradicated.

3. p < 0.05 compared to Esomeprazole magnesium delayed-release capsules plus clarithromycin.

4. p < 0.05 compared to Esomeprazole magnesium delayed-release capsules alone.

Table 14: H. pylori Eradication Rates at 4 Weeks after 10 Day Treatment Regimen % of Adult Patients Cured [95% Confidence Interval] (Number of Patients)
Study Treatment Group Per-Protocol 1 Intent-to-Treat 2
191 Esomeprazole Magnesium Delayed-Release Capsules plus amoxicillin and clarithromycin 84% 3 [78, 89] (n=196) 77% 3 [71, 82] (n=233)
Esomeprazole Magnesium Delayed-Release Capsules plus clarithromycin 55% [48, 62] (n=187) 52% [45, 59] (n=215)
193 Esomeprazole Magnesium Delayed-Release Capsules plus amoxicillin and clarithromycin 85% 4 [74, 93] (n=67) 78% 4 [67, 87] (n=74)
Esomeprazole Magnesium Delayed-Release Capsules 5% [0, 23] (n=22) 4% [0, 21] (n=24)

The percentage of patients with a healed baseline duodenal ulcer by 4 weeks after the 10 day treatment regimen in the esomeprazole magnesium delayed-release capsules plus amoxicillin and clarithromycin group was 75% (n=156) and 57% (n=60) respectively, in the 191 and 193 studies (per-protocol analysis).

14.7 Pathological Hypersecretory Conditions, Including Zollinger-Ellison Syndrome, in Adults

In a multicenter, open-label dose-escalation study of 21 adult patients (15 males and 6 females, 18 Caucasian and 3 Black, mean age of 56 years) with pathological hypersecretory conditions, such as Zollinger-Ellison Syndrome, esomeprazole magnesium delayed-release capsules significantly inhibited gastric acid secretion. The initial dosage esomeprazole magnesium delayed-release capsules was 40 mg twice daily in 19 patients and 80 mg twice daily in 2 patients. Total daily doses ranging from 80 mg to 240 mg for 12 months maintained gastric acid output below the target levels of 10 mEq/h in patients without prior gastric acid-reducing surgery and below 5 mEq/hr in patients with prior gastric acid-reducing surgery. At the Month 12 final visit, 18/20 (90%) patients had Basal Acid Output (BAO) under satisfactory control (median BAO = 0.17 mmol/hr). Of the 18 patients evaluated with a starting dose of 40 mg twice daily, 13 (72%) had their BAO controlled with the original dosing regimen at the final visit. See Table 15.

Table 15: Adequate Acid Suppression at Final Visit by Dosage Regimen in Adult Patients with Pathological Hypersecretory Conditions

1. One patient was not evaluated

Esomeprazole Magnesium Delayed-Release Capsules dose at the Month 12 visit BAO under adequate control at the Month 12 visit (N=20) 1
40 mg twice daily 13/15
80 mg twice daily 4/4
80 mg three times daily 1/1

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