Lansoprazole (Page 9 of 12)

14.2 Eradication of H. pylori to Reduce the Risk of Duodenal Ulcer Recurrence

Randomized, double-blind clinical studies performed in the U.S. in patients with H. pylori and duodenal ulcer disease (defined as an active ulcer or history of an ulcer within one year) evaluated the efficacy of lansoprazole in combination with amoxicillin and clarithromycin as triple 14 day therapy or in combination with amoxicillin as dual 14 day therapy for the eradication of H. pylori. Based on the results of these studies, the safety and efficacy of two different eradication regimens were established:

Triple therapy: Lansoprazole 30 mg twice daily/amoxicillin 1 g twice daily/clarithromycin 500 mg twice daily

Dual therapy: Lansoprazole 30 mg three times daily/amoxicillin 1 g three times daily

All treatments were for 14 days. H. pylori eradication was defined as two negative tests (culture and histology) at four to six weeks following the end of treatment.

Triple therapy was shown to be more effective than all possible dual therapy combinations. Dual therapy was shown to be more effective than both monotherapies. Eradication of H. pylori has been shown to reduce the risk of duodenal ulcer recurrence.

A randomized, double-blind clinical study performed in the U.S. in patients with H. pylori and duodenal ulcer disease (defined as an active ulcer or history of an ulcer within one year) compared the efficacy of lansoprazole triple therapy for 10 and 14 days. This study established that the 10 day triple therapy was equivalent to the 14 day triple therapy in eradicating H. pylori (Tables 11 and 12) [see Indications and Usage ( 1.2)]

Table 11. H. pylori Eradication Rates – Triple Therapy (lansoprazole/amoxicillin/clarithromycin) Percent of Patients Cured [95% Confidence Interval] (Number of patients)
Study	Duration	Triple Therapy Evaluable Analysis*	Triple Therapy Intent-to-Treat Analysis †
M93-131	14 days	92 ‡	86 ‡
		[80.0–97.7]	[73.3–93.5]
		(N=48)	(N=55)
M95-392	14 days	86 §	83 §
		[75.7–93.6]	[72.0–90.8]
		(N=66)	(N=70)
M95-399 ¶	14 days	85	82
		[77.0–91.0]	[73.9–88.1]
		(N=113)	(N=126)
	10 days	84	81
		[76.0–89.8]	[73.9–87.6]
		(N=123)	(N=135)

* Based on evaluable patients with confirmed duodenal ulcer (active or within one year) and H. pylori infection at baseline defined as at least two of three positive endoscopic tests from CLOtest, histology and/or culture. Patients were included in the analysis if they completed the study. Additionally, if patients dropped out of the study due to an adverse event related to the study drug, they were included in the evaluable analysis as failures of therapy.
^† Patients were included in the analysis if they had documented H. pylori infection at baseline as defined above and had a confirmed duodenal ulcer (active or within one year). All dropouts were included as failures of therapy.
^‡ (p<0.05) versus lansoprazole/amoxicillin and lansoprazole/clarithromycin dual therapy
^§ (p<0.05) versus clarithromycin/amoxicillin dual therapy. ^¶ The 95% confidence interval for the difference in eradication rates, 10-day minus 14-day is (-10.5, 8.1) in the evaluable analysis and (-9.7, 9.1) in the intent-to-treat analysis.

Table 12 H. pylori Eradication Rates – 14 Day Dual Therapy (lansoprazole/amoxicillin) Percent of Patients Cured [95% Confidence Interval] (Number of patients)
Study	Dual Therapy Evaluable Analysis*	Dual Therapy Intent-to-Treat Analysis †
M93-131	77 ‡	70 ‡
	[62.5–87.2]	[56.8–81.2]
	(N=51)	(N=60)
M93-125	66 §	61 §
	[51.9–77.5]	[48.5–72.9]
	(N=58)	(N=67)

* Based on evaluable patients with confirmed duodenal ulcer (active or within one year) and H. pylori infection at baseline defined as at least two of three positive endoscopic tests from CLOtest, histology and/or culture. Patients were included in the analysis if they completed the study. Additionally, if patients dropped out of the study due to an adverse event related to the study drug, they were included in the analysis as failures of therapy.
^† Patients were included in the analysis if they had documented H. pylori infection at baseline as defined above and had a confirmed duodenal ulcer (active or within one year). All dropouts were included as failures of therapy.
^‡ (p<0.05) versus lansoprazole alone. ^§ (p<0.05) versus lansoprazole alone or amoxicillin alone.

14.3 Maintenance of Healed Duodenal Ulcers

Lansoprazole has been shown to prevent the recurrence of duodenal ulcers. Two independent, double-blind, multicenter, controlled trials were conducted in patients with endoscopically confirmed healed duodenal ulcers. Patients remained healed significantly longer and the number of recurrences of duodenal ulcers was significantly less in patients treated with lansoprazole than in patients treated with placebo over a 12-month period (Table 13) [see Indications and Usage ( 1.4)]

Table 13 Endoscopic Remission Rates
Trial	Drug	No. of Pts.	Percent in Endoscopic Remission
			0–3 mo.	0–6 mo.	0–12 mo.
#1	Lansoprazole 15 mg daily	86	90%*	87%*	84%*
	Placebo	83	49%	41%	39%
#2	Lansoprazole 30 mg daily	18	94%*	94%*	85%*
	Lansoprazole 15 mg daily	15	87%*	79%*	70%*
	Placebo	15	33%	0%	0%

%=Life Table Estimate *(p≤0.001) versus placebo.

In trial #2, no significant difference was noted between lansoprazole 15 mg and 30 mg in maintaining remission.

14.4 Gastric Ulcer

In a U.S. multicenter, double-blind, placebo-controlled study of 253 patients with endoscopically documented gastric ulcer, the percentage of patients healed at four and eight weeks was significantly higher with lansoprazole 15 mg and 30 mg once a day than with placebo ( Table 14) [see Indications and Usage ( 1.4)]

Table 14. Gastric Ulcer Healing Rates
	Lansoprazole			Placebo (N=64)
Week	15 mg daily (N=65)	30 mg daily (N=63)	60 mg daily (N=61)
4	64.6%*	58.1%*	53.3%*	37.5%
8	92.2%*	96.8%*	93.2%*	76.7%

* (p≤0.05) versus placebo.

Patients treated with any lansoprazole dose reported significantly less day and night abdominal pain along with fewer days of antacid use and fewer antacid tablets used per day than the placebo group.

Independent substantiation of the effectiveness of lansoprazole 30 mg was provided by a meta-analysis of published and unpublished data.