14.3 Treatment of Symptomatic GERD in Adults
Two U.S., multicenter, double-blind, placebo controlled studies were conducted in 316 adult patients with daytime and nighttime heartburn. Patients reported 5 or more periods of moderate to very severe heartburn during the placebo treatment phase the week prior to randomization. Patients were confirmed by endoscopy to have no esophageal erosions.
The percentage of heartburn free daytime and/or nighttime periods was greater with 20 mg rabeprazole sodium delayed-release tablets compared to placebo over the 4 weeks of study in Study RAB-USA-2 (47% vs. 23%) and Study RAB-USA-3 (52% vs. 28%). The mean decreases from baseline in average daytime and nighttime heartburn scores were significantly greater for rabeprazole sodium delayed-release tablets 20 mg as compared to placebo at week 4. Graphical displays depicting the daily mean daytime and nighttime scores are provided in Figures 2 to 5.
Figure 2: Mean Daytime Heartburn Scores RAB-USA-2
Figure 4: Mean Daytime Heartburn Scores RAB-USA-3
Figure 5: Mean Nighttime Heartburn Scores RAB-USA-3
In addition, the combined analysis of these two studies showed 20 mg of rabeprazole sodium delayed-release tablets significantly improved other GERD-associated symptoms (regurgitation, belching, and early satiety) by week 4 compared with placebo (all p values <0.005).
A dose of 20 mg rabeprazole sodium delayed-release tablets also significantly reduced daily antacid consumption versus placebo over 4 weeks (p<0.001). The recommended dosage of rabeprazole sodium delayed-release tablets is 20 mg once daily for 4 weeks.
In a U.S., randomized, double-blind, multicenter study assessing the effectiveness of 20 mg and 40 mg of rabeprazole sodium delayed-release tablets once daily versus placebo for healing endoscopically defined duodenal ulcers, 100 patients were treated for up to four weeks. Rabeprazole sodium delayed-release tablets were significantly superior to placebo in producing healing of duodenal ulcers. The percentages of patients with endoscopic healing are presented below:
|* p≤0.001 versus placebo|
|Week||Rabeprazole sodium delayed-release tablets||Placebo N=33|
|20 mg once daily N=34||40 mg once daily N=33|
At Weeks 2 and 4, significantly more patients in the rabeprazole sodium delayed-release tablets 20 and 40 mg groups reported complete resolution of ulcer pain frequency (p≤0.018), daytime pain severity (p≤0.023), and nighttime pain severity (p≤0.035) compared with placebo patients. The only exception was the 40 mg group versus placebo at Week 2 for duodenal ulcer pain frequency (p=0.094). Significant differences in resolution of daytime and nighttime pain were noted in both rabeprazole sodium delayed-release tablets groups relative to placebo by the end of the first week of the study. Significant reductions in daily antacid use were also noted in both rabeprazole sodium delayed-release tablets groups compared to placebo at Weeks 2 and 4 (p<0.001).
An international randomized, double-blind, active-controlled trial was conducted in 205 patients comparing 20 mg rabeprazole sodium delayed-release tablets once daily with 20 mg omeprazole once daily. The study was designed to provide at least 80% power to exclude a difference of at least 10% between rabeprazole sodium delayed-release tablets and omeprazole, assuming four-week healing response rates of 93% for both groups. In patients with endoscopically defined duodenal ulcers treated for up to four weeks, rabeprazole sodium delayed-release tablets were comparable to omeprazole in producing healing of duodenal ulcers. The percentages of patients with endoscopic healing at two and four weeks are presented below:
|Week||Rabeprazole sodium delayed-release tablets 20 mg once daily N=102||Omeprazole 20 mg once daily N=103||95% Confidence Interval for the Treatment Difference (Rabeprazole sodium delayed-release tablets-Omeprazole)|
Rabeprazole sodium delayed-release tablets and omeprazole were comparable in providing complete resolution of symptoms.
The recommended dosage of rabeprazole sodium delayed-release tablets is 20 mg once daily for 4 weeks.
14.5 Helicobacter pylori Eradication in Patients with Peptic Ulcer Disease or Symptomatic Non-Ulcer Disease in Adults
The U.S. multicenter study was a double-blind, parallel-group comparison of rabeprazole sodium delayed-release tablets, amoxicillin, and clarithromycin for 3, 7, or 10 days vs. omeprazole, amoxicillin, and clarithromycin for 10 days. Therapy consisted of rabeprazole 20 mg twice daily, amoxicillin 1000 mg twice daily, and clarithromycin 500 mg twice daily (RAC) or omeprazole 20 mg twice daily, amoxicillin 1000 mg twice daily, and clarithromycin 500 mg twice daily (OAC). Patients with H. pylori infection were stratified in a 1:1 ratio for those with peptic ulcer disease (active or a history of ulcer in the past five years) [PUD] and those who were symptomatic but without peptic ulcer disease [NPUD], as determined by upper gastrointestinal endoscopy. The overall H. pylori eradication rates, defined as negative 13 C-UBT for H. pylori ≥6 weeks from the end of the treatment are shown in the following table. The eradication rates in the 7-day and 10-day RAC regimens were found to be similar to 10-day OAC regimen using either the Intent-to-Treat (ITT) or Per-Protocol (PP) populations. Eradication rates in the RAC 3-day regimen were inferior to the other regimens.
Table 13: Helicobacter pylori Eradication at ≥6 Weeks After the End of Treatment
|Treatment Group Percent (%) of Patients Cured (Number of Patients)||Difference (RAC – OAC) [95% Confidence Interval]|
|7-day RAC*||10-day OAC|
|Per Protocol a||84.3% (N=166)||81.6% (N=179)||2.8 [- 5.2, 10.7]|
|Intent-to-Treat b||77.3% (N=194)||73.3% (N=206)||4.0 [- 4.4, 12.5]|
|10-day RAC*||10-day OAC|
|Per Protocol a||86.0% (N=171)||81.6% (N=179)||4.4 [- 3.3, 12.1]|
|Intent-to-Treat b||78.1% (N=196)||73.3% (N=206)||4.8 [- 3.6, 13.2]|
|3-day RAC||10-day OAC|
|Per Protocol a||29.9% (N=167)||81.6% (N=179)||- 51.6 [- 60.6, -- 42.6]|
|Intent-to-Treat b||27.3% (N=187)||73.3% (N=206)||- 46.0 [- 54.8, -- 37.2]|
a Patients were included in the analysis if they had H. pylori infection documented at baseline, defined as a positive 13 C-UBT plus rapid urease test or culture and were not protocol violators. Patients who dropped out of the study due to an adverse event related to the study drug were included in the evaluable analysis as failures of therapy.
b Patients were included in the analysis if they had documented H. pylori infection at baseline as defined above and took at least one dose of study medication. All dropouts were included as failures of therapy.
* The 95% confidence intervals for the difference in eradication rates for 7-day RAC minus 10-day RAC are (-9.3, 6.0) in the PP population and (-9.0, 7.5) in the ITT population.
The recommended dosage of rabeprazole sodium delayed-release tablets is 20 mg twice daily with amoxicillin and clarithromycin for 7 days.
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