Analysis of 2-Week Data from Two Randomized, Controlled Trials Conducted in Subjects with Frequent Heartburn Treated with Esomeprazole 20 mg

Abstract

Purpose

These secondary analyses used data from 2 similarly designed studies in subjects experiencing frequent heartburn to evaluate the efficacy of esomeprazole 20 mg once daily for 2 weeks, which reflects the approved over-the-counter dosage and duration.

Methods

Subjects without endoscopically identified erosive esophagitis who were experiencing heartburn for ≥6 months and ≥4 of 7 days prior to baseline (study 1, N = 368; study 2, N = 349) were randomly assigned to receive double-blind treatment with esomeprazole 40 or 20 mg (administered as esomeprazole magnesium trihydrate 44.5 and 22.3 mg, respectively) or placebo once daily for 4 weeks. Subjects recorded the severity of heartburn in a daily diary, and investigators assessed subjects at each study visit. Two-week assessments were the primary end points of interest in these analyses and included the percentage of subjects with complete heartburn resolution (no episodes during 7 consecutive days), time to sustained complete heartburn resolution (the first of 7 consecutive episode-free days), and heartburn relief (no episodes other than ≤1 mild episode during 7 consecutive days).

Findings

At week 2, the percentages of subjects who experienced complete heartburn resolution were significantly greater with esomeprazole 40 mg (study 1, 26.1%; study 2, 35.3%) and 20 mg (study 1, 25.2%; study 2, 35.7%) compared with placebo (study 1, 9.0%; study 2, 3.4%) (all, P ≤ 0.001). Beginning on day 1, the percentages of subjects who experienced sustained heartburn resolution was significantly greater in the groups treated with esomeprazole 40 mg (study 1, 19%; study 2, 19%; P < 0.0001) and 20 mg (study 1, 10%; study 2, 15%; P < 0.05) compared with the group that received placebo (study 1, 2%; study 2, 1%). Additionally, at week 2, the percentages of subjects experiencing heartburn relief were significantly greater with esomeprazole 40 mg (study 1, 35.3%; study 2, 40.5%) and 20 mg (study 1, 34.5%; study 2, 46.4%) compared with placebo (study 1, 16.5%; study 2, 8.6%) (all, P ≤ 0.001).

Implications

The results of this study demonstrate that once-daily treatment with esomeprazole 20 mg for 2 weeks effectively resolved subjects׳ heartburn compared with placebo, beginning on day 1. Studies precede FDA Act 801 clinical trial registration and results submission requirements.

Introduction

The estimated prevalence of gastroesophageal reflux (GER) symptoms, including heartburn and/or acid regurgitation, ranges from 18% to 28% in North America and 9% to 34% in Europe, while in East Asia the rate is only 7% to 9%.1, 2 The occurrence of heartburn has been increasing each year, particularly in Western countries, and the prevalence increases with age.1, 3, 4 The frequency and severity of GER symptoms vary from person to person; therefore, treatment must be tailored toward an individual׳s given symptom profile.3, 5 Both moderate and severe GER symptoms produce significant impairments in occupational and psychosocial functioning, cause sleep disruptions, increase health care resource utilization, and reduce overall health-related quality of life.6, 7, 8, 9

Proton pump inhibitors (PPIs) are among the most effective and, therefore, widely used treatments for GER symptoms.⁵ A Cochrane Database systematic review of short-term (2- to 8-week) clinical trials of PPIs, histamine-2 receptor antagonists (H2RAs), and prokinetics demonstrated the effectiveness of these commonly utilized treatments in managing GER symptoms.¹⁰ These analyses found that PPIs offer a benefit over H2RAs and prokinetics, particularly in those whose diagnosis is based on symptomology (ie, the presence of heartburn) and not on endoscopic testing. Individuals can often manage mild GER symptoms by modifying their lifestyles and dietary choices, while those with moderate symptoms may treat them with over-the-counter (OTC) options prior to seeking formal medical attention in a health care setting.11, 12 These individuals often utilize self-care treatment options such as OTC antacids and PPIs to manage their symptoms.5, 13

Esomeprazole is a PPI approved by the US Food and Drug Administration (FDA) for short-term (14 days) OTC use for treating frequent (≥2 d/wk) heartburn.¹⁴ In the European Union, esomeprazole has been approved for treating GER symptoms, such as heartburn and acid regurgitation, at the same dosage for the same duration.¹⁵ Data from 2 identically designed large-scale, multicenter, randomized, double-blind, placebo-controlled, parallel-group trials of esomeprazole in subjects with chronic heartburn without erosive esophagitis¹⁶ supported the switch from prescription to OTC status in the European Union. To formally publish these data in the literature, the current secondary analyses present data collected during the first 2 weeks of these studies to characterize the efficacy and tolerability of short-term esomeprazole 20 mg treatment utilizing doses and durations that are consistent with the approved OTC regimen.