Analysis of the symptom response to esomeprazole 20 mg over days 1-4 of a 14-day course of treatment for frequent heartburn: results of two randomised controlled trials

Abstract

Background: Drug exposure and corresponding antisecretory effects increase over the first 4-5 days of esomeprazole treatment. To date, this effect has not been correlated with symptomatic improvement. Therefore, the efficacy of esomeprazole was evaluated on days 1-4 and 5-14 using pooled data from two identical randomised, double-blind, placebo-controlled studies conducted in subjects with frequent heartburn who are likely to self-treat with over-the-counter medications.

Methods: Adults without confirmed diagnoses of gastro-oesophageal reflux disease experiencing heartburn 2 or more days per week in the past 4 weeks were randomly assigned to treatment with esomeprazole 20 mg or placebo once daily for 14 days following a 1-week placebo run-in period (esomeprazole: n=330; placebo: n=321). Heartburn episodes were documented in daily diaries. The current analyses evaluated the change in baseline percentage of heartburn-free days across days 1-4 and 5-14.

Results: Change in the percentage of heartburn-free days from the run-in was significantly greater with esomeprazole compared with placebo (p<0.001) starting on days 1-4. The greatest treatment benefit was observed during days 5-14. During this period, esomeprazole-treated subjects increased their heartburn-free time over the run-in period by 32.5% compared with 14.3% with placebo (p<0.001).

Conclusions: Frequent heartburn sufferers treated with esomeprazole 20 mg had significantly more heartburn-free days relative to placebo throughout the studies. Maximal clinical benefits coincided with the estimated timing of maximal pharmacokinetic and pharmacodynamic effects and duration of acid control on days 5-14.

Trial registration number: NCT01370525; NCT01370538.

Keywords: esomeprazole; gastric acid/secretion; heartburn; proton-pump inhibitor.

Conflict of interest statement

Competing interests: DP reports personal fees from Takeda and Horizon outside the submitted work and has served as a consultant for AstraZeneca, Pfizer, Takeda and Horizon. ALM, HW and CP are former employees of Pfizer Consumer Healthcare.

Figures

Figure 1

Study design. *More frequent heartburn defined as 6 or more days of heartburn during the run-in period. †Less frequent heartburn defined as fewer than 6 days of heartburn during the run-in period. qd, once a day.

Figure 2

Change in the least squares mean percentage of heartburn-free days from the run-in period. (A) In the full analysis set. (B) In subjects with more frequent heartburn (defined as 6 or more days of heartburn during the run-in period). (C) In subjects with less frequent heartburn (defined as fewer than 6 days of heartburn during the run-in period). *p