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.