PI-048 - COMPARISON OF PHARMACOKINETICS AND PHARMACODYNAMICS OF HIP1802 AND NEXIUM®: A RANDOMIZED, OPEN-LABEL, MULTIPLE DOSE, CROSSOVER TRIAL.

H. Ryu¹, B. Kim¹, J. Oh², S. Lee¹; ¹Seoul National University Bundang Hospital, Seoul, Republic of Korea, ²Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea.

Background: HIP1802 is a newly developed bi-layer, magnesium hydroxide containing tablet of esomeprazole for the treatment of gastroesophageal reflux disease (GERD). The aim of this study was to evaluate the pharmacokinetics (PKs), and pharmacodynamics (PDs) after single and multiple oral doses of HIP1802 compared to the reference drug, Nexium®.

Methods: A randomized, open-label, 2-sequence, 2-period, multiple-dose, crossover study was conducted in healthy adults. In each period, subjects received once-daily oral doses of HIP1802 40 mg or Nexium® 40 mg for seven days, with a 14-day washout in between periods. Serial blood samples were collected up to 24 hours post-dose for PK assessment, and non-compartmental analysis was performed. 24-hour intragastric pH was monitored at baseline, after the first and the 7th dose. The geometric mean ratios (GMRs) and their 90% confidence interval (CI) for the PK and PD parameters of HIP1802 to Nexium® were calculated.

Results: A total of 46 out of 49 randomized subjects completed the study. The median time (range) to reach the peak esomeprazole concentration after single oral dose of HIP1802 administration was 0.48 (0.32-4.00) hours, showing the characteristics of immediate release formulation. The GMR (90% CI) for the area under the esomeprazole concentration time curve in the steady state (AUCtau) was 1.1001 (1.0607 - 1.1410). The GMR (90% CI) for the percent decrease of integrated gastric acidity from baseline for 24-hour, were 0.9913 (0.9513 – 1.0329) and 1.0286 (0.9950 – 1.0635) for single and multiple doses, respectively.

Conclusion: HIP1802 was rapidly absorbed, and the suppression of gastric acid secretion as well as the overall systemic exposure were similar to Nexium®, expecting the similar therapeutic efficacy in GERD.