Acid-suppressive effect of tegoprazan 12.5 mg BID: a phase 1 comparative study with tegoprazan 25 mg QD and famotidine 20 mg BID

Tegoprazan is a potassium-competitive acid blocker that directly inhibits the gastric proton pump, whereas famotidine is a histamine-2 receptor antagonist that indirectly suppresses acid secretion with known tolerance to repeated dosing. This phase 1 study evaluated the pharmacokinetics, pharmacodynamics, and safety of tegoprazan 12.5 mg twice daily (BID) compared with tegoprazan 25 mg once daily (QD) and famotidine 20 mg BID in healthy subjects. Thirty-six participants were randomized to one of the 3 regimens for 14 days. In pharmacokinetic analysis, tegoprazan 12.5 mg BID showed lower steady-state Cmax but higher trough concentrations than 25 mg QD, while overall systemic exposure was comparable, with a Day 14 geometric mean ratio for area under the concentration-time curve over 24 hours of 1.08 (90% confidence interval, 0.85-1.36). Pharmacodynamic assessment using 24-hour intragastric pH monitoring demonstrated superior and sustained acid suppression with tegoprazan 12.5 mg BID. On Day 14, the percentage of time with intragastric pH > 3 over 24 hours was 75.1% with tegoprazan 12.5 mg BID, compared with 55.4% with 25 mg QD and 40.3% with famotidine. Both tegoprazan regimens maintained relatively consistent acid suppression from Day 1 to Day 14 (71.8% to 75.1% and 56.4% to 55.4%), whereas famotidine showed a decline (65.3% to 40.3%). Similar time-dependent patterns were observed during the nighttime period and in the supine position. Tegoprazan 12.5 mg BID was well tolerated, with no adverse events reported in this group. These findings suggest that low-dose tegoprazan 12.5 mg BID provides safe and sustained acid suppression.