Randomized, Placebo-Controlled, Crossover Pharmacodynamic Study Comparing the Effects of Zegerid® Capsule to Prevacid® Delayed-Release Capsule

Abstract

Purpose: The primary objective was to evaluate the difference in the onset of action between two PPIs in fasting subjects on the seventh day of treatment. The secondary objectives included evaluations such as the difference in the onset of action in fasting subjects on the 1st day of treatment, the median time to an intragastric pH >4.0 for 10 consecutive minutes after drug administration on day 1 and day 7 of treatment, etc. Methods: Subjects were healthy male or female non-Asian adults within the age range of 18-65 years. Subjects were randomized to a three-way crossover to either Zegerid Capsules (20 mg omeprazole/1100 mg sodium bicarbonate), Prevacid Capsules (15 mg lansoprazole), or no-treatment. The treatment or no-treatment periods were 7 days. There was a minimum two-week washout period between treatments. Subjects underwent a 24-hour intragastric pH study on the first and seventh days of each period. A total of 63 subjects were randomized, and 59 completed per protocol. The primary efficacy endpoint was the earliest time for which a statistically significant difference between the median intragastric pH scores for three consecutive five-minute intervals at steady-state on day 7. Secondary efficacy endpoints included evaluation of primary efficacy endpoint on day one, determination of the time to sustained difference in inhibition of intragastric acidity between the two active study treatments on day 1 and day 7, etc. A total of 14 subjects experienced 21 treatment-emergent adverse events. Results: Zegerid achieved significant difference over Prevacid on day 7 for all of the five-minutes postdose intervals beginning at the 10-15 minute interval (p = 0.0242) and sustaining through the 115-120 minute interval (p = 0.0170). On day 7, over the 24-hour period, Zegerid maintained pH > 3.5 and 4 significantly longer than Prevacid (p=0.0075), and held the pH > 3.5 and 4 more than 50% of the time (at least 12 hours; p=0.0209). Zegerid maintained the pH >4 significantly longer than Prevacid during the first four hours after dosing, with the first dose on day 1 (p= 0.0021), and the last dose on day 7 (p <0.0001). Conclusion: Zegerid capsules provide a significantly stronger acid suppressing pharmacodynamic effect, both in onset and duration of effect, than Prevacid capsules. The results also confirmed significant pH control over placebo in both active treatments. Both Zegerid and Prevacid were safe and well-tolerated. Disclosure - Dr. McGraw, and O'Mullane are employees of Merck. Dr. Pratha is a Merck consultant, and was the investigator. Mr. Tobin is employed by the CRO that provided study support services for Merck (performed the analyses, etc.). This research was supported by an industry grant from Merck.