Study design.
This was an open-label, 3-period, fixed sequence, drug-drug interaction study. In Period 1, day 1, subjects received a single oral dose of TBP-PI-HBr 600 mg (2 × 300 mg tablets) at hour 0 (Treatment A). In Period 2, day 1, subjects received a single oral dose of 20 mL aluminum hydroxide 800 mg/magnesium hydroxide 800 mg/simethicone 80 mg suspension with a single oral dose of TBP-PI-HBr 600 mg at hour 0 (Treatment B). In Period 3, days 1 through 5, subjects received a single oral dose of omeprazole 40 mg once daily (QD), at hour -2 (relative to the expected dosing time of TBP-PI-HBr on day 5) (Treatment C). On day 5, a single oral dose of 600 mg TBP-PI-HBr was administered at hour 0. A washout period of at least 7 days was included between dosing in Period 1 and Period 2, and between dosing in Period 2 and Period 3.On day -1 of Period 1, subjects reported to the clinic and commenced a 10-h overnight fast. On the morning of day 1 of Period 1, subjects received study drug with 240 mL of tap water. Water (except water provided with each dosing) was restricted 1 h prior to and 1 h after each study drug administration, but was allowed as needed at all other times. Subjects continued to fast for at least 4 h post dose on day 1 of Period 1. Subjects also fasted overnight for at least 10 h prior to dosing on day 1 of Period 2, and on day 5 of Period 3. Subjects continued the fast for at least 4 h post dose on day 1 of Period 2, and on day 5 of Period 3. On days 1 through 4 of Period 3, subjects fasted for at least 1 h prior to dosing, and remained fasted for at least 2 h post dose. In Periods 1 and 3, each dose of TBP-PI-HBr or omeprazole was administered orally with approximately 240 mL of water. In Period 2, 20 mL of aluminum hydroxide/magnesium hydroxide/simethicone suspension was administered orally, and the dosing vessel was rinsed twice with 60 mL of water to ensure complete consumption of the dose. TBP-PI-HBr was administered immediately after the aluminum hydroxide/magnesium hydroxide/simethicone dose with the remaining 100 mL of dosing water.