Abstract

The novel Type B gamma-aminobutyric acid (GABA_B)-receptor agonist lesogaberan (AZD3355) has been evaluated as an add-on to proton pump inhibitor treatment for gastroesophageal reflux disease, but the effect of food on the bioavailability of this compound has not been assessed. In this openlabel crossover study, healthy males received single 100 mg doses of lesogaberan (oral solution (A) or oral modified release (MR) capsules with a dissolution rate of 50% (B) or 100% (C) over 4 h) with and without food. Blood plasma concentrations of lesogaberan were assessed over 48 h. A log-transformed geometric mean C_max and AUC ratio within the 90% confidence interval (CI) range (0.80 – 1.25) was defined as excluding a clinically relevant food effect. Overall, 57 subjects completed the study. Only the oral lesogaberan solution had a fed/fasting C_max ratio outside the 90% CI range (C_max ratio: 0.76). AUC ratios were within the 90% CI limits for all three lesogaberan formulations. The only substantial change in tmax associated with food intake was observed for the oral solution (1.0 h without food, 1.8 h with food). In conclusion, a clinically relevant food effect could be excluded for the lesogaberan MR formulations, but not for the oral lesogaberan solution.

Author Details

Authors

• Bo Fransson¹
• Debra G. Silberg²
• Mohammad Niazi³
• Frank Miller¹
• Magnus Ruth³
• Ann Aurell Holmberg³

Departments

• ¹ AstraZeneca R&D, Södertälje, Sweden,
• ² AstraZeneca LP, Wilmington, DE, USA and
• ³ AstraZeneca R&D, Mölndal, Sweden

Address

Ann Aurell Holmberg
AstraZeneca R&D
431 83, Mölndal, Sweden
Email: [email protected]

Citation