Lofexidine Food Effect Study in Healthy Volunteers

This is a single-dose, open-label, randomized, two-period, two-way crossover, food-effect study in which 12 healthy adult subjects will receive two separate single-dose administrations of lofexidine 400 μg (2 x 200 μg tablet). In one study period, subjects will be administered the study treatment following an overnight fast of at least 10 hours. In the other study period subjects will fast overnight for at least 10 hours, then begin consuming an FDA standard high-calorie, high-fat breakfast meal 30 minutes prior to administration of the study drug. Subjects will be assigned numbers in an ascending order, based on successful completion of the screening process. Subjects will receive each of the treatments listed below in randomized fashion during the two treatment periods: Treatment A: Test Formulation Lofexidine 400 μg Dose = 2 x 200 μg tablet administered under fasted conditions US WorldMeds, LLC Treatment B: Test Formulation Lofexidine 400 μg Dose = 2 x 200 μg tablet administered under fed conditions US WorldMeds, LLC Each drug administration will be separated by a washout period of at least seven days. Each dose will be orally administered along with 240 mL (8 fl. oz.) of room temperature tap water. After dosing, no food will be allowed until 4 hours post-dose. Except for the 240 mL of room temperature tap water provided with the dose, no water may be consumed for 1 hour prior through 1 hour post dose. Meals will be the same and scheduled at approximately the same times relative to dose for each study period. In order to prevent adverse events (AEs) of hypotension, all subjects will have intravenous (IV) access established at each check-in and will be administered normal saline (NS) at a continuous rate of 150 cc/hour until 1 hour prior to each dose administration. The IV catheter will remain in place for at least 12 hours postdose so that additional fluid can be administered if needed. If symptoms or clinically significant hypotension persist, IV fluid administration may continue for more than 12 hours, until it is no longer needed as determined by the Investigator. Subjects who withdraw from the study may be replaced. During each study period, 6 mL blood samples will be obtained prior to each dosing and following each dose at selected times through 48 hours post-dose. A total of 28 pharmacokinetic blood samples will be collected from each subject, 14 samples in each study period. Plasma pharmacokinetic samples will be analyzed for lofexidine using a validated analytical method. Appropriate pharmacokinetic parameters will be calculated for each formulation using non-compartmental methods. In addition, blood will be drawn and urine will be collected for clinical laboratory testing at screening and at the end of the study.