Bioavailability Study Comparing Tolvaptan Administered Via Nasogastric Tube to Tolvaptan Tablets Swallowed Intact

This study is an open 2-treatment, 2-period, 2-sequence crossover study to compare the
relative bioavailability of tolvaptan tablets to tolvaptan NG in 28 healthy adults. The
study will be conducted at the University of North Carolina (UNC) Hospital in the Clinical
Translational Research Center (CTRC). The study will consist of three phases (screening and
two drug administration visits). Subjects will be randomized to one of the two treatment
sequences; either tolvaptan oral tablets swallowed intact followed by a tablet crushed and
administered via nasogastric (NG) tube, or the reverse sequence. Because enrollment will be
staggered and males and females enrolled, the randomization will be blocked (groups of 4) to
minimize imbalance in assignment to the two sequences during the enrollment period, and will
be used in a bidirectional fashion to balance gender, with males entering with the lowest
subject numbers (#1, #2, etc.), and females with the highest subject numbers (#32, #31,
etc.) in the randomization schedule. The biomedical informatics core will generate the
randomization schedule. During each inpatient phase, pharmacokinetic parameters will be
monitored for 36 hours. Subjects will remain in the CTRC for 24 hours after each drug
administration to allow for adequate pharmacokinetic sampling. Subjects will return to the
clinic on study days 2 and 9 of the study schedule for 30 and 36 hour blood samples.
Subjects will then undergo a one-week washout period and then will be crossed over to the
alternative mode of administration. Subjects will be discharged from the study after vital
signs are checked on study days 2 and 9 of the study schedule at 36 hours, assuming the
subject is hemodynamically stable.