Bioavailability Study Comparing Tolvaptan Administered Via Nasogastric Tube to Tolvaptan Tablets Swallowed Intact
Condition: Healthy
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of the study is to compare the relative bioavailability and pharmacokinetics of
      tolvaptan 15 mg tablets administered orally versus tolvaptan via nasogastric (NG) tube in
      healthy male and female subjects.

      This study is an open 2-treatment, 2-period, 2-sequence crossover study to compare the
      relative bioavailability of tolvaptan tablets to tolvaptan given via nasogastric tube in 28
      healthy adults. 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 tube, or the reverse sequence. Serial pharmacokinetic samples will be collected
      following each tolvaptan administration and safety assessments will be performed. The
      relative bioavailability of tolvaptan administered via nasogastric tube will be compared to
      tolvaptan tablets swallowed intact.
    

Detailed description: 
      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.
    

Intervention name(s): Tolvaptan; Tolvaptan
Intervention type(s): Drug; Drug
Intervention description(s): Tolvaptan 15 mg administered once orally as an intact tablet.; Tolvaptan 15 mg administered once via nasogastric tube.
Other intervention name(s): Samsca; Samsca
Intervention MeSH terms: Tolvaptan
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Bioavailability