Effects of Tolvaptan in Healthy Adults

• Status: Completed
• Trial end date: 2016-03-01
• Target enrollment: 0
• Participant gender: Male

Summary

Tolvaptan is one of new class of medications approved for treatment of low blood sodium (hyponatremia). It works by interfering with the effect of the antidiuretic hormone, vasopressin, thereby increasing urine output and decreasing body water. However, the magnitude of these effects vary from person to person. Thus, the efficacy of tolvaptan is less reliable than an infusion of a concentrated salt solution for emergency, short term treatment of hyponatremia.

This study is designed to test 3 hypotheses about the variable efficacy of tolvaptan.

1. The variable effect on urine output is due to individual differences in blood vasopressin which counteracts the effects of tolvaptan.

2. The differences in blood vasopressin are due to individual differences in the amount secreted in response to a rise in blood sodium.

3. The variable effect on blood sodium is due mainly to the variable effect on urine output and can be corrected by maintaining water intake below urine output.

The study has 2 parts and will be performed in 12 healthy adult males.

1. Six subjects will receive tolvaptan at a dose of 60 mg by mouth and six subjects will receive tolvaptan at 30 mg by mouth. Blood and urine will be collected hourly for 6 hours and water will be ingested in prescribed amounts. For the next 16 hours, subjects will drink at will and blood and urine will be collected 4 more times.

2. One week later, the same subjects will receive a concentrated salt solution (3% saline) by vein for 6 hours. During this time, blood and urine will be collected hourly but drinking will not be permitted. For the next 4 hours, subjects will be allowed to drink at will while blood and urine are collected twice more.

The volume, concentration and creatinine content of each urine will be determined. Blood will be analyzed for sodium, vasopressin and, in the first study, tolvaptan.

• Phase: Phase 4
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Northwestern University
• Collaborator: Otsuka America Pharmaceutical
• Treatments: Tolvaptan

Criteria

Inclusion Criteria:

• Males

• 21-55 years of age

• No major health problems or current medications

• Must be willing/able to avoid grapefruit products for 1 week prior to admission

Exclusion Criteria:

• Females

• Body weight > or < 15% of ideal

• Known allergy to tolvaptan

• Participation in another research study in previous 2 months

• Inability to sense thirst