Effects of Tolvaptan in Healthy Adults

NCT01973140 | Completed Phase 4 DMC

• 1 other identifier: STU00071984
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief 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. 1.The variable effect on urine output is due to individual differences in blood vasopressin which counteracts the effects of tolvaptan.
2. 2.The differences in blood vasopressin are due to individual differences in the amount secreted in response to a rise in blood sodium.
3. 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.
4. 4.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.
5. 5.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.

Conditions

Healthy

Keywords

Tolvaptan; Aquaretic Efficacy

Outcome Measures

Primary Outcomes (1)

• Levels of plasma vasopressin, urine osmolarity and plasma tolvaptan

  The relationship of urine osmolarity to each of three variables-plasma vasopressin. plasma tolvaptan and the ratio of plasma vasopressin to plasma tolvaptan- will be compared to determine which correlates best. The hypothesis predicts that the best fit will be between urine osmolarity and the ratio of plasma vasopressin to tolvaptan indicating that the variable effect of tolvaptan on urine output is due to competition with individual differences in plasma vasopressin.

  Throughout the 22 hours of the tolvaptan study .

Secondary Outcomes (1)

• Regression relationship of plasma vasopressin to plasma osmolarity/sodium during tolvaptan and saline infusion studies.

  During first 6 hours of each treatment

Other Outcomes (1)

• Relation of plasma sodium/osmolarity to time during tolvaptan and saline infusion studies.

  During first 6 hours of each study.

Study Arms (1)

Tolvaptan and Hypertonic saline infusion

OTHER

Tolvaptan 60 mg or 30 mg tablet by mouth for the first part of the study. A week later, infusion of hypertonic saline.

Drug: Tolvaptan; Drug: Hypertonic saline infusion

Interventions

Tolvaptan DRUG

Adult male volunteers will be given a given a 60mg or a 30 mg dose of tolvaptan. Blood and urine samples will be collected at specified time points for the next 24 hours.

Also known as: Samsca

Tolvaptan and Hypertonic saline infusion

Hypertonic saline infusion DRUG

A week after the first intervention(tolvaptan), the subjects will undergo a hypertonic saline infusion for 6 hours. Blood and urine samples will be collected at specified time points until 4hour hours after the infusion.

Also known as: 3% saline solution

Tolvaptan and Hypertonic saline infusion

Eligibility Criteria

• Age: 21 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Males
• years of age
• No major health problems or current medications
• Must be willing/able to avoid grapefruit products for 1 week prior to admission

You may not qualify if:

• Females
• Body weight \> or \< 15% of ideal
• Known allergy to tolvaptan
• Participation in another research study in previous 2 months
• Inability to sense thirst

Sponsors & Collaborators

• Northwestern University: lead
• Otsuka America Pharmaceutical: collaborator

Study Sites (1)

Clinical Research Unit Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

Location

MeSH Terms

Interventions

Tolvaptan; Saline Solution

Intervention Hierarchy (Ancestors)

Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Gary L Robertson, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 19, 2013
• First Posted: October 31, 2013
• Study Start: November 1, 2013
• Primary Completion: December 1, 2015
• Study Completion: March 1, 2016
• Last Updated: September 28, 2016

Record last verified: 2016-09

Locations

US (1)