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Effects of Tolvaptan in Healthy Adults

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ClinicalTrials.gov Identifier: NCT01973140
Recruitment Status : Completed
First Posted : October 31, 2013
Last Update Posted : September 28, 2016
Sponsor:
Collaborator:
Otsuka America Pharmaceutical
Information provided by (Responsible Party):
Gary Robertson, Northwestern University

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. 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.


Condition or disease Intervention/treatment Phase
Healthy Drug: Tolvaptan Drug: Hypertonic saline infusion Phase 4

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 17 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Official Title: Variation in the Aquaretic Efficacy of Tolvaptan in Healthy Adults
Study Start Date : November 2013
Actual Primary Completion Date : December 2015
Actual Study Completion Date : March 2016

Resource links provided by the National Library of Medicine

Drug Information available for: Tolvaptan

Arm Intervention/treatment
Tolvaptan and Hypertonic saline infusion
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
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.
Other Name: Samsca

Drug: Hypertonic saline infusion
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.
Other Name: 3% saline solution




Primary Outcome Measures :
  1. Levels of plasma vasopressin, urine osmolarity and plasma tolvaptan [ Time Frame: Throughout the 22 hours of the tolvaptan study . ]
    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.


Secondary Outcome Measures :
  1. Regression relationship of plasma vasopressin to plasma osmolarity/sodium during tolvaptan and saline infusion studies. [ Time Frame: During first 6 hours of each treatment ]
    The regression relationships of plasma vasopressin to plasma osmolarity/sodium during hypertonic saline infusion and tolvaptan administration will be compared to determine if, as predicted by the hypothesis, the slopes are similar within each subject but different between subjects.


Other Outcome Measures:
  1. Relation of plasma sodium/osmolarity to time during tolvaptan and saline infusion studies. [ Time Frame: During first 6 hours of each study. ]
    The relationship of plasma osmolarity/sodium to the number of hours from the start of the treatment will be calculated by regression analysis and compared to determine of the correlation coefficients differ. The hypothesis predicts the correlations will not differ indicating that the effect of tolvaptan on plasma osmolarity/sodium is as predictable as that of saline infusion when fluid intake is adjusted for variations in urine output.



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Ages Eligible for Study:   21 Years to 55 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01973140


Locations
United States, Illinois
Clinical Research Unit Northwestern Memorial Hospital
Chicago, Illinois, United States, 60611
Sponsors and Collaborators
Northwestern University
Otsuka America Pharmaceutical
Investigators
Principal Investigator: Gary L Robertson, MD Northwestern University

Responsible Party: Gary Robertson, Principal Investigator, Northwestern University
ClinicalTrials.gov Identifier: NCT01973140     History of Changes
Other Study ID Numbers: STU00071984
First Posted: October 31, 2013    Key Record Dates
Last Update Posted: September 28, 2016
Last Verified: September 2016

Keywords provided by Gary Robertson, Northwestern University:
Tolvaptan
Aquaretic Efficacy

Additional relevant MeSH terms:
Tolvaptan
Antidiuretic Hormone Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Natriuretic Agents
Physiological Effects of Drugs