Effects of Tolvaptan vs Fluid Restriction in Hospitalized Subjects With Dilutional Hyponatremia

NCT ID: NCT01227512

Last Updated: 2014-10-30

Study Results

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE3

Total Enrollment

124 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-10-31

Study Completion Date

2013-05-31

Brief Summary

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The purpose of this study is to determine if hospitalized patients with symptomatic hyponatremia treated with tolvaptan are in the hospital for less time than patients treated with fluid restriction. The study will also test if tolvaptan is better than fluid restriction in treating the symptoms of hyponatremia in hospitalized patients.

Detailed Description

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Conditions

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Hyponatremia Dilutional Hyponatremia Inappropriate ADH Syndrome

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Participants

Study Groups

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Tolvaptan 15-60mg

Oral tablet without fluid restriction. After the initial dose, daily dose may be titrated based on response.

Group Type EXPERIMENTAL

tolvaptan

Intervention Type DRUG

15 mg titrated to 30 mg then 60 mg once daily as oral tablet for up to 7 days based on response.

Fluid Restriction

Placebo tablet with prescribed fluid restriction. After the initial dose, level of fluid restriction may titrated based response.

Group Type ACTIVE_COMPARATOR

Fluid Restriction

Intervention Type OTHER

Placebo tablet once daily with prescribed daily fluid intake of 1500 mL, then intensifying to 2 lower volumes of fluid intake for up to 7 days based on response.

Since all particpants were blinded to treatment, titration to stricter fluid restriction followed the same algorithm as tolvaptan, increasing both the level of fluid restriction and increasing the placebo "dose"

Interventions

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tolvaptan

15 mg titrated to 30 mg then 60 mg once daily as oral tablet for up to 7 days based on response.

Intervention Type DRUG

Fluid Restriction

Placebo tablet once daily with prescribed daily fluid intake of 1500 mL, then intensifying to 2 lower volumes of fluid intake for up to 7 days based on response.

Since all particpants were blinded to treatment, titration to stricter fluid restriction followed the same algorithm as tolvaptan, increasing both the level of fluid restriction and increasing the placebo "dose"

Intervention Type OTHER

Other Intervention Names

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SAMSCA OPC-41061 OPC-156

Eligibility Criteria

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Inclusion Criteria

* Hyponatremia in clinically euvolemic or hypervolemic states, defined as serum sodium \< 130 mEq/L prior to randomization
* Clinically significant symptoms of hyponatremia, defined as a CGI-S score between 3-6, inclusive
* Female subjects of child bearing potential who agree to remain abstinent or to practice double-barrier forms of birth control from screening through 30 days following first dose on IMP

Exclusion Criteria

* Women who are pregnant or breast feeding, and females of childbearing potential who are not using acceptable contraceptive methods (such as barrier contraceptives or methods that result in a failure rate of less than 1%)
* Hyponatremia in hypovolemic states, defined as the presence of clinical and historical evidence of extracellular fluid volume depletion, including but not limited to skin turgor, orthostatic changes in blood pressure or heart rate, dry mucous membranes, or a response to IV saline challenge
* Subjects who are likely to require prolonged hospitalization for reasons other than hyponatremia, eg. new femoral fracture, surgeries requiring extended recovery
* Recent prior treatment for hyponatremia: hypertonic saline (including normal saline challenge) (within 8 hours of baseline) or urea, lithium, demeclocycline, conivaptan or tolvaptan (within 4 days of baseline). Includes any treatment, other than fluid restriction for the purpose of increasing serum sodium.
* Hyponatremia symptoms of a severity (eg, CGI = 7) such that they require immediate intervention with hypertonic saline; or are expected to require such therapy within 48 hours
* Causes of neurological symptoms which are attributable to psychological (psychosis), structural (dementia of the Alzheimer's type, stroke, transient ischemic attack, multi-infarct dementia) or other metabolic causes (eg. hyper- or hypo-: oxemia, glycemia, calcemia, ammonemia, etc)
* Acute and transient hyponatremia associated with head trauma or severe neurological injury (eg. stroke, subdural hematoma)or the use of recreational drugs.
* History of hyponatremia known to be due to severe, untreated hypothyroidism/adrenal insufficiency
* Subjects with psychogenic polydipsia
* Systolic arterial blood pressure \< 90 mmHg at screening
* History of hypersensitivity and/or idiosyncratic reaction to benzazepine or benzazepine derivatives (such as benazepril), or tolvaptan
* History of drug or medication abuse within the 3 months prior to screening, or current alcohol abuse
* Uncontrolled diabetes mellitus defined as glucose \> 300 mg/dL \[16.7 mmol/L\]
* Current urinary tract obstruction (eg, obstructive benign prostatic hypertrophy)
* Current condition of anuria
* Serum creatinine \> 3.5 mg/dL at screening
* Terminally ill or moribund condition with little chance of short-term (eg, 30 day) survival
* Subjects whose hyponatremia is the result of any medication that can safely be withdrawn (examples of drugs often not withdrawn include: anticonvulsants \[eg, carbamazepine\] and antipsychotics \[eg, haloperidol\])
* Patients receiving DDAVP within 2 days of screening
* Patients with history of active variceal bleeding within the past 30 days, without prior approval from sponsor medical monitor
* Participation in another investigational drug trial within the past 30 days
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Otsuka Pharmaceutical Development & Commercialization, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Ann Dandurand, MD

Role: STUDY_DIRECTOR

Otsuka Pharmaceutical Development & Commercialization, Inc.

Locations

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Otsuka Investigational Site

Birmingham, Alabama, United States

Site Status

Otsuka Investigational Site

Birmingham, Alabama, United States

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Otsuka Investigational Site

Mobile, Alabama, United States

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Otsuka Investigational Site

Azusa, California, United States

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Otsuka Investigational Site

Banning, California, United States

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Otsuka Investigational Site

Culver City, California, United States

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Otsuka Investigational Site

Fountain Valley, California, United States

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Otsuka Investigational Site

Los Angeles, California, United States

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Otsuka Investigational Site

Los Angeles, California, United States

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Otsuka Investigational Site

Northridge, California, United States

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Otuska Investigational Site

Orange, California, United States

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Otsuka Investigational Site

Yorba Linda, California, United States

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Otsuka Investigational Site

Denver, Colorado, United States

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Otsuka Investigational Site

Washington D.C., District of Columbia, United States

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Otsuka Investigational Site

Jacksonville, Florida, United States

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Jacksonville, Florida, United States

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Jacksonville, Florida, United States

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Orlando, Florida, United States

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Port Charlotte, Florida, United States

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Savannah, Georgia, United States

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Elizabethtown, Kentucky, United States

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Baltimore, Maryland, United States

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Springfield, Massachusetts, United States

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Saginaw, Michigan, United States

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Southfield, Michigan, United States

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Minneapolis, Minnesota, United States

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Rochester, Minnesota, United States

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Jackson, Mississippi, United States

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St Louis, Missouri, United States

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Grand Island, Nebraska, United States

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Omaha, Nebraska, United States

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Haddon Heights, New Jersey, United States

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Otsuka Investigational Site

Newark, New Jersey, United States

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Buffalo, New York, United States

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Buffalo, New York, United States

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Jamaica, New York, United States

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New York, New York, United States

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The Bronx, New York, United States

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Cincinnati, Ohio, United States

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Cleveland, Ohio, United States

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Columbus, Ohio, United States

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Fairfield, Ohio, United States

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Toledo, Ohio, United States

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Oklahoma City, Oklahoma, United States

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Bethleham, Pennsylvania, United States

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Philadelphia, Pennsylvania, United States

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Philadelphia, Pennsylvania, United States

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West Reading, Pennsylvania, United States

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Providence, Rhode Island, United States

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Otsuka Investigational Site

Galveston, Texas, United States

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Otsuka Investigational Site

Houston, Texas, United States

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Otsuka Investigational Site

Mission, Texas, United States

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Otsuka Investigational Site

San Antonio, Texas, United States

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Otsuka Investigational Site

San Antonio, Texas, United States

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Otsuka Investigational Site

Fairfax, Virginia, United States

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Otsuka Investigational Site

Madison, Wisconsin, United States

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Countries

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United States

Other Identifiers

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156-08-275

Identifier Type: -

Identifier Source: org_study_id

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