Phase 3b, Multicenter, Randomized, Single-blind, Parallel Group Trial of the Effects of Titrated Oral SAMSCA(r) (Tolvaptan) 15, 30, or 60 mg QD Compared to Placebo Plus Fluid Restriction on Length of Hospital Stay and Symptoms in Subjects Hospitalized With Dilutional Hyponatremia

Otsuka Pharmaceutical Development & Commercialization, Inc.2 sites in 1 country124 target enrollmentOctober 2010

ConditionsHyponatremia Dilutional Hyponatremia Inappropriate ADH Syndrome

Interventionstolvaptan Fluid Restriction

Drugstolvaptan

Overview

Phase: Phase 3
Intervention: tolvaptan
Conditions: Hyponatremia
Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
Enrollment: 124
Locations: 2
Primary Endpoint: Length of Hospital Stay (LoS)
Status: Terminated
Last Updated: 11 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

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.

Registry

clinicaltrials.gov

Start Date

October 2010

End Date

May 2013

Last Updated

11 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Otsuka Pharmaceutical Development & Commercialization, Inc.

Responsible Party

Sponsor

Eligibility Criteria

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

Arms & Interventions

Tolvaptan 15-60mg

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

Intervention: tolvaptan

Fluid Restriction

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

Intervention: Fluid Restriction

Outcomes

Primary Outcomes

Length of Hospital Stay (LoS)

Time Frame: 45 days

LoS was time to clinically ready to be hospital discharged (CRBD) from study treatment initiation, disregarding prolonged hospitalization due solely to social factors.

Secondary Outcomes

Change From Baseline to 48 Hour Post Dose in Clinical Global Impression-Severity (CGI-S) of Hyponatremia Symptoms.(Baseline to 48 hours post dose)
Change From Baseline to 24 and 72 Hours Post Dose in CGI-S of Hyponatremia Symptoms.(Baseline to 24 and 72 hours post dose)
Change From Baseline to 48 Hours Post Dose in Clinical Global Impression - Improvement (CGI-I) Score of Hyponatremia Symptoms.(Baseline to 48 hours post dose)
Change From Baseline in Serum Sodium Concentration (24 Hour Area Under the Curve [AUC]).(0 to 72 hours)
Time to First 2-point Improvement in CGI-S Score.(Up to 72 hours)
Percentage of Participants With Clinical Global Impression-Improvement (CGI-I) Score Improved to a Score of 1 or 2.(48 hours post dose)
Percentage of Participants Requiring Rescue Therapy for Hyponatremia(7 days)