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

This study has been terminated.
(Recruitment challenges and results of interim futility analysis, which showed less than likely to achieve primary endpoint goal-length of hospital stay.)
Sponsor:
Information provided by (Responsible Party):
Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier:
NCT01227512
First received: October 22, 2010
Last updated: May 6, 2013
Last verified: May 2013

October 22, 2010
May 6, 2013
October 2010
May 2013   (final data collection date for primary outcome measure)
Length of Hospital Stay [ Time Frame: 45 days ] [ Designated as safety issue: No ]
Compare treatment with tolvaptan without fluid restriction to placebo with fluid restriction [ Time Frame: 14 days ] [ Designated as safety issue: No ]
The primary efficacy endpoint for this trial is to compare treatment with tolvaptan without fluid restriction to placebo with fluid restriction on time to hospital discharge from trial treatment initiation through Day 14 post-dose.
Complete list of historical versions of study NCT01227512 on ClinicalTrials.gov Archive Site
  • CGI-S Score [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
    Change from baseline in Clinical Global Impression-Severity(CGI-S) of hyponatremia symptoms.
  • CGI-S Score [ Time Frame: 24 and 72 hours ] [ Designated as safety issue: No ]
    Change from baseline in Clinical Global Impression-Severity(CGI-S) of hyponatremia symptoms.
  • CGI-I score [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
    Clinical Global Impression - Improvement(CGI-I)score of hyponatremia symptoms.
  • Serum Sodium Concentration [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
    Change from baseline in serum sodium concentration(24 hour AUC).
  • Time to 2-point improvement in CGI-S score [ Time Frame: 7 days ] [ Designated as safety issue: No ]
  • Percentage of responders [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
    Clinical Global Impression-Improvement (CGI-I) score improved to a score of 1 or 2.
  • Rescue Therapy [ Time Frame: 7 days ] [ Designated as safety issue: No ]
    Percentage of subjects requiring rescue therapy for hyponatremia.
  • Key secondary: Change in CGI-S of hyponatremia symptoms from pretreatment baseline to 48 hours post first dose, or at discharge/rescue therapy if earlier [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
  • Change in CGI-S of hyponatremia symptoms from pretreatment baseline at 24 and 72 hours post first dose, or at discharge/rescue therapy if earlier [ Time Frame: 24 and 72 hours ] [ Designated as safety issue: No ]
  • Clinical Global Impression - Improvement scale (CGI-I) score at 48 hours post first dose or discharge/rescue therapy, if earlier. [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
  • Percentage of subjects requiring rescue therapy for hyponatremia through Day 7 post first dose [ Time Frame: 7 days ] [ Designated as safety issue: Yes ]
  • Time to 2-point improvement in CGI-S score [ Time Frame: 7 days ] [ Designated as safety issue: No ]
  • Percentage of responders (CGI-I score of 1 = very much improved or 2 = much improved) at 48 hours post first dose or discharge/rescue therapy, if earlier [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
  • Descriptive summary statistics for standard safety assessments [ Time Frame: 24, 48, and 72 hours ] [ Designated as safety issue: Yes ]
    Adverse events, vital signs, laboratory tests, and physical examinations
Not Provided
Not Provided
 
Effects of Tolvaptan vs Fluid Restriction in Hospitalized Subjects With Dilutional Hyponatremia
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

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.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
  • Hyponatremia
  • Dilutional Hyponatremia
  • Inappropriate ADH Syndrome
  • Drug: tolvaptan
    15 mg titrated to 30 mg then 60 mg once daily as oral tablet for up to 7 days based on response.
    Other Names:
    • SAMSCA
    • OPC-41061
    • OPC-156
  • Other: 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.
  • Experimental: Tolvaptan 15-60mg
    Oral tablet without fluid restriction. After the initial dose, daily dose may be titrated based on response.
    Intervention: Drug: tolvaptan
  • Active Comparator: Fluid Restriction
    Placebo tablet with prescribed fluid restriction. After the initial dose, level of fluid restriction may titrated based response.
    Intervention: Other: Fluid Restriction
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
124
May 2013
May 2013   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01227512
156-08-275
No
Otsuka Pharmaceutical Development & Commercialization, Inc.
Otsuka Pharmaceutical Development & Commercialization, Inc.
Not Provided
Study Director: Ann Dandurand, MD Otsuka Pharmaceutical Development & Commercialization, Inc.
Otsuka Pharmaceutical Development & Commercialization, Inc.
May 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP