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

• Register: ClinicalTrials.gov
• Last refreshed on: 19 October 2017
• Main ID: NCT01227512
• Date of registration: 22/10/2010
• Prospective Registration: No
• Primary sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
• Public title: Effects of Tolvaptan vs Fluid Restriction in Hospitalized Subjects With Dilutional Hyponatremia SALACIA
• Scientific title: 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
• Date of first enrolment: October 2010
• Target sample size: 124
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT01227512
• Study type: Interventional
• Phase: Phase 3

Countries of recruitment

United States

Contacts

• Name: Ann Dandurand, MD
• Affiliation: Otsuka Pharmaceutical Development & Commercialization, Inc.

Key inclusion & exclusion 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

- 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



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Dilutional Hyponatremia

Hyponatremia

Inappropriate ADH Syndrome

Intervention(s)

Drug: tolvaptan

Other: Fluid Restriction

Primary Outcome(s)

Length of Hospital Stay (LoS) [Time Frame: 45 days]

Secondary Outcome(s)

Percentage of Participants Requiring Rescue Therapy for Hyponatremia [Time Frame: 7 days]

Change From Baseline to 48 Hours Post Dose in Clinical Global Impression - Improvement (CGI-I) Score of Hyponatremia Symptoms. [Time Frame: Baseline to 48 hours post dose]

Change From Baseline in Serum Sodium Concentration (24 Hour Area Under the Curve [AUC]). [Time Frame: 0 to 72 hours]

Change From Baseline to 48 Hour Post Dose in Clinical Global Impression-Severity (CGI-S) of Hyponatremia Symptoms. [Time Frame: Baseline to 48 hours post dose]

Time to First 2-point Improvement in CGI-S Score. [Time Frame: Up to 72 hours]

Change From Baseline to 24 and 72 Hours Post Dose in CGI-S of Hyponatremia Symptoms. [Time Frame: Baseline to 24 and 72 hours post dose]

Percentage of Participants With Clinical Global Impression-Improvement (CGI-I) Score Improved to a Score of 1 or 2. [Time Frame: 48 hours post dose]

Secondary ID(s)

156-08-275

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 17/10/2014
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01227512