“SALT Trial” Study of Ascending Levels of Tolvaptan in Hyponatremia

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2015
• Main ID: NCT00072683
• Date of registration: 07/11/2003
• Prospective Registration: No
• Primary sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
• Public title: “SALT Trial” Study of Ascending Levels of Tolvaptan in Hyponatremia
• Scientific title: Multicenter, Randomized, Double-Blind, Placebo-Controlled, Efficacy and Safety Study of the Effects of Titrated Oral Tolvaptan Tablets in Patients With Hyponatremia
• Date of first enrolment: April 2003
• Target sample size: 240
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT00072683
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment
• Phase: Phase 3

Countries of recruitment

United States

Contacts

• Name: Nestor Molfino, MD
• Affiliation: Otsuka Pharmaceutical Development & Commercialization, Inc.

Key inclusion & exclusion criteria

Inclusion Criteria

- Hyponatremia in euvolemic or hypervolemic states, defined as serum sodium <135 mEq/L
prior to randomization.

- Able to give Informed Consent

Exclusion Criteria

- Women who are breast feeding and females of childbearing potential who are not using
acceptable contraceptive methods

- Hyponatremia in hypovolemic states.

- Acute and transient hyponatremia associated with head trauma or post-operative state.

- Hyponatremia due to uncontrolled hypothyroidism or uncontrolled adrenal
insufficiency.

- Cardiac surgery within 30 days of potential study enrollment, excluding percutaneous
coronary interventions.

- History of a myocardial infarction within 30 days of potential study enrollment.

- History of sustained ventricular tachycardia or ventricular fibrillation within 30
days, unless in the presence of an automatic implantable cardioverter defibrillator.

- Severe angina including angina at rest or at slight exertion and/or unstable angina.

- History of a cerebrovascular accident within the last 30 days. 10) Subjects with
psychogenic polydipsia may not be included, however subjects with other psychiatric
illness may be included.

- Systolic arterial blood pressure <90 mmHg.

- History of hypersensitivity and/or idiosyncratic reaction to benzazepine or
benzazepine derivatives (such as benazepril).

- History of drug or medication abuse within the past year,or current alcohol abuse.

- Uncontrolled diabetes mellitus defined as fasting glucose >300mg/dL.

- Urinary tract obstruction except BPH if non-obstructive.

- Previous participation in another clinical drug trial within the past 30 days.

- Previous participation in this or any other tolvaptan clinical trial.

- Terminally ill or moribund condition with little chance of short term survival.

- Serum creatinine >3.5 mg/dL.

- Serum sodium <120 mEq/L with associated neurologic impairment, i.e. symptoms such as
apathy, confusion, seizures.

- Patients with progressive or episodic neurologic disease such as multiple sclerosis
or history of multiple strokes.

- Child-Pugh score greater than 10 (unless approved)

- Patients receiving intravenous fluids at a rate greater than KVO (Keep Vein Open).

- Hyponatremia due to lab artifacts

- Patients receiving AVP or its analogs for treatment of any condition.

- Patients receiving within 7 days of randomization, other medications for treatment of
hyponatremia specifically: demeclocycline, lithium carbonate or urea

- Patients likely requiring IV saline for correction of symptomatic or asymptomatic
severe hyponatremia during the course of the study.

- Severe pulmonary artery hypertension

- Hyponatremia should not be the result of any medication that can safely be withdrawn



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

Health Condition(s) or Problem(s) studied

Water-Electrolyte Imbalances

Hyponatremias

Water Intoxication

Inappropriate ADH Syndrome

Intervention(s)

Drug: tolvaptan

Primary Outcome(s)

The average daily area under the curve of change from baseline in serum sodium level up to Day 30 within

The average daily area under the curve of change from baseline in serum sodium level up to Day 4 within the double-blind on therapy period. and/or

Secondary Outcome(s)

Percentage of patients requiring fluid restriction at any time during the double-blind on therapy period of the study.

The average daily area under the curve of change from baseline in serum sodium level up to Day 30 within the double-blind on therapy period for patients with severe hyponatremia (serum sodium <130 mEq/L at baseline).

Change from baseline in serum sodium at Day 4.

Safety:Adverse events,vital signs,clinical laboratory tests,12- lead electrocardiograms.

Change from baseline in body weight at Day 1 (hypervolemic patients only).

Change from baseline in serum sodium at Day 30.

Categorical change in serum sodium at Day 4 and Day 30 for patients with baseline serum sodium <130 mEq/L.

Percentage of patients with normalized serum sodium at Day 30.

Percentage of patients with normalized serum sodium at Day 4.

The average daily area under the curve of change from baseline in serum sodium level up to Day 4 within the double-blind on therapy period for patients with severe hyponatremia (serum sodium <130 mEq/L at baseline).

Time to first normalization in serum sodium.

Urine output at Day 1.

PK:Plasma tolvaptan and DM-4103 concentrations.

Fluid balance at Day 1 (hypervolemic patients only).

The percentage of patients who are designated as treatment failure due to the need for saline infusion,with or without fluid restriction.

Categorical change in serum sodium at Day 4 and Day 30 for patients with baseline serum sodium =130 mEq/L.

Change from baseline in the SF-12 (health survey)Physical Component Summary (PCS)and Mental Component Summary (MCS)scales at Week 1 and Day 30.

Secondary ID(s)

156-02-235

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Otsuka Pharmaceutical Co., Ltd.