Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Oral Lixivaptan Capsules in Subject With Euvolemic Hyponatremia

CardioKine

Status and phase

Completed

Phase 3

Conditions

Hyponatremia With Normal Extracellular Fluid Volume

Treatments

Drug: lixivaptan

Drug: placebo

Study type

Interventional

Funder types

Industry

Identifiers

NCT00660959

CK-LX3405

Details and patient eligibility

About

The present study is designed to confirm and extend the observation from previous studies that lixivaptan therapy corrects hyponatremia, in euvolemic subject, including subjects with SIADH.

Full description

Phase I Phase II clinical trials have demonstrated that lixivaptan may play an important role in treating hyponatremia and the signs and symptoms of water retention associated with HF, liver cirrhosis with ascites (LCWA) and syndrome of inappropriate antidiuretic hormone (SIADH). Lixivaptan was previously evaluated in disease states characterized by hyponatremia with euvolemia (SIADH)and hyponatremia combined with fluid overload (HF, LCWA). Lixivaptan resulted in correction in hyponatremia together with a marked aquaresis in subject with volume overload. The present study is designed to confirm and extend the observation from previous studies that lixivaptan therapy corrects hyponatremia, in euvolemic subject, including subjects with SIDH.

Enrollment

106 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Written informed consent
Men or women aged 18 or older
Diagnosis of euvolemic hyponatremia (120 ≤ Na+<130 mEq/L)
Hospitalized or willing to be admitted to a monitored setting for approximately the first 48 hours of treatment

Exclusion criteria

Pregnant or breast-feeding women, or women planning to become pregnant or to breastfeed
Symptomatic hyponatremia (e.g., lethargy, coma, seizures, changes in mental status attributable to hyponatremia)
Acute or transient hyponatremia (e.g., associated with head trauma or postoperative state)
Hyponatremia in hypovolemic states. Hypovolemic hyponatremia is defined as the presence of clinical evidence of extracellular fluid volume depletion
Hyponatremia as a result of any medication that can safely be withdrawn
Hyponatremia due to hypothyroidism or adrenal insufficiency
Diagnosis of psychogenic polydipsia
Receiving within 7 days of enrollment, other medication for treatment of hyponatremia specifically: demeclocycline, lithium carbonate, urea, or conivaptan
Use of radiotherapy and chemotherapy within 2 wks of randomization
Likely to require, or to receive IV saline for correction of symptomatic or asymptomatic severe hyponatremia during the course of the study
Supine systolic arterial blood pressure of ≤ 90 mmHg
Serum creatinine >3.0 mg/dL
History of uncontrolled type 2 diabetes mellitus
Severe pulmonary artery hypertension: patients whose condition is expected to deteriorate with sudden shifts in fluid volumes and cardiac filling pressures
Established diagnosis of New York Heart Association (NYHA) class III or IV heart failure
History of myocardial infarction, unstable angina or evidence of active ischemia within 30 days prior to screening
History of cerebral vascular accident (CVA) within 60 days prior to screening
Established diagnosis of nephrotic syndrome
Advanced liver disease or documented diagnosis of cirrhosis or alcoholic hepatitis
Urinary tract obstruction (benign prostatic hypertrophy [BPH] allowed if non-obstructive)
History of alcohol abuse or illicit drug use within the past 6 months
Terminally ill or moribund condition with little chance of short-term survival
Receiving vasopressin or its analogs for treatment of any condition
Known allergy to any vasopressin antagonist
Previous participation in a lixivaptan study
Recipient of any investigational treatment (drug or device) within 30 days prior to baseline visit
Unable to take oral medications