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

Phase 3

Completed

• Conditions: Hyponatremia With Normal Extracellular Fluid Volume
• Interventions: Drug: lixivaptan; Drug: placebo

• Registration Number: NCT00660959
• Lead Sponsor: CardioKine Inc.

Brief Summary

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.

Detailed 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.

Study Timeline

• Study Start: 2008-04
• Study First Submitted: 2008-04-15
• Study First Submitted QC: 2008-04-17
• Study First Posted: 2008-04-18
• Primary Completion: 2010-06
• Status Verified: 2010-11
• Disposition First Submitted: 2011-06-20
• Disposition First Submitted QC: 2011-06-20
• Last Update Submitted: 2011-06-20
• Disposition First Posted: 2011-06-28
• Last Update Posted: 2011-06-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 106

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Active Comparator	lixivaptan	lixivaptan
Placebo	placebo	placebo

Primary Outcome Measures

Name	Time	Method
Average daily area under the curve (AUC) of change from baseline in serum sodium concentrations up to 72 hrs in lixivaptan treated subjects compared to placebo	60 days

Secondary Outcome Measures

Name	Time	Method
Change from baseline in serum sodium on Day 30	60 days
Percentage of subjects achieving normalized serum sodium (Na+ ≥ 135 mEq/L)	60 days
Time to first normalization of serum sodium (Na+≥135 mEq/L)	60 days

Trial Locations

Locations (30)

Poona Hospital and Research Centre; 🇮🇳 Pune, Maharashtra, India

RTR Medical Group; 🇺🇸 Savannah, Georgia, United States

Four Rivers Clinical Research, Inc.; 🇺🇸 Paducah, Kentucky, United States

Clinical Trial Network; 🇺🇸 Houston, Texas, United States

Beth Israel Deaconess Medical Center; 🇺🇸 Boston, Massachusetts, United States

Research Site 1; 🇵🇱 Warszawa, Poland

PsyPharma Global; 🇺🇸 Phoenix, Arizona, United States

Research Site; 🇵🇱 Warszawa, Poland

The George Washington University Medical Faculty Associates; 🇺🇸 Washington, District of Columbia, United States

Healthcare Clinical Data, Inc; 🇺🇸 North Miami, Florida, United States

Louisiana Research Associates, Inc.; 🇺🇸 New Orleans, Louisiana, United States

Kettlie Joseph Daniels MD, Inc; 🇺🇸 Toledo, Ohio, United States

Atrium Medical Center; 🇺🇸 Middletown, Ohio, United States

Internal Medicine Northwest; 🇺🇸 Tacoma, Washington, United States

Aspen Clinical Research; 🇺🇸 Orem, Utah, United States

UZ Gasthulsberg; 🇧🇪 Leuven, Belgium

Baby Memorial Hospital; 🇮🇳 Calicut, Kerala, India

Centre Hospitalier de Tubize; 🇧🇪 Tubize, Belgium

The Glennan Center for Geriatrics and Gerontology; 🇺🇸 Norfolk, Virginia, United States

Sir Ganga Ram Hospital; 🇮🇳 Old Rajinder Nagar, New Delhi, India

Research SIte; 🇩🇪 Konstanz, Germany

Vidya Sagar Institute of Mental Health and Neurosciences; 🇮🇳 New Delhi, India

Fortis Escorts Hospital; 🇮🇳 Jaipur, Rajastan, India

Deenanath Mengeshkar Hospital & Research Centre; 🇮🇳 Erandawane, Pune, India

Niepubliczny Zaklad Opieki Zdrowotney; 🇵🇱 Wilgury, Lodz, Poland

Samodzielny Publiczny Szpital Wojewodzki im. Papieza Jana Pawla II; 🇵🇱 Zamosc, Poland

Erie County Medical Center; 🇺🇸 Buffalo, New York, United States

SunStar Geriatrics Healthcare; 🇺🇸 Georgetown, Texas, United States

Cleveland Clinic Florida; 🇺🇸 Weston, Florida, United States

Three Rivers Health and Rehabilitation; 🇺🇸 Windsor, North Carolina, United States