Clinical trial NCT00660959: Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Oral Lixivaptan Capsules in Subject With Euvolemic Hyponatremia
Official title: Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Oral Lixivaptan Capsules in Subject With Euvolemic Hyponatremia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hyponatremia With Normal Extracellular Fluid Volume
Keywords: Euvolemic
Hyponatremia
Serum Sodium
Fluid Overload
Vasopressin Antagonist
Lead sponsor: CardioKine Inc.
Sponsor class: INDUSTRY
Collaborators: name: Cardiokine Biopharma, LLC
name: Biogen
First posted: 2008-04-18
Enrollment: 106
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: 60 days
Secondary outcomes:
measure: Change from baseline in serum sodium on Day 30
timeFrame: 60 days
measure: Percentage of subjects achieving normalized serum sodium (Na+ ≥ 135 mEq/L)
timeFrame: 60 days
measure: Time to first normalization of serum sodium (Na+≥135 mEq/L)
timeFrame: 60 days
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Research Site 1
state: Alabama
city: Phoenix
country: United States
facility: PsyPharma Global
state: Arizona
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Los Angeles
country: United States
facility: Research Site 1
state: California
city: Roseville
country: United States
facility: Research Site 1
state: California
city: Aurora
country: United States
facility: Research Site
state: Colorado
city: Washington
country: United States
facility: The George Washington University Medical Faculty Associates
state: District of Columbia
city: North Miami
country: United States
facility: Healthcare Clinical Data, Inc
state: Florida
city: Weston
country: United States
facility: Cleveland Clinic Florida
state: Florida
city: Augusta
country: United States
facility: Research Site
state: Georgia
city: Savannah
country: United States
facility: RTR Medical Group
state: Georgia
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Iowa City
country: United States
facility: Research Site 1
state: Iowa
city: Paducah
country: United States
facility: Four Rivers Clinical Research, Inc.
state: Kentucky
city: New Orleans
country: United States
facility: Louisiana Research Associates, Inc.
state: Louisiana
city: Belmont
country: United States
facility: Research Site
state: Massachusetts
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Kansas City
country: United States
facility: Research Site
state: Missouri
city: Las Vegas
country: United States
facility: Research Site 1
state: Nevada
city: Albany
country: United States
facility: Research Site 1
state: New York
city: Buffalo
country: United States
facility: Erie County Medical Center
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: Windsor
country: United States
facility: Three Rivers Health and Rehabilitation
state: North Carolina
city: Middletown
country: United States
facility: Atrium Medical Center
state: Ohio
city: Toledo
country: United States
facility: Kettlie Joseph Daniels MD, Inc
state: Ohio
city: Camp Hill
country: United States
facility: Research Site 1
state: Pennsylvania
city: Doylestown
country: United States
facility: Research Site 1
state: Pennsylvania
city: Norristown
country: United States
facility: Research Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: Research Site 1
state: Pennsylvania
city: Providence
country: United States
facility: Research Site
state: Rhode Island
city: Columbia
country: United States
facility: Research Site 1
state: South Carolina
city: Georgetown
country: United States
facility: SunStar Geriatrics Healthcare
state: Texas
city: Houston
country: United States
facility: Clinical Trial Network
state: Texas
city: Orem
country: United States
facility: Aspen Clinical Research
state: Utah
city: Norfolk
country: United States
facility: The Glennan Center for Geriatrics and Gerontology
state: Virginia
city: Tacoma
country: United States
facility: Internal Medicine Northwest
state: Washington
city: Leuven
country: Belgium
facility: UZ Gasthulsberg
city: Tubize
country: Belgium
facility: Centre Hospitalier de Tubize
city: Greenfield Park
country: Canada
facility: Research SIte
state: Quebec
city: Montreal
country: Canada
facility: Research Site 1
state: Quebec
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Berlin
country: Germany
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Dresden
country: Germany
facility: Research Site
city: Giessen
country: Germany
facility: Research Site
city: Hannover
country: Germany
facility: Research Site
city: Heidelberg
country: Germany
facility: Research Site
city: Konstanz
country: Germany
facility: Research SIte
city: Magdeburg
country: Germany
facility: Research Site
city: Munchen
country: Germany
facility: Research Site
city: Wurzburg
country: Germany
facility: Research Site
city: Calicut
country: India
facility: Baby Memorial Hospital
state: Kerala
city: Pune
country: India
facility: Poona Hospital and Research Centre
state: Maharashtra
city: Old Rajinder Nagar
country: India
facility: Sir Ganga Ram Hospital
state: New Delhi
city: Erandawane
country: India
facility: Deenanath Mengeshkar Hospital & Research Centre
state: Pune
city: Jaipur
country: India
facility: Fortis Escorts Hospital
state: Rajastan
city: New Delhi
country: India
facility: Vidya Sagar Institute of Mental Health and Neurosciences
city: Wilgury
country: Poland
facility: Niepubliczny Zaklad Opieki Zdrowotney
state: Lodz
city: Bydgoszcz
country: Poland
facility: Research Site
city: Ciechanow
country: Poland
facility: Research Site 1
city: Katowice
country: Poland
facility: Research Site
city: Lodz
country: Poland
facility: Research Site 1
city: Lublin
country: Poland
facility: Research Site
city: Podlaski
country: Poland
facility: Research Site 1
city: Warszawa
country: Poland
facility: Research Site 1
city: Warszawa
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site 1
city: Warszawa
country: Poland
facility: Research Site 1
city: Zamosc
country: Poland
facility: Samodzielny Publiczny Szpital Wojewodzki im. Papieza Jana Pawla II
Study officials:
References: