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

Hyponatremia With Normal Extracellular Fluid Volume Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00660959
• Other study ID #: CK-LX3405
• Status: Completed
• Phase: Phase 3
• First received: April 15, 2008
• Last updated: June 20, 2011
• Start date: April 2008

Study information

• Verified date: November 2010
• Source: CardioKine Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutionl Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 106
• Est. primary completion date: June 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hyponatremia
• Hyponatremia With Normal Extracellular Fluid Volume

Intervention

Drug:
• lixivaptan
oral capsule
• placebo
oral capsule

Locations

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

Sponsors (3)

Lead Sponsor	Collaborator
CardioKine Inc.	Biogen, Cardiokine Biopharma, LLC

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  Germany,  India,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Change from baseline in serum sodium on Day 30		60 days	No
Secondary	Percentage of subjects achieving normalized serum sodium (Na+ = 135 mEq/L)		60 days	No
Secondary	Time to first normalization of serum sodium (Na+=135 mEq/L)		60 days	No