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

Sponsors and Collaborators:	CardioKine Inc. Cardiokine Biopharma, LLC Biogen Idec
Information provided by:	CardioKine Inc.
ClinicalTrials.gov Identifier:	NCT00660959

Purpose

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.

Condition	Intervention	Phase
Hyponatremia	Drug: lixivaptan Drug: placebo	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Oral Lixivaptan Capsules in Subject With Euvolemic Hyponatremia

Resource links provided by NLM:

Drug Information available for: Lixivaptan

U.S. FDA Resources

Further study details as provided by CardioKine Inc.:

Primary Outcome Measures:

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 [ Time Frame: 60 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Change from baseline in serum sodium on Day 30 [ Time Frame: 60 days ] [ Designated as safety issue: No ]
Percentage of subjects achieving normalized serum sodium (Na+ ≥ 135 mEq/L) [ Time Frame: 60 days ] [ Designated as safety issue: No ]
Time to first normalization of serum sodium (Na+≥135 mEq/L) [ Time Frame: 60 days ] [ Designated as safety issue: No ]

Estimated Enrollment:	100
Study Start Date:	April 2008
Estimated Study Completion Date:	July 2010
Estimated Primary Completion Date:	June 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Experimental lixivaptan	Drug: lixivaptan oral capsule
Placebo: Placebo Comparator placebo	Drug: placebo oral capsule

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

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00660959

Contacts

Contact: Cardiokine Biopharma, LLC

215-399-1200

Show 47 Study Locations

Sponsors and Collaborators

CardioKine Inc.

Cardiokine Biopharma, LLC

Biogen Idec

More Information

No publications provided

Responsible Party:	Cardiokine, Inc ( Cardiokine, Inc )
Study ID Numbers:	CK-LX3405
Study First Received:	April 15, 2008
Last Updated:	August 20, 2009
ClinicalTrials.gov Identifier:	NCT00660959 History of Changes
Health Authority:	United States: Food and Drug Administration; United States: Institutionl Review Board

Keywords provided by CardioKine Inc.:

Hyponatremia
Serum Sodium
Fluid Overload

Heart Failure
Acute Heart Failure
Vasopressin Antagonist

Study placed in the following topic categories:

Arginine Vasopressin
Heart Failure
Metabolic Diseases
Hyponatremia

Vasopressins
Water-Electrolyte Imbalance
Metabolic Disorder

Additional relevant MeSH terms:

Metabolic Diseases
Hyponatremia
Water-Electrolyte Imbalance

ClinicalTrials.gov processed this record on September 11, 2009