A Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety and Tolerability of Oral Lixivaptan Capsules in Subjects With Euvolemic Hyponatremia
- Registration Number
- NCT00876798
- Lead Sponsor
- CardioKine Inc.
- Brief Summary
The purpose of this study is to evaluate the safety and tolerability of oral lixivaptan capsules in subjects with Euvolemic Hyponatremia.
- Detailed Description
Phase I and 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, LCWA, and SIADH. Lixivaptan was previously evaluated in disease states characterized by hyponatremia with euvolemia (SIADH) and hyponatremia combined with fluid overload (HF, LCWA). Lixivaptan demonstrated correction in serum sodium concentration together with marked aquaresis in subjects with hyponatremia.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 206
- Written informed consent.
- Men or women aged 18 or older.
- Diagnosis of euvolemic hyponatremia (Na+ < 135 mEq/L).
- Willing to be observed in a monitored setting for approximately the first 8 hours following treatment initiation (first dose).
- In the Investigator's judgement the patient has adequate visual and auditory acuity to allow participation in the trial.
- Pregnant or breast-feeding women, or women planning to become pregnant or to breastfeed.
- Overt symptoms of hyponatremia requiring immediate medical intervention (e.g., coma, seizures).
- Acute or transient hyponatremia (e.g., associated with head trauma, postoperative state, or use of radiotherapy and/or chemotherapy).
- Hyponatremia in hypovolemic states (e.g., due to fluid loss through vomiting, diarrhea, burns, etc.). Hypovolemic hyponatremia is defined as the presence of clinical evidence of extracellular fluid volume depletion.
- Hyponatremia in hypervolemic states (e.g., congestive heart failure). Hypervolemia is defined as a presence of increased total body water with signs of edema.
- Pseudohyponatremia (i.e., hyponatremia resulting from a laboratory artifact).
- Hypertonic hyponatremia (e.g., hyponatremia in the setting of hyperglycemia).
- Hyponatremia as a result of any medication that can safely be withdrawn.
- Hyponatremia due to hypothyroidism or adrenal insufficiency.
- Current diagnosis of psychogenic polydipsia.
- Receiving within 7 days of enrollment other medication for treatment of hyponatremia, specifically: demeclocycline, lithium carbonate, urea, or any vasopressin antagonist.
- Supine systolic arterial blood pressure of ≤ 90 millimeters of mercury (mmHg).
- Serum creatinine > 3.0 mg/dL (> 265.2 mol/L).
- Hypokalemia based on clinical sign/symptoms or lab findings (e.g., serum potassium < 3.5 mEq/L).
- Uncontrolled diabetes mellitus as defined by the Investigators (e.g., hemoglobin - glycosylated [HbA1c] > 9%).
- ST-segment elevation myocardial infarction (STEMI) within 30 days or active myocardial ischemia at the time of enrollment.
- History of cerebral vascular accident (CVA) within 30 days prior to screening.
- Severe malnutrition in the Investigator's judgment (e.g., body mass index [BMI] < 17).
- Advanced liver disease or documented diagnosis of cirrhosis or alcoholic hepatitis.
- Urinary tract obstruction (benign prostatic hypertrophy [BPH] allowed if non-obstructive).
- History of chronic drug/medication abuse within the past 6 months or current alcohol abuse.
- 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 within 30 days prior to baseline visit.
- Unable to take oral medications.
- Significant neurological disorders (e.g., permanent neurological deficits, probable Alzheimer's disease, normal pressure hydrocephalus, Parkinsonian dementia complex, multi-infarct dementia, mixed dementia, or Huntington's disease).
- Conditions limiting access to water or an inability to respond to thirst (e.g., hydrophobia, or non-communicative).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 2 Placebo Placebo 1 Lixivaptan Lixivaptan
- Primary Outcome Measures
Name Time Method To demonstrate that lixivaptan is safe and effective in achieving and maintaining increased serum sodium concentration in subjects with SIADH and other conditions of euvolemic hyponatremia. 6 months
- Secondary Outcome Measures
Name Time Method If lixivaptan demonstrates improvement in serum sodium, % of subjects achieving normalized serum sodium, % of subjects requiring fluid restriction, prevention of worsening hyponatremia, and the change from baseline to complete TMT-B. 6 months
Trial Locations
- Locations (89)
Innovative Research of West Florida, Inc.
🇺🇸Clearwater, Florida, United States
Galiz Research
🇺🇸Miami, Florida, United States
Miami Jewish Home and Hospital for the Aged
🇺🇸Miami, Florida, United States
Nephrology Associates of South Miami
🇺🇸Miami, Florida, United States
Royal Care Nursing Home
🇺🇸Fountain Valley, California, United States
Executive Health and Research Associates
🇺🇸Atlanta, Georgia, United States
RTR Medical Group
🇺🇸Savannah, Georgia, United States
Four Rivers Clinical Research
🇺🇸Paducah, Kentucky, United States
Levindale Hebrew Geriatric Center and Hospital
🇺🇸Baltimore, Maryland, United States
LifeBridge Health, Inc./ Courtland Gardens Nursing & Rehabilitation Center
🇺🇸Baltimore, Maryland, United States
Stephen R. Smith
🇺🇸Baltimore, Maryland, United States
Genesis Clinical Research & Consulting, LLC
🇺🇸Fall River, Massachusetts, United States
Mercury Street Medical Group
🇺🇸Butte, Montana, United States
Memorial Hermann - Memorial City Research Center
🇺🇸Houston, Texas, United States
Clinical Research and Consulting Center
🇺🇸Fairfax, Virginia, United States
Presidio ospedaliero zona aretina, Ospedale San Donato di Arezzo
🇮🇹Pietro Nenni, Arezzo, Italy
Medicina II, Arcispedale Santa Maria Nuova
🇮🇹Reggio Emilia, Italy
SOD Clinica di Endocrinologia a Malatte del Metabolismo
🇮🇹Torette di Ancona, Italy
Birmingham Nursing and Rehabilitation East
🇺🇸Birmingham, Alabama, United States
PsyPharma Clinical Research, Inc.
🇺🇸Phoenix, Arizona, United States
COR Clinical Research LLC
🇺🇸Oklahoma City, Oklahoma, United States
Hilltop Physicians Inc
🇺🇸Cincinnati, Ohio, United States
InVisions Consultants, LLC
🇺🇸San Antonio, Texas, United States
Rochester General Hospital
🇺🇸Rochester, New York, United States
Coastal Nephrology Associates Reserach Center
🇺🇸Port Charlotte, Florida, United States
Toulon Health Care Center
🇺🇸Toulon, Illinois, United States
Southern Arizona VA Health Care System (SAVAHCS)
🇺🇸Tucson, Arizona, United States
Parkview Rehabilitation and Nursing
🇺🇸Little Rock, Arkansas, United States
Healthscan Research, LLC
🇺🇸Montgomery, Alabama, United States
Searcy Medical Center
🇺🇸Searcy, Arkansas, United States
AV Institute, Inc.
🇺🇸Carson, California, United States
Sarah S. Olelewe, MD, Inc.
🇺🇸Hawthorne, California, United States
Olive View - UCLA Medical Center
🇺🇸Sylmar, California, United States
Torrance Clinical Research
🇺🇸Lomita, California, United States
Naples Institute for Clinical Research
🇺🇸Bonita Springs, Florida, United States
Jacksonville Center for CLinical Research
🇺🇸Jacksonville, Florida, United States
Scientific Clinical Research, Inc.
🇺🇸North Miami, Florida, United States
Piedmont Clinical Trials
🇺🇸North Miami, Florida, United States
Rockdale Medicall Research Associates
🇺🇸Conyers, Georgia, United States
Natchitoches Internal Medicine
🇺🇸Natchitoches, Louisiana, United States
Research Integrity, LLC
🇺🇸Owensboro, Kentucky, United States
Western New England Renal & Transplant Assciates, PC
🇺🇸Springfield, Massachusetts, United States
SLU Care Doctors Office Building
🇺🇸Saint Louis, Missouri, United States
Millenium Psychiatric Associates
🇺🇸St Louis, Missouri, United States
Buffalo VA Medical Center
🇺🇸Buffalo, New York, United States
Erie County Medical Center/SUNY at Buffalo affiliate
🇺🇸Buffalo, New York, United States
Internal Medical Associates of Grand Island, PC
🇺🇸Grand Island, Nebraska, United States
Parker Jewish Institute for Health Care and Rehabilitation
🇺🇸New Hyde PArk, New York, United States
Medical Research Development Associates, LLC
🇺🇸Springfield Gardens, New York, United States
Three Rivers Health and Rehabilitation
🇺🇸Windsor, North Carolina, United States
Lillestol Research LLC
🇺🇸Fargo, North Dakota, United States
Valley Medical Research
🇺🇸Centerville, Ohio, United States
Providence Health Partners - Center for Clinical Research
🇺🇸Dayton, Ohio, United States
Your Diabetes Endocrine Nutrition Group, Inc.
🇺🇸Mentor, Ohio, United States
Carolina Diabetes and Kidney Center
🇺🇸Sumter, South Carolina, United States
Northeast Clinical Research Center
🇺🇸Bethlehem, Pennsylvania, United States
Translational Neuroscience, LLC/Drexel University College of Medicine
🇺🇸Conshohocken, Pennsylvania, United States
Ilumina CLinical Associates
🇺🇸Indiana, Pennsylvania, United States
Senior Adults Specialty Research
🇺🇸Austin, Texas, United States
South Texas Institutes of Health
🇺🇸McAllen, Texas, United States
ASpen CLinical Research
🇺🇸Orem, Utah, United States
McGuire VA Medical Center
🇺🇸Richmond, Virginia, United States
Universal Research Group
🇺🇸Tacoma, Washington, United States
Universal Clinical Research & Technology, Inc.
🇺🇸Orlando, Florida, United States
University Clinical Research & Technology, Inc.
🇺🇸Orlando, Florida, United States
Senior Care of Colorado, PC
🇺🇸Aurora, Colorado, United States
Apollo Hospitals
🇮🇳Tanil Nadu, Chennai, India
Hadassah Medical Organization, Hadassah University Hospital, Ein Karem
🇮🇱Kiryat Hadassah, Jerusalem, Israel
The Endocrine Institute, Rabin Medical Center, Beilinson Hospital
🇮🇱Petah Tikvah, Israel
Hospital Nacional Guillermo Almenara Irigoyen-EsSalud.
🇵🇪Lima, Peru
Bhatia Hospital, G-1 Ward
🇮🇳Mumbia, Maharashtra, India
Jehangir Clinical Development Centre Pvt. Ltd.
🇮🇳Pune, Maharashtra, India
Kovai Medical Centre & Hospital
🇮🇳Tamil Nadu, Coimbatore, India
Hospital Nacional Arzobispo Loayza
🇵🇪Lima, Peru
Dayanand Medical College and Hospital
🇮🇳Tagore Nagar, Ludhiana, India
Instituto Biomedico de Investigacion A.C.
🇲🇽Aguascalientes, Mexico
PsyPharma Clinical Research
🇺🇸Phoenix, Arizona, United States
Hospital Erasme
🇧🇪Bruzelles, Belgium
Smt G.R. Doshi & Smt K.M. Mehta Institute of Kidney Diseases & Reseacrh Cnetre (IKDRC) & Dr. H.L. Trivedi Institute of Transplantation Services (ITS)
🇮🇳Asarwa, Ahmedabad, India
Kamineni Hospitals
🇮🇳Hyderabad, Andhra Pradesh, India
M. S. Ramaiah Memorial Hospital
🇮🇳Bangalore, Karnataka, India
Justice K. S. Hedge Charitable Hospital
🇮🇳Karnataka, Mangalore, India
Department of Neurology St. John's Medical College & Hospital
🇮🇳Bangalore, India
Tel Aviv Sourasky Medical Center
🇮🇱Tel Aviv, Israel
John J. Hainkel Jr Home and Rehabilitation Center
🇺🇸New Orleans, Louisiana, United States
Fakultni nemocnice Ostrava Neurologicke oddeleni
🇨🇿Ostrava, Poruba, Czech Republic
Klinika nefrologie VFN a 1.LF UK
🇨🇿Nemocnice 2, Praha, Czech Republic
Diabetic and Endocrine Unit, Hillel Yaffe Medical Center
🇮🇱Hadera, Israel
Hospital General "Dr. Santiago Ramon Y Cajal" I.S.S.S.T.E.
🇲🇽Durango, Mexico