Clinical trial NCT00876798: A Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety and Tolerability of Oral Lixivaptan Capsules in Subjects With Euvolemic Hyponatremia
Official title: A Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety and Tolerability of Oral Lixivaptan Capsules in Subjects With Euvolemic Hyponatremia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Euvolemic Hyponatremia
Keywords: Euvolemic Hyponatremia
SIADH
Serum Sodium
Lead sponsor: CardioKine Inc.
Sponsor class: INDUSTRY
Collaborators: name: Cardiokine Biopharma, LLC
name: Biogen
First posted: 2009-04-07
Enrollment: 206
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 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.

Eligibility criteria: Inclusion Criteria:

1. Written informed consent.
2. Men or women aged 18 or older.
3. Diagnosis of euvolemic hyponatremia (Na+ \< 135 mEq/L).
4. Willing to be observed in a monitored setting for approximately the first 8 hours following treatment initiation (first dose).
5. In the Investigator's judgement the patient has adequate visual and auditory acuity to allow participation in the trial.

Exclusion Criteria:

1. Pregnant or breast-feeding women, or women planning to become pregnant or to breastfeed.
2. Overt symptoms of hyponatremia requiring immediate medical intervention (e.g., coma, seizures).
3. Acute or transient hyponatremia (e.g., associated with head trauma, postoperative state, or use of radiotherapy and/or chemotherapy).
4. 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.
5. Hyponatremia in hypervolemic states (e.g., congestive heart failure). Hypervolemia is defined as a presence of increased total body water with signs of edema.
6. Pseudohyponatremia (i.e., hyponatremia resulting from a laboratory artifact).
7. Hypertonic hyponatremia (e.g., hyponatremia in the setting of hyperglycemia).
8. Hyponatremia as a result of any medication that can safely be withdrawn.
9. Hyponatremia due to hypothyroidism or adrenal insufficiency.
10. Current diagnosis of psychogenic polydipsia.
11. Receiving within 7 days of enrollment other medication for treatment of hyponatremia, specifically: demeclocycline, lithium carbonate, urea, or any vasopressin antagonist.
12. Supine systolic arterial blood pressure of ≤ 90 millimeters of mercury (mmHg).
13. Serum creatinine \> 3.0 mg/dL (\> 265.2 mol/L).
14. Hypokalemia based on clinical sign/symptoms or lab findings (e.g., serum potassium \< 3.5 mEq/L).
15. Uncontrolled diabetes mellitus as defined by the Investigators (e.g., hemoglobin - glycosylated \[HbA1c\] \> 9%).
16. ST-segment elevation myocardial infarction (STEMI) within 30 days or active myocardial ischemia at the time of enrollment.
17. History of cerebral vascular accident (CVA) within 30 days prior to screening.
18. Severe malnutrition in the Investigator's judgment (e.g., body mass index \[BMI\] \< 17).
19. Advanced liver disease or documented diagnosis of cirrhosis or alcoholic hepatitis.
20. Urinary tract obstruction (benign prostatic hypertrophy \[BPH\] allowed if non-obstructive).
21. History of chronic drug/medication abuse within the past 6 months or current alcohol abuse.
22. Terminally ill or moribund condition with little chance of short-term survival.
23. Receiving vasopressin or its analogs for treatment of any condition.
24. Known allergy to any vasopressin antagonist.
25. Previous participation in a lixivaptan study.
26. Recipient of any investigational treatment within 30 days prior to baseline visit.
27. Unable to take oral medications.
28. 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).
29. Conditions limiting access to water or an inability to respond to thirst (e.g., hydrophobia, or non-communicative).

Primary outcomes:
measure: 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.
timeFrame: 6 months
Secondary outcomes:
measure: 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.
timeFrame: 6 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Birmingham Nursing and Rehabilitation East
state: Alabama
city: Montgomery
country: United States
facility: Healthscan Research, LLC
state: Alabama
city: Phoenix
country: United States
facility: PsyPharma Clinical Research, Inc.
state: Arizona
city: Phoenix
country: United States
facility: PsyPharma Clinical Research
state: Arizona
city: Tucson
country: United States
facility: Southern Arizona VA Health Care System (SAVAHCS)
state: Arizona
city: Little Rock
country: United States
facility: Parkview Rehabilitation and Nursing
state: Arkansas
city: Searcy
country: United States
facility: Searcy Medical Center
state: Arkansas
city: Carson
country: United States
facility: AV Institute, Inc.
state: California
city: Fountain Valley
country: United States
facility: Royal Care Nursing Home
state: California
city: Hawthorne
country: United States
facility: Sarah S. Olelewe, MD, Inc.
state: California
city: Lomita
country: United States
facility: Torrance Clinical Research
state: California
city: Sylmar
country: United States
facility: Olive View - UCLA Medical Center
state: California
city: Aurora
country: United States
facility: Senior Care of Colorado, PC
state: Colorado
city: Bonita Springs
country: United States
facility: Naples Institute for Clinical Research
state: Florida
city: Clearwater
country: United States
facility: Innovative Research of West Florida, Inc.
state: Florida
city: Jacksonville
country: United States
facility: Jacksonville Center for CLinical Research
state: Florida
city: Miami Springs
country: United States
facility: Galiz Research
state: Florida
city: Miami
country: United States
facility: Miami Jewish Home and Hospital for the Aged
state: Florida
city: Miami
country: United States
facility: Galiz Research
state: Florida
city: Miami
country: United States
facility: Nephrology Associates of South Miami
state: Florida
city: North Miami
country: United States
facility: Piedmont Clinical Trials
state: Florida
city: North Miami
country: United States
facility: Scientific Clinical Research, Inc.
state: Florida
city: Orlando
country: United States
facility: Universal Clinical Research & Technology, Inc.
state: Florida
city: Orlando
country: United States
facility: University Clinical Research & Technology, Inc.
state: Florida
city: Port Charlotte
country: United States
facility: Coastal Nephrology Associates Reserach Center
state: Florida
city: Atlanta
country: United States
facility: Executive Health and Research Associates
state: Georgia
city: Conyers
country: United States
facility: Rockdale Medicall Research Associates
state: Georgia
city: Savannah
country: United States
facility: RTR Medical Group
state: Georgia
city: Toulon
country: United States
facility: Toulon Health Care Center
state: Illinois
city: Owensboro
country: United States
facility: Research Integrity, LLC
state: Kentucky
city: Paducah
country: United States
facility: Four Rivers Clinical Research
state: Kentucky
city: Natchitoches
country: United States
facility: Natchitoches Internal Medicine
state: Louisiana
city: New Orleans
country: United States
facility: John J. Hainkel Jr Home and Rehabilitation Center
state: Louisiana
city: Baltimore
country: United States
facility: Levindale Hebrew Geriatric Center and Hospital
state: Maryland
city: Baltimore
country: United States
facility: LifeBridge Health, Inc./ Courtland Gardens Nursing & Rehabilitation Center
state: Maryland
city: Baltimore
country: United States
facility: Stephen R. Smith
state: Maryland
city: Fall River
country: United States
facility: Genesis Clinical Research & Consulting, LLC
state: Massachusetts
city: Springfield
country: United States
facility: Western New England Renal & Transplant Assciates, PC
state: Massachusetts
city: Saint Louis
country: United States
facility: SLU Care Doctors Office Building
state: Missouri
city: St Louis
country: United States
facility: Millenium Psychiatric Associates
state: Missouri
city: Butte
country: United States
facility: Mercury Street Medical Group
state: Montana
city: Grand Island
country: United States
facility: Internal Medical Associates of Grand Island, PC
state: Nebraska
city: Buffalo
country: United States
facility: Buffalo VA Medical Center
state: New York
city: Buffalo
country: United States
facility: Erie County Medical Center/SUNY at Buffalo affiliate
state: New York
city: New Hyde PArk
country: United States
facility: Parker Jewish Institute for Health Care and Rehabilitation
state: New York
city: Rochester
country: United States
facility: Rochester General Hospital
state: New York
city: Springfield Gardens
country: United States
facility: Medical Research Development Associates, LLC
state: New York
city: Windsor
country: United States
facility: Three Rivers Health and Rehabilitation
state: North Carolina
city: Fargo
country: United States
facility: Lillestol Research LLC
state: North Dakota
city: Centerville
country: United States
facility: Valley Medical Research
state: Ohio
city: Cincinnati
country: United States
facility: Hilltop Physicians Inc
state: Ohio
city: Dayton
country: United States
facility: Providence Health Partners - Center for Clinical Research
state: Ohio
city: Mentor
country: United States
facility: Your Diabetes Endocrine Nutrition Group, Inc.
state: Ohio
city: Oklahoma City
country: United States
facility: COR Clinical Research LLC
state: Oklahoma
city: Bethlehem
country: United States
facility: Northeast Clinical Research Center
state: Pennsylvania
city: Conshohocken
country: United States
facility: Translational Neuroscience, LLC/Drexel University College of Medicine
state: Pennsylvania
city: Indiana
country: United States
facility: Ilumina CLinical Associates
state: Pennsylvania
city: Sumter
country: United States
facility: Carolina Diabetes and Kidney Center
state: South Carolina
city: Austin
country: United States
facility: Senior Adults Specialty Research
state: Texas
city: Houston
country: United States
facility: Memorial Hermann - Memorial City Research Center
state: Texas
city: McAllen
country: United States
facility: South Texas Institutes of Health
state: Texas
city: San Antonio
country: United States
facility: InVisions Consultants, LLC
state: Texas
city: Orem
country: United States
facility: ASpen CLinical Research
state: Utah
city: Fairfax
country: United States
facility: Clinical Research and Consulting Center
state: Virginia
city: Richmond
country: United States
facility: McGuire VA Medical Center
state: Virginia
city: Tacoma
country: United States
facility: Universal Research Group
state: Washington
city: Bruzelles
country: Belgium
facility: Hospital Erasme
city: Ostrava
country: Czech Republic
facility: Fakultni nemocnice Ostrava Neurologicke oddeleni
state: Poruba
city: Nemocnice 2
country: Czech Republic
facility: Klinika nefrologie VFN a 1.LF UK
state: Praha
city: Asarwa
country: India
facility: Smt G.R. Doshi & Smt K.M. Mehta Institute of Kidney Diseases & Reseacrh Cnetre (IKDRC) & Dr. H.L. Trivedi Institute of Transplantation Services (ITS)
state: Ahmedabad
city: Hyderabad
country: India
facility: Kamineni Hospitals
state: Andhra Pradesh
city: Tanil Nadu
country: India
facility: Apollo Hospitals
state: Chennai
city: Tamil Nadu
country: India
facility: Kovai Medical Centre & Hospital
state: Coimbatore
city: Bangalore
country: India
facility: M. S. Ramaiah Memorial Hospital
state: Karnataka
city: Tagore Nagar
country: India
facility: Dayanand Medical College and Hospital
state: Ludhiana
city: Mumbia
country: India
facility: Bhatia Hospital, G-1 Ward
state: Maharashtra
city: Pune
country: India
facility: Jehangir Clinical Development Centre Pvt. Ltd.
state: Maharashtra
city: Karnataka
country: India
facility: Justice K. S. Hedge Charitable Hospital
state: Mangalore
city: Bangalore
country: India
facility: Department of Neurology St. John's Medical College & Hospital
city: Kiryat Hadassah
country: Israel
facility: Hadassah Medical Organization, Hadassah University Hospital, Ein Karem
state: Jerusalem
city: Hadera
country: Israel
facility: Diabetic and Endocrine Unit, Hillel Yaffe Medical Center
city: Petah Tikvah
country: Israel
facility: The Endocrine Institute, Rabin Medical Center, Beilinson Hospital
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Pietro Nenni
country: Italy
facility: Presidio ospedaliero zona aretina, Ospedale San Donato di Arezzo
state: Arezzo
city: Reggio Emilia
country: Italy
facility: Medicina II, Arcispedale Santa Maria Nuova
city: Torette di Ancona
country: Italy
facility: SOD Clinica di Endocrinologia a Malatte del Metabolismo
city: Aguascalientes
country: Mexico
facility: Instituto Biomedico de Investigacion A.C.
city: Durango
country: Mexico
facility: Hospital General "Dr. Santiago Ramon Y Cajal" I.S.S.S.T.E.
city: Lima
country: Peru
facility: Hospital Nacional Guillermo Almenara Irigoyen-EsSalud.
city: Lima
country: Peru
facility: Hospital Nacional Arzobispo Loayza
Study officials:
References: