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

Euvolemic Hyponatremia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00876798
• Other study ID #: CK-LX3430
• Status: Completed
• Phase: Phase 3
• First received: April 6, 2009
• Last updated: June 20, 2011
• Start date: June 2009

Study information

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

Clinical Trial Summary

The purpose of this study is to evaluate the safety and tolerability of oral lixivaptan capsules in subjects with Euvolemic Hyponatremia.

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 information / eligibility

• Status: Completed
• Enrollment: 206
• Est. primary completion date: November 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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).

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

• Euvolemic Hyponatremia
• Hyponatremia

Intervention

Drug:
• Lixivaptan
Capsules, 25mg lixivaptan or matching placebo once daily. Study medication can be titrated up to 50mg or 100mg once daily. Acceptable dosages are once daily administration of 25mg, 50mg, or 100mg as a single dose.
• Placebo
Capsule. Subjects will be randomized (3:1) on an outpatient basis to 25 mg lixivaptan or matching placebo, once daily.

Locations

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	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	Yes