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

June 20, 2011 updated by: CardioKine Inc.
The purpose of this study is to evaluate the safety and tolerability of oral lixivaptan capsules in subjects with Euvolemic Hyponatremia.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

206

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Bruzelles, Belgium, 1070
        • Hospital Erasme
  • Czech Republic
    • Poruba
      • Ostrava, Poruba, Czech Republic, 70852
        • Fakultni nemocnice Ostrava Neurologicke oddeleni
    • Praha
      • Nemocnice 2, Praha, Czech Republic, 12808
        • Klinika nefrologie VFN a 1.LF UK
  • India
      • Bangalore, India, 560034
        • Department of Neurology St. John's Medical College & Hospital
    • Ahmedabad
      • Asarwa, Ahmedabad, India, 380 016
        • Smt G.R. Doshi & Smt K.M. Mehta Institute of Kidney Diseases & Reseacrh Cnetre (IKDRC) & Dr. H.L. Trivedi Institute of Transplantation Services (ITS)
    • Andhra Pradesh
      • Hyderabad, Andhra Pradesh, India, 500 068
        • Kamineni Hospitals
    • Chennai
      • Tanil Nadu, Chennai, India, 600 006
        • Apollo Hospitals
    • Coimbatore
      • Tamil Nadu, Coimbatore, India, 54013
        • Kovai Medical Centre & Hospital
    • Karnataka
      • Bangalore, Karnataka, India, 560054
        • M. S. Ramaiah Memorial Hospital
    • Ludhiana
      • Tagore Nagar, Ludhiana, India, 141 001
        • Dayanand Medical College and Hospital
    • Maharashtra
      • Mumbia, Maharashtra, India, 400 007
        • Bhatia Hospital, G-1 Ward
      • Pune, Maharashtra, India, 411 001
        • Jehangir Clinical Development Centre Pvt. Ltd.
    • Mangalore
      • Karnataka, Mangalore, India, 575018
        • Justice K. S. Hedge Charitable Hospital
  • Israel
      • Hadera, Israel, 38100
        • Diabetic and Endocrine Unit, Hillel Yaffe Medical Center
      • Petah Tikvah, Israel, 49100
        • The Endocrine Institute, Rabin Medical Center, Beilinson Hospital
      • Tel Aviv, Israel, 64239
        • Tel Aviv Sourasky Medical Center
    • Jerusalem
      • Kiryat Hadassah, Jerusalem, Israel, 91120
        • Hadassah Medical Organization, Hadassah University Hospital, Ein Karem
  • Italy
      • Reggio Emilia, Italy, 42100
        • Medicina II, Arcispedale Santa Maria Nuova
      • Torette di Ancona, Italy, 60126
        • SOD Clinica di Endocrinologia a Malatte del Metabolismo
    • Arezzo
      • Pietro Nenni, Arezzo, Italy, 52100
        • Presidio ospedaliero zona aretina, Ospedale San Donato di Arezzo
  • Mexico
      • Aguascalientes, Mexico, 20127
        • Instituto Biomedico De Investigacion A.C.
      • Durango, Mexico, 34070
        • Hospital General "Dr. Santiago Ramon Y Cajal" I.S.S.S.T.E.
  • Peru
      • Lima, Peru, Lima 1
        • Hospital Nacional Arzobispo Loayza
      • Lima, Peru, Lima 13
        • Hospital Nacional Guillermo Almenara Irigoyen-EsSalud.
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35205
        • Birmingham Nursing and Rehabilitation East
      • Montgomery, Alabama, United States, 36109
        • Healthscan Research, LLC
    • Arizona
      • Phoenix, Arizona, United States, 85050
        • PsyPharma Clinical Research, Inc.
      • Phoenix, Arizona, United States, 85050
        • PsyPharma Clinical Research
      • Tucson, Arizona, United States, 85723
        • Southern Arizona VA Health Care System (SAVAHCS)
    • Arkansas
      • Little Rock, Arkansas, United States, 72204
        • Parkview Rehabilitation and Nursing
      • Searcy, Arkansas, United States, 72143
        • Searcy Medical Center
    • California
      • Carson, California, United States, 90746
        • AV Institute, Inc.
      • Fountain Valley, California, United States, 92708
        • Royal Care Nursing Home
      • Hawthorne, California, United States, 90250
        • Sarah S. Olelewe, MD, Inc.
      • Lomita, California, United States, 90717
        • Torrance Clinical Research
      • Sylmar, California, United States, 91342
        • Olive View - UCLA Medical Center
    • Colorado
      • Aurora, Colorado, United States, 80014
        • Senior Care of Colorado, PC
    • Florida
      • Bonita Springs, Florida, United States, 34134
        • Naples Institute for Clinical Research
      • Clearwater, Florida, United States, 33756
        • Innovative Research of West Florida, Inc.
      • Jacksonville, Florida, United States, 32216
        • Jacksonville Center for Clinical Research
      • Miami, Florida, United States, 33173
        • Nephrology Associates of South Miami
      • Miami, Florida, United States, 33137
        • Miami Jewish Home and Hospital for the Aged
      • Miami, Florida, United States, 33145
        • Galiz Research
      • Miami Springs, Florida, United States, 33166
        • Galiz Research
      • North Miami, Florida, United States, 33161
        • Scientific Clinical Research, Inc.
      • North Miami, Florida, United States, 33161
        • Piedmont Clinical Trials
      • Orlando, Florida, United States, 32833
        • Universal Clinical Research & Technology, Inc.
      • Orlando, Florida, United States, 32833
        • University Clinical Research & Technology, Inc.
      • Port Charlotte, Florida, United States, 33952
        • Coastal Nephrology Associates Reserach Center
    • Georgia
      • Atlanta, Georgia, United States, 30342
        • Executive Health and Research Associates
      • Conyers, Georgia, United States, 30094
        • Rockdale Medicall Research Associates
      • Savannah, Georgia, United States, 31419
        • RTR Medical Group
    • Illinois
      • Toulon, Illinois, United States, 61483
        • Toulon Health Care Center
    • Kentucky
      • Owensboro, Kentucky, United States, 42303
        • Research Integrity, LLC
      • Paducah, Kentucky, United States, 42003
        • Four Rivers Clinical Research
    • Louisiana
      • Natchitoches, Louisiana, United States, 71457
        • Natchitoches Internal Medicine
      • New Orleans, Louisiana, United States, 70118
        • John J. Hainkel Jr Home and Rehabilitation Center
    • Maryland
      • Baltimore, Maryland, United States, 21215
        • Levindale Hebrew Geriatric Center and Hospital
      • Baltimore, Maryland, United States, 21215
        • LifeBridge Health, Inc./ Courtland Gardens Nursing & Rehabilitation Center
      • Baltimore, Maryland, United States, 21234
        • Stephen R. Smith
    • Massachusetts
      • Fall River, Massachusetts, United States, 02720
        • Genesis Clinical Research & Consulting, LLC
      • Springfield, Massachusetts, United States, 01107
        • Western New England Renal & Transplant Assciates, PC
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • SLU Care Doctors Office Building
      • St Louis, Missouri, United States, 63044
        • Millenium Psychiatric Associates
    • Montana
      • Butte, Montana, United States, 59701
        • Mercury Street Medical Group
    • Nebraska
      • Grand Island, Nebraska, United States, 68803
        • Internal Medical Associates of Grand Island, PC
    • New York
      • Buffalo, New York, United States, 14215
        • Buffalo VA Medical Center
      • Buffalo, New York, United States, 14215
        • Erie County Medical Center/SUNY at Buffalo affiliate
      • New Hyde PArk, New York, United States, 11040
        • Parker Jewish Institute for Health Care and Rehabilitation
      • Rochester, New York, United States, 14621
        • Rochester General Hospital
      • Springfield Gardens, New York, United States, 11413
        • Medical Research Development Associates, LLC
    • North Carolina
      • Windsor, North Carolina, United States, 27983
        • Three Rivers Health and Rehabilitation
    • North Dakota
      • Fargo, North Dakota, United States, 58103
        • Lillestol Research LLC
    • Ohio
      • Centerville, Ohio, United States, 45459
        • Valley Medical Research
      • Cincinnati, Ohio, United States, 45224
        • Hilltop Physicians Inc
      • Dayton, Ohio, United States, 45439
        • Providence Health Partners - Center for Clinical Research
      • Mentor, Ohio, United States, 44060
        • Your Diabetes Endocrine Nutrition Group, Inc.
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73103
        • COR Clinical Research LLC
    • Pennsylvania
      • Bethlehem, Pennsylvania, United States, 18017
        • Northeast Clinical Research Center
      • Conshohocken, Pennsylvania, United States, 19428
        • Translational Neuroscience, LLC/Drexel University College of Medicine
      • Indiana, Pennsylvania, United States, 15701
        • Ilumina Clinical Associates
    • South Carolina
      • Sumter, South Carolina, United States, 29150
        • Carolina Diabetes and Kidney Center
    • Texas
      • Austin, Texas, United States, 78757
        • Senior Adults Specialty Research
      • Houston, Texas, United States, 77024
        • Memorial Hermann - Memorial City Research Center
      • McAllen, Texas, United States, 78501
        • South Texas Institutes of Health
      • San Antonio, Texas, United States, 78229
        • InVisions Consultants, LLC
    • Utah
      • Orem, Utah, United States, 84058
        • Aspen Clinical Research
    • Virginia
      • Fairfax, Virginia, United States, 22030
        • Clinical Research and Consulting Center
      • Richmond, Virginia, United States, 23249
        • McGuire VA Medical Center
    • Washington
      • Tacoma, Washington, United States, 98405
        • Universal Research Group

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: 2
Placebo
Drug: Placebo
Capsule. Subjects will be randomized (3:1) on an outpatient basis to 25 mg lixivaptan or matching placebo, once daily.
Experimental: 1
Lixivaptan
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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.
Time Frame: 6 months
6 months

Secondary Outcome Measures

Outcome Measure
Time Frame
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.
Time Frame: 6 months
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

CardioKine Inc.

Collaborators

Biogen
Cardiokine Biopharma, LLC

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2009

Primary Completion (Actual)

November 1, 2010

Study Registration Dates

First Submitted

April 6, 2009

First Submitted That Met QC Criteria

April 6, 2009

First Posted (Estimate)

April 7, 2009

Study Record Updates

Last Update Posted (Estimate)

June 28, 2011

Last Update Submitted That Met QC Criteria

June 20, 2011

Last Verified

November 1, 2010

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CK-LX3430

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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