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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00876798
Recruitment Status : Completed
First Posted : April 7, 2009
Last Update Posted : June 28, 2011
Sponsor:
Collaborators:
Cardiokine Biopharma, LLC
Biogen
Information provided by:
CardioKine Inc.

Tracking Information
First Submitted Date  ICMJE April 6, 2009
First Posted Date  ICMJE April 7, 2009
Last Update Posted Date June 28, 2011
Study Start Date  ICMJE June 2009
Actual Primary Completion Date November 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 6, 2009)
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 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 6, 2009)
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 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE A Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety and Tolerability of Oral Lixivaptan Capsules in Subjects With Euvolemic Hyponatremia
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Euvolemic Hyponatremia
Intervention  ICMJE
  • 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.
  • Drug: Placebo
    Capsule. Subjects will be randomized (3:1) on an outpatient basis to 25 mg lixivaptan or matching placebo, once daily.
Study Arms  ICMJE
  • Experimental: 1
    Lixivaptan
    Intervention: Drug: Lixivaptan
  • Placebo Comparator: 2
    Placebo
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 20, 2011)
206
Original Estimated Enrollment  ICMJE
 (submitted: April 6, 2009)
200
Study Completion Date  ICMJE Not Provided
Actual Primary Completion Date November 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   Czech Republic,   India,   Israel,   Italy,   Mexico,   Peru,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00876798
Other Study ID Numbers  ICMJE CK-LX3430
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Cesare Orlandi, MD, Cardiokine Biopharma LLC
Study Sponsor  ICMJE CardioKine Inc.
Collaborators  ICMJE
  • Cardiokine Biopharma, LLC
  • Biogen
Investigators  ICMJE Not Provided
PRS Account CardioKine Inc.
Verification Date November 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP