International, Multicenter, Open-Label and Randomized Withdrawal Study of Oral Lixivaptan in Heart Failure Patients With Chronic Hyponatremia

This study has been withdrawn prior to enrollment.
(Created Extension study - This study was no longer feasible)
Sponsor:
Collaborators:
Cardiokine Biopharma, LLC
Biogen Idec
Information provided by:
CardioKine Inc.
ClinicalTrials.gov Identifier:
NCT00876876
First received: April 3, 2009
Last updated: November 19, 2010
Last verified: November 2010
  Purpose

To demonstrate that after 12 weeks of open-label lixivaptan treatment, serum sodium is maintained in hyponatremic patients continuing to receive lixivaptan compared to placebo during the 4 week double blind treatment period.


Condition Intervention Phase
Hypervolemic Hyponatremia
Drug: Lixivaptan
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: International, Multicenter, Open-Label and Randomized Withdrawal Study of Oral Lixivaptan in Heart Failure Patients With Chronic Hyponatremia

Resource links provided by NLM:


Further study details as provided by CardioKine Inc.:

Primary Outcome Measures:
  • To demonstrate that after 12 weeks of open-label lixivaptan treatment, serum sodium is maintained in hyponatremic patients continuing to receive lixivaptan compared to placebo during the 4 week double blind treatment period. [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To demonstrate that after 12 weeks of open-label lixivaptan treatment, improvements in the time to complete the Trail Making Test (Part B) will be maintained in patients continuing to receive lixivaptan. [ Time Frame: 20 weeks ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 300
Study Start Date: July 2009
Estimated Study Completion Date: December 2010
Estimated Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo QD or BID
Placebo QD or BID
Drug: Lixivaptan
Capsules containing 25, or 50 mg doses of oral lixivaptan to be administered BID or QD Lixivaptan will be administered for 12 weeks in the Open-Label Period which will be followed by a 4 week Randomized, Placebo-Controlled period.
Experimental: Lixivaptan QD or BID
Lixivaptan QD or BID
Drug: Lixivaptan
Capsules containing 25, or 50 mg doses of oral lixivaptan to be administered BID or QD Lixivaptan will be administered for 12 weeks in the Open-Label Period which will be followed by a 4 week Randomized, Placebo-Controlled period.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Men and Women with age greater than or equal to 18 years.
  2. Prior successful participation in a randomized, blinded, placebo-controlled Phase 3 lixivaptan study of hyponatremia in Heart Failure (Protocol CK-LX3401) with evidence of continued need for therapy as follows:

    • Patient completed full course of treatment (e.g., either placebo or lixivaptan). Treatment assignments for Protocol CK-LX3401 will not be unblinded prior to participation in the extension study.
    • Baseline serum sodium concentration < 135 mEq/L following a 30 day post treatment follow-up period in a lixivaptan hyponatremia parent trial. Repeat measures of serum sodium are allowed; the last serum sodium result within 24 hours prior to randomization will serve as the qualifying measurement.
  3. The patient has clinical evidence of volume overload with at least one of the following:

    • Dyspnea
    • Pulmonary congestion (rales)
    • Peripheral edema
    • Increased jugular venous pressure and/or hepatic congestion with ascites
    • Chest x-ray consistent with CHF; OR
    • Plasma BNP ≥150 pg/mL or NT pro-BNP ≥ 450 pg/mL

Exclusion Criteria:

  1. Women who are pregnant (positive pregnancy test), breastfeeding or who will not adhere to the reproductive precautions as outlined in this protocol and in the informed consent form.
  2. Inability to provide informed consent.
  3. Acute severe hyponatremia with overt symptoms of hyponatremia requiring immediate medical intervention (e.g., coma, seizures).
  4. Acute or transient hyponatremia (e.g., associated with head trauma or postoperative state).
  5. Hyponatremia in hypovolemic states. Hypovolemia is defined as the presence of clinical evidence of fluid volume depletion.
  6. Euvolemic Hyponatremia (e.g., SIADH, etc.). Euvolemic hyponatremia is defined as low serum sodium in the presence of normal total body sodium due to mild to moderate increases in total body water without edema.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Cesare Orlandi, MD, Cardiokine Biopharma, LLC
ClinicalTrials.gov Identifier: NCT00876876     History of Changes
Other Study ID Numbers: CK-LX3422
Study First Received: April 3, 2009
Last Updated: November 19, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by CardioKine Inc.:
hypervolemic hyponatremia
serum sodium
fluid overload
heartfailure
acute heart failure
vasopressin antagonist

Additional relevant MeSH terms:
Heart Failure
Hyponatremia
Heart Diseases
Cardiovascular Diseases
Water-Electrolyte Imbalance
Metabolic Diseases

ClinicalTrials.gov processed this record on September 18, 2014