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

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.

Study Overview

• Status: Withdrawn
• Conditions: Hypervolemic Hyponatremia
• Intervention / Treatment: Drug: Lixivaptan

• Study Type: Interventional
• Enrollment (Anticipated): 300
• Phase: Phase 3

Participation Criteria

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. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: 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	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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.	12 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
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.	20 weeks

Collaborators and Investigators

• Sponsor: CardioKine Inc.
• Collaborators: Biogen; Cardiokine Biopharma, LLC

Study record dates

Study Major Dates

• Study Start: July 1, 2009
• Primary Completion (ANTICIPATED): August 1, 2010
• Study Completion (ANTICIPATED): December 1, 2010

Study Registration Dates

• First Submitted: April 3, 2009
• First Submitted That Met QC Criteria: April 6, 2009
• First Posted (ESTIMATE): April 7, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): November 23, 2010
• Last Update Submitted That Met QC Criteria: November 19, 2010
• Last Verified: November 1, 2010

More Information

Terms related to this study

• Keywords: acute heart failure; fluid overload; heartfailure; hypervolemic hyponatremia; serum sodium; vasopressin antagonist
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Metabolic Diseases; Water-Electrolyte Imbalance; Heart Failure; Hyponatremia
• Other Study ID Numbers: CK-LX3422