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

Study Overview
=================
Brief Summary
-----------------
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.

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

Conditions
-----------------
Hypervolemic Hyponatremia

Intervention / Treatment
-----------------
* Drug: Lixivaptan


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Men and Women with age greater than or equal to 18 years. 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. 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: 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. Inability to provide informed consent. Acute severe hyponatremia with overt symptoms of hyponatremia requiring immediate medical intervention (e.g., coma, seizures). Acute or transient hyponatremia (e.g., associated with head trauma or postoperative state). Hyponatremia in hypovolemic states. Hypovolemia is defined as the presence of clinical evidence of fluid volume depletion. 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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo QD or BID<br>Placebo QD or BID | Drug: Lixivaptan<br>* 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.<br>|
| Experimental: Lixivaptan QD or BID<br>Lixivaptan QD or BID | Drug: Lixivaptan<br>* 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.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
hypervolemic hyponatremia, serum sodium, fluid overload, heartfailure, acute heart failure, vasopressin antagonist