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

Phase 3

Withdrawn

• Conditions: Hypervolemic Hyponatremia
• Interventions: Drug: Lixivaptan

• Registration Number: NCT00876876
• Lead Sponsor: CardioKine Inc.

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2009-04-03
• Study First Submitted QC: 2009-04-06
• Study First Posted: 2009-04-07
• Study Start: 2009-07
• Primary Completion: 2010-08
• Status Verified: 2010-11
• Last Update Submitted: 2010-11-19
• Last Update Posted: 2010-11-23
• Study Completion: 2010-12

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: 300

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Lixivaptan QD or BID	Lixivaptan	Lixivaptan QD or BID
Placebo QD or BID	Lixivaptan	Placebo QD or BID

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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