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

Hypervolemic Hyponatremia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT00876876
• Other study ID #: CK-LX3422
• Status: Withdrawn
• Phase: Phase 3
• First received: April 3, 2009
• Last updated: November 19, 2010
• Start date: July 2009
• Est. completion date: December 2010

Study information

• Verified date: November 2010
• Source: CardioKine Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 300
• Est. completion date: December 2010
• Est. primary completion date: August 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Heart Failure
• Hypervolemic Hyponatremia
• Hyponatremia

Intervention

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.

Locations

Country	Name	City	State
n/a

Sponsors (3)

Lead Sponsor	Collaborator
CardioKine Inc.	Biogen, Cardiokine Biopharma, LLC

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	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	Yes