A Study to Assess the Safety and Effects of Intravenous (IV) Conivaptan on the Hepatic Hemodynamic Response in Cirrhotic Patients

Study Overview
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Brief Summary
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To evaluate the safety of IV conivaptan in stable euvolemic or hypervolemic cirrhotic patients, and to characterize the effects of IV conivaptan on the hepatic hemodynamic response in patients with cirrhosis.

Official Title
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A Phase 2, Randomized, Double Blind, Placebo Controlled, Dose Escalation Study to Assess the Safety and Effects of Intravenous Conivaptan on the Hepatic Hemodynamic Response in Stable Euvolemic or Hypervolemic Cirrhotic Patients

Conditions
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Liver Cirrhosis

Intervention / Treatment
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* Drug: conivaptan
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved written Informed Consent and appropriate privacy language as per national regulations must be obtained from the subject or legally authorized representative prior to any study-related procedures (including withdrawal of prohibited medication, if applicable) Subject is euvolemic or hypervolemic (edematous) secondary to cirrhosis Subject has clinical evidence of portal hypertension by the presence of esophageal varices, ascites or both Exclusion Criteria: Clinical evidence of volume depletion or dehydration Subject has a history of bleeding from esophageal varices within three months before the start of the study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Regimen 1 Conivaptan 12.5 mg<br>Conivaptan intravenous loading dose (10 mg) + 2.5 mg continuous infusion over 6.5 hours | Drug: conivaptan<br>* IV<br>|
| Experimental: Regimen 2 Conivaptan 25 mg<br>Conivaptan intravenous loading dose (20 mg) + 5 mg continuous infusion over 6.5 hours | Drug: conivaptan<br>* IV<br>|
| Placebo Comparator: Regimen 3 Placebo<br>Placebo continuous intravenous infusion over 6.5 hours | Drug: Placebo<br>* IV<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Hepatic Venous Pressure Gradient (HVPG) at 0.5, 1, and 1.5 Hours Post Dose | Change from baseline is calculated as time point minus baseline. Baseline procedures were performed prior to study drug administration. | Baseline and 0.5, 1, and 1.5 hours post dose | 
| Change From Baseline in Hepatic Blood Flow (HBF) at 0.5, 1, and 1.5 Hours Post Dose | Change from baseline is calculated as time point minus baseline. Baseline procedures were performed prior to study drug administration. | Baseline and 0.5, 1, and 1.5 hours post dose | 
| Change From Baseline in Hepatic Mean Arterial Pressure (MAP) at 0.5, 1, and 1.5 Hours Post Dose | Change from baseline is calculated as time point minus baseline. Baseline procedures were performed prior to study drug administration. | Baseline and 0.5, 1, and 1.5 hours post dose | 
| Change From Baseline in Blood Pressure at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Change from baseline is calculated as time point minus baseline. Baseline procedures were performed prior to study drug administration. | Baseline and 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 hours, and Day 8 post dose | 
| Change From Baseline in Heart Rate at 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 Hours, and Day 8 Post Dose | Change from baseline is calculated as time point minus baseline. Baseline procedures were performed prior to study drug administration. | Baseline and 0.5, 1, 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 9, 12, and 24 hours, and Day 8 post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Serum Sodium Levels at 0.5, 1, 2.5, 4, 6.5, 9, 12, and 24 Hours and on Day 8 Post Dose | Baseline serum sodium value is the last measurement prior to dosing. Change from baseline is calculated as time point minus baseline. | Baseline and 0.5, 1, 2.5, 4, 6.5, 9, 12, and 24 hours and on Day 8 post dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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conivaptan, Liver Cirrhosis, Hypertension, Portal