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

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

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.

Study Overview

• Status: Completed
• Conditions: Liver Cirrhosis
• Intervention / Treatment: Drug: Placebo; Drug: conivaptan

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain

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:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Cumberland Pharmaceuticals
• Investigators: Study Director: Art Wheeler, MD, Cumberland Pharmaceuticals, Inc.

Publications and helpful links

Helpful Links

• (Link to Prescribing Information)

Study record dates

Study Major Dates

• Study Start: December 1, 2007
• Primary Completion (Actual): November 1, 2008
• Study Completion (Actual): November 1, 2008

Study Registration Dates

• First Submitted: January 2, 2008
• First Submitted That Met QC Criteria: January 2, 2008
• First Posted (Estimate): January 14, 2008

Study Record Updates

• Last Update Posted (Estimate): May 15, 2014
• Last Update Submitted That Met QC Criteria: April 30, 2014
• Last Verified: April 1, 2014

More Information

Terms related to this study

• Keywords: Liver Cirrhosis; Hypertension, Portal; conivaptan
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Liver Cirrhosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Natriuretic Agents; Antidiuretic Hormone Receptor Antagonists; Conivaptan
• Other Study ID Numbers: 087-CL-089; 2007-001661-15 (EudraCT Number)