Preliminary Efficacy and Tolerability of NCX-1000 After Repeated Oral Doses in Patients With Elevated Portal Pressure

Phase 2

Terminated

• Conditions: Portal Hypertension
• Interventions: Drug: NCX-1000; Drug: Placebo

• Registration Number: NCT00414869
• Lead Sponsor: Forest Laboratories

Brief Summary

Chronic liver diseases are often characterized by portal hypertension, a major complication involving haemodynamic changes due to increased intrahepatic vascular resistance. It has become well established that nitric oxide (NO) plays a crucial role in the haemodynamic abnormalities that develop in chronic portal hypertension.

NCX-1000 is a NO-releasing derivative of ursodeoxycholic acid that would compensate for the defective liver NO production in cirrhosis.

This study intends to demonstrate the desired therapeutic activity (reduction in portal pressure) in a small number of target patients, to assess the safety and tolerability after repeated oral administrations of NCX-1000, and to get preliminary pharmacokinetic data in this population.

Detailed Description

Brief summary is complete. Study is closed.

Study Timeline

• Study Start: 2005-11
• Study First Submitted: 2006-12-21
• Study First Submitted QC: 2006-12-21
• Study First Posted: 2006-12-22
• Primary Completion: 2007-02
• Study Completion: 2007-02
• Status Verified: 2017-02
• Last Update Submitted: 2017-02-07
• Last Update Posted: 2017-02-09

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 11

Inclusion Criteria

• Male or non-pregnant female patients of at least 18 years old
• HVPG > 12 mm Hg in fasting state on Day 1
• Free of any other condition (except liver failure) that may alter absorption, distribution, or elimination of drugs

Exclusion Criteria

• Oesophageal bleeding in the previous 30 days
• Known intolerance to ursodeoxycholic acid or nitrates
• Liver cancer or liver metastasis from another cancer
• Portal hypertension secondary to venous thrombosis
• Presence of Transjugular Intrahepatic Portosystemic Shunt (TIPS)
• Severe liver failure (Child-Pugh C)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
NCX-1000	NCX-1000	Experimental drug under evaluation
Placebo	Placebo	Placebo powder

Primary Outcome Measures

Name	Time	Method
The Hepatic Venous Pressure Gradient (HVPG) will be evaluated at entry (Day 1) and after the Maximal Tolerated Dose (MTD) on Day 16, in fasting and post-prandial (after a standardized liquid breakfast) states.	Day1 and Day 16	The portal pressure, as determined by HVPG, was obtained by subtracting the free hepatic venous pressure from the wedged hepatic venous pressure and rounded to the nearest 0.5 or integer value.The pressures were recorded 3 times for each evaluation and the HVPG value was the mean of the 3 Recordings

Secondary Outcome Measures

Name	Time	Method
Safety parameters: systolic and diastolic blood pressures, heart rate, physical examination, laboratory tests and Adverse Events (AEs)	At various times	Usual safety parameters. Blood pressures were assessed every 30 minutes for 4 hours after drug intake. Other parameters were assessed or reported at Study visits
Plasma levels of NCX-1000 and its main metabolites will be evaluated to get preliminary pharmacokinetic data.	0, 1, 2, 3, and 4 hours after the first 3 doses anf after the last dose	Usual pharmacokinetic (PK) evaluation

Trial Locations

Locations (1)

Hospital Clinic i Provincial de Barcelona; 🇪🇸 Barcelona, Spain