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

Condition(s) targeted: Portal Hypertension

Intervention: NCX-1000 (Drug)

Phase: Phase 2

Status: Terminated

Sponsored by: Axcan Pharma

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.

Official title: Preliminary Efficacy And Tolerability Of Oral NCX-1000 After Repeated Administrations In Patients With Portal Hypertension: A Double-Blind Dose Escalating Study

Study design: Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome: 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.

Secondary outcome:

Safety parameters: systolic and diastolic blood pressures, heart rate, physical examination, laboratory tests and Adverse Events (AEs)

Plasma levels of NCX-1000 and its main metabolites will be evaluated to get preliminary pharmacokinetic data.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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)

Hospital Clinic i Provincial de Barcelona, Barcelona 08036, Spain

Starting date: November 2005
Ending date: February 2007
Last updated: November 16, 2007