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

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

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.

Study Overview

• Status: Terminated
• Conditions: Portal Hypertension
• Intervention / Treatment: Drug: NCX-1000; Drug: Placebo

Detailed Description

Brief summary is complete. Study is closed.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 2

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic i Provincial de Barcelona

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:

• 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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo powder	Drug: Placebo; Inactive powder matching NCX-1000
Experimental: NCX-1000; Experimental drug under evaluation	Drug: NCX-1000; 500 mg powder sachets to be taken as 1, 2, or 4 sachets twice daily, PO x 16 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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	Day1 and Day 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety parameters: systolic and diastolic blood pressures, heart rate, physical examination, laboratory tests and Adverse Events (AEs)	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	At various times
Plasma levels of NCX-1000 and its main metabolites will be evaluated to get preliminary pharmacokinetic data.	Usual pharmacokinetic (PK) evaluation	0, 1, 2, 3, and 4 hours after the first 3 doses anf after the last dose

Collaborators and Investigators

• Sponsor: Forest Laboratories
• Investigators: Principal Investigator: Jaime Bosch, MD, Clinic Barcelona Hospital Universatiri

Study record dates

Study Major Dates

• Study Start: November 1, 2005
• Primary Completion (Actual): February 1, 2007
• Study Completion (Actual): February 1, 2007

Study Registration Dates

• First Submitted: December 21, 2006
• First Submitted That Met QC Criteria: December 21, 2006
• First Posted (Estimate): December 22, 2006

Study Record Updates

• Last Update Posted (Estimate): February 9, 2017
• Last Update Submitted That Met QC Criteria: February 7, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: Fibrosis; Nitric oxide; Liver; Portal pressure
• Additional Relevant MeSH Terms: Digestive System Diseases; Cardiovascular Diseases; Vascular Diseases; Liver Diseases; Hypertension; Hypertension, Portal
• Other Study ID Numbers: NCXDE05-02