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

Sponsor:	Axcan Pharma
Information provided by:	Axcan Pharma
ClinicalTrials.gov Identifier:	NCT00414869

Purpose

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.

Condition	Intervention	Phase
Portal Hypertension	Drug: NCX-1000 Drug: Placebo	Phase II

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Preliminary Efficacy And Tolerability Of Oral NCX-1000 After Repeated Administrations In Patients With Portal Hypertension: A Double-Blind Dose Escalating Study

Resource links provided by NLM:

MedlinePlus related topics: High Blood Pressure

Drug Information available for: NCX-1000

U.S. FDA Resources

Further study details as provided by Axcan Pharma:

Primary Outcome Measures:

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. [ Time Frame: Day1 and Day 16 ] [ Designated as safety issue: No ]
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:

Safety parameters: systolic and diastolic blood pressures, heart rate, physical examination, laboratory tests and Adverse Events (AEs) [ Time Frame: At various times ] [ Designated as safety issue: Yes ]
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. [ Time Frame: 0, 1, 2, 3, and 4 hours after the first 3 doses anf after the last dose ] [ Designated as safety issue: No ]
Usual PK evaluation

Enrollment:	11
Study Start Date:	November 2005
Study Completion Date:	February 2007
Primary Completion Date:	February 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: NCX-1000 Experimental drug under evaluation	Drug: NCX-1000 500 mg powder sachets to be taken as 1, 2, or 4 sachets BID PC x 16 days
Placebo Comparator: Placebo Placebo powder	Drug: Placebo Inactive powder matching NCX-1000

Detailed Description:

Brief summary is complete. Study is closed

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00414869

Locations

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

Sponsors and Collaborators

Axcan Pharma

Investigators

Principal Investigator:

Jaime Bosch, MD

Clinic Barcelona Hospital Universatiri

More Information

No publications provided

Responsible Party:	Jean Spenard, Sr director, Clin Prog & Pharmacol, Axcan / Aptalis Pharma
ClinicalTrials.gov Identifier:	NCT00414869 History of Changes
Other Study ID Numbers:	NCXDE05-02
Study First Received:	December 21, 2006
Last Updated:	October 31, 2011
Health Authority:	Spain: Agencia Española de Medicamentos y Productos Sanitarios - AEMPS

Keywords provided by Axcan Pharma:

Liver
Portal pressure
Fibrosis
Nitric oxide

Additional relevant MeSH terms:

Hypertension
Hypertension, Portal
Vascular Diseases

Cardiovascular Diseases
Liver Diseases
Digestive System Diseases

ClinicalTrials.gov processed this record on February 09, 2012