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

This study has been terminated.
(Preliminary analysis of 11 patients did not demonstrate the efficacy required.)
Sponsor:
Information provided by:
Axcan Pharma
ClinicalTrials.gov Identifier:
NCT00414869
First received: December 21, 2006
Last updated: October 31, 2011
Last verified: May 2010
  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 2

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:


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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
Cardiovascular Diseases
Digestive System Diseases
Liver Diseases
Vascular Diseases

ClinicalTrials.gov processed this record on November 24, 2014