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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00414869
Recruitment Status : Terminated (Preliminary analysis of 11 patients did not demonstrate the efficacy required.)
First Posted : December 22, 2006
Last Update Posted : February 9, 2017
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Portal Hypertension Drug: NCX-1000 Drug: Placebo Phase 2

Detailed Description:
Brief summary is complete. Study is closed.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 11 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Care Provider, 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
Study Start Date : November 2005
Actual Primary Completion Date : February 2007
Actual Study Completion Date : February 2007

Arm Intervention/treatment
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
Placebo Comparator: Placebo
Placebo powder
Drug: Placebo
Inactive powder matching NCX-1000

Primary Outcome Measures :
  1. 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 ]
    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 :
  1. Safety parameters: systolic and diastolic blood pressures, heart rate, physical examination, laboratory tests and Adverse Events (AEs) [ Time Frame: 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

  2. 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 ]
    Usual pharmacokinetic (PK) evaluation

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00414869

Hospital Clinic i Provincial de Barcelona
Barcelona, Spain, 08036
Sponsors and Collaborators
Forest Laboratories
Principal Investigator: Jaime Bosch, MD Clinic Barcelona Hospital Universatiri

Responsible Party: Forest Laboratories Identifier: NCT00414869     History of Changes
Other Study ID Numbers: NCXDE05-02
First Posted: December 22, 2006    Key Record Dates
Last Update Posted: February 9, 2017
Last Verified: February 2017

Keywords provided by Forest Laboratories:
Portal pressure
Nitric oxide

Additional relevant MeSH terms:
Hypertension, Portal
Vascular Diseases
Cardiovascular Diseases
Liver Diseases
Digestive System Diseases
Ursodeoxycholic Acid
Cholagogues and Choleretics
Gastrointestinal Agents