NCT00414869

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.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
11

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Nov 2005

Shorter than P25 for phase_2

Geographic Reach
1 country

1 active site

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

Study Start

First participant enrolled

November 1, 2005

Completed
1.1 years until next milestone

First Submitted

Initial submission to the registry

December 21, 2006

Completed
1 day until next milestone

First Posted

Study publicly available on registry

December 22, 2006

Completed
1 month until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2007

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2007

Completed
Last Updated

February 9, 2017

Status Verified

February 1, 2017

Enrollment Period

1.3 years

First QC Date

December 21, 2006

Last Update Submit

February 7, 2017

Conditions

Portal Hypertension

Keywords

LiverPortal pressureFibrosisNitric oxide

Outcome Measures

Primary Outcomes (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.

    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 Outcomes (2)

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

    At various times

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

    0, 1, 2, 3, and 4 hours after the first 3 doses anf after the last dose

Study Arms (2)

NCX-1000

EXPERIMENTAL

Experimental drug under evaluation

Drug: NCX-1000

Placebo

PLACEBO COMPARATOR

Placebo powder

Drug: Placebo

Interventions

NCX-1000DRUG

500 mg powder sachets to be taken as 1, 2, or 4 sachets twice daily, PO x 16 days

NCX-1000
PlaceboDRUG

Inactive powder matching NCX-1000

Placebo

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Hospital Clinic i Provincial de Barcelona

Barcelona, 08036, Spain

Location

MeSH Terms

Conditions

Hypertension, PortalFibrosis

Interventions

2-methyl-3-(2-((4-nitrooxybutyloxy)carbonyl)vinyl)phenyl ursodeoxycholic acid ester

Condition Hierarchy (Ancestors)

Liver DiseasesDigestive System DiseasesPathologic ProcessesPathological Conditions, Signs and Symptoms

Study Officials

  • Jaime Bosch, MD

    Clinic Barcelona Hospital Universatiri

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 21, 2006

First Posted

December 22, 2006

Study Start

November 1, 2005

Primary Completion

February 1, 2007

Study Completion

February 1, 2007

Last Updated

February 9, 2017

Record last verified: 2017-02

Locations

ES(1)