Portal Hypertension
Conditions
Keywords
Liver, Portal pressure, Fibrosis, Nitric oxide
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.
Detailed description
Brief summary is complete. Study is closed.
Interventions
DRUGNCX-1000
500 mg powder sachets to be taken as 1, 2, or 4 sachets twice daily, PO x 16 days
DRUGPlacebo
Inactive powder matching NCX-1000
Sponsors
Forest Laboratories
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. | 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
| Measure | Time frame | Description |
|---|---|---|
| Safety parameters: systolic and diastolic blood pressures, heart rate, physical examination, laboratory tests and Adverse Events (AEs) | 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 |
| 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 | Usual pharmacokinetic (PK) evaluation |
Countries
Spain
Outcome results
None listed