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

Study Overview
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Brief Summary
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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
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Brief summary is complete. Study is closed.

Official Title
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Preliminary Efficacy And Tolerability Of Oral NCX-1000 After Repeated Administrations In Patients With Portal Hypertension: A Double-Blind Dose Escalating Study

Conditions
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Portal Hypertension

Intervention / Treatment
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* Drug: NCX-1000
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NCX-1000<br>Experimental drug under evaluation | Drug: NCX-1000<br>* 500 mg powder sachets to be taken as 1, 2, or 4 sachets twice daily, PO x 16 days<br>|
| Placebo Comparator: Placebo<br>Placebo powder | Drug: Placebo<br>* Inactive powder matching NCX-1000<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety parameters: systolic and diastolic blood pressures, heart rate, physical examination, laboratory tests and Adverse Events (AEs) | 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 | At various times | 
| Plasma levels of NCX-1000 and its main metabolites will be evaluated to get preliminary pharmacokinetic data. | Usual pharmacokinetic (PK) evaluation | 0, 1, 2, 3, and 4 hours after the first 3 doses anf after the last dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Liver, Portal pressure, Fibrosis, Nitric oxide