Preliminary Efficacy and Tolerability of NCX-1000 After Repeated Oral Doses in Patients With Elevated Portal Pressure
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.
|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|
- 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.
- 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
|Study Start Date:||November 2005|
|Study Completion Date:||February 2007|
|Primary Completion Date:||February 2007 (Final data collection date for primary outcome measure)|
Experimental drug under evaluation
500 mg powder sachets to be taken as 1, 2, or 4 sachets BID PC x 16 days
Placebo Comparator: Placebo
Inactive powder matching NCX-1000
Brief summary is complete. Study is closed