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

Portal Hypertension Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00414869
• Other study ID #: NCXDE05-02
• Status: Terminated
• Phase: Phase 2
• First received: December 21, 2006
• Last updated: February 7, 2017
• Start date: November 2005
• Est. completion date: February 2007

Study information

• Verified date: February 2017
• Source: Forest Laboratories
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

Brief summary is complete. Study is closed.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 11
• Est. completion date: February 2007
• Est. primary completion date: February 2007
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Hypertension
• Hypertension, Portal
• Portal Hypertension

Intervention

Drug:
• NCX-1000
500 mg powder sachets to be taken as 1, 2, or 4 sachets twice daily, PO x 16 days
• Placebo
Inactive powder matching NCX-1000

Locations

Country	Name	City	State
Spain	Hospital Clinic i Provincial de Barcelona	Barcelona

Sponsors (1)

Lead Sponsor	Collaborator
Forest Laboratories

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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