A Study to Investigate the Safety and Effect of the Study Drug (FE 204205) in Patients With Cirrhotic Portal Hypertension

Portal Hypertension Clinical Trial

Official title:

A Placebo Controlled, Double-blind, Randomised Trial Investigating Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics After Intravenous Administration of FE 204205 in Patients With Cirrhotic Portal Hypertension

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02929407
• Other study ID #: 000249
• Secondary ID: 2016-001078-13
• Status: Terminated
• Phase: Phase 1
• Start date: November 2016
• Est. completion date: September 27, 2017

Study information

• Verified date: June 2019
• Source: Ferring Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this trial is to investigate safety, tolerability, pharmacodynamics (PD), and pharmacokinetics (PK) after intravenous (IV) administration of FE 204205 in patients with cirrhotic portal hypertension.

Description:

The trial aimed to evaluate the safety, tolerability, PK and PD of IV FE 204205 in cirrhotic patients with portal hypertension and was planned in 2 parts:

Part 1 of the trial was open‑label where six subjects were planned to receive three ascending doses of FE 204205, given as infusion over 2 hours on three consecutive days.

Part 2 was planned as a randomised, placebo‑controlled, double‑blind investigation evaluating the effects of a single dose of FE 204205 on portal haemodynamics in 20 subjects who would have received either the maximum tolerated dose (as defined in Part 1) of FE 204205 (n=16) or placebo (n=4).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 4
• Est. completion date: September 27, 2017
• Est. primary completion date: September 27, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Confirmed evidence of cirrhosis

• From medical history anticipated hepatic venous pressure gradient greater than equal to (=)12 mmHg

Exclusion Criteria:

• Co-existing disease e.g. significant organ failure and decompensated cirrhosis

• Type 1 hepatorenal syndrome

• Acute-on-chronic liver failure

• Hepatic encephalopathy =grade 2

• Hepatocellular carcinoma

• History of underlying chronic heart disease

• Use of vasopressin or terlipressin within 7 days prior to dosing

Related Conditions & MeSH terms

• Hypertension
• Hypertension, Portal
• Portal Hypertension

Intervention

Drug:
• FE 204205
In Part 1 of the trial, each subject will receive increasing IV doses of FE 204205, given once daily as 2 hour infusion, on three consecutive days. In Part 2 of the trial, each subject will receive a 2 hour IV infusion of the maximum tolerated dose of FE 204205 as defined in Part 1 of the trial.
• Placebo
In Part 2 of the trial, each subject will receive a 2 hour IV infusion of placebo.

Locations

Country	Name	City	State
Spain	Hospital Clinic de Barcelona, Departamento hepatología	Barcelona

Sponsors (1)

Lead Sponsor	Collaborator
Ferring Pharmaceuticals

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Hepatic Venous Pressure Gradient (HVPG)	The trial was terminated early due to low recruitment. Only four subjects were enrolled into the open-label, exploratory Part 1 of the trial, and only three of these four subjects (all receiving different dosing regimens) completed the trial and the HVPG assessments prior to the early termination decision. No subjects were enrolled into the randomized, double-blind, placebo-controlled Part 2 of the trial. As only Part 2 of the trial would have been appropriately powered, and the three subjects with HVPG assessments from Part 1 all received different dosing regimens, no meaningful statistical analysis could be conducted.	From baseline (pre-dose) to 2 hours after start of infusion
Primary	Type, Frequency and Intensity of Adverse Events (AEs)	The trial was terminated early due to low recruitment. Only four subjects (all received different dosing regimens) were enrolled into open-label, exploratory Part 1 of the trial, prior to the early termination. No subjects were enrolled in the randomized, double-blind, placebo-controlled Part 2 of the trial. Thus no meaningful statistical analysis could be conducted.; Due to the low number of subjects and individual dosing regimens, AEs were pooled for all dose levels.	Up to Day 14
Primary	Change in Systolic and Diastolic Blood Pressure	The trial was terminated early due to low recruitment. Only four subjects (all received different dosing regimens) were enrolled into open-label, exploratory Part 1 of the trial, prior to the early termination. No subjects were enrolled in the randomized, double-blind, placebo-controlled Part 2 of the trial. Thus no meaningful statistical analysis could be conducted.	From baseline (pre-dose) up to Day 14
Primary	Change in Plasma Lactate Levels	The trial was terminated early due to low recruitment. Only four subjects (all received different dosing regimens) were enrolled into open-label, exploratory Part 1 of the trial, prior to the early termination. No subjects were enrolled in the randomized, double-blind, placebo-controlled Part 2 of the trial. Thus no meaningful statistical analysis could be conducted.	From baseline (pre-dose) to 3 hours after start of infusion
Primary	Pharmacokinetics: Maximum Concentration Observed (Cmax)	The trial was terminated early due to low recruitment. Only four subjects (all received different dosing regimens) were enrolled into open-label, exploratory Part 1 of the trial, prior to the early termination. No subjets were enrolled in the randomized, double-blind, placebo-controlled Part 2 of the trial. Thus no meaningful statistical analysis could be conducted.	Pre-dose, 0.5, 1, 2, 3, and 4 hours after start of infusion
Primary	Pharmacokinetics: Area Under the Concentration-time Curve to Infinity (AUC)	The trial was terminated early due to low recruitment. Only four subjects were enrolled (all received different dosing regimens) into open-label, exploratory Part 1 of the trial, prior to the early termination. No subjects were enrolled in the randomized, double-blind, placebo-controlled Part 2 of the trial. Thus no meaningful statistical analysis could be conducted.	Pre-dose, 0.5, 1, 2, 3, and 4 hours after start of infusion
Primary	Pharmacokinetics: Total Systemic Clearance (CL)	The trial was terminated early due to low recruitment. Only four subjects (all received different dosing regimens) were enrolled into open-label, exploratory Part 1 of the trial, prior to the early termination. No subjects were enrolled in the randomized, double-blind, placebo-controlled Part 2 of the trial. Thus no meaningful statistical analysis could be conducted.	Pre-dose, 0.5, 1, 2, 3, and 4 hours after start of infusion
Primary	Pharmacokinetics: Elimination Half-life (t1/2)	The trial was terminated early due to low recruitment. Only four subjects were enrolled (all received different dosing regimens) into open-label, exploratory Part 1 of the trial, prior to the early termination. No subjects were enrolled in the randomized, double-blind, placebo-controlled Part 2 of the trial. Thus no meaningful statistical analysis could be conducted.	Pre-dose, 0.5, 1, 2, 3, and 4 hours after start of infusion
Primary	Pharmacokinetics: Volume of Distribution Associated With the Terminal Phase (Vz)	The trial was terminated early due to low recruitment. Only four subjects were enrolled (all received different dosing regimens) into open-label, exploratory Part 1 of the trial, prior to the early termination. No subjects were enrolled in the randomized, double-blind, placebo-controlled Part 2 of the trial. Thus no meaningful statistical analysis could be conducted.	Pre-dose, 0.5, 1, 2, 3, and 4 hours after start of infusion
Primary	Change in Electrocardiogram (ECG) Parameters	The trial was terminated early due to low recruitment. Only four subjects were enrolled (all received different dosing regimens) into open-label, exploratory Part 1 of the trial, prior to the early termination. No subjects were enrolled in the randomized, double-blind, placebo-controlled Part 2 of the trial. Thus no meaningful statistical analysis could be conducted.	From baseline (pre-dose) up to Day 14
Primary	Change in Blood Gas (PaO2)	The trial was terminated early due to low recruitment. Only four subjects were enrolled (all received different dosing regimens) into open-label, exploratory Part 1 of the trial, prior to the early termination. No subjects were enrolled in the randomized, double-blind, placebo-controlled Part 2 of the trial. Thus no meaningful statistical analysis could be conducted.	From baseline (pre-dose) to 3 hours after start of infusion
Primary	Change in Blood Gas (PaCO2)	The trial was terminated early due to low recruitment. Only four subjects (all received different dosing regimens) were enrolled into open-label, exploratory Part 1 of the trial, prior to the early termination. No subjects were enrolled in the randomized, double-blind, placebo-controlled Part 2 of the trial. Thus no meaningful statistical analysis could be conducted.	From baseline (pre-dose) to 3 hours after start of infusion