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

Phase 1

Terminated

Conditions: Portal Hypertension

Interventions: Drug: Placebo
Drug: FE 204205

Registration Number: NCT02929407

Lead Sponsor: Ferring Pharmaceuticals

Brief 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.

Detailed 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 & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 4

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	-
FE 204205	FE 204205	-

Primary Outcome Measures

Name	Time	Method
Pharmacokinetics: Maximum Concentration Observed (Cmax)	Pre-dose, 0.5, 1, 2, 3, and 4 hours after start of infusion	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.
Change in Electrocardiogram (ECG) Parameters	From baseline (pre-dose) up to Day 14	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.
Change in Blood Gas (PaCO2)	From baseline (pre-dose) to 3 hours after start of infusion	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.
Pharmacokinetics: Elimination Half-life (t1/2)	Pre-dose, 0.5, 1, 2, 3, and 4 hours after start of infusion	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.
Change in Plasma Lactate Levels	From baseline (pre-dose) to 3 hours after start of infusion	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.
Pharmacokinetics: Volume of Distribution Associated With the Terminal Phase (Vz)	Pre-dose, 0.5, 1, 2, 3, and 4 hours after start of infusion	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.
Change in Hepatic Venous Pressure Gradient (HVPG)	From baseline (pre-dose) to 2 hours after start of infusion	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.
Type, Frequency and Intensity of Adverse Events (AEs)	Up to Day 14	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.
Pharmacokinetics: Total Systemic Clearance (CL)	Pre-dose, 0.5, 1, 2, 3, and 4 hours after start of infusion	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.
Change in Systolic and Diastolic Blood Pressure	From baseline (pre-dose) up to Day 14	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.
Pharmacokinetics: Area Under the Concentration-time Curve to Infinity (AUC)	Pre-dose, 0.5, 1, 2, 3, and 4 hours after start of infusion	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.
Change in Blood Gas (PaO2)	From baseline (pre-dose) to 3 hours after start of infusion	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.