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

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Primary Purpose

Status

Terminated

Phase

Phase 1

Locations

Spain

Study Type

Interventional

Intervention

FE 204205

Placebo

About this trial

This is an interventional treatment trial for Portal Hypertension

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Hospital Clinic de Barcelona, Departamento hepatología

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

FE 204205

Placebo

Arm Description

Outcomes

Primary Outcome Measures

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Secondary Outcome Measures

Full Information

NCT ID

NCT02929407

First Posted

September 13, 2016

Last Updated

June 28, 2019

Sponsor

Ferring Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT02929407

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

June 2019

Overall Recruitment Status

Terminated

Why Stopped

Trial terminated due to difficult recruitment

Study Start Date

November 2016 (Actual)

Primary Completion Date

September 27, 2017 (Actual)

Study Completion Date

September 27, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Ferring Pharmaceuticals

4. Oversight

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Portal Hypertension

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

4 (Actual)

8. Arms, Groups, and Interventions

Arm Title

FE 204205

Arm Type

Experimental

Arm Title

Placebo

Arm Type

Placebo Comparator

Intervention Type

Drug

Intervention Name(s)

FE 204205

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

In Part 2 of the trial, each subject will receive a 2 hour IV infusion of placebo.

Primary Outcome Measure Information:

Title

Change in Hepatic Venous Pressure Gradient (HVPG)

Description

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.

Time Frame

From baseline (pre-dose) to 2 hours after start of infusion

Title

Type, Frequency and Intensity of Adverse Events (AEs)

Description

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.

Time Frame

Up to Day 14

Title

Change in Systolic and Diastolic Blood Pressure

Description

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.

Time Frame

From baseline (pre-dose) up to Day 14

Title

Change in Plasma Lactate Levels

Description

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.

Time Frame

From baseline (pre-dose) to 3 hours after start of infusion

Title

Pharmacokinetics: Maximum Concentration Observed (Cmax)

Description

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.

Time Frame