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

NCT02929407 | Terminated Phase 1 Results

• 2 other identifiers: 0002492016-001078-13
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

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.

Conditions

Portal Hypertension

Outcome Measures

Primary Outcomes (12)

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

Study Arms (2)

FE 204205

EXPERIMENTAL

Drug: FE 204205

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

FE 204205 DRUG

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.

FE 204205

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Confirmed evidence of cirrhosis
• From medical history anticipated hepatic venous pressure gradient greater than equal to (≥)12 mmHg

You may not qualify if:

• 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

Sponsors & Collaborators

• Ferring Pharmaceuticals: lead

Study Sites (1)

Hospital Clinic de Barcelona, Departamento hepatología

Barcelona, Spain

Location

MeSH Terms

Conditions

Hypertension, Portal

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases

Results Point of Contact

• Title: Global Clinical Compliance
• Organization: Ferring Pharmaceuticals

DK0-Disclosure@ferring.com

Study Officials

• Global Clinical Compliance

  Ferring Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 13, 2016
• First Posted: October 11, 2016
• Study Start: November 1, 2016
• Primary Completion: September 27, 2017
• Study Completion: September 27, 2017
• Last Updated: July 12, 2019
• Results First Posted: July 12, 2019

Record last verified: 2019-06

Locations

ES (1)