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

• ClinicalTrials.gov Identifier: NCT02929407
• Recruitment Status: Terminated
• First Posted: October 11, 2016
• Results First Posted: July 12, 2019
• Last Update Posted: July 12, 2019
• Sponsor: Ferring Pharmaceuticals
• Information provided by (Responsible Party): Ferring Pharmaceuticals

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.

Condition or disease	Intervention/treatment	Phase
Portal Hypertension	Drug: FE 204205; Drug: Placebo	Phase 1

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).

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 4 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: November 2016
• Actual Primary Completion Date: September 27, 2017
• Actual Study Completion Date: September 27, 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: FE 204205	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 Comparator: Placebo	Drug: Placebo; In Part 2 of the trial, each subject will receive a 2 hour IV infusion of placebo.

Outcome Measures

Primary Outcome Measures :

1. Change in Hepatic Venous Pressure Gradient (HVPG) [ Time Frame: 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.
2. Type, Frequency and Intensity of Adverse Events (AEs) [ Time Frame: 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.

3. Change in Systolic and Diastolic Blood Pressure [ Time Frame: 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.
4. Change in Plasma Lactate Levels [ Time Frame: 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.
5. Pharmacokinetics: Maximum Concentration Observed (Cmax) [ Time Frame: 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.
6. Pharmacokinetics: Area Under the Concentration-time Curve to Infinity (AUC) [ Time Frame: 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.
7. Pharmacokinetics: Total Systemic Clearance (CL) [ Time Frame: 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.
8. Pharmacokinetics: Elimination Half-life (t1/2) [ Time Frame: 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.
9. Pharmacokinetics: Volume of Distribution Associated With the Terminal Phase (Vz) [ Time Frame: 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.
10. Change in Electrocardiogram (ECG) Parameters [ Time Frame: 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.
11. Change in Blood Gas (PaO2) [ Time Frame: 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.
12. Change in Blood Gas (PaCO2) [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

Spain

Hospital Clinic de Barcelona, Departamento hepatología

Barcelona, Spain

Sponsors and Collaborators

Ferring Pharmaceuticals

Investigators

• Study Director: Global Clinical Compliance; Ferring Pharmaceuticals

  Study Documents (Full-Text)

Documents provided by Ferring Pharmaceuticals:

Study Protocol and Statistical Analysis Plan  [PDF] January 17, 2017

More Information

• Responsible Party: Ferring Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02929407
• Other Study ID Numbers: 000249; 2016-001078-13 ( EudraCT Number )
• First Posted: October 11, 2016
• Results First Posted: July 12, 2019
• Last Update Posted: July 12, 2019
• Last Verified: June 2019

Additional relevant MeSH terms:

Hypertension, Portal; Hypertension; Vascular Diseases; Cardiovascular Diseases; Liver Diseases; Digestive System Diseases