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
Overview
- Phase
- Phase 1
- Intervention
- FE 204205
- Conditions
- Portal Hypertension
- Sponsor
- Ferring Pharmaceuticals
- Enrollment
- 4
- Locations
- 1
- Primary Endpoint
- Pharmacokinetics: Maximum Concentration Observed (Cmax)
- Status
- Terminated
- Last Updated
- 6 years ago
Overview
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).
Investigators
Eligibility 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
Arms & Interventions
FE 204205
Intervention: FE 204205
Placebo
Intervention: Placebo
Outcomes
Primary Outcomes
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.