Portal Hypertension
Conditions
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).
Interventions
DRUGFE 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.
DRUGPlacebo
In Part 2 of the trial, each subject will receive a 2 hour IV infusion of placebo.
Sponsors
Ferring Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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: 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. |
| 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. |
| 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. |
| 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. |
| 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 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 (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. |
| 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. |
Countries
Spain
Participant flow
Recruitment details
The trial was terminated early due to low recruitment. Only four subjects were enrolled into the open-label, exploratory Part 1 of the trial (all receiving different dosing regimens), and no subjects were enrolled into the randomized, double-blind, placebo-controlled Part 2 of the trial prior to early termination.
Pre-assignment details
A total of five subjects were screened, of which, four subjects were enrolled in Part 1 of the trial.
Participants by arm
| Arm | Count |
|---|---|
| FE 204205 FE 204205, given once daily as 2 hour IV infusion, on three consecutive days. The dose in each subject was escalated from one day to the next if all dose escalation criteria were met.
The dosing regimen for each subject is given below:
Subject 101: Day 1: 0.0325 mg; Subject 102: Day 1: 0.01 mg, Day 2: 0.026 mg, Day 3: 0.05 mg; Subject 103: Day 1: 0.01 mg, Day 2: 0.01 mg, Day 3: 0.01 mg; Subject 105: Day 1: 0.01 mg, Day 2: 0.01 mg, Day 3: 0.026 mg. | 4 |
| Total | 4 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
Baseline characteristics
| Characteristic | FE 204205 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 4 |
| other Total, other adverse events | 2 / 4 |
| serious Total, serious adverse events | 2 / 4 |
Outcome results
Primary
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.
Time frame: From baseline (pre-dose) to 3 hours after start of infusion
Population: There were too few subjects for statistical analysis (see measure description).
Primary
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.
Time frame: From baseline (pre-dose) to 3 hours after start of infusion
Population: There were too few subjects for statistical analysis (see measure description).
Primary
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.
Time frame: From baseline (pre-dose) up to Day 14
Population: There were too few subjects for statistical analysis (see measure description).
Primary
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.
Time frame: From baseline (pre-dose) to 2 hours after start of infusion
Population: There were too few subjects for statistical analysis (see measure description).
Primary
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.
Time frame: From baseline (pre-dose) to 3 hours after start of infusion
Population: There were too few subjects for statistical analysis (see measure description).
Primary
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.
Time frame: From baseline (pre-dose) up to Day 14
Population: There were too few subjects for statistical analysis (see measure description).
Primary
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.
Time frame: Pre-dose, 0.5, 1, 2, 3, and 4 hours after start of infusion
Population: There were too few subjects for statistical analysis (see measure description).
Primary
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.
Time frame: Pre-dose, 0.5, 1, 2, 3, and 4 hours after start of infusion
Population: There were too few subjects for statistical analysis (see measure description).
Primary
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.
Time frame: Pre-dose, 0.5, 1, 2, 3, and 4 hours after start of infusion
Population: There were too few subjects for statistical analysis (see measure description).
Primary
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.
Time frame: Pre-dose, 0.5, 1, 2, 3, and 4 hours after start of infusion
Population: There were too few subjects for statistical analysis (see measure description).
Primary
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.
Time frame: Pre-dose, 0.5, 1, 2, 3, and 4 hours after start of infusion
Population: There were too few subjects for statistical analysis (see measure description).
Primary
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.
Time frame: Up to Day 14
Population: There were too few subjects for statistical analysis (see measure description).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| FE 204205 | Type, Frequency and Intensity of Adverse Events (AEs) | Frequency of AEs | 3 Participants |
| FE 204205 | Type, Frequency and Intensity of Adverse Events (AEs) | Intensity of AEs (Mild) | 1 Participants |
| FE 204205 | Type, Frequency and Intensity of Adverse Events (AEs) | Intensity of AEs (Moderate) | 1 Participants |
| FE 204205 | Type, Frequency and Intensity of Adverse Events (AEs) | Intensity of AEs (Severe) | 1 Participants |
| FE 204205 | Type, Frequency and Intensity of Adverse Events (AEs) | Type of AEs (Serious) | 2 Participants |
| FE 204205 | Type, Frequency and Intensity of Adverse Events (AEs) | Type of AEs (Non-serious) | 2 Participants |