Clinical trial NCT02929407: 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
Overall status: TERMINATED
Phase: PHASE1
Conditions: Portal Hypertension
Lead sponsor: Ferring Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2016-10-11
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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

Primary outcomes:
measure: Change in Hepatic Venous Pressure Gradient (HVPG)
timeFrame: From baseline (pre-dose) to 2 hours after start of infusion
measure: Type, Frequency and Intensity of Adverse Events (AEs)
timeFrame: Up to Day 14
measure: Change in Systolic and Diastolic Blood Pressure
timeFrame: From baseline (pre-dose) up to Day 14
measure: Change in Plasma Lactate Levels
timeFrame: From baseline (pre-dose) to 3 hours after start of infusion
measure: Pharmacokinetics: Maximum Concentration Observed (Cmax)
timeFrame: Pre-dose, 0.5, 1, 2, 3, and 4 hours after start of infusion
measure: Pharmacokinetics: Area Under the Concentration-time Curve to Infinity (AUC)
timeFrame: Pre-dose, 0.5, 1, 2, 3, and 4 hours after start of infusion
measure: Pharmacokinetics: Total Systemic Clearance (CL)
timeFrame: Pre-dose, 0.5, 1, 2, 3, and 4 hours after start of infusion
measure: Pharmacokinetics: Elimination Half-life (t1/2)
timeFrame: Pre-dose, 0.5, 1, 2, 3, and 4 hours after start of infusion
measure: Pharmacokinetics: Volume of Distribution Associated With the Terminal Phase (Vz)
timeFrame: Pre-dose, 0.5, 1, 2, 3, and 4 hours after start of infusion
measure: Change in Electrocardiogram (ECG) Parameters
timeFrame: From baseline (pre-dose) up to Day 14
measure: Change in Blood Gas (PaO2)
timeFrame: From baseline (pre-dose) to 3 hours after start of infusion
measure: Change in Blood Gas (PaCO2)
timeFrame: From baseline (pre-dose) to 3 hours after start of infusion
Secondary outcomes:
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona, Departamento hepatología
Study officials:
affiliation: Ferring Pharmaceuticals
name: Global Clinical Compliance
role: STUDY_DIRECTOR
References: