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| ID | Type | Description | Link |
|---|---|---|---|
| 2016-001078-13 | EudraCT Number |
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Trial terminated due to difficult recruitment
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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.
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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| FE 204205 | Experimental |
| |
| Placebo | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Global Clinical Compliance | Ferring Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital Clinic de Barcelona, Departamento hepatologÃa | Barcelona | Spain |
A total of five subjects were screened, of which, four subjects were enrolled in Part 1 of the trial.
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | FE 204205 | FE 204205, given once daily as 2 hour intravenous (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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | There were too few subjects for statistical analysis (see measure description). | Posted | From baseline (pre-dose) to 2 hours after start of infusion |
|
AEs were recorded from obtaining the informed consent to the follow-up visit. In part 1 of the trial, AEs were recorded from obtaining the informed consent (up to 21 days before first administration of FE 204205) to the end-of-trial visit (between 7 and 14 days after first administration of FE 204205). Part 2 of the trial was never initiated.
An AE was defined as any untoward medical occurrence in a subject participating in a clinical trial. An AE could be any unfavourable and unintended sign, symptom or disease temporally associated with the use of the investigational medicinal product (IMP), whether or not considered to be caused by the IMP.
Due to the low number of subjects and individual dosing regimens, AEs were pooled for all dose levels.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Arterial Hypertension | Vascular disorders | MedDRA (19.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (19.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Global Clinical Compliance | Ferring Pharmaceuticals | DK0-Disclosure@ferring.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jan 17, 2017 | Mar 28, 2019 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D006975 | Hypertension, Portal |
| ID | Term |
|---|---|
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
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| Placebo | Drug | In Part 2 of the trial, each subject will receive a 2 hour IV infusion of placebo. |
|
| 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 |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
|
| 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. | There were too few subjects for statistical analysis (see measure description). | Posted | Count of Participants | Participants | Up to Day 14 |
|
|
|
| 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. | There were too few subjects for statistical analysis (see measure description). | Posted | From baseline (pre-dose) up to Day 14 |
|
|
| 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. | There were too few subjects for statistical analysis (see measure description). | Posted | From baseline (pre-dose) to 3 hours after start of infusion |
|
|
| 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. | There were too few subjects for statistical analysis (see measure description). | Posted | Pre-dose, 0.5, 1, 2, 3, and 4 hours after start of infusion |
|
|
| 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. | There were too few subjects for statistical analysis (see measure description). | Posted | Pre-dose, 0.5, 1, 2, 3, and 4 hours after start of infusion |
|
|
| 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. | There were too few subjects for statistical analysis (see measure description). | Posted | Pre-dose, 0.5, 1, 2, 3, and 4 hours after start of infusion |
|
|
| 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. | There were too few subjects for statistical analysis (see measure description). | Posted | Pre-dose, 0.5, 1, 2, 3, and 4 hours after start of infusion |
|
|
| 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. | There were too few subjects for statistical analysis (see measure description). | Posted | Pre-dose, 0.5, 1, 2, 3, and 4 hours after start of infusion |
|
|
| 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. | There were too few subjects for statistical analysis (see measure description). | Posted | From baseline (pre-dose) up to Day 14 |
|
|
| 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. | There were too few subjects for statistical analysis (see measure description). | Posted | From baseline (pre-dose) to 3 hours after start of infusion |
|
|
| 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. | There were too few subjects for statistical analysis (see measure description). | Posted | From baseline (pre-dose) to 3 hours after start of infusion |
|
|
| 0 |
| 4 |
| 2 |
| 4 |
| 2 |
| 4 |
| Diarrhoea | Gastrointestinal disorders | MedDRA (19.0) | Systematic Assessment |
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| Hepatic Encephalopathy | Nervous system disorders | MedDRA (19.0) | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (19.0) | Systematic Assessment |
|
| Limb discomfort | Musculoskeletal and connective tissue disorders | MedDRA (19.0) | Systematic Assessment |
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| Osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA (19.0) | Systematic Assessment |
|
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA (19.0) | Systematic Assessment |
|
| Asterixis | Nervous system disorders | MedDRA (19.0) | Systematic Assessment |
|
The only disclosure restriction on the PI is that the sponsor can review the draft manuscript prior to publication and can request delay of publication where any contents are deemed patentable by the sponsor or confidential to the sponsor. Comments will be given within four weeks from receipt of the draft manuscript. Additional time may be required to allow Ferring to seek patent protection of the invention.
| Title | Measurements |
|---|---|
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| Intensity of AEs (Severe) |
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| Type of AEs (Serious) |
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| Type of AEs (Non-serious) |
|