TRimetazidine for acUte on Chronic Liver Failure STudy

NCT03737448 | Suspended Phase 1 DMC

• 1 other identifier: MP-0614-001
• Study Type: interventional
• Target: 30
• Locations: 5 countries
• Sites: 24

Brief Summary

The study will assess the pharmacokinetics (PK), tolerability, and safety of oral trimetazidine administered to subjects with AD (ACLF Grade 0) or with ACLF Grade 1 or 2.

Conditions

Acute-On-Chronic Liver Failure

Outcome Measures

Primary Outcomes (2)

• plasma pharmacokinetics

  Cmax

  28 days

• plasma pharmacokinetics

  AUC

  28 days

Secondary Outcomes (1)

• Incidence of treatment-emergent adverse events [Safety and Tolerability]

  90 days

Study Arms (2)

Group 1

EXPERIMENTAL

* AD with serum creatinine ≥ 1 and \< 2 mg/dL, OR * ACLF 1 with * liver failure and serum creatinine ≥ 1.5 and \< 2 mg/dl, or * liver failure and West Haven grade 1-2 hepatic encephalopathy, or * coagulation failure and serum creatinine ≥ 1.5 and \< 2 mg/dl, or * coagulation failure and West Haven grade 1-2 hepatic encephalopathy, OR * ACLF 2 with * liver failure and coagulation failure, or * liver failure and West Haven grade 3-4 hepatic encephalopathy.

Drug: Trimetazidine

Group 2

EXPERIMENTAL

* ACLF 1 with renal failure (serum creatinine ≥ 2.0 and \< 3.5 mg/dL), OR * ACLF 2 with * liver failure and renal failure (serum creatinine ≥ 2.0 and \< 3.5 mg/dL), or * coagulation failure and renal failure (serum creatinine ≥ 2.0 and \< 3.5 mg/dL).

Drug: Trimetazidine

Interventions

Trimetazidine DRUG

Subjects with receive up to 60 mg daily

Group 1; Group 2

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 to 75 years, inclusive, at screening.
• Stable diagnosis of AD, ACLF Grade 1 or ACLF Grade 2 for no less than 2 days (as determined at the discretion of the investigator)\*.
• Anticipated duration of hospital stay of at least 7 days.
• For Group 1:
• AD with SCr ≥ 1 and \< 2 mg/dL, OR
• ACLF 1 with
• Tbil ≥ 12 mg/dL, SCr ≥ 1.5 and \< 2 mg/dl, and HE 0-2, or
• Tbil ≥ 12 mg/dL, and SCr \< 1.5 mg/dL, and HE 1-2, or
• INR ≥ 2.5, SCr ≥ 1.5 and \< 2 mg/dl, and HE 0-2, or
• INR ≥ 2.5, SCr \< 1.5 mg/dL, and HE 1-2, OR
• ACLF 2 with
• Tbil ≥ 12 mg/dL, INR ≥ 2.5, and SCr \< 2 mg/dL, or
• Tbil ≥ 12 mg/dL, HE 3-4, and SCr \< 2 mg/dL
• For Group 2:
• ACLF 1 with SCr ≥ 2.0 and \< 3.5 mg/dL, OR

You may not qualify if:

• Diagnosis of AD or ACLF (of any grade) \>14 days before enrollment\*.
• Circulatory failure.
• Respiratory failure i.e. PaO2/FiO2 ≤ 200 and/or baseline SpO2/FiO2 ≤ 214.
• Brain failure (West Haven grade 3 or 4 hepatic encephalopathy) with coagulation failure (INR \> 2.5).
• Gastrointestinal bleeding within 72 hours prior to enrollment. (Subjects who fail this criterion may qualify after 72 hours).
• Uncontrolled bacterial infection (urinary tract infection, spontaneous bacterial peritonitis, pneumonia, bacteremia, soft tissue infections, etc.) (as determined at the discretion of the investigator).
• Invasive fungal infection.
• Platelet count \<30,000 cells/mL.
• White blood cell count \<1000 cells/uL.
• Patients on hemodialysis or continuous venovenous hemofiltration.
• Patients who have undergone or are scheduled for imminent organ transplantation. (Patients may be on a transplant list as long as no date has been set for transplantation)
• Hospitalization for ACLF within the 3 months prior to screening.
• History of hepatocellular carcinoma, unless within Milan Criteria (up to 3 lesions each \< 3 cm or 1 lesion \< 5 cm; no extrahepatic involvement; no evidence of gross vascular invasion).
• Active non-hepatic malignancy.
• Parkinson's disease, Parkinsonian-type symptoms (gait disorder, tremor, etc.), restless leg syndrome or other movement disorders other than asterixis.

Sponsors & Collaborators

• Martin Pharmaceuticals: lead

Study Sites (24)

Medical University of Graz

Graz, Austria

Location

Medical University of Innsbruck

Innsbruck, Austria

Location

Medical University of Vienna

Vienna, Austria

Location

University of Antwerp

Antwerp, Belgium

Location

Erasme Hospital

Brussels, Belgium

Location

Hospital Claude Huriez

Lille, France

Location

Hospital Pitie-Salpetriere

Paris, France

Location

Rennes University Hospital

Rennes, France

Location

Hôpital Paul Brousse

Villejuif, France

Location

University of Essen

Essen, Germany

Location

JW Goethe Clinic

Frankfurt, Germany

Location

Universitätsklinikum Halle Klinik und Poliklinik für Innere Medizin I

Halle, Germany

Location

University of Hannover

Hanover, Germany

Location

University of Heidelberg

Heidelberg, Germany

Location

University of Leipzig

Leipzig, Germany

Location

University of Münster

Münster, Germany

Location

Hospital Clinic

Barcelona, Spain

Location

Hospital Valle de Hebron

Barcelona, Spain

Location

Hospital Reina Sofia

Córdoba, Spain

Location

Hospital Gregorio Marañón

Madrid, Spain

Location

Hospital Puerta de Hierro

Madrid, Spain

Location

Hospital Ramon y Cajal

Madrid, Spain

Location

Hospital Marques de Valdecilla Santander

Santander, Spain

Location

Hospital Virgen del Rocio

Seville, Spain

Location

MeSH Terms

Conditions

Acute-On-Chronic Liver Failure

Interventions

Trimetazidine

Condition Hierarchy (Ancestors)

Liver Failure, Acute; Liver Failure; Hepatic Insufficiency; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Chief Medical Officer

  Martin Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 7, 2018
• First Posted: November 9, 2018
• Study Start: November 28, 2018
• Primary Completion: June 30, 2021
• Study Completion: June 30, 2021
• Last Updated: March 4, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

BE (2); AU (3); FR (4); DE (7); ES (8)