ornithine phenylacetate IV (MNK-6105) / Mallinckrodt, Yaqrit - LARVOL DELTA

Yaqrit prepares phase 3 for ammonia scavenger in hepatic encephalopathy (GlobeNewswire) - "Yaqrit...announced today that its recently acquired ammonia scavenger, L-ornithine phenylacetate (OPA), is progressing to phase 3 for treatment of acute hepatic encephalopathy, a life-threatening complication of decompensated cirrhosis....IV formulation to enter phase 3 in 2025; oral formulation to enter phase 2b trials for HE prevention and phase 2a for urea cycle disorders."

New P2b trial • New P3 trial • Hepatic Encephalopathy

MNK-6105 for Patients With Cirrhosis and High Ammonia Levels Affecting Brain Function (clinicaltrials.gov) - P3; N=0; Withdrawn; Sponsor: Mallinckrodt; N=400 ➔ 0; Not yet recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal • CNS Disorders • Fibrosis • Hepatic Encephalopathy • Hepatology • Immunology

MNK-6105 for Patients With Cirrhosis and High Ammonia Levels Affecting Brain Function (clinicaltrials.gov) - P3; N=400; Not yet recruiting; Sponsor: Mallinckrodt; Trial completion date: Dec 2022 ➔ Jul 2025; Trial primary completion date: Nov 2022 ➔ Apr 2025

Clinical • Trial completion date • Trial primary completion date • CNS Disorders • Fibrosis • Hepatic Encephalopathy • Hepatology • Immunology

Bile-duct ligation renders the brain susceptible to hypotension induced neuronal degeneration: implications of ammonia. (PubMed, J Neurochem) - "In a separate group, BDL rats were treated for MHE with the ammonia-lowering strategy ornithine phenylacetate (OP; MNK-6105), administered orally (1g/kg) for 3 weeks before induction of hypotension...Our findings demonstrate that rats with chronic liver disease and MHE are more susceptible to hypotension-induced neuronal cell degeneration. This highlights MHE at the time of LT is a risk factor for poor neurological outcome post-transplant and that treating for MHE pre-LT might reduce this risk."

Journal • CNS Disorders • Fibrosis • Hepatic Encephalopathy • Hepatology • Hypotension • Immunology • Mood Disorders • Psychiatry • Transplantation • CASP3

MNK-6105 for Patients With Cirrhosis and High Ammonia Levels Affecting Brain Function (clinicaltrials.gov) - P3; N=0; Withdrawn; Sponsor: Mallinckrodt; N=400 ➔ 0; Not yet recruiting ➔ Withdrawn

Clinical • Enrollment change • Trial withdrawal • CNS Disorders • Fibrosis • Hepatic Encephalopathy • Hepatology • Immunology

MNK-6105 for Patients With Cirrhosis and High Ammonia Levels Affecting Brain Function (clinicaltrials.gov) - P3; N=400; Not yet recruiting; Sponsor: Mallinckrodt; Initiation date: Aug 2020 ➔ Mar 2021

Trial initiation date • CNS Disorders • Fibrosis • Hepatic Encephalopathy • Hepatology • Immunology

MNK-6105 for Patients With Cirrhosis and High Ammonia Levels Affecting Brain Function (clinicaltrials.gov) - P3; N=400; Not yet recruiting; Sponsor: Mallinckrodt; Initiation date: Apr 2020 ➔ Aug 2020

Clinical • Trial initiation date • Fibrosis • Hepatic Encephalopathy • Hepatology

MNK-6105 for Patients With Cirrhosis and High Ammonia Levels Affecting Brain Function (clinicaltrials.gov) - P3; N=400; Not yet recruiting; Sponsor: Mallinckrodt

Clinical • New P3 trial

MNK-6105 for Patients With Cirrhosis and High Ammonia Levels Affecting Brain Function (clinicaltrials.gov) - P3; N=400; Not yet recruiting; Sponsor: Mallinckrodt; Initiation date: Nov 2019 ➔ Apr 2020

Clinical • Trial initiation date

OCERA OP: Metabolism of Ornithine Phenylacetate (clinicaltrials.gov) - P=N/A; N=20; Active, not recruiting; Sponsor: Texas A&M University; Trial completion date: Apr 2018 ➔ Apr 2021

Clinical • Trial completion date