A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 3 Study to Evaluate the Efficacy, Safety, and Tolerability of MNK6105 (an Intravenous Formulation of L-Ornithine Phenylacetate) in Hospitalized Patients With Cirrhosis and Hyperammonemia Associated With an Episode of Hepatic Encephalopathy

This study is for patients with cirrhosis and hepatic encephalopathy who are in the hospital. This means they have a high ammonia level which is affecting their brain function.
All patients will receive the standard of (regular) care. Each will have an equal chance (like flipping a coin) of receiving the experimental drug or placebo along with the standard care.
Each patient will have tests during the first 24 hours, receive treatment for up to 5 days, and have 30 days of follow-up.

Start Date01 Nov 2021

Sponsor / Collaborator

Mallinckrodt Plc

NCT03712280

/ CompletedPhase 2

A Randomized, Open-Label, Phase 2a Comparator Study to Assess the Pharmacodynamics, Safety and Pharmacokinetics of Oral Administration MNK6106 (L-Ornithine Phenylacetate) Versus Rifaximin in Subjects With Hepatic Cirrhosis and a History of Prior Episodes of Hepatic Encephalopathy

The main reason for this study is to see how the study drug interacts with the body.
It will compare different doses of the study drug with a drug already in use.
Participants will be adults with liver disease that has affected the brain in the past.

Start Date01 Dec 2018

Sponsor / Collaborator

Mallinckrodt Plc

NCT03846843

/ CompletedPhase 1

An Open-Label, Two-Part, Phase 1/2a, Crossover Study to Determine the Absolute Bioavailability and Pharmacokinetics of Oral Immediate-Release Doses of OCR-002 in Subjects With Varying Degrees of Cirrhosis

This is an open-label Phase 1, 2-part, crossover study in approximately 33 adult subjects (12 subjects in Part 1 and 21 subjects in Part 2), with varying degrees of cirrhosis with analysis of pharmacokinetic (PK) data after Part 1 to guide dose regimen selection and PK sampling time points for OCR-002 in Part 2.

Start Date15 Aug 2016

Sponsor / Collaborator

OCERA Therapeutics LLC

100 Clinical Results associated with Ornithine Phenylacetate

100 Translational Medicine associated with Ornithine Phenylacetate

100 Patents (Medical) associated with Ornithine Phenylacetate

17,636

Literatures (Medical) associated with Ornithine Phenylacetate

01 Oct 2025·JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS

Metabolomics uncovers Rubus idaeus-mediated recovery of energy and arginine metabolism in liver injury

Article

Author: Xu, Yudan ; Fu, Tengteng ; Tao, Yi ; Deng, Yuling ; Lan, Enna ; Zhang, Lei ; Yang, Xujin

The global incidence of acute liver injury continues to rise, posing a significant threat to public health. While both raw and processed Rubus idaeus Linnaeus (RI) demonstrate hepatoprotective properties, their mechanisms require further elucidation. This study employed UPLC-Q-TOF/MS-based serum metabolomics to delineate the distinct liver-protective mechanisms of raw and processed RI in a murine model of acute liver injury. Following ten days of intragastric administration with low, medium, and high doses of raw and processed RI extracts, mice received intraperitoneal injection of 50 % carbon tetrachloride in olive oil. Serum levels of aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP), as well as liver levels of superoxide dismutase (SOD), malondialdehyde (MDA), and hydroxyproline (Hyp), were measured via ELISA. Liver histopathology was examined using Hematoxylin and Eosin (HE), Masson, and Sirius Red staining. Treatment with both raw and processed RI significantly reduced serum AST, ALT, and ALP levels while decreasing hepatic MDA and Hyp content compared to the model group. Conversely, SOD activity showed marked elevation. Metabolomic profiling identified 39 significantly altered endogenous metabolites in the model group, with subsequent characterization of 22, 23, and 7 distinctive biomarkers in the raw, salt-processed, and wine-processed RI treatment groups, respectively. These biomarkers predominantly associated with energy metabolism and arginine metabolism. Furthermore, the phenolic and flavonoid compounds in RI, known for their anti-inflammatory and antioxidant properties, played a key role in mitigating liver damage induced by CCl₄. These findings provide strong evidence supporting the potential use of both raw and processed RI in the development of hepatoprotective health products.

01 Oct 2025·COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY

Metabolomic analysis reveals paraquat-induced metabolic alternation in BV2 microglia: Focus on glutamate metabolism

Article

Author: Han, Yaxin ; Li, Jiayi ; Zhou, Zhijun ; Zhang, Jiming ; Chang, Xiuli ; Gu, Qiuyun ; Qin, Xutong ; Wang, Zheng

Paraquat (PQ), a commonly used contact herbicide, is known to induce oxidative stress and energy depletion, leading to cell death. Chronic low-dose exposure to PQ has been associated with an increased risk of Parkinson's disease, with microglia playing a significant role in its pathogenesis. However, little research has been conducted on the specific effects of PQ on microglial metabolism. This study employs ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS) to investigate the metabolic changes in BV2 microglial cells exposed to varying concentrations of 0, 2.5, 5, 10, and 20 μM of PQ. A dose-response fitting model was constructed to determine the effective concentrations and identify sensitive differential metabolites (DMs). Furthermore, reverse transcription-PCR (RT-PCR) was used to assess the expression levels of key genes involved in glutamate metabolism, namely SLC7A11, GLS and SLC38A1. The study identified 40 intracellular inter-group DMs, mainly enriched in amino acid metabolic pathways. d-Glucosamine 6-phosphate and pantothenic acid were identified as the most sensitive DMs. Glutamate emerged as a pivotal metabolite, with its upregulation being accompanied by a significant increase in SLC7A11 expression increasing with PQ concentration, indicating an enhanced cellular response to oxidative stress via glutathione synthesis. Moreover, increased expression of GLS and SLC38A1 was observed exclusively at the 2.5 concentration group, suggesting a shift in glutamate synthesis mechanisms depending on PQ exposure levels. These findings contribute to the understanding of PQ's impact on microglial metabolism and its potential role in neurodegenerative diseases.

01 Sep 2025·FOOD CHEMISTRY

Metabolic remodeling during fructification of enoki mushroom

Article

Author: Shaba, Chikondi ; Urban, Pawel L

This study investigated the patterns of change and differences in metabolites between white and golden enoki (Flammulina velutipes) mycelium and across stages of fruit-body growth of golden enoki, which was cultured under controlled conditions. Metabolic differences were observed between the mycelium, juvenile and aged caps, and the stipe, which highlight stage-specific shifts in metabolite concentrations. Nucleotides had significantly lower concentrations in mycelium and displayed progressively smaller fold changes as the mushroom matured. These nucleotides could be valuable as biomarkers for fruit-body formation and early development. Glycine, homocitrulline, lysine, ornithine, urea, and proline were predominantly present in the mycelium and have potential for use in food supplementation due to their documented health benefits. Of particular interest is ornithine, which was the sole metabolite that was downregulated in the cap and has potential as a biomarker for cap-stipe differentiation.

News (Medical) associated with Ornithine Phenylacetate

07 May 2025

·www.globenewswire.com

Yaqrit’s HE candidates set for phase 3 as company shows underpinning data at EASL

Improved disease staging tool for hepatic encephalopathy, approved for use by FDA in phase 3 trials of IV ammonia scavenger (YAQ006)Dose-response data of oral ammonia scavenger (YAQ007) for prevention of HE recurrenceIn vivo demonstration of ammonia scavenger mechanism of action highlights potential synergistic combination with TLR-4 antagonist (YAQ005) LONDON, May 07, 2025 (GLOBE NEWSWIRE) -- Yaqrit, a late clinical-stage company developing life-saving treatments for advanced liver diseases, is this week revealing data on the progress of both its phase 3 and phase 2b/3 candidate drugs – YAQ006 (IV) and YAQ007 (oral) - for hepatic encephalopathy (HE) at the forthcoming European Association for the Study of the Liver (EASL) Congress, Amsterdam May 7-10th in advance of its clinical trials. Collectively, the data provide an enhanced understanding of the mechanism of action, determine treatment-initiation and endpoints within the HE patient population and define the dosage of YAQ007 (the oral formulation of the ammonia scavenger) to be used for the prevention of recurrence of overt HE. “EASL 2025 represents a great opportunity for Yaqrit to share data with clinicians and researchers in the liver disease community as we approach late-stage clinical investigation of YAQ006 and YAQ007,” said Troels Jordansen, Yaqrit’s Chief Executive Officer. “There are clear unmet medical needs in advanced liver disease: the EASL presentations demonstrate that Yaqrit is on course to put the right drug in the right patients at the right time and at the right dosage.” YAQ006 and YAQ007 are, respectively, the intravenous and oral formulations of L-ornithine phenylacetate (L-OPA), a potent ammonia-scavenging agent. Yaqrit is preparing to start a phase 3 trial with YAQ006 for hospital treatment of overt HE, a life-threatening complication of decompensated cirrhosis and a phase 2b/3 trial with YAQ007 for outpatient use to prevent recurrence of overt HE. One key disclosure at EASL is the development of a patient-staging protocol – mHEST (modified Hepatic Encephalopathy Staging Tool). Use of mHEST has been approved by the US Food and Drug Administration (FDA) to evaluate the primary endpoint of ‘clinically meaningful improvement’ for the phase 3 trial of YAQ006 in patients with overt HE. The strong levels of inter- and intra-rater concordance within mHEST will reduce dependence on subjective assessment and interpretation, helping clinical investigators at various centers make consistent choices in patient selection and endpoint attainment across the trial. Development and validation of the modified hepatic encephalopathy staging tool (mHEST) for grading of hepatic encephalopathy for accurate assessment and regulated clinical trials (SAT-210). Prof. Rajiv Jalan, Saturday 10th May. The dose-setting clinical study for YAQ007 (oral formulation of L-OPA) is described in a second EASL presentation. Patients who received 4 g of YAQ007 twice daily showed a decrease in plasma ammonia that was 6 times the decrease seen with rifaximin (550mg twice daily), an antibiotic used in the current standard treatment for hepatic encephalopathy. There was no significant difference in adverse events. Randomized, open-label, phase 2a comparator study to assess the pharmacodynamics, safety and pharmacokinetics of oral administration of mnk6106 (l-ornithine phenylacetate) vs. rifaximin in subjects with hepatic cirrhosis and a previous history of hepatic encephalopathy (SAT-209). Prof. Rajiv Jalan, Saturday 10th May. Transcription and metabolic analysis in mouse models of HE provides evidence that the mode of action of L-OPA may be complementary to that of YAQ005, a TLR4 antagonist, in treating hyperammonemia. This raises the possibility of improved therapeutic strategies in the future. Transcriptomic and metabolic insights into hyperammonemia: the complementary therapeutic roles of toll-like receptor 4 inhibitor and ornithine phenylacetate (THU-182). Dr. Supachaya Sriphoosanaphan, Thursday 8th May. “In treating and preventing advanced liver disease with multiple complicating factors in play, there is no substitute for understanding, whether in controlling clinical trial variables or understanding mechanisms of drug action,” said Professor Rajiv Jalan, Yaqrit’s Founder and Chief Medical Officer. “These impressive data underpin confidence in the clinical pathway for Yaqrit’s pipeline assets.” Information on Yaqrit’s eight presentations at EASL 2025 can be found on Yaqrit’s website under latest news. The full abstracts will be available on the EASL Congress website from 08:30AM CEST on 7th May 2025. Contact Company Troels Jordansen Email: Troels@Yaqrit.com Tel: +31 6 1834 5326 Contact Investors Mary-Ann Chang Email: Mary-Ann@Yaqrit.com Tel: +44 7483 284 853 About Yaqrit Yaqrit is a clinical-stage company discovering and developing innovative treatments for patients with advanced liver disease at high risk of hospitalization and death. Yaqrit’s pipeline includes three novel therapeutics at phase 2-3 of development and two medical devices providing acute and chronic treatments for advanced cirrhosis and acute-on-chronic liver failure where there is an urgent need for more effective treatments. More information is available at www.Yaqrit.com About Hepatic Encephalopathy Hepatic encephalopathy (HE) is a potentially reversible neurological dysfunction associated with excess ammonia in the blood. As many as 40% of decompensated cirrhosis patients are at risk of developing hepatic encephalopathy, with over 80,000 patients hospitalized in the US every year with overt episodes. The recurrence of hepatic encephalopathy is high: a second episode will follow the initial overt event within a year in 40-50% of patients.

Clinical ResultPhase 3Phase 2

13 Feb 2025

·www.globenewswire.com

Yaqrit prepares phase 3 for ammonia scavenger in hepatic encephalopathy

Acute and chronic treatment for hepatic encephalopathy acquired from Mallinckrodt Pharmaceuticals in September 2024 Extended pre-clinical, clinical and IP package includes FDA and EMA orphan drug and FDA fast track designations 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 Feb. 11, 2025 -- Yaqrit, a late clinical-stage company developing life-saving treatments for advanced liver disease, 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. Development will be via Yaqrit’s newly formed subsidiary Amalive Limited, named to reflect the profound impact of ammonia levels in the lives of patients with advanced liver disease. Amalive is preparing an IV formulation for the phase 3, adapting the trial design based on clinical experience and using AI modelling to guide patient selection. In parallel, Amalive will progress an oral formulation into phase 2b trials for outpatient use in the prevention of HE recurrence. Amalive is also developing an oral liquid formulation to treat and prevent hyperammonaemia associated with urea cycle enzyme disorders, a rare genetic disease that affects children. “OPA is a key asset for Yaqrit, a potentially great molecule both clinically and commercially, and the creation of subsidiary dedicated to its development will ensure its full potential is realized,” said Troels Jordansen, Chief Executive Officer of Yaqrit. “For Yaqrit, this also opens the opportunity for further therapeutic and commercial collaborations. With the right partner, we are ready to advance this important treatment into phase 3, building on the accelerated lowering of blood-ammonia already demonstrated in life-threatening HE.” Yaqrit acquired full global rights, including development and commercial, for OPA in any indication from Mallinckrodt Pharmaceuticals in the second half of 2024. Mallinckrodt Pharmaceuticals will receive payments upon the achievement of certain late-stage milestones, plus royalties on sales. “OPA consolidates Yaqrit’s leading position in the development of novel therapies for liver disease,” said Professor Rajiv Jalan, Founder and Chief Medical Officer of Yaqrit. “OPA addresses ammonia toxicity, a frequent, high-mortality event in vulnerable, advanced liver disease patients. Not only can OPA directly impact the prospects of millions of patients with late-stage liver disease, but it also opens a window for additional interventions in this severely underserved population.” OPA was discovered at the Liver Failure Group, University College London, by Professor Rajiv Jalan, Yaqrit’s founder. Earlier development of OPA, including phase 2a and phase 2b studies of both IV and oral forms was undertaken at Ocera Therapeutics, a subsidiary of Mallinckrodt Pharmaceuticals. The available clinical data indicated that OPA reduces levels of toxic ammonia more rapidly than standard of care, facilitating resolution of hepatic encephalopathy, which is one of the most prevalent complications of advanced liver disease1. By removing neurotoxic levels of ammonia from the blood, OPA has the potential to rapidly lower the risk of mortality and multi-organ-failure. Yaqrit is a clinical-stage company discovering and developing innovative treatments for patients with advanced liver disease at high risk of hospitalization and death. Yaqrit’s pipeline includes three novel therapeutics at phase 2-3 of development and two medical devices providing acute and chronic treatments for advanced cirrhosis and acute-on-chronic liver failure where there is an urgent need for more effective treatments. More information is available at www.Yaqrit.com In over 10 million patients worldwide per year, liver cirrhosis progresses from an asymptomatic (compensated) form to the decompensated form at which point the liver can no longer undertake its usual functions. This leads to complications such as jaundice, infections, encephalopathy, ascites and bleeding. The most severe form of decompensation is the occurrence of multiorgan failure, a condition referred to as acute-on-chronic liver failure. These complications lead to increased morbidity with median survival falling from more than 12 years for compensated cirrhosis to about two years for decompensated cirrhosis and less than 3-months for those with multiorgan failure. Hepatic encephalopathy (HE) is a potentially reversible neurological dysfunction associated with excess ammonia in the blood. As many as 40% of decompensated cirrhosis patients are at risk of developing hepatic encephalopathy, with approximately 200,000 patients hospitalized in the US every year with acute episodes. The recurrence of hepatic encephalopathy is high: a second episode will follow the initial acute event within a year in 40-50% of patients. 1 OCR002-HE209 Phase 2b Efficacy/Safety of Ornithine Phenylacetate in Hospitalized Cirrhotic Patients with Hepatic Encephalopathy The content above comes from the network. if any infringement, please contact us to modify.

Orphan DrugFast Track

02 Nov 2017

·www.biospace.com

Mallinckrodt Pays $117M for This Bay Area Biotech and Its Failed Liver Drug

Mallinckrodt has agreed to buy Ocera Therapeutics in a deal that could hit $117M. Staines-Upon-Thames, UK-based Mallinckrodt has agreed to buy Redwood City, Calif.,-based Ocera Therapeutics in a deal that could hit $117 million. Ocera is a clinical-stage biopharma company that focuses on orphan diseases and serious liver diseases. Along with the company, Mallinckrodt picks up Oceras’ developmental product OCR-002, an ammonia scavenger being evaluated for hepatic encephalopathy (HE), a neuropsychiatric syndrome associated with hyperammonemia, a complication of acute or chronic liver disease. The compound is a Phase II drug with both intravenous (IV) and oral formulations. The drug failed to meet its primary endpoint in Ocera’s Phase II STOP-HE clinical trial, although it did hit secondary endpoints. Mallinckrodt believes the trial design was at fault, not the drug, and after the buyout, will work with the U.S. Food and Drug Administration (FDA) to work on a pathway to regulatory approval and a subsequent launch of the IV formulation by 2022 and the oral formulation by 2024. OCR-002’s secondary endpoints showed the drug is a potent ammonia scavenger that caused a significant reduction in circulating ammonia. In a post-hoc analysis of the data, the company noted that the extent of ammonia reduction in patients correlated strongly with clinical improvement. That response rate also appeared to increase with dose levels, which hints that some of the patients in the trial were under-dosed. “We believe OCR-002 has the potential to help thousands of patients whose hepatic encephalopathy is insufficiently treated by current therapies,” said Linda Grais, president and chief executive officer of Ocera, in a statement. “We’re excited by the additional development capability and commercial reach that can be gained by becoming part of Mallinckrodt. With this focus, I’m confident this important treatment can be successfully brought to market.” Under the terms of the deal, Mallinckrodt will buy outstanding shares of Ocera common stock for $1.52 per share, or about $42 million. There is also a Contingent Value Right (CVR) to receive one or more payments in cash of up to $2.58 per share, which could reach $75 million, based on hitting specific development and sales milestones. About 30 to 35 million patients in the U.S. have chronic liver disease, which in some cases can advance to cirrhosis. About 5.5 million people in the U.S. have liver cirrhosis. Cirrhosis inhibits the liver’s ability to remove toxins from the body, such as ammonia. Hepatic encephalopathy results from too much ammonia in the blood. HE is not limited to cirrhosis, but has been seen in other liver diseases such as acute liver failure or bypass shunts. The companies estimate that with 200,000 patients in the U.S. hospitalized every year with acute HE, the potential U.S. market is $5 to $7 billion, with $2 to $3 billion in acute treatment and $3 to $4 billion for recurrent incidents. No intravenous therapies have been approved by the FDA to treat acute HE. “Hepatic encephalopathy can be a debilitating condition, affecting brain function and, in some cases, resulting in coma or death,” said Steven Romano, Mallinckrodt’s chief scientific officer and executive vice president, in a statement. “We look forward to bringing this much-needed treatment option to patients who suffer from this condition.”

Phase 2AcquisitionClinical Result

100 Deals associated with Ornithine Phenylacetate

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D09942	-	-	-

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Fibrosis	Phase 3	-	Mallinckrodt Plc	01 Nov 2021
Hepatic Encephalopathy	Phase 3	-	Mallinckrodt Plc	01 Nov 2021
Hyperammonemia	Phase 3	-	Mallinckrodt Plc	01 Nov 2021
Liver Cirrhosis	Phase 2	United States	Mallinckrodt Plc	01 Dec 2018
Liver Cirrhosis	Phase 2	Puerto Rico	Mallinckrodt Plc	01 Dec 2018
Chemical and Drug Induced Liver Injury	Phase 2	United States	OCERA Therapeutics LLC	01 Jun 2012
Liver Failure, Acute	Phase 2	United States	OCERA Therapeutics LLC	01 Jun 2012

Clinical Result

Indication

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Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01966419 (STOP-HE, Pubmed \| Clin Gastroenterol Hepatol) Manual	Phase 2	Hepatic Encephalopathy	226	Ornithine Phenylacetate	sikndtsrwr(thcayvrmme) = kthnahqjax rowvlxfwhe (ttnrnqfarh, 34 - 69) View more	Negative	01 Dec 2021
				Placebo	sikndtsrwr(thcayvrmme) = loqsborhcd rowvlxfwhe (ttnrnqfarh, 53 - 98) View more
NCT01966419 (STOP-HE, CTgov)	Phase 2	Hepatic Encephalopathy \| Fibrosis \| Hyperammonemia	231	placebo intravenous infusion (Placebo)	lsrwkqiwqk = bpnsdnzmtt ryvigwlmxe (yjfgtpairb, khfuquuauc - ukoqicvgzz) View more	-	16 Sep 2021
				ornithine phenylacetate (Ornithine Phenylacetate)	lsrwkqiwqk = qmaviexucs ryvigwlmxe (yjfgtpairb, kxsaoexbyu - gjhplqmzxj) View more
NCT03712280 (CTgov)	Phase 2	Hepatic Encephalopathy \| Liver Cirrhosis	50	MNK6106 (Group A: MNK6106 2 Grams (Tid))	zeesxccvpy(eklmdawske) = rroruiwmcy dbmlkkhpbx (wixpiirsoa, 23.4) View more	-	20 Jul 2021
				MNK6106 (Group B: MNK6106 4 Grams (Bid))	zeesxccvpy(eklmdawske) = srxnejjsjo dbmlkkhpbx (wixpiirsoa, 35.0) View more

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