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

17,441

Literatures (Medical) associated with Ornithine Phenylacetate

01 Aug 2025·FOOD CHEMISTRY

Variation in composition of storage proteins, minor proteins and amino acids across faba bean cultivars

Article

Author: Nielsen, Søren Drud-Heydary ; Xiao, Tianzhen ; Le, Thao T ; Olesen, Esben ; Larsen, Lotte Bach ; Poulsen, Nina Aagaard ; Roland, Ida Schwartz

This study aimed to investigate variations in protein profiles and amino acid (AA) compositions in faba bean seeds among 10 different cultivars. The compositions of salt-soluble proteins and AA were identified and quantified by label-free nano LC-MS/MS and LC-MS/MS (Triple Quadrupole), respectively. The protein contents (dry basis) in faba bean seeds were measured using the DUMAS method, ranging from 21.6 % to 26.8 %. By nano LC-MS/MS, 103 unique proteins were identified under point mutation monitoring analysis and of these, 61 proteins were quantified by label-free quantification. In all cultivars, vicilin and legumin were the most abundant proteins, respectively, varying from 16 to 39 % and 12 to 34 % of total protein content (w/w). The relative abundance of minor proteins like Bowman-Birk proteinase inhibitors was quantified to constitute around 1 % of the total protein content (w/w). There were 400 mg essential amino acids (EAAs) detected per gram protein, where histidine showed the highest concentration (64-82 mg/g protein) in all faba beans.

01 Aug 2025·FOOD CHEMISTRY

Metabolomics unravels the formation pathway of advanced glycation end products in preserved egg yolk mediated by OH− during pickling

Article

Author: Xiang, Xiaole ; Dong, Shiqin ; Li, Shugang ; Huang, Yiqun ; Ye, Lin ; Yu, Zhuosi ; He, Yu ; Chen, Le

Metabolomics was first applied to explore the formation pathway and regulatory factors for advanced glycation end products (AGEs) in preserved egg yolk (PEY) during pickling. Most reactions that contributed to formation of AGEs, including oxidation and/or degradation of matrix/precursors and Maillard reaction, occurred primarily in PEY in early stage, and lipid oxidation occurred prior to protein oxidation. Additionally, the formation of N^ε-carboxymethyl-lysine (CML) in PEY was mainly attributed to glyoxal derived from D-glucuronic acid in early stage based on the correlation between metabolites and AGEs. Reactive oxygen radicals from oxidized lipids also promoted the enrichment of CML and N^ε-carboxymethyl-lysine (CEL). Moreover, during later stage, the accumulation of CEL was enhanced through methylglyoxal from Schiff bases, and acidic compounds could inhibit AGEs via hindering Maillard reaction. This manuscript pioneered the application of metabolomics to reveal the formation pathway of AGEs, and will provide new perspective on AGEs formation in foods.

01 Aug 2025·JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS

A predictive metabolomic model for FLT3 and NPM1 mutations in Acute Myeloid Leukemia patients

Article

Author: Toprak, Selami Koçak ; Özcan, Muhit ; Gerekci Yeşi Lyurt, Selin ; Özen, Can ; Koyun, Derya

Cytogenetic abnormalities and gene mutations are essential for planning AML treatment. However, in Turkey, test results typically take 14-30 days. This delay emphasizes a critical need for rapid methods to deliver clinical data in urgent cases requiring immediate treatment decisions. To address this need, our objective was to develop a quick prediction method for NPM1 (Nucleophosmin-1) and FLT3 (FMS-like tyrosine kinase 3) mutations using LC-MS/MS (Liquid Chromatography-Tandem Mass Spectrometry) targeted metabolomics to detect these common and clinically important mutations in de novo AML patients (n = 42) through patient groups and a healthy group. We analyzed metabolic patterns using LC-MS/MS measurements of amino acids and acyl carnitines, key components critical to AML prognosis. The data were then subjected to multivariate analysis techniques. Principal Component Analysis (PCA) revealed that the model explained 79 % of the total variance among the sample groups. To further enhance class discrimination, we conducted Partial Least Squares-Discriminant Analysis (PLS-DA), resulting in R2Y and Q2 values of 0.845 and 0.619, respectively. Using the PLS-DA model, VIP (Variable Importance Projection) identified key metabolites with scores > 1.5, including C0 carnitine, glutamic acid, aspartic acid, tryptophan, histidine, isoleucine, and alpha-aminobutyric acid, respectively, highlighting their potential significance in distinguishing mutation groups. To ensure the validity of the PLS-DA model and evaluate potential overestimation, we validated the model using cross-validation and permutation test, demonstrating its robustness and reliability. Our preliminary model, developed through a targeted metabolomics approach, shows strong fit and predictive capability in determining the mutation status of NPM1 and FLT3 in AML patients.

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

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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	gbtpdhewrq(xgqlszlakp) = xrescejklc sfonodlctv (diptoftlll, 34 - 69) View more	Negative	01 Dec 2021
				Placebo	gbtpdhewrq(xgqlszlakp) = foahmxqhlw sfonodlctv (diptoftlll, 53 - 98) View more
NCT01966419 (STOP-HE, CTgov)	Phase 2	Hepatic Encephalopathy \| Fibrosis \| Hyperammonemia	231	placebo intravenous infusion (Placebo)	mcirqyyyev = hohoromjiv ghwpugbkqq (xqrsjkovpa, chduxiiwwp - vgkyjsxruj) View more	-	16 Sep 2021
				ornithine phenylacetate (Ornithine Phenylacetate)	mcirqyyyev = tnsiihnrjs ghwpugbkqq (xqrsjkovpa, cbnlbecqnw - wwevlmydwj) View more
NCT03712280 (CTgov)	Phase 2	Hepatic Encephalopathy \| Liver Cirrhosis	50	MNK6106 (Group A: MNK6106 2 Grams (Tid))	givdxzthzz(thqqspeiry) = qurhdalrfk bkxiarwfxf (avmrkfgezb, 23.4) View more	-	20 Jul 2021
				MNK6106 (Group B: MNK6106 4 Grams (Bid))	givdxzthzz(thqqspeiry) = moiiadyzev bkxiarwfxf (avmrkfgezb, 35.0) View more

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