A Randomized, Open-Label, Phase 2a Study to Assess the Safety, Pharmacodynamics, and Pharmacokinetics of YAQ007 Versus Rifaximin in Cirrhosis
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2026
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| author | Ballester, Maria Pilar Carbonell-Asins, Juan Elshabrawi, Ahmed Rubin, Darren Winkle, Peter Lawitz, Eric Stoici, Roxanna Kayali, Zeid Ortiz Lasanta, Grisell Hassanein, Tarek Jalan, Rajiv |
| author_facet | Ballester, Maria Pilar Carbonell-Asins, Juan Elshabrawi, Ahmed Rubin, Darren Winkle, Peter Lawitz, Eric Stoici, Roxanna Kayali, Zeid Ortiz Lasanta, Grisell Hassanein, Tarek Jalan, Rajiv |
| contents | <p>Background & Aims: Ammonia is central in the pathogenesis of hepatic<br>encephalopathy (HE), but there are no approved treatments targeting ammonia. LOrnithine<br>Phenylacetate (YAQ007) is a novel drug, which effectively reduces ammonia<br>when administered intravenously. This exploratory Phase 2a study evaluated the<br>short-term pharmacodynamics, pharmacokinetics, and safety of oral YAQ007 in<br>patients with cirrhosis and a history of overt HE.<br>Approach & Results: In this randomized, open-label, multicenter study, 48-cirrhosis<br>patients (28 male, mean of 57.2 years, Child-Pugh of 8 and MELD score of 10) were<br>randomized (1:1:1:1) to one of three YAQ007 dosing regimens (2 g three times daily;<br>4 g twice daily; 4 g three times daily) or rifaximin (550 mg twice daily) for 5 days under<br>inpatient conditions. A decrease of ammonia at day-5 was observed in group C<br>(p=0.009) and group B (p=0.002). After multivariable adjustment, treatment Group B<br>vs Group D, bilirubin, INR and sodium (p<0.05) remained significant factors for<br>absolute ammonia reduction. Urinary phenylacetylglutamine excretion increased on<br>day 5 compared to day 1 across all YAQ007 dose groups (p<0.001). Exposure–<br>response relationships were variable, and a clear dose–response relationship was not<br>demonstrated. Overall, 20 (55.6%) patients who received YAQ007 and 5 (41.7%) who<br>received rifaximin had at least 1 treatment-emergent adverse events, with mainly mild<br>gastrointestinal and neurological symptoms.<br>Conclusions: In this Phase 2a study, oral YAQ007 demonstrated short-term<br>ammonia-lowering activity at doses ≥4 g BID. Given the exploratory design, these<br>findings are hypothesis-generating and support further clinical evaluation.</p> |
| format | Recurso digital |
| id | zenodo_https___doi_org_10_5281_zenodo_18845290 |
| institution | Zenodo |
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| publishDate | 2026 |
| publisher | Zenodo |
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| spellingShingle | A Randomized, Open-Label, Phase 2a Study to Assess the Safety, Pharmacodynamics, and Pharmacokinetics of YAQ007 Versus Rifaximin in Cirrhosis Ballester, Maria Pilar Carbonell-Asins, Juan Elshabrawi, Ahmed Rubin, Darren Winkle, Peter Lawitz, Eric Stoici, Roxanna Kayali, Zeid Ortiz Lasanta, Grisell Hassanein, Tarek Jalan, Rajiv Hepatic Encephalopathy Rifaximin Ammonia Ornithine Phenylacetate Cirrhosis <p>Background & Aims: Ammonia is central in the pathogenesis of hepatic<br>encephalopathy (HE), but there are no approved treatments targeting ammonia. LOrnithine<br>Phenylacetate (YAQ007) is a novel drug, which effectively reduces ammonia<br>when administered intravenously. This exploratory Phase 2a study evaluated the<br>short-term pharmacodynamics, pharmacokinetics, and safety of oral YAQ007 in<br>patients with cirrhosis and a history of overt HE.<br>Approach & Results: In this randomized, open-label, multicenter study, 48-cirrhosis<br>patients (28 male, mean of 57.2 years, Child-Pugh of 8 and MELD score of 10) were<br>randomized (1:1:1:1) to one of three YAQ007 dosing regimens (2 g three times daily;<br>4 g twice daily; 4 g three times daily) or rifaximin (550 mg twice daily) for 5 days under<br>inpatient conditions. A decrease of ammonia at day-5 was observed in group C<br>(p=0.009) and group B (p=0.002). After multivariable adjustment, treatment Group B<br>vs Group D, bilirubin, INR and sodium (p<0.05) remained significant factors for<br>absolute ammonia reduction. Urinary phenylacetylglutamine excretion increased on<br>day 5 compared to day 1 across all YAQ007 dose groups (p<0.001). Exposure–<br>response relationships were variable, and a clear dose–response relationship was not<br>demonstrated. Overall, 20 (55.6%) patients who received YAQ007 and 5 (41.7%) who<br>received rifaximin had at least 1 treatment-emergent adverse events, with mainly mild<br>gastrointestinal and neurological symptoms.<br>Conclusions: In this Phase 2a study, oral YAQ007 demonstrated short-term<br>ammonia-lowering activity at doses ≥4 g BID. Given the exploratory design, these<br>findings are hypothesis-generating and support further clinical evaluation.</p> |
| title | A Randomized, Open-Label, Phase 2a Study to Assess the Safety, Pharmacodynamics, and Pharmacokinetics of YAQ007 Versus Rifaximin in Cirrhosis |
| topic | Hepatic Encephalopathy Rifaximin Ammonia Ornithine Phenylacetate Cirrhosis |
| url | https://doi.org/10.5281/zenodo.18845290 |