A randomized, open-label, phase 2a study to assess the safety, pharmacodynamics, and pharmacokinetics of YAQ007 versus rifaximin in cirrhosis.
Maria Pilar Ballester, Juan Antonio Carbonell-Asins, Ahmed Elshabrawi et al.
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In 30 seconds
This randomized, open-label, multicenter phase 2a study compared three oral YAQ007 regimens with rifaximin in 48 patients with cirrhosis and a history of overt hepatic encephalopathy. Treatment was given for 5 days under inpatient conditions. Ammonia decreased by day 5 in the YAQ007 4 g twice-daily group (p =0.002) and 4 g three-times-daily group (p =0.009); the authors concluded that oral YAQ007 showed short-term ammonia-lowering activity at doses ≥4 g BID. The exploratory findings support further evaluation, while a clear dose-response relationship was not demonstrated.
Key findings
- Ammonia decreased by day 5 in the YAQ007 4 g twice-daily group (p =0.002) and 4 g three-times-daily group (p =0.009).
- Urinary phenylacetylglutamine excretion increased from day 1 to day 5 across all YAQ007 dose groups (p <0.001).
- At least one treatment-emergent adverse event occurred in 20 (55.6%) YAQ007 recipients and 5 (41.7%) rifaximin recipients; events were mainly mild gastrointestinal or neurological symptoms.
- Exposure-response relationships varied, and the study did not demonstrate a clear dose-response relationship.
Why it matters
Ammonia is implicated in hepatic encephalopathy, and these results provide early clinical evidence that oral YAQ007 may lower ammonia in patients with cirrhosis and prior overt encephalopathy. The findings are pharmacodynamic and short-term, however, and do not establish clinical benefit for encephalopathy or comparative effectiveness against rifaximin.
What to keep in mind
The exploratory phase 2a study assessed short-term outcomes over 5 days in 48 patients; exposure-response findings were variable and no clear dose-response relationship was demonstrated.