Bausch Health and Salix Pharmaceuticals have announced the study design of their Phase 3 RED-C clinical trial program, evaluating a next-generation rifaximin formulation for the prevention of overt hepatic encephalopathy (OHE). The details were presented at The Liver Meeting 2024, the annual meeting of the American Association for the Study of Liver Diseases (AASLD). The investigational drug, rifaximin SSD-40IR, is designed to delay the onset of first OHE hospitalization in patients with cirrhosis. Currently, there are no globally approved medications for primary prophylaxis to delay the first episode of OHE in cirrhosis.
RED-C Trial Design
The RED-C program consists of two identically designed, Phase 3, randomized, double-blind, placebo-controlled trials. These trials are enrolling adults with cirrhosis and medically controlled ascites who have no documented history of OHE. The studies are being conducted across 398 study sites in 17 countries. Participants are randomly assigned to receive either rifaximin SSD-40IR or a placebo.
The primary endpoint of the trials is the time to the first OHE-related hospitalization. OHE diagnosis will be confirmed by a Clinical Event Adjudication Committee using AASLD guidelines, including the detection of disorientation and asterixis.
Rifaximin SSD-40IR: A Novel Formulation
Rifaximin SSD-40IR is an investigational soluble solid dispersion (SSD) immediate-release formulation. It is designed to enhance gastrointestinal solubility while minimizing systemic exposure. This may lead to better outcomes in preventing OHE compared to existing treatments. According to the study abstract, this formulation could offer a significant advantage in managing this serious complication of cirrhosis.
Enrollment and Patient Characteristics
Enrollment in both trials is now complete. Trial 1 enrolled 524 patients, while Trial 2 enrolled 518 patients. A significant portion of the study sites enrolling patients were located in the US (92.6% and 41.7% in trials 1 and 2, respectively). The majority of participants in each trial were men, and the median Model for End-Stage Liver Disease (MELD) score in both trials was 10. Additionally, 56.9% and 54.9% of participants in trials 1 and 2, respectively, were classified as Child-Pugh class A.
Anticipated Topline Data
Topline data from the RED-C trials are anticipated in the first half of 2026. These results could potentially pave the way for a new therapeutic option to address the unmet need for cirrhotic patients at risk of developing OHE. "Considering the significant unmet need for cirrhotic patients, the RED-C phase 3 trials have been rigorously designed to assess a potential new option to delay the onset of the first overt hepatic encephalopathy event, and to potentially, delay time to all-cause hospitalization," said Aimee Lenar, Executive Vice President of US Pharma at Bausch Health.
