Relevant concomitant care permitted or prohibited during the trials {11d}
NASH, oedema
EVENTS, OEDEMA, TORSADE DE POINTES
Stable doses of concomitant therapies for chronic conditions are permissible throughout the trials, provided that neither the condition nor treatment leads to exclusion of the patient. Specifically, NSBB or carvedilol use is permitted, but these concomitant therapies should not be newly initiated during the trials; endoscopic variceal ligation is permitted during the trials, as required. Patients who develop oedema or gastrointestinal events will be managed by standard of care, such as diuretics. Use of NO–sGC–cyclic guanosine monophosphate pathway-activating therapies (NO donors, phosphodiesterase-5 inhibitors, non-specific phosphodiesterase inhibitors or sGC stimulators), organic anion-transporting polypeptide 1B1/3 inhibitors, concomitant therapies known to inhibit or induce uridine glucuronyl transferase enzymes or concomitant therapies with a known risk of torsade de pointes are not allowed during participation in the trials. In the 1366.0029 trial, the use of other sodium glucose co-transporter 2 or sodium glucose co-transporter 1/2 inhibitors is not allowed in patients with NASH. These restrictions apply from within five half-lives prior to randomisation until the end of the study; therapies with a known risk of torsade de pointes are restricted from screening until the end of the study. If patients are taking concomitant therapy that is metabolised by cytochrome P450 (CYP) 3A4 and/or CYP2C8 which has a narrow therapeutic index and/or is a sensitive substrate, close monitoring for AEs is recommended.