Mass balance and absolute bioavailability of avenciguat (14C) after intravenous or oral administration in healthy male participants
Year: 2026
Type: article
Study design: Clinical Trial
Abstract: Avenciguat, a potent nitric oxide-independent activator of soluble guanylyl cyclase, is being evaluated in chronic kidney disease and systemic sclerosis. We assessed avenciguat absolute bioavailability and mass balance. Open-label Phase 1 trial in healthy men. Doses: Part A, 3 mg [14C]-avenciguat single dose (oral solution); Part B, 3 mg unlabeled avenciguat (tablet) then 30 µg [14C]-avenciguat (intravenous). Primary endpoints: Part A, mass balance and recovery of [14C] radioactivity in excreta; Part B, absolute bioavailability. Safety and pharmacokinetics were evaluated. In Part A (N = 6), geometric mean recovery of [14C] radioactivity was 90.0% (range 80.6–96.0%). Elimination was mainly via feces (geometric mean 85.3%; range 76.5–91.3%); urine (4.66%; range 4.10–5.31%). In Part B (N = 6), the absolute bioavailability of avenciguat was 83.0%. In pooled plasma, the predominant drug-related component was avenciguat (mean 86.8%); the acyl glucuronide metabolite represented 5.2% of radioactivity. Drug-related adverse events (AEs) occurred in 33.3% (4/12) of participants, mostly mild, with one moderate presyncope event. No AEs leading to discontinuation were reported. Avenciguat was generally well tolerated and was primarily excreted unchanged in feces and minimally excreted in urine. After oral administration, avenciguat has high oral bioavailability. ClinicalTrials.gov (NCT05515328). Chronic kidney disease is a condition in which the kidneys are permanently damaged over several years. Current treatments slow the rate of kidney damage in some people but can cause serious side effects affecting the kidneys and heart. Avenciguat is a new medicine that is being studied as a possible treatment for people with chronic kidney disease. The investigators gave 12 healthy volunteers a single dose of avenciguat that was tagged with a label so it could be tracked. The drug was given as either a tablet or a drink. At set timepoints the investigators collected blood, urine and feces samples from the volunteers. These samples were used to find out how much of the drug was absorbed by the body (detected in blood samples) and how the drug was removed from the body (detected in urine or feces samples). The investigators also asked the volunteers to record any side effects after taking the medicine. Investigators found that after taking avenciguat, most of the dose (83%) was absorbed by the body. While in the blood, avenciguat was mostly in its original active form and was not broken down by the body. The body then gradually removed the drug, with most being removed in feces (about 85% of the dose) and a small amount removed in urine (about 5% of the dose). Four out of the 12 people had a side effect that the investigator thought was linked to avenciguat. One person had stomachache and three people felt faint.
Source: Figshare
Authors: Joseph, David, Wong, Diane, Mitra, Pallabi, Auclair, Adam M., Wolfgang, Taylor, Gao, Eric, Herich, Lena, Tiessen, Renger
Subfield: Pharmacology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7118716031
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