BOSTON, MA—The investigational oral pentamidine isethionate formulation VLX103 is safe and well tolerated at the once-daily 300mg to 900 mg dose, according to findings from a pharmacodynamic Phase 1 trial reported at The Liver Meeting® 2016.
The findings also suggested that “a possible hepatoprotective effect may be associated with short-term VLX103 therapy, in patients with liver disease and high ALT/AST,” reported Marc Bilodeau, MD, of CHUM St. Luc in Montreal, Quebec, Canada.
Parenteral pentamidine has been used to treat P. carinii infection in patients with HIV/AIDS but is associated with toxicities. In contrast, VLX103 is hepatoselective, which should reduce toxicities in other organs.
In the Study, 4 ascending doses (300mg, 600mg, 900mg, and 1200mg) of either VLX103 or placebo were administered over 3 days to adult patients with cirrhosis and early stage hepatocellular carcinoma. Study patients were aged ≥18 years and had radiologically established diagnosis of hepatocellular carcinoma with tumor diameter ≤5cm. Also, the study included those with a Barcelona score of 0 or A or presence of cirrhosis with a Child-Pugh score of A or B.
Study patients underwent thermal liver-tumor ablation after the treatment. Plasma ALT and AST activity were used as an efficacy assessment endpoint. Safety endpoints included adverse events occurrence, vital signs, clinical chemistry and hematology laboratory parameters, and physical exams including EKG.
“Among the 28 patients randomized, the three lowest doses were well tolerated,” Dr. Bilodeau reported. “Most adverse events reported were mild, of a GI nature, considered unrelated to VLX103 and resolved completely without any sequelae.” During the study, a total of 114 non-serious adverse events occurred where the majority were treatment-emergent.
In general, the 1,200mg once-daily regimen was associated with more severe gastrointestinal (GI) adverse events but was safe from a biochemical, hematological and physical standpoint, the authors noted. These adverse events were resolved through dose reduction or splitting.
“Nonetheless, no clinically significant safety lab abnormality was reported at all four doses tested, including liver function tests,” Dr. Bilodeau said.