Berberine ursodeoxycholate safe, effective in primary sclerosing cholangitis

Treatment with HTD1801, an ionic salt of berberine and ursodeoxycholic acid with pleiotropic mechanisms of action, appears to substantially improve outcomes in patients with primary sclerosing cholangitis (PSC), according to a study.

Researchers conducted an 18-week proof-of-concept study to evaluate the efficacy and safety of HTD1801 in patients with PSC. The study had three 6-week periods: a placebo-controlled period, a treatment extension period, and a randomized treatment withdrawal period. Change from baseline in alkaline phosphatase (ALP) at week 6 was the primary outcome.

Fifty-five patients were included in the trial, of whom 35 (64 percent) had inflammatory bowel disease, and 22 (40 percent) had previously received ursodeoxycholic acid. They were initially randomized to receive HTD1801 500 mg twice a day (BID; n=15), HTD1801 1,000 mg BID (n=24), or placebo (n=16).

Mean ALP values at baseline were 414 U/L in the placebo group, 397 U/L in the HTD1801 500-mg group, and 335 U/L in the HTD1801 1,000-mg group.

ALP significantly decreased at week 6 with HTD1801 (least square mean: HTD1801 500 mg BID, −53 U/L; p=0.016; HTD1801 1,000 mg BID, −37 U/L; p=0.019) compared with placebo (98 U/L). These reductions persisted through week 18 in patients who remained on therapy, but ALP increased in those who switched to placebo during period 3.

HTD1801 was well tolerated. Although four patients experienced serious adverse events, none of which were related to HTD1801.

“PSC is a fibroinflammatory disease of the bile ducts leading to cirrhosis and hepatic decompensation,” the researchers said. “There are no approved pharmaceutical therapies for PSC."