Trial testing golexanolone as PBC treatment delayed
Companies working to resolve ‘technical issues’ with capsule production
A Phase 1b/2 trial testing Umecrine Cognition’s golexanolone in primary biliary cholangitis (PBC) patients with cognitive symptoms and fatigue has been delayed due to technical issues in the production of the medication’s oral capsules.
That’s according to a press release from Karolinska Development, a life sciences investment company that holds the majority of Umecrine. The delay is not associated with patient safety issues, and Umecrine is working with the treatment supplier to solve the problem, Karolinska said.
PBC is a chronic form of cholangitis, a condition characterized by inflammation of the bile ducts, the tubes that carry the digestive fluid bile from the liver to the intestines.
This leads to a toxic accumulation of bile in the liver, damaging the organ, and bile acid leakage into the bloodstream that causes cholangitis symptoms such as itchy skin and jaundice (yellowing of the skin and white part of the eyes).
Patients may also experience fatigue and cognitive impairment, characterized by concentration and memory problems.
Targeting cognitive symptoms as part of PBC treatment
It’s not fully understood what causes cognitive symptoms in people with PBC, but excessive activation of GABA-A receptors by a neuromodulator molecule, allopregnanolone, is thought to play a role. Overactivation of GABA-A receptors is known to cause cognitive issues and sedation.
Golexanolone is an oral therapy that works by suppressing the effects of allopregnanolone on GABA-A receptors. According to Umecrine, golexanolone does not completely block the receptors’ function, unlike other GABA-A suppressors, and is therefore expected to have a more favorable safety profile.
The medication is being tested in a Phase 1b/2 clinical trial (EudraCT2022-000422-16) involving PBC patients with clinically significant fatigue and cognitive symptoms and no permanent liver scarring, or scarring that allows the liver to function.
The first part of the trial assessed safety, tolerability, and pharmacological properties of 40 mg oral capsules of golexanolone, given twice daily for five days. Results showed that the therapy was generally safe and allowed the determination of the optimal doses to move to the study’s Phase 2 portion.
In this part of the trial, adult patients ages 18 to 75 will receive golexanolone at two dose levels, twice daily for 28 days (about one month). Goals of this part include assessing the PBC treatment’s effect on patients’ cognitive function, fatigue, daytime sleepiness, and health-related quality of life, as well as the investigator-reported overall impression of treatment effects.
Umecrine is also testing golexanolone in people with hepatic encephalopathy, a condition characterized by brain dysfunction due to severe liver disease. Data from a Phase 2a trial showed that the therapy safely improved cognitive function in this patient population.
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