STOCKHOLM/UMEÅ. Umecrine Cognition AB, a Karolinska Development (Nasdaq Stockholm: KDEV) portfolio company today announced positive results from its Phase 1b multiple ascending dose trial in healthy male subjects with GR3027, a novel orally active GABAA receptor modulating steroid antagonist, in development for treatment of hepatic encephalopathy (HE) in patients with liver cirrhosis.
The ongoing Phase 1b/2a study (protocol UCAB-CT-02) is designed to evaluate the safety and pharmacokinetics of multiple ascending doses of GR3027 in healthy adults and patients with cirrhosis, as well as its potential effect on cognitive function in patients with cirrhosis and covert HE.
In the recently completed 1b phase of the trial, 18 healthy adult male subjects were randomized to receive GR3027 or placebo (6:2) at doses ranging from 50 mg QD (once daily) to 100 mg BID (twice daily) for five consecutive days. GR3027 was well tolerated; adverse events were mild and no dose-limiting toxicity was observed throughout the dose range up to the Study Maximal Dose (SMD) of 100 mg BID. The pharmacokinetic profile was excellent; systemic exposure varied linearly with dose and there was no evidence of drug accumulation during steady state dosing over the dose range studied.
“Umecrine Cognition is, as far as known, the only company that has a drug candidate in development to reduce the risk of consciousness disorders and other serious CNS related symptoms associated with liver failure. We are very encouraged by the favorable safety, tolerability and pharmacokinetic profile of GR3027 in our Phase 1 trials,” said Magnus Doverskog, CEO of Umecrine Cognition.
Umecrine Cognition’s single- and multiple ascending dose trials have enrolled a total of 90 healthy adult subjects and demonstrated excellent tolerability without evidence of dose-limiting toxicity up to single oral doses of 200 mg and steady state dosing of 100 mg BID.
Results of the previously reported allopregnanolone challenge study indicate that GR3027, administered at doses as low as 30 or even 3mg, well within the range that is well tolerated in adult males, enter the CNS and reverse the inhibitory effects of neurosteroids on brain function at allopregnanolone concentrations higher than those described in HE patients.
”These findings collectively suggest that GR3027 represents a promising new treatment for human disorders attributable to the GABA-A receptor mediated inhibitory effects of neurosteroids on brain function,”concluded Magnus Doverskog, CEO of Umecrine Cognition.
For further information, please contact:
Magnus Doverskog, CEO, Umecrine Cognition AB
Phone: +46 (0)73 039 20 52, e-mail: [email protected]
TO THE EDITORS
About Umecrine Cognition AB
Umecrine Cognition, a Karolinska Development (Nasdaq Stockholm: KDEV) portfolio company, is developing a potential therapy that represents a new target class relevant for several major CNS-related disorders. The primary focus is to develop a treatment for life-threatening overt Hepatic Encephalopathy and long-term treatment in minimal Hepatic Encephalopathy in patients with liver disease, a growing area with high unmet medical need. The current lack of therapeutics that directly addresses the neurocognitive signs and symptoms of Hepatic Encephalopathy makes a novel treatment likely to become a major contribution for the treatment of this disorder. For more information, please visit www.umecrinecognition.com.