China-based Hua Medicine (HKG: 2552) has announced the successful completion of a Phase Ia study for its second-generation glucokinase activator (GKA) HM-002-1005 in the United States. The study focused on the safety, tolerability, and pharmacokinetics of HM-002-1005, a prodrug of dorzagliatin (HMS5552), in 40 subjects with type 2 diabetes (T2D).
Phase Ia Study Design and Findings
The randomized, double-blind, placebo-controlled, single-dose Phase Ia study assessed HM-002-1005 in the US. The single ascending dose (SAD) study demonstrated that HM-002-1005 tablets can be rapidly converted to HMS5552 within the human body, with minimal exposure levels of the prodrug in both blood and urine. This indicates a favorable pharmacokinetic profile for the drug candidate.
Pharmacokinetic Comparisons and Future Studies
The biological half-life (t1/2) after a single dose of HM-002-1005 tablets was prolonged compared to dorzagliatin tablets. The maximum plasma concentration (Cmax) of HMS5552 after a 184.5mg single dose of HM-002-1005 was comparable to the plasma concentration of HMS5552 after a 75mg single dose of dorzagliatin tablet. Similarly, the daily area under the curve (AUC) of HMS5552 in plasma after a single dose of HM-002-1005 tablets was comparable to the exposure level of HMS5552 after a 75mg twice-daily (BID) dose of dorzagliatin tablets. These results suggest that HM-002-1005 has the potential to offer similar therapeutic effects with a more convenient dosing regimen.
A multiple ascending dose (MAD) clinical study for HM-002-1005 is expected to commence in China and the US following optimization of the dosage form. This next phase of clinical trials will further evaluate the safety and efficacy of HM-002-1005 in a broader context, building on the promising results from the Phase Ia study.-Fineline Info & Tech
