DA8010, an investigational muscarinic M3 receptor antagonist, led to significant changes in 24-hour urinary frequency as well as episodes of urgency and incontinence compared with placebo in patients with overactive bladder, according to a study presented by Hee Seo Son, MD, of the Yonsei University Health System in South Korea, at the 2021 American Urological Association Annual Meeting.
Preclinical studies in mice show the novel agent DA8010 features high binding affinity for the human muscarinic M3 receptor, as well as significant selectivity for bladder smooth muscle cells. In this study, Dr. Son and colleagues assessed the efficacy, safety, and optimal dosage of the investigational therapy in 306 patients (70% female) with overactive bladder.
The phase 2 study, conducted across 12 centers in South Korea, included patients 19 years and older who had symptoms of overactive bladder for 3 months or longer. Patients were randomly assigned to either DA8010 2.5 mg or 5 mg, an active reference group consisting of solifenacin succinate 5 mg, or placebo. Treatment was administered for 12 weeks.
Investigators assessed changes in the 24-hour frequency at the 12-week follow-up period as well as changes in episodes of urgency and incontinence, average/maximum voided volume, and nocturia. Patient-perceived evaluations were also conducted.
At 12 weeks, the mean values for the change in the 24-hr frequency were -1.01 for placebo, -1.22 for DA8010 2.5 mg, and -1.67 for DA8010 5 mg. The change in 24-hour frequency was markedly different between the DA8010 5 mg arm and the placebo group (p=0.0413).
Treatment with DA8010 2.5 mg and DA8010 5 mg led to appreciable differences in the change in the 24-hour frequency compared with placebo at 4 weeks (DA8010 2.5 mg vs placebo: p=0.0391; DA8010 5 mg: p=0.0001), and 8 weeks (DA8010 2.5 mg vs placebo: p=0.0335; DA8010 5 mg: p=0.0210).
In contrast, the mean change in the 24-hour frequency at 12 weeks was -1.56 for the solifenacin 5 mg group, with no statistically significant difference observed between DA8010 2.5 mg (p=0.4098), or DA8010 5 mg (p=0.8540).
The use of DA8010 5 mg was also associated with significant differences in the change in the number of urgency episodes compared with placebo at both 4 weeks (p=0.0278), and 8 weeks (p=0.0092).
Moreover, a higher proportion of adverse drug reactions were reported in the DA8010 5 mg (18.4%) and solifenacin 5 mg (17.3%) groups relative to the placebo (4%), and DA8010 2.5 mg (6.7%) arms. There were no serious drug-related adverse events reported during the study.
According to the researchers, there is currently a planned phase 3 study on the efficacy and safety of DA8010.