Novel treatment effective against overactive bladder in phase 2 study

The novel muscarinic M3 receptor antagonist DA8010 significantly reduced urine frequency and urgency episodes compared with placebo in adults with overactive bladder, according to recent findings.

Hee Seo Son, MD, PhD, of Yonsei University College of Medicine in South Korea, presented the study data at the virtual American Urological Association meeting.

Son and colleagues conducted the phase 2, randomized, double-blind, parallel-group, active reference- and placebo-controlled trial at 12 centers in South Korea. The study cohort included 306 patients, 69.93% of whom were women. The patients had symptoms of overactive bladder for 3 months prior to enrollment.

The researchers randomly assigned patients to receive one of four treatments: 2.5 mg of DA8010; 5 mg of DA8010; 5 mg of VESIcare (solifenacin succinate; Astellas Pharma) or placebo. The treatments were administered once daily for 12 weeks. The researchers evaluated DA8010 for its clinical efficacy, safety and optimal dosage.

At 12 weeks, the mean values for 24-hour frequency were -1.01 in the placebo group, -1.22 in the DA8010 2.5-mg group, -1.56 in the solifenacin succinate group and -1.67 in the DA8010 5-mg group.

The difference in mean frequency was insignificant in the DA8010 groups compared with the solifenacin succinate group. However, compared with placebo, both DA8010 treatment doses exhibited significant differences in 24-hour frequency at 4 and 8 weeks, and this difference remained significant at 12 weeks (P = .0413). Also, the 5 mg dose of DA8010 was associated with significant reductions in the number of urgency episodes at 4 (P = .0278) and 8 (P = .0092) weeks compared with placebo, according to the researchers.

Adverse drug reactions occurred in 3.95% of patients in the placebo group, 6.67% of patients in the DA8010 2.5-mg group, 18.42% of patients in the DA8010 5-mg group and 17.33% of patients in the solifenacin succinate group.

“We could observe dose-dependent efficacy and dose-dependent incidence of adverse drug reactions in DA-8010 2.5mg and 5mg,” Son told Healio Primary Care. “However, most of the side effects were mild, and there was no significant difference in the incidence of overall adverse drug reactions between both doses of DA-8010 and solifenacin 5 mg. Therefore, both doses of DA-8010 are also confirmed to be safe in [overactive bladder] patients.”

DA-8010 will advance to phase 3 development, Son and colleagues said. The phase 3 study will assess adverse drug reactions grouped by age, according to Son.