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INTRODUCTION AND OBJECTIVE:

DA8010 is a novel muscarinic M3 receptor antagonist. Prior preclinical studies have verified that DA8010 has high binding affinity for human muscarinic M3 receptor and significant selectivity for bladder smooth muscle cells over salivary gland cells in mice. We aimed to evaluate the clinical efficacy, safety, and optimal dosage of DA8010 in patients with overactive bladder (OAB).

METHODS:

This study is a phase 2, randomized, double-blind, parallel-group, active reference- and placebo-controlled trial, conducted at 12 centers in South Korea. Male and female patients aged ≥19 years with symptoms of OAB for ≥3 months were enrolled. A total of 306 patients (69.93% female) were randomized to 12 weeks of treatment in 1 of 4 groups: two experimental groups (DA8010 2.5 mg or 5 mg), an active reference group (Solifenacin succinate 5 mg), or a placebo group. Changes in (Δ) 24 hr frequency at 12 weeks (primary end point), episodes of urgency and incontinence, average/maximum voided volume, nocturia, and subjective patient evaluations were analyzed.

RESULTS:

In the full analysis set, mean (standard deviation) [median] values for Δ 24 hr frequency at 12 weeks were -1.01 (2.44) [-1.33] for placebo, -1.22 (2.05) [-1.33] for DA8010 2.5mg, and -1.67 (2.25) [-1.67] for DA8010 5mg. There was a significant difference between DA8010 5mg and placebo (p=0.0413) (Figure). At 4 and 8 weeks, both DA8010 2.5mg (p=0.0391 at 4 weeks, p=0.0335 at 8 weeks) and DA8010 5mg (p=0.0001 at 4 weeks, p=0.0210 at 8 weeks) showed significant differences in Δ 24 hr frequency, compared with placebo. In Solifenacin 5mg group, Δ 24 hr frequency at 12 weeks was -1.56 (2.17) [-1.67], showing no significant difference from either DA8010 2.5 mg (p=0.4098) or DA8010 5 mg (p=0.8540). DA8010 5mg achieved significant differences in ∆ number of urgency episodes, compared with placebo, at 4 (p=0.0278) and 8 (p=0.0092) weeks. Adverse drug reactions (ADRs) were observed in 3.95% of placebo, 6.67% of DA8010 2.5mg, 18.42% of DA8010 5mg, and 17.33% of Solifenacin 5mg groups. No serious drug related adverse events were observed in any patient.

CONCLUSIONS:

Both DA8010 2.5mg and 5mg showed clinical efficacy without serious ADRs. A phase 3 study on subdivided efficacy and safety will be conducted.

Source of Funding:

Dong-A ST Co., Ltd., Seoul, Republic of Korea

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