Efficacy and Safety of DA-8010, a Novel M3 Antagonist, in Patients With Overactive Bladder: A Randomized, Double-Blind Phase 2 Study

Hee Seo Son, Cheol Young Oh, Myung Soo Choo, Hyeong Gon Kim, Joon Chul Kim, Kyu Sung Lee, Dong Gil Shin, Sung Yong Cho, Seong Jin Jeong, Ju Tae Seo, Hana Yoon, Hong Sang Moon, Jang Hwan Kim

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Abstract

Purpose: DA-8010 is a novel muscarinic M3 receptor antagonist with significant selectivity for bladder over salivary gland in preclinical studies. We evaluated the clinical efficacy and safety of DA-8010 in overactive bladder (OAB) patients. Methods: This phase 2, randomized, double-blind, parallel-group, active reference- and placebo-controlled trial was conducted at 12 centers in South Korea (NCT03566134). Patients aged ≥ 19 years with OAB symptoms for ≥ 3 months were enrolled. Three hundred six patients (30.07% male) were randomized to 12 weeks of treatment among 4 groups; 2 experimental groups (DA-8010 2.5 or 5 mg), an active reference group (solifenacin 5 mg), and a placebo group. The change from the baseline of (= ∆) 24-hour frequency at 12 weeks (primary endpoint), episodes of urgency, overall/urgency urinary incontinence, average/maximum voided volume, nocturia, and patients' subjective responses were analyzed. Results: In the full analysis set, the mean (standard deviation) [median] values for ∆ 24-hour frequency at 12 weeks were -1.01 (2.44) [-1.33] for placebo, -1.22 (2.05) [-1.33] for DA-8010 2.5 mg, and -1.67 (2.25) [-1.67] for DA-8010 5 mg; DA-8010 5 mg showed a significant decrease compared with placebo (P = 0.0413). At 4 and 8 weeks, both DA-8010 2.5 mg (P = 0.0391 at 4 weeks, P = 0.0335 at 8 weeks) and DA-8010 5 mg (P = 0.0001 at 4 weeks, P = 0.0210 at 8 weeks) showed significant decrease in ∆ 24-hour frequency compared with placebo. DA-8010 5 mg achieved a significant decrease 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 DA-8010 2.5 mg, 18.42% of DA-8010 5 mg, and 17.33% of solifenacin 5 mg groups. No serious ADRs were observed in any patient. Conclusions: Both DA-8010 2.5 mg and 5 mg showed therapeutic efficacy for OAB without serious ADRs. Therefore, both dosages of DA-8010 can advance to a subsequent large-scale phase 3 trial.

Original languageEnglish
Pages (from-to)119-128
Number of pages10
JournalInternational Neurourology Journal
Volume26
Issue number2
DOIs
StatePublished - Jun 2022

Keywords

  • DA-8010
  • Muscarinic antagonists
  • Muscarinic M3
  • Overactive
  • Receptor
  • Urinary bladder

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