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.
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.
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.
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.
International neurourology journal. 2022 Jun 30 [Epub]
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
Department of Urology and Urological Science Institute, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea., Department of Urology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Korea., Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea., Department of Urology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea., Department of Urology, Bucheon St. Mary's Hospital, The Catholic University College of Medicine, Seoul, Korea., Department of Urology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea., Department of Urology, Pusan National University Hospital, Pusan National University School of Medicine, Busan, Korea., Department of Urology, Seoul National University Hospital, Seoul National University School of Medicine, Seoul, Korea., Department of Urology, Seoul National University Bundang Hospital, Seoul National University School of Medicine, Seongnam, Korea., JTS Urology Center; Department of Urology, Cheil General Hospital and Women's Healthcare Center, Dankook University College of Medicine, Seoul, Korea., Department of Urology, Ewha Womans University Medical Center, Ewha Womans University College of Medicine, Seoul, Korea., Department of Urology, Hanyang University Guri Hospital, Hanyang University College of Medicine, Seoul, Korea.