Masaki Yoshida1,2, Momokazu Gotoh3, Osamu Yokoyama4,5, Hidehiro Kakizaki6, Tomonori Yamanishi7, Osamu Yamaguchi8. 1. Department of Urology, Sakurajyuji Hospital, Kumamoto, Japan. 2. National Center for Geriatrics and Gerontology, Aichi, Japan. 3. Japan Community Health Care Organization Chukyo Hospital, Aichi, Japan. 4. Department of Urology, Harue Hospital, Fukui, Japan. 5. Department of Urology, University of Fukui, Fukui, Japan. 6. Department of Renal and Urologic Surgery, Asahikawa Medical University, Hokkaido, Japan. 7. Department of Urology, Continence Center, Dokkyo Medical University, Tochigi, Japan. 8. Fukushima Medical University, 1 Hikarigaoka, Fukushima-shi, Fukushima, 960-1295, Japan. oyamagu52@gmail.com.
Abstract
PURPOSE: This multicenter, randomized, double-blind, placebo-controlled phase 2 study evaluated the efficacy and safety of TAC-302, a novel drug that restores neurite outgrowth, in patients with detrusor underactivity (DU) and overactive bladder (OAB). METHODS: After 2-4 weeks of observation, patients were randomized 2:1 to receive oral TAC-302 200 mg or placebo twice daily for 12 weeks. The primary endpoint was detrusor contraction strength, estimated by bladder contractility index (BCI) for males and projected isovolumetric pressure 1 (PIP1) for females. Secondary endpoints included changes in bladder voiding efficiency (BVE) and safety. RESULTS: Seventy-six patients were included (TAC-302, n = 52; placebo, n = 24). The mean (standard deviation [SD]) BCI for males was 64.6 (16.6) at baseline and 75.2 (21.1) at week 12 (p < 0.001) with TAC-302 (n = 27), and 61.3 (16.6) and 60.5 (16.7) (p = 0.82) with placebo (n = 11). The respective mean (SD) PIP1 for females was 18.8 (6.6) and 29.4 (9.4) (p < 0.001) with TAC-302 (n = 15), and 20.6 (7.5) and 25.5 (9.6) (p = 0.14) with placebo (n = 7). TAC-302 significantly increased BCI in males and BVE in both sexes. TAC-302 efficacy on OAB was not clearly shown. The incidences of adverse events (AEs), serious AEs, and AEs leading to dose interruption were similar between groups; no adverse drug reactions occurred. CONCLUSION: Considering the significant effects on BCI in males and BVE in both sexes, TAC-302 may benefit patients with DU. REGISTRATION: ClinicalTrials.gov Identifier NCT03175029 registered 6/5/2017.
PURPOSE: This multicenter, randomized, double-blind, placebo-controlled phase 2 study evaluated the efficacy and safety of TAC-302, a novel drug that restores neurite outgrowth, in patients with detrusor underactivity (DU) and overactive bladder (OAB). METHODS: After 2-4 weeks of observation, patients were randomized 2:1 to receive oral TAC-302 200 mg or placebo twice daily for 12 weeks. The primary endpoint was detrusor contraction strength, estimated by bladder contractility index (BCI) for males and projected isovolumetric pressure 1 (PIP1) for females. Secondary endpoints included changes in bladder voiding efficiency (BVE) and safety. RESULTS: Seventy-six patients were included (TAC-302, n = 52; placebo, n = 24). The mean (standard deviation [SD]) BCI for males was 64.6 (16.6) at baseline and 75.2 (21.1) at week 12 (p < 0.001) with TAC-302 (n = 27), and 61.3 (16.6) and 60.5 (16.7) (p = 0.82) with placebo (n = 11). The respective mean (SD) PIP1 for females was 18.8 (6.6) and 29.4 (9.4) (p < 0.001) with TAC-302 (n = 15), and 20.6 (7.5) and 25.5 (9.6) (p = 0.14) with placebo (n = 7). TAC-302 significantly increased BCI in males and BVE in both sexes. TAC-302 efficacy on OAB was not clearly shown. The incidences of adverse events (AEs), serious AEs, and AEs leading to dose interruption were similar between groups; no adverse drug reactions occurred. CONCLUSION: Considering the significant effects on BCI in males and BVE in both sexes, TAC-302 may benefit patients with DU. REGISTRATION: ClinicalTrials.gov Identifier NCT03175029 registered 6/5/2017.