A Randomized Double-blind Placebo-controlled Phase 2 Dose-ranging Study of OnabotulinumtoxinA in Men with Benign Prostatic Hyperplasia

• Published in: European urology Vol. 63; no. 3; pp. 496 - 503
• Main Authors: Marberger, Michael, Chartier-Kastler, Emmanuel, Egerdie, Blair, Lee, Kyu-Sung, Grosse, Joachim, Bugarin, Denise, Zhou, Jihao, Patel, Anand, Haag-Molkenteller, Cornelia
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier B.V 01.03.2013; Elsevier
• Subjects: Aged; Benign prostatic hyperplasia; Biological and medical sciences; Botulinum toxin; Botulinum Toxins, Type A - administration & dosage; Botulinum Toxins, Type A - adverse effects; Dose-Response Relationship, Drug; Double-Blind Method; Gynecology. Andrology. Obstetrics; Humans; Injections, Intralesional; Lower urinary tract symptoms; Lower Urinary Tract Symptoms - drug therapy; Lower Urinary Tract Symptoms - etiology; Male; Male genital diseases; Medical sciences; Middle Aged; Nephrology. Urinary tract diseases; Neuromuscular Agents - administration & dosage; Neuromuscular Agents - adverse effects; OnabotulinumtoxinA; Placebos; Prostatic Hyperplasia - complications; Prostatic Hyperplasia - drug therapy; Quality of life; Treatment Outcome; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland; Urology; OnabotulinumtoxinA; Benign prostatic hyperplasia; Lower urinary tract symptoms; Botulinum toxin; Quality of life; Nephrology; Clostridium botulinum; Prostate disease; Clostridiales; Metalloendopeptidases; Male; Posology; Urology; Voiding dysfunction; Bontoxilysin; Randomization; Phase II trial; Bacteria; Adult; Benign neoplasm; Male genital diseases; Dose; Human; Urinary system disease; Enzyme; Urinary tract disease; Peptidases; Toxin; Clostridiaceae; Placebo; Hydrolases
• ISSN: 0302-2838; 1873-7560
• DOI: 10.1016/j.eururo.2012.10.005

Abstract Background Botulinum toxin treatment has been investigated as a minimally invasive alternative to oral medications in men with lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (LUTS/BPH). Objective To explore the efficacy of onabotulinumtoxinA 100 U, 200 U, and 300 U versus placebo in men with LUTS/BPH in a phase 2 dose-ranging study. Design, setting, and participants A multicenter double-blind randomized, placebo-controlled 72-wk study enrolled men ≥50 yr of age with LUTS/BPH, International Prostate Symptom Score (IPSS) ≥12, total prostate volume (TPV) 30–100 ml, and maximum flow rate (Qmax ) 5–15 ml/s. Intervention Single transperineal ( n = 63) or transrectal ( n = 311) administration of placebo ( n = 94) or onabotulinumtoxinA 100 U ( n = 95), 200 U (n = 94), or 300 U (n = 97) into the prostate transition zone. Outcome measurements and statistical analysis The primary efficacy end point was a change from baseline in IPSS at week 12. Secondary end points were Qmax , TPV, and transition zone volume (TZV). Analysis of covariance and the Cochran-Mantel-Haenszel method assessed the efficacy and proportion of IPSS responders. Adverse events (AEs) were assessed. Results and limitations Significant improvements from baseline in IPSS, Qmax , TPV, and TZV were observed for all groups, including placebo, at week 12 ( p < 0.001), with no significant differences between onabotulinumtoxinA and placebo. However, in an exploratory post hoc analysis, a significant reduction in IPSS versus placebo was observed with onabotulinumtoxinA 200 U in prior α-blocker users ( n = 180) at week 12. AEs were comparable across all groups. Conclusions Reductions in LUTS/BPH symptoms were seen in all groups, including placebo, with no significant between-group differences owing to a large placebo effect from the injectable therapy. The findings from the post hoc analysis in men previously treated with α-blockers will be further explored in an appropriately designed study. Trial registration http://www.Clinical Trials.gov; NCT00284518.