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

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) 30–100ml, and maximum flow rate (Q max ) 5–15ml/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 Q max , 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, Q max , TPV, and TZV were observed for all groups, including placebo, at week 12 ( p 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.