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

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, placebocontrolled 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 (Q(max)) 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 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 < 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 alpha-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 alpha-blockers will be further explored in an appropriately designed study.