Sildenafil/Clomipramine Combo Boosts Outcomes in Premature Ejaculation

Du Geon Moon, MD, PhD
Credit: Korea University College of Medicine

Use of a combination therapy could be a game-changer for management of premature ejaculation (PE).

Results of a phase 3 trial presented at the American Urological Association's (AUA) 2025 Annual Meeting suggest a combination of sildenafil 50 mg and clomipramine 15 mg provided significant improvements in ejaculatory latency time and multiple patient-reported outcome measures relative to clomipramine 15 mg or sildenafil 50 mg alone.

“This is the first approved multicenter phase 3 trial of sildenafil 50 mg/clomipramine 15 mg combination for the treatment of premature ejaculation in the world and designate as incrementally modifying the drug,” said Du Geon Moon, MD, PhD, a professor in the Department of Urology at Korea University College of Medicine. “The study results suggest that the on-demand therapy of this combination has the potential in the treatment of the PE without ED for better efficacy with similar safety as clomipramine alone for PE.”

Despite being among the most common sexual health disorders, with estimates suggesting prevalence could exceed 30% of men, satisfactory management of PE remains an elusive target for urologists. With no agents sporting indications specific to PE, providers are left with the challenge of determining proper treatments, with common choices including selective serotonin reuptake inhibitors, topical anesthetics, and behavioral therapies.

Sponsored by CTC Bio, the AUA 2025 study from NAME was a 3-arm, prospective, randomized, double-blind, active-controlled, multi-center trial. The trial enrolled 795 men with PE without erectile dysfunction across 24 sites in Korea between October 2019 and April 2022. For the purpose of analysis, PE was defined based on DSM-V criteria, a PEDT score of 11 or higher, and an intravaginal ejaculatory latency time (IELT) of less than 3 minutes.

A total of 265 participants were randomized to clomipramine 15 mg (Group A), 266 were randomized to sildenafil 50 mg (Group B), and 264 were randomized to a combination of clomipramine 15 mg and sildenafil 50 mg (Group C). The primary outcome of interest for the study were stopwatch-measured IELT at 12 weeks. Additional outcomes of interested included changes in Premature Ejaculation Profile (PEP) and Patient Global Impression of Change (PGIC).¹

Results of the trial indicated all groups showed significant increases in IELT over 12 weeks:

• Group A: 191.72±12.72 seconds (P <.001)
• Group B: 168.35±12.29 seconds (P <.001)
• Group C: 279.41±20.06 seconds(P <.001)

Further analysis demonstrated the increase in IELT was significantly greater in group C compared to either monotherapy group (each P <.001). Improvements in PEP scores were 91.46%, 85.59%, and 96.10% for groups A, B, and C, respectively, with group C achieving significantly greater rates of improvement than groups A (P = .037) or B (P <.001). Additionally, a consistent trend was observed for PGIC score improvements, with improvement rates of 41.87%, 34.50%, and 54.98%, respectively, again favoring group C relative to groups A (P = .004) and B (P <.001).¹

Safety data suggested treatment-emergent adverse events occurred among 17.36%, 16.17%, and 25.00% of patients in groups A, B, and C, respectively, with no statistically significant differences between groups (P = .098). The most common treatment-emergent adverse events in group C were headache (9.09%), nausea (7.58%), flushing (7.95%), and dizziness (3.41%). Nearly all adverse events were mild to moderate in severity, and no serious treatment-emergent adverse events were reported.¹

Reference:

1. Moon DG, Lee WK, Kim JH. IP10-04 EFFICACY AND SAFETY OF ON-DEMAND THERAPY WITH CLOMIPRAMINE/SILDENAFIL COMBINATION COMPARED TO CLOMIPRAMINE OR SILDENAFIL ALONE IN PATIENTS WITH PREMATURE EJACULATION: MULTI-CENTER, PHASE 3 TRIAL.

2. J Urol. 2025;213(5S):e538. doi:10.1097/01.JU.0001109900.23127.a9.04 Crowdis M, Leslie SW, Nazir S. Premature Ejaculation. In: StatPearls. Treasure Island (FL): StatPearls Publishing; May 30, 2023.