Efficacy and safety of on-demand therapy with clomipramine/sildenafil combination compared to on-demand therapy with clomipramine or sildenafil alone in patients with premature ejaculation: A prospective, randomized, double-blinded, active-controlled, 3-treatment arm, parallel, multi-center, phase 3 trial

초록

Introduction & Objectives: Premature ejaculation (PE) is the most common male sexual dysfunction, with various treatment options. Clomipramine is commonly used for PE, and is considered first-line pharmacotherapy in recent AUA guidelines. Sildenafil has a positive effect for PE in several clinical trials. Meanwhile, many studies have demonstrated that several selective serotonin reuptake inhibitors (SSRIs) combined with sildenafil is superior to SSRI or sildenafil monotherapy for PE. However, there are no studies on the utility of clomipramine combined with sildenafil. We assessed the efficacy and safety of on-demand therapy with clomipramine 15mg/sildenafil 50mg combination compared with clomipramine or sildenafil alone in men with PE without ED. Materials & Methods: This prospective, randomized, double-blinded, active-controlled, 3-treatment arm, multi-center trial enrolled 795 men with PE without ED. Subjects were recruited between October 2019 and April 2022 at 24 institutions in Korea. PE was defined as (1) history on DSM-V, (2) PEDT 211 score, and (3) IELT <3 minute. Subjects were divided into three groups: Clomipramine 15mg (group A, n=265), sildenafil 50mg (group B, n=266) and clomipramine 15mg/sildenafil 50mg (group C, n=264). During 12 weeks, stopwatch-measured IELT and patients reported outcomes (PEP, PGIC) were measured. Any treatment-emergent adverse events (TEAEs) were also recorded. Results: Over 12 weeks, IELT increased by 191.72 ± 12.72 seconds (p<0.001), 168.35 ± 12.29 seconds (p<0.001), and 279.41 ± 20.06 seconds (p<0.001) in group A, B and C, respectively. Increase of IELT was significantly greater in group C than in group A or group B (each p<0.001). In PEP score, the improvement rates were 91.46%, 85.59%, and 96.10% in groups A, B, and C, respectively. Improvement rate of PEP score was higher in group C than group A or B (p=0.037 and <0.001, respectively). In PGIC score, the improvement rates were 41.87%, 34.50%, and 54.98% in groups A, B, and C, respectively. Improvement rate of PGIC score was higher in group C than group A or B (p=0.004 and <0.001, respectively). TEAEs occurred in 17.36%, 16.17%, and 25.00% of groups A, B, and C, respectively. TEAEs in group C seemed to occur more frequently than in groups A or B, but there was no statistical difference between groups (p=0.098). TEAEs occurred in order of headache (9.09%), nausea (7.58%), flushing (7.95%) and dizziness (3.41%) in group C. Almost all TEAEs were mild to moderate (99.58%), and there was no serious TEAE. Conclusions: On-demand therapy with clomipramine 15mg/sildenafil 50mg combination showed better results in terms of IELT, PEP, and PGIC, and was similar in safety, compared to that with clomipramine 15mg or sildenafil 50mg alone.