A Double-Blind, Placebo-Controlled Parallel Group Study to Evaluate the Effect of a Single Oral Dose of 5-HT1A Antagonist GSK958108 on Ejaculation Latency Time in Male Patients Suffering From Premature Ejaculation

Abstract

Background: Premature ejaculation (PE) is a common male neurobiological sexual disorder, related to a disturbance in central serotonin (5-hydroxytryptamine or 5-HT) neurotransmission.

Aim: To assess the efficacy of a single oral dose of 5HT_1A receptor antagonist GSK958108 on ejaculation latency time (ELT) in male subjects suffering from PE.

Methods: A total of 35 male subjects were enrolled in a Phase 1 double-blind, placebo-controlled, parallel group masturbation-model study. All subjects completed the study. No subject was withdrawn from the study. There were no major protocol deviations reported during the study.

Outcomes: The primary outcome of the study was to evaluate the effect of a single oral dose of 5HT_1A receptor antagonist GSK958108 on ELT as measured in the masturbation model; additionally, we investigated drug's safety and tolerability.

Results: In the 3 mg GSK958108 treatment group, the ELT was estimated to be 16% longer (1.542 vs 1.328, 95% CI: -16% to +61%) than if the subjects had taken placebo. In the 7 mg GSK958108 treatment group, the ELT was estimated to be 77% longer (2.346 vs 1.328, 95% CI: +28% to +144%) than in the placebo group. The systemic exposure to GSK958108 increased with dosage between 3 mg and 7 mg. A significant trend toward an increase of ELT was observed with increasing plasma concentrations of GSK958108. A total of 4 patients all treated with 7 mg dose experienced minor drug related adverse events (5 adverse events in 4 patients): somnolence (n = 3), headache (n = 1), tinnitus (n = 1).

Clinical implications: In the current double-blind, placebo-controlled parallel group study the 5HT_1A receptor antagonist GSK958108 was tested in 3 mg and 7 mg doses for PE treatment in humans. It was shown that GSK958108 significantly delayed ejaculation showing a new and safe alternative in PE treatment.

Strengths & limitations: The present study showed innovative results suggesting an important role of 5HT_1A receptor antagonist in the PE treatment. However, the use of masturbation model and the small population are the main limitations of this investigation.

Conclusion: 5HT_1A receptor antagonist GSK958108 3 mg per day and 7 mg per day was found to be well-tolerated, safe and effective for the treatment of PE subjects and demonstrated a strong association between 5HT1A receptors and ejaculation control in humans (NCT00861484). Migliorini F, Tafuri A, Bettica P, et al. A Double-Blind, Placebo-Controlled Parallel Group Study to Evaluate the Effect of a Single Oral Dose of 5-HT1A Antagonist GSK958108 on Ejaculation Latency Time in Male Patients Suffering From Premature Ejaculation. J Sex Med 2021;18:63-71.

Keywords: 5HT(1A) Antagonist; Ejaculation Disorders; Ejaculation Latency Time; Premature Ejaculation.