Effects of NLS-133, a Potential Non-Hormonal "On-Demand" Male Contraceptive

Overview

NLS-133-CLIN001 is a Phase 2a study designed to assess the safety, tolerability, and effects of NLS-133 (combination of two FDA-approved agents) compared to an active control (FDA-approved pharmacologic agent) or placebo on semen volume and sperm count in 10 in healthy men. Participants will be randomized in a crossover design to receive a single dose of NLS-133, an active control or placebo either 90 or 180 minutes prior to collection of semen. Sperm parameters measured will be count, motility and morphology. A brief questionnaire will be completed by each subject during each treatment cycle that addresses orgasm and ejaculation quality. Safety monitoring will include adverse event reporting, laboratory assessments, and vital signs.

The aim of study NLS-133-CLIN001is to determine the time frame NLS-133 (combination of two FDA-approved agents) affected ejaculation, semen volume and sperm count in young, normal men. NLS-133 responses will be compared to responses observed after oral placebo and active control (FDA-approved pharmacological agent) treatments. This is a randomized, double-blind, placebo-controlled, crossover (6-way) trial of 10 men who will receive oral capsules 90 and 180 minutes prior to semen collection by masturbation. There will be at least a 72 hour washout period between dosing cycles. Semen volume, if any, and sperm count and morphology (if possible based on semen volume) will be assessed. Subjects will also answer a brief questionnaire regarding orgasm and ejaculation quality during masturbation. Lastly, time to ejaculation and orgasm will be measured by a stopwatch to determine any impact on the time to orgasm or ejaculation by the study treatments. A brief questionnaire about orgasm and ejaculation quality will be completed subjects during each treatment cycle. Safety monitoring will include adverse event reporting, laboratory assessments, and vital signs. Statistical analyses will be as follows. Means and standard deviations will be calculated for ejaculate volumes and sperm counts at each time point after dosing, stratified by dose. The main outcome for this study is the Semen volume and total sperm count by dose at each time point. This outcome will be compared by Friedman's ANOVA with a Dunnett's post-hoc test. Secondary outcomes include time to ejaculation by dose and orgasm quality scores using the Derogatis questionnaire and other questions as well as serum silodosin and guanfacine concentrations by dose and time and will also be analyzed by Friedman's ANOVA with a Dunnett's post-hoc test. All analyses will be performed using STATA version 10, (College Park, TX). For all comparisons an alpha of \<0.05 without correction for multiple comparisons will be considered significant.