Abstract
D. Gross: None. C. Wang: None. S.T. Page: None. R. Sitruk-Ware: None. M. Creinin: None. R.A. Anderson: None. A. Edelman: None. D. Turok: None. J. Kinuthia: None. J. Vinay: None. K.T. Barnhart: None. K. Gemzell Danielsson: None. F. Mhlanga: None. C. Fitzgerald: None. C.M. Meriggiola: None. D.F. Archer: None. A. Lazorwitz: None. J.K. Amory: None. R.S. Swerdloff: None. W.J. Bremner: None. M. Lee: None. J.M. Kroopnick: None. D. Blithe: None.
Background: The development of a safe, highly effective, and reliably reversible male contraceptive method is an unmet worldwide need. While studies have shown that some hormonal agents have potential efficacy for male contraception, the slow onset of spermatogenic suppression may be a limitation. Co-administration of a progestin with testosterone reduces time to sperm suppression compared to testosterone alone. Studies using injectable hormones showed an average of 12 or more weeks to reach sperm suppression to ≤1 million/mL, the goal for effective contraception. A Phase IIb Clinical Trial of daily Nestorone (Nes) (segesterone acetate) and Testosterone (T) combination gel is currently evaluating contraceptive efficacy, as well as safety, acceptability, reversibility, and timeline to sperm suppression. Objective: To assess the time to sperm suppression (concentration ≤1 million/mL) with daily self-administration of Nes 8 mg/T 74 mg combination gel in healthy males. Design: Couples were screened and enrolled into the study. The male partner began daily skin application of Nes 8 mg/T 74 mg gel/5 mL. We evaluated the time from the first gel application until the first observed sperm concentration reached ≤1 million/mL. In the original protocol, local site sperm concentration assessments were scheduled at 4-week intervals. The protocol was amended to add a visit at week 6 while the study was ongoing; however, some subjects had reached week 8 or 9 prior to full protocol approval to include the intervening visit. Results: Of 222 participants enrolled to use Nes 8 mg/T 74 mg gel and had a sperm assessment at ≥3 weeks after treatment began, 192 (86%) achieved suppression to ≤1 million/mL during treatment. At 5 weeks of treatment, 40 participants (21%) were suppressed to ≤1 million/mL. By 8 and 9 weeks, 100 (52%) and 122 (64%), respectively, were suppressed. Due to delays in local protocol amendment approval, 54 participants did not have a visit between week 5 and week 8 or 9. Of those, 21 subjects were suppressed at their first follow-up visit after week 5. Thus, they were assigned a suppression time at week 8 or 9 but may have been suppressed earlier. Overall, the median observed time to suppression for those who suppressed was 8 weeks, with 157 (82%) and 166 (86%) suppressed within 12 and 15 weeks, respectively, of initiating treatment. Conclusion: More than 80% of participants using this novel male hormonal contraceptive gel formulation containing Nestorone 8 mg and Testosterone 74 mg showed suppressed sperm output within 12 weeks, a rate that appears to be faster than prior studies with other hormonal regimens. In view of this timeline based on the available data, more complete early assessment at weeks 4, 5, and 6 may have revealed a faster average time to suppression. A more rapid time to suppression may increase the attractiveness and acceptability to potential users.
Sunday, June 2, 2024