Introduction: Since the introduction of modern contraception in 1960, the focus has been on women, with a large assortment of hormonal and nonhormonal contraceptive options available for females. In contrast, male contraceptive options currently include only condoms, vasectomy, and the withdrawal method. Here we present the initial results from a first in human clinical trial of ADAM, a nonhormonal, nonpermanent, hydrogel-based contraceptive. Methods: The preliminary safety and efficacy of ADAM® (Contraline, Inc.), a highly biocompatible nonhormonal, nonpermanent hydrogel designed for injection into the vas deferens, was assessed in an open-label, single-arm, prospective, multi-center, dose-ranging clinical trial with up to 30 male subjects with normal semen parameters, ages 25-65 years. After institutional review and ethics board approval, an initial cohort of 4 men were implanted with the first dose and rate of the ADAM® hydrogel (120uL at 800uL/min) under general anesthesia at the time of this writing. A no scalpel vasectomy (NSV) approach was used to identify and externalize the vas deferens, followed by cannulation with a 24G over-the-needle catheter, and ADAM® injection using a proprietary, automated injection device. An additional 26 men will be implanted with variable doses pending initial safety and efficacy data. Participants will be monitored for changes in semen parameters and for adverse events for up to 36 months, or until the average of two semen analyses demonstrates ?? 15 million sperm/mL. Men who do not achieve azoospermia within 6 months, and all men at 36 months, will be offered a vasectomy. Results: A volume of 120uL of ADAM® was implantated intravasally into 4 men with a mean?SD age 41.3?7.3 years and baseline semen parameters of volume 2.15?0.81 mL, pH 8.14?0.13, concentration 78.45?28.12 M/mL, motility 56.8?7.5%, morphology 13.5?3.7% normal forms, TMC 70.0?15.7 M sperm. Implantations resulted in no serious adverse events within 2 weeks of the procedure, with post-procedure recovery characteristics similar to those in men receiving vasectomy. Post-procedure semen analyses at 14?3 days demonstrated volume 1.9?1.0 mL, pH 8.3?0.2, concentration 1.1?1.2 M/mL, motility 0.0?0.0%, and TMC of 0.5?0.6 sperm. Two patients had azoospermia and a third only 5 motile and 6 immotile sperm / 30 HPF in the initial post-procedure sample. Conclusions: Intravasal injection of ADAM® into human male vas deferens is feasible, and initially safe and effective at rapidly inducing near-azoospermia. Additional data will define the longer-term safety and efficacy of ADAM® and its feasibility as a male contraceptive. SOURCE OF Funding: Contraline, Inc., Charlottesville, VA; Male Contraceptive Initiative, Durham, NC.
