Testing NLS-133 as a non-hormonal, on-demand male contraceptive.

Effects of NLS-133, a Potential Non-Hormonal "On-Demand" Male Contraceptive, on Semen Volume and Sperm Count in Normal Men: A Double-Blind, Placebo-Controlled Trial

This will test whether a single oral dose of NLS-133 taken 90 or 180 minutes before ejaculation can reduce semen volume and sperm count in healthy men aged 18–55.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 10 (estimated)
• Ages: 18 Years to 55 Years
• Sex: Male
• Sponsor: Next Life Sciences (industry)
• Locations: 1 site (Seattle, Washington)
• Trial ID: NCT07393334 on ClinicalTrials.gov

What this trial studies

This randomized, double-blind, placebo-controlled crossover Phase 2a trial enrolls 10 healthy men who will receive single oral doses of NLS-133, an active comparator, or placebo before producing semen samples in clinic. Each participant will complete multiple dosing cycles with at least a 72-hour washout, with semen collection by masturbation 90 or 180 minutes after dosing. Primary outcomes are semen volume and total sperm count, and secondary measures include sperm motility, morphology, timed ejaculation, and a brief questionnaire on orgasm and ejaculation quality. Safety monitoring includes adverse event reporting, laboratory tests, and vital signs.

Who should consider this trial

Good fit: Ideal candidates are healthy men aged 18–55 with normal baseline semen parameters who can attend clinic visits and provide supervised semen samples.

Not a fit: Men with known infertility or hypogonadism, erectile dysfunction, inability to produce clinic-collected semen samples, significant medical illness, or who require prohibited medications are unlikely to benefit from this intervention.

Why it matters

Potential benefit: If successful, NLS-133 could provide men with a short-acting, non-hormonal on-demand contraceptive option that lowers semen output and the risk of conception when used appropriately.

How similar studies have performed: On-demand non-hormonal male contraception is a relatively novel approach: some early or preclinical work with related agents has suggested effects on semen parameters, but there is not yet large-scale clinical proof of effectiveness.

Eligibility criteria

Inclusion Criteria:

1. Male, age 18-55.
2. Normal physical examination and testicular volume \>15 cc
3. No significant medical history that would impact the safety of the study.
4. No current use of drugs that comprise NLS-133
5. Normal values on baseline hematology, blood chemistry and liver function tests and serum testosterone.
6. Normal baseline sperm parameters (semen volume \>1.4 cc, sperm concentration \>15 million/ml, motility \>40% and morphology \>4%).
7. Willing and able to comply with all study requirements and procedures.

Exclusion Criteria:

1. History or evidence of erectile dysfunction.
2. Inability to produce semen samples in clinic setting.
3. Significant chronic or acute medical illness.
4. Previous or current ethanol or illicit drug abuse.
5. Evidence of significant underlying disease (based on results of the physical exam and the routine labs).
6. Known infertility or hypogonadism.
7. Planned or anticipated use of any prohibited medications during participation in the study. These include use of sex hormones for treatment, testosterone, anabolic steroids, retinoic acid (e.g., Accutane®), vitamin A, other drugs known to inhibit spermatogenesis, opioids, cocaine, methamphetamine, and/or the consumption of \>4 alcoholic beverages daily.
8. Presence of moderate-to-severe pulmonary or cardiovascular disease
9. Known active hepatitis B, hepatitis C, human immunodeficiency virus (HIV), or COVID-19 infection.
10. History of malignancy within 5 years before the Screening Visit, except fully treated and resolved non-metastatic squamous or basal cell carcinoma of the skin.
11. Known active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, antifungals, antiparasitics or antiprotozoals during the Screening period.
12. Any other acute or chronic medical or psychiatric condition or laboratory abnormality that could increase the risk associated with study participation in the judgment of the investigator would make the participant inappropriate for entry into the study.
13. Participation in another investigational clinical trial within the last 30 days.
14. Participants who live in detention on court order or on regulatory action.
15. Related to sponsor or staff involved in the conduct of the study.

Where this trial is running

Seattle, Washington

• Population Center for Research in Human Reproduction and Departments of Medicine, University of Washington — Seattle, Washington, United States (RECRUITING)

Study contacts

• Study coordinator: John K Amory, MD, MPH, MSc

Conditions: Male Contraception, Semen Volume, Sperm Motility, Effect of NLS-133 on semen volume and semen parameters