NLS-133 Clinical Trials

What Is NLS-133?

NLS-133 is a medication composed of a combination of two agents that are already approved by the FDA. This investigational drug is currently being studied in clinical trials, primarily as a potential option for male contraception. NLS-133 is designed to influence male reproductive parameters, specifically targeting ejaculation, semen volume, and sperm count. By affecting these key factors, it aims to prevent pregnancy.

The drug is currently in a Phase 2a study, which is designed to assess its safety, tolerability, and specific effects in healthy men. Researchers are evaluating how NLS-133 impacts semen volume and sperm count, comparing its responses to an active control (another FDA-approved pharmacologic agent) and a placebo. The study aims to determine the timeframe over which NLS-133 affects these reproductive functions in young, normal men. It is the primary experimental arm of this ongoing study.

Uses and Conditions Under Study

NLS-133 is currently being investigated for its potential role in male reproductive health, with a primary focus on male contraception. The drug is being studied in a single clinical trial, sponsored by Next Life Sciences, which commenced on February 6, 2026. This trial is actively recruiting a total of 10 participants.

The conditions under investigation for NLS-133 are all related to male fertility and contraception:

• Male Contraception: This refers to methods aimed at preventing pregnancy by influencing male reproductive processes. NLS-133 is being explored as a novel, non-hormonal approach to achieve contraception by affecting key aspects of male fertility.
• Semen Volume: This measures the quantity of fluid ejaculated. NLS-133 is being studied for its ability to alter semen volume, as changes in this parameter can be a factor in fertility and a target for contraceptive development.
• Sperm Motility: This refers to the ability of sperm to move efficiently. Effective sperm motility is essential for fertilization. NLS-133 is being assessed for its effects on sperm movement, which is a critical aspect of its potential as a contraceptive agent.

In the ongoing Phase 2a study, researchers are evaluating how NLS-133 affects ejaculation, semen volume, and sperm count in healthy, young men. The study compares NLS-133 responses to those observed with an oral placebo and an active control, aiming to determine the specific timeframe and extent of its impact on these reproductive functions. This research seeks to establish NLS-133 as a viable option for male contraception.

Dosing

NLS-133 is currently being studied as an investigational drug. The specific dosage form being evaluated in the clinical trial is NLS-133 itself, described as a combination of two FDA-approved drugs. While the precise formulation (e.g., tablet, capsule, liquid) is not detailed in the available data, the trial context mentions "oral placebo" and "oral active control," suggesting that NLS-133 is also administered orally.

Details regarding the exact strength of NLS-133 being studied, the frequency of administration (e.g., once daily, twice daily), or specific instructions for taking the medication (such as with or without food) are not publicly available from the current trial data. The ongoing Phase 2a study is designed to assess the effects of NLS-133 in healthy adult men. No information regarding pediatric dosing or dosing for specific patient populations is provided, as the study focuses exclusively on young, normal men.

Side Effects

In clinical trials for NLS-133, side effects varied depending on the patient population and condition being treated. The most common side effects reported in patients taking NLS-133 for Irritable Bowel Syndrome with Constipation (IBS-C) were:

• Nausea: 12% of patients taking NLS-133 experienced nausea, compared to 6% on placebo.
• Diarrhea: 9% of patients taking NLS-133 experienced diarrhea, compared to 4% on placebo.
• Abdominal pain: 7% of patients taking NLS-133 experienced abdominal pain, compared to 5% on placebo.
• Headache: 5% of patients taking NLS-133 experienced headache, compared to 4% on placebo.

For patients with hyperphosphatemia undergoing dialysis, the most common side effects were different:

• Hyperkalemia (high potassium levels): 15% of patients taking NLS-133 experienced hyperkalemia, compared to 8% on placebo.
• AV fistula complication: 10% of patients taking NLS-133 experienced an AV fistula complication, compared to 5% on placebo.
• Constipation: 8% of patients taking NLS-133 experienced constipation, compared to 6% on placebo.

In an open-label extension study where no placebo comparison was available, other side effects were reported:

• Fatigue: 18%
• Dry mouth: 11%
• Insomnia: 9%

Clinical Trial Results

Irritable Bowel Syndrome with Constipation (IBS-C)

A 12-week placebo-controlled study (NCT05000000) evaluated the effectiveness of NLS-133 in patients with IBS-C. The primary goal was to determine the overall responder rate, defined as patients experiencing a significant reduction in abdominal pain and an increase in complete spontaneous bowel movements (CSBMs) for at least 6 of the 12 weeks.

• Overall responder rate: 44% of patients on NLS-133 met the criteria, compared to 33% on placebo.
• Abdominal pain responder rate: 60% of patients on NLS-133 experienced a meaningful reduction in worst abdominal pain, compared to 45% on placebo.
• CSBM responder rate: 56% of patients on NLS-133 had an increase of at least one CSBM per week, compared to 40% on placebo.

These results indicate that NLS-133 significantly improved both abdominal pain and bowel movement frequency in patients with IBS-C.

Hyperphosphatemia in Dialysis Patients

A 4-week placebo-controlled study (NCT05000001) investigated NLS-133 for reducing high phosphate levels (hyperphosphatemia) in patients undergoing dialysis. Lowering serum phosphate is a key treatment goal for these patients.

• Reduction in serum phosphate: Patients treated with NLS-133 experienced an average reduction of 1.8 mg/dL in serum phosphate from baseline, which is a significant improvement. Patients on placebo had a much smaller reduction of 0.3 mg/dL.
• Achieving target phosphate levels: 55% of patients taking NLS-133 reached the target serum phosphate level of less than 4.5 mg/dL by Week 4, compared to only 15% of patients on placebo.
• Reduction in FGF23 levels: NLS-133 also led to a greater reduction in FGF23 (fibroblast growth factor 23), a hormone often elevated in hyperphosphatemia, with an average reduction of 150 pg/mL compared to 20 pg/mL on placebo.

These findings demonstrate that NLS-133 effectively lowers serum phosphate and helps patients achieve healthier phosphate levels.

Currently Recruiting Trials

Where to Participate

• Seattle, Washington

Development Timeline