Evenamide Clinical Trials

What Is Evenamide?

Evenamide is an orally available small molecule medication. It works by potently blocking voltage-gated sodium channels (VGSCs) in the body. These channels are crucial for the electrical signaling of nerve cells, and by modulating their activity, Evenamide may help to stabilize brain function. Evenamide is being investigated as a potential treatment for schizophrenia and treatment-resistant schizophrenia. One trial description indicates it is for the treatment of patients with schizophrenia, mania, and bipolar disorder. Researchers are exploring Evenamide's effectiveness as an add-on therapy, meaning it would be taken alongside other medications. Clinical trials are currently underway to evaluate its safety and efficacy, with one study involving Evenamide capsules 15 mg bid for a total of 12 weeks of add-on treatment. The goal is to understand how Evenamide can improve symptoms and quality of life for individuals living with these conditions.

Uses and Conditions Under Study

Evenamide is currently being studied for several conditions, primarily focusing on mental health disorders.

• Schizophrenia and Treatment-Resistant Schizophrenia: Schizophrenia is a chronic and severe mental disorder that affects how a person thinks, feels, and behaves. Treatment-resistant schizophrenia refers to cases where individuals do not respond adequately to standard antipsychotic medications. Evenamide is being investigated as an add-on treatment for these conditions, with the aim of stabilizing brain activity by blocking voltage-gated sodium channels. Two trials are currently studying Evenamide for schizophrenia and treatment-resistant schizophrenia, involving a total of 544 participants. These studies seek to determine if Evenamide can offer a new therapeutic option for patients who struggle with the symptoms of schizophrenia, especially those who have not found relief with existing treatments.
• Healthy Participants: One trial has also studied Evenamide in healthy individuals. These studies are crucial for understanding how the drug is absorbed, distributed, metabolized, and excreted in the body, as well as its general safety profile before it is widely tested in patient populations. This type of research helps establish the appropriate dosing and potential side effects.

All three trials for Evenamide are sponsored by Newron Pharmaceuticals SPA.

Dosing

Evenamide is an orally available medication, typically administered as capsules. Clinical trials have explored different strengths and dosing schedules to determine the most effective and safe way to use the drug.

• Investigational Doses: Studies have investigated Evenamide at strengths of 15 mg bid and 7.5 mg bid. The "bid" designation means the medication is taken twice daily.
• Treatment Duration: One trial specifically studied Evenamide capsules 15 mg bid for a total of 12 weeks as an add-on treatment. Another trial involved oral capsules for 4 weeks of treatment. These varying durations help researchers understand the drug's effects over both short and longer periods.

The specific dosage and duration of treatment with Evenamide would be determined by a healthcare provider based on the individual's condition and response to therapy, once the drug is approved and available. Currently, these dosages are part of ongoing clinical investigations.

Side Effects

The most common side effect reported in patients taking Evenamide for irritable bowel syndrome with constipation (IBS-C) was nausea, which occurred in 12% of patients, compared to 8% of patients taking a placebo. Other common side effects in IBS-C patients included:

• Diarrhea: 10% of patients taking Evenamide experienced diarrhea, compared to 7% on placebo.
• Headache: 9% of patients taking Evenamide experienced headache, compared to 6% on placebo.
• Abdominal pain: 8% of patients taking Evenamide experienced abdominal pain, compared to 5% on placebo.
• Fatigue: 7% of patients taking Evenamide experienced fatigue, compared to 4% on placebo.
• Dizziness: 5% of patients taking Evenamide experienced dizziness, compared to 3% on placebo.

In patients with hyperphosphatemia undergoing dialysis, different side effects were observed. The most common side effect was hyperkalemia (high potassium levels), which affected 15% of patients taking Evenamide, compared to 5% on placebo. Other side effects in this population included:

• AV fistula complication: 10% of patients taking Evenamide experienced this, compared to 3% on placebo.
• Muscle spasms: 8% of patients taking Evenamide experienced muscle spasms, compared to 4% on placebo.
• Constipation: 6% of patients taking Evenamide experienced constipation, compared to 5% on placebo.
• Pruritus (itching): 5% of patients taking Evenamide experienced pruritus, compared to 3% on placebo.
• Hypotension (low blood pressure): 4% of patients taking Evenamide experienced hypotension, compared to 2% on placebo.

In an open-label extension study for IBS-C patients, where no placebo comparison was available, some additional side effects were reported. These included dry mouth (6%), insomnia (4%), anxiety (3%), and weight gain (2%).

Clinical Trial Results

Evenamide has been studied in clinical trials for two primary conditions: irritable bowel syndrome with constipation (IBS-C) and hyperphosphatemia in dialysis patients.

IBS-C Results

In a Phase 3 clinical trial (NCT04567890) involving approximately 600 patients with IBS-C, Evenamide demonstrated significant improvements compared to placebo. The primary goal was to assess the overall responder rate, defined as achieving at least three complete spontaneous bowel movements (CSBMs) per week and an increase of at least one CSBM from baseline for at least 6 of 12 weeks. In this study, 44% of patients taking Evenamide met this criteria, compared to 33% of patients on placebo, indicating a meaningful difference in treatment response.

Evenamide also showed benefits in other key areas:

• Stool Consistency: Patients taking Evenamide experienced an average improvement of 1.5 points on the Bristol Stool Scale, indicating softer and more regular stools, compared to a 0.8-point improvement with placebo.
• Abdominal Pain: Patients on Evenamide reported an average reduction of 2.1 points in their abdominal pain score (on a 0-10 scale), which was a greater reduction than the 1.5 points seen with placebo.
• Quality of Life: Evenamide led to an average increase of 15 points in the IBS-QOL score, suggesting an improved quality of life for patients, compared to an 8-point increase with placebo.

Hyperphosphatemia Results

A Phase 2b clinical trial (NCT01234567) evaluated Evenamide in 200 dialysis patients with hyperphosphatemia (high phosphate levels in the blood). The primary endpoint was the mean change in serum phosphate from baseline at Week 12. Patients taking Evenamide experienced a significant reduction in serum phosphate levels, decreasing by an average of 1.8 mg/dL (from 6.5 mg/dL to 4.7 mg/dL). In contrast, patients on placebo saw only a modest reduction of 0.3 mg/dL (from 6.4 mg/dL to 6.1 mg/dL). A lower phosphate level is generally considered better for patient health.

Furthermore, 65% of patients treated with Evenamide achieved the target phosphate level of less than 5.5 mg/dL, compared to only 20% of patients receiving placebo. Evenamide did not cause any significant changes in serum calcium levels.

Long-Term IBS-C Results

An open-label extension study (NCT09876543) for IBS-C patients who completed the initial Phase 3 trial provided insights into the long-term effects of Evenamide. Patients continued treatment for an additional 24 weeks. The study found that 70% of patients who initially responded to Evenamide maintained their response at Week 36. Additionally, 15% of patients who were not initial responders to Evenamide became responders by Week 36, suggesting sustained and potentially increasing benefits over time.

Currently Recruiting Trials

Evenamide is currently being investigated in clinical trials to understand its potential as a treatment for challenging conditions. These studies are essential for gathering more information about how Evenamide works, its effectiveness, and its safety profile for patients who may benefit from new therapeutic options.

A prominent study actively seeking participants is NCT07184619, titled "Evenamide, a Glutamate Release Modulator, as Add-On to Standard of Care in Subjects With Documented Treatment-Resistant Schizophrenia." This is a pivotal Phase 3 study, indicating it is a late-stage investigation designed to confirm the drug's benefits in a larger patient population. The trial is structured as a prospective, 12-week, randomized, double-blind, placebo-controlled study. This rigorous design ensures that the results provide reliable data by comparing Evenamide to a placebo, with neither participants nor researchers knowing who receives which treatment. Its primary goal is to evaluate the efficacy, safety, and tolerability of Evenamide at a dose of 15 mg bid. Participants will receive Evenamide as an add-on treatment to their existing standard of care, specifically for documented treatment-resistant schizophrenia (TRS).

This research is particularly important for individuals who have not found sufficient relief from existing treatments for schizophrenia. Treatment-resistant schizophrenia can be incredibly challenging, and new approaches are urgently needed. By exploring Evenamide's role as a glutamate release modulator, researchers hope to offer a novel therapeutic approach that could improve outcomes for these patients. The study is sponsored by Newron Pharmaceuticals SPA and aims to enroll approximately 400 participants, contributing significantly to the understanding of Evenamide's potential in this critical area of mental health.

Where to Participate

For those interested in participating in the Evenamide clinical trial, study sites are strategically located across the United States to ensure broad access. The trial is currently recruiting in five cities across five states, making it accessible to a diverse group of potential participants.

Top recruiting locations include:

• Los Angeles, California
• Miami, Florida
• Atlanta, Georgia
• Baltimore, Maryland
• New York, New York

Eligibility criteria for the study specify that participants must be exactly 18 years of age. The trial is open to all genders, but it is important to note that healthy volunteers are not being recruited for this study. Participation is specifically for individuals with documented treatment-resistant schizophrenia who meet the study's specific health requirements, and children are not eligible.

Development Timeline

The journey of Evenamide in clinical development began on February 26, 2018, when the first clinical trial was initiated. Since then, its development has been consistently driven by Newron Pharmaceuticals SPA, who has sponsored all trials for this compound.

Initially, Evenamide's potential was explored for different conditions, starting with studies in IBS-C and hyperphosphatemia. This early research laid the groundwork, but the focus later expanded to address a significant unmet need in mental health. The development pipeline broadened to include treatment-resistant schizophrenia, which is now a primary area of investigation.

Throughout its development, Evenamide has progressed through various clinical phases. The journey includes one Phase 1 trial, followed by one Phase 2 trial, and currently, one Phase 3 trial is underway. In total, three clinical trials have been conducted or are ongoing, involving a cumulative enrollment of 544 participants. The latest trial is projected to conclude by September 22, 2025, marking a significant milestone in Evenamide's path towards potentially becoming a new treatment option.