What Is Cenobamate?
Cenobamate is an FDA-approved medication for the treatment of partial-onset (focal) seizures in adults aged 18 years and older. It is approved for use as monotherapy in the United States, and also in Europe and other countries worldwide. Cenobamate is a small molecule that has been studied in a total of 14 clinical trials, with 5 trials currently recruiting participants and 6 trials completed. These studies have involved a total of 1,492 participants since the first trial began on July 31, 2017. While its precise mechanism of action is not detailed in the provided trial descriptions, it is classified as an anti-seizure medication. Beyond its approved indication, cenobamate is also being investigated for other forms of epilepsy, such as generalized epilepsy and focal onset seizures. Research also includes studies in healthy volunteers and individuals with hepatic impairment to assess its safety and how it is processed in different patient groups.
Uses and Conditions Under Study
Cenobamate is primarily studied for its role in treating various seizure disorders. It is being investigated for conditions such as Epilepsy, Generalized Epilepsy, Focal Epilepsy With and Without Secondary Generalization, Focal Onset Seizure, and Focal Seizure. These studies aim to understand how cenobamate can help patients who have not achieved adequate control with other anti-seizure medications. A total of 6 trials are exploring cenobamate's effectiveness across these specific seizure-related conditions, including one trial for a broader Neurologic Disorder.
Beyond seizure treatment, cenobamate is also studied in healthy individuals. These 4 trials involving Healthy, Healthy Volunteer, and Healthy Volunteers aim to assess the drug's safety, how it is absorbed, distributed, metabolized, and excreted in the body without the confounding factors of a disease state. This helps researchers understand the drug's basic pharmacology.
Furthermore, one trial is specifically dedicated to understanding cenobamate's effects in individuals with Hepatic Impairment. This research is crucial for determining appropriate dosing adjustments for patients with liver problems, ensuring the drug can be used safely and effectively in this population.
The development of cenobamate is supported by several sponsors, including SK Life Science, Inc., which has sponsored 9 trials, and Ono Pharmaceutical Co., Ltd., sponsoring 3 trials.
Dosing
Cenobamate is typically administered orally, usually as a tablet, and is taken once daily. Dosing often begins with a lower strength and is gradually increased over time, a process known as titration, to find the most effective and tolerable dose for each patient.
Initial doses in studies have started as low as 12.5 mg once daily, with titration schedules increasing the dose to 25 mg, then 50 mg, and further to target doses like 100 mg or 200 mg per day. The daily dose may be adjusted based on the patient's response and tolerability, with some studies allowing for increases up to a maximum of 400 mg per day. For instance, one study involved a 6-week titration phase starting at 12.5 mg/day, followed by a 26-week maintenance phase at 100 mg/day.
While cenobamate is approved for adults, studies have also investigated its use in pediatric populations, specifically in children aged 2 to less than 18 years old. Dosing in these younger populations, as well as in adults with Hepatic Impairment, is carefully evaluated to ensure safety and efficacy. Administration methods have included oral intake via tablet, and in some cases, through nasogastric (NGT) or gastrostomy (G-tube) for specific dosing regimens.
Side Effects
The provided data on Cenobamate's side effects comes from a bioavailability and food effect study (NCT04690751). This study primarily investigates how the drug is absorbed and processed by the body under different conditions, rather than its overall safety profile in a large patient population. In this study, the number of participants who experienced any treatment-emergent adverse event was recorded across three different treatment groups:
- In Treatment A, 8 participants experienced a treatment-emergent adverse event.
- In Treatment B, 8 participants experienced a treatment-emergent adverse event.
- In Treatment C, 7 participants experienced a treatment-emergent adverse event.
Specific types or frequencies of individual side effects were not detailed in the available results from this study. This data does not include a comparison to a placebo group, as the study focused on comparing different formulations and the impact of food on drug absorption. For a comprehensive understanding of Cenobamate's side effects, information from larger, placebo-controlled clinical trials would typically be reviewed.
Clinical Trial Results
The clinical results for Cenobamate are drawn from a bioavailability and food effect study (NCT04690751). This type of study investigates how the body absorbs, distributes, metabolizes, and excretes a drug, and how food might influence these processes. It does not evaluate the drug's effectiveness in treating a specific condition, but rather its behavior within the body under different administration scenarios (e.g., as an oral suspension versus a tablet, or with food).
The study compared three different treatment conditions (Treatment A, Treatment B, and Treatment C) and measured several key pharmacokinetic outcomes:
Area Under the Concentration Curve (AUC)
The Area Under the Concentration Curve (AUC) measures the total amount of drug that enters the bloodstream over time, indicating the overall exposure to the drug. A higher AUC generally means more drug has been absorbed into the body.
- For the total exposure (from 0 to infinity), the median AUC was 308.0 μg•h/mL for Treatment A, 309.5 μg•h/mL for Treatment B, and 296.0 μg•h/mL for Treatment C.
- For exposure up to the last measurable concentration, the median AUC was 304.0 μg•h/mL for Treatment A, 302.5 μg•h/mL for Treatment B, and 277.0 μg•h/mL for Treatment C.
These results suggest similar overall drug exposure across the three treatments, with Treatment C showing slightly lower median AUC values in both measurements.
Maximum Concentration (Cmax)
Cmax represents the highest concentration of the drug observed in the bloodstream after administration. This indicates the peak level the drug reaches in the body.
- The median Cmax was 4.880 μg/mL for Treatment A, 4.680 μg/mL for Treatment B, and 3.860 μg/mL for Treatment C.
Treatment A and B resulted in higher peak drug concentrations compared to Treatment C.
Time to Maximum Concentration (Tmax)
Tmax is the time it takes for the drug to reach its maximum concentration in the bloodstream. This indicates how quickly the drug reaches its peak level.
- The median Tmax was 3.000 hours for Treatment A, 0.750 hours for Treatment B, and 5.000 hours for Treatment C.
Treatment B demonstrated the fastest absorption, reaching peak concentration in a median of 0.750 hours, while Treatment C had the slowest absorption, taking a median of 5.000 hours to reach its peak.
Currently Recruiting Trials
Research into Cenobamate continues, with several clinical trials actively seeking participants to further understand its safety and effectiveness. These studies explore its use across different age groups and types of epilepsy, aiming to improve treatment options for patients.
One ongoing Phase 3 study, NCT07594158, sponsored by Ono Pharmaceutical Co., Ltd., is evaluating the safety, efficacy, and pharmacokinetics of ONO-2017 (Cenobamate) in Japanese pediatric subjects aged 2 to 17 years old with partial-onset (focal) seizures. This trial aims to enroll 20 patients.
Another study, NCT06716801, sponsored by Aziende Chimiche Riunite Angelini Francesco S.p.A, is collecting real-world data on the clinical response to Cenobamate as an early add-on treatment. This observational study, targeting 300 patients, focuses on adults with focal epilepsy not adequately controlled by current treatments in France, Germany, and Spain.
Ono Pharmaceutical Co., Ltd. also sponsors NCT06590896, a Phase 2 trial investigating the long-term safety and tolerability of Cenobamate in 100 Japanese subjects with partial onset seizures.
Additionally, a Phase 3 study, NCT06579573, also from Ono Pharmaceutical Co., Ltd., is examining the efficacy and safety of ONO-2017 in combination with other antiepileptic drugs for Japanese epileptic patients with generalized tonic-clonic seizures. This trial plans to enroll 15 patients.
Finally, NCT03961568 is an open-label extension study sponsored by SK Life Science, Inc., offering a 52-week safety evaluation of Cenobamate for 145 subjects who completed a prior core study (YKP3089C025) for primary generalized tonic clonic seizures in the setting of idiopathic generalized epilepsy.
Where to Participate
Clinical trials for Cenobamate are conducted across a broad geographic area, with study sites located in 16 cities across 13 states. These locations provide opportunities for diverse patient populations to participate in ongoing research.
Some of the top participating locations include:
- La Jolla, California
- Miami, Florida
- Tampa, Florida
- Honolulu, Hawaii
- Boise, Idaho
- Scarborough, Maine
- Bethesda, Maryland
- Golden Valley, Minnesota
- Rochester, Minnesota
- Columbia, Missouri
General eligibility for Cenobamate studies often includes individuals aged 2 to 18 years, with participation open to all genders. These trials typically do not recruit healthy volunteers, focusing specifically on patients with relevant medical conditions.
Development Timeline
The development journey for Cenobamate began with its first clinical trial on July 31, 2017. Since then, a total of 14 trials have been initiated, involving 1,492 participants, to thoroughly investigate its potential as a treatment.
Early research phases included one Early Phase 1 and five Phase 1 trials, exploring initial safety and dosing. As development progressed, Cenobamate moved into a Phase 2 trial, and currently includes five Phase 3 studies and one Phase 4 study, indicating advanced stages of investigation.
Initially, the drug's pipeline explored conditions such as IBS-C and hyperphosphatemia. However, the focus significantly expanded to various forms of epilepsy, including Generalized Epilepsy, Focal Epilepsy With and Without Secondary Generalization, Focal Onset Seizure, Partial Epilepsy, and Primary Generalized Tonic Clonic Seizures in the Setting of Idiopathic Generalized Epilepsy. Studies have also included healthy volunteers and individuals with hepatic impairment to understand its profile more comprehensively. SK Life Science, Inc. has been a primary driver of this research, sponsoring nine trials, alongside contributions from Ono Pharmaceutical Co., Ltd., Aziende Chimiche Riunite Angelini Francesco S.p.A, and Brigham and Women's Hospital. The latest planned trial activity extends into May 18, 2026, demonstrating ongoing commitment to its research.