Evaluation of PRAX-628 on Photoparoxysmal EEG Response in Epilepsy Patients with Intermittent Photic Stimulation: A Phase 2, Single-Blind, Placebo-Controlled Study
- Trial ID
- 2023-504803-10-00
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this Phase 2, single-blind, placebo-controlled trial is to evaluate the **pharmacodynamic** effect of PRAX-628 compared with placebo on the IPS-induced photoparoxysmal electroencephalogram response (IPS-induced PPR) in participants with epilepsy. This objective is clinically relevant as it aims to determine the efficacy of PRAX-628 in modulating the photoparoxysmal response, which is a critical factor in managing epilepsy associated with photic stimulation.
Secondary objectives include:
- Evaluating the **pharmacokinetics** of PRAX-628 in participants with epilepsy and IPS-induced PPR.
- Assessing the **tolerability** and safety of PRAX-628 compared to placebo in this patient population.
Participants
The clinical trial involves **participants** diagnosed with epilepsy, specifically those exhibiting an IPS-induced photoparoxysmal electroencephalogram response (IPS-induced PPR). The study population comprises both male and female subjects aged between 18 and 65 years. Participants are required to be in good health, aside from their epilepsy condition, as determined by medical history, physical examination, and laboratory evaluations conducted at Screening and Baseline. The trial includes individuals with a body mass index (BMI) ranging from 18 to 35 kg/m² and a minimum body weight of 50 kg. Participants may be on 0 to 3 anti-epileptic medications. The study does not involve a vulnerable population. Lifestyle considerations such as diet and physical activity are not specified. The sponsor has not provided information regarding the total number of participants in the trial.
Plans and Procedures
The clinical trial is designed as a **single-blind**, placebo-controlled study to evaluate the pharmacodynamic effects of **PRAX-628** on the **IPS-induced photoparoxysmal electroencephalogram response** in participants with epilepsy. The trial will assess the safety, tolerability, and pharmacokinetics of PRAX-628, administered in capsule form, with a maximum daily dose of 45 mg. The study will involve a fixed-sequence design, where participants will receive both the active treatment and placebo in a controlled manner. The trial is expected to conclude by April 30, 2024, with recruitment having commenced on May 6, 2023.
Participants will undergo a series of study visits, beginning with a screening visit to confirm eligibility based on criteria such as age, epilepsy diagnosis, and health status. The inclusion criteria specify that participants must be between 18 and 65 years old, have a history of epilepsy, and demonstrate an IPS-induced PPR with a standardized photosensitivity range of at least 4 points. The screening will also include a medical history review, physical examination, and laboratory evaluations. Following the screening, eligible participants will proceed to the baseline visit, where further assessments will be conducted to establish initial health parameters.
Throughout the trial, participants will attend follow-up visits to monitor the primary endpoint, which is the reduction or abolishment of the IPS-induced PPR. Secondary endpoints include measuring plasma concentrations of PRAX-628, maximum observed concentration (Cmax), time to maximum observed concentration (tmax), and area under the concentration-time curve (AUC24). Additionally, the incidence and severity of adverse events, changes in vital signs, clinical laboratory results, and electrocardiogram parameters will be evaluated. The end-of-study visit will conclude the trial, where final assessments will be made to determine the overall impact of the treatment.
Participant involvement is expected to last for the duration of the trial, with conditions for early termination including non-compliance with study requirements or the occurrence of significant adverse events. The trial aims to provide valuable insights into the efficacy and safety of PRAX-628 in managing epilepsy-related photoparoxysmal responses, contributing to the broader understanding of treatment options for this condition.
Treatment
The clinical trial involves the administration of **PRAX-628**, an investigational medication developed by Praxis Precision Medicines Inc. **PRAX-628** is provided in a **capsule** form and is of chemical origin. The active substance, also named **PRAX-628**, is administered orally. The maximum daily dose is 45 mg, with the same amount being the total dose for the treatment period. The treatment period is limited to one day. The medication is not formulated for pediatric use and is not classified as an orphan drug. The trial aims to evaluate the pharmacodynamic effects of **PRAX-628** in participants with epilepsy who exhibit a photoparoxysmal electroencephalogram response to intermittent photic stimulation.
In addition to the experimental treatment, a **placebo** is utilized as a comparator in this single-blind, placebo-controlled trial. The placebo is designed to match the experimental treatment in appearance but does not contain the active substance. The use of a placebo allows for the assessment of the true pharmacodynamic effects of **PRAX-628** by providing a baseline for comparison. The placebo is administered in a manner consistent with the experimental treatment to ensure blinding and maintain the integrity of the trial results.
Efficacy
Efficacy in this clinical trial will be assessed primarily through the reduction or abolishment of the **IPS-induced photoparoxysmal electroencephalogram response (PPR)** in participants with epilepsy. This primary endpoint will be evaluated to determine the pharmacodynamic effect of PRAX-628 compared to placebo. Secondary endpoints include the measurement of plasma concentrations of PRAX-628, maximum observed concentration (Cmax), time to maximum observed concentration (tmax), and the area under the concentration-time curve from time zero to 24 hours (AUC24). Additionally, the incidence and severity of adverse events, changes in vital sign measurements, clinical laboratory results, and electrocardiogram (ECG) parameters will be monitored.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Men or women between 18 and 65 years of age, inclusive.
- Diagnosis and history of epilepsy for which they are taking 0 to 3 anti-epileptic medications
- Epileptic patients showing a IPS-induced PPR with a standardized photosensitivity range (SPR) of at least 4 points in at least one eye condition at Screening and Baseline
- In good health (with the exception of epilepsy) as determined at Screening and Baseline by medical history, physical examination, and laboratory evaluations
- Has a body mass index (BMI) at Screening between 18 and 35 kg/m2 (inclusive), and a total body weight of at least 50 kg
- Female of childbearing potential who are not pregnant or breastfeeding, have a negative serum pregnancy test at Screening and a negative urine pregnancy test at Baseline and are not planning to get pregnant for the duration of the trial
- Female of nonchildbearing potential by reason of surgery or at least 1 year postmenopausal (ie, 12 months since last menses) with confirmation by follicle‑stimulating hormone (FSH) at Screening only, or Female of childbearing potential who is willing to use a highly effective method or methods of contraception as defined in this protocol and for the duration prescribed in this protocol, or Male who is willing and able to use a highly effective method or methods of contraception as defined in this protocol and for the duration prescribed in this protocol
- Able and willing to provide written informed consent and to comply with all study requirements
Exclusion Criteria
- A history of only non-epileptic seizures.
- Any finding that, in the judgment of the investigator, is a clinically significant abnormality, including serum chemistry, hematology, coagulation, and urinalysis test values (abnormal test results may be repeated for confirmation).
- An elevation of ≥2.5× upper limit of normal (ULN) for aspartate aminotransferase (AST) or alanine aminotransferase (ALT)/ serum glutamic pyruvic transaminase or ≥1.5xULN for total bilirubin.
- Positive test for HIV, hepatitis B (HBsAg), or hepatitis C.
- History of drug or alcohol abuse.
- Positive drug or alcohol test at Screening or Baseline. (Abnormal test results may be repeated for confirmation.)
- Smoker of more than 10 cigarettes per day prior to Screening or who use tobacco products equivalent to more than 10 cigarettes per day and unable to abstain from smoking while in the unit.
- Use of an investigational drug or device within 90 days or 5 half-lives preceding the first dose of study drug, whichever is longer.
- Use of prescription or nonprescription drugs or dietary or herbal supplements of clinical concern within 7 days or within 5 times the elimination half-life (whichever is longer) prior to the first dose of study drug. Refer to the relevant section(s) of the protocol for potential exceptions which must be approved by the sponsor/designee.
- Any vaccination within 14 days of the first dose of study drug.
- Other ongoing central nervous system (CNS) disease, such as an active CNS infection, demyelinating disease, degenerative neurological disease or any CNS disease deemed to be progressive during the course of the study that may confound the interpretation of the study results.
- Blood donation (including plasma donations) or significant blood loss of approximately 500 mL or more within 90 days (male) or 120 days (female) prior to first dose of study drug.
- Presence or history of any allergy or hypersensitivity to any component of the study drug product, or history of severe allergy or anaphylaxis to a drug, food, or other exposure
- Unwilling or unable to comply with the lifestyle considerations described in this protocol.
- An employee or family member of an employee of the sponsor, or an employee or family member of the study site staff
- Receiving any antiseizure drug (ASD) or non-pharmacological intervention (including ketogenic diet and vagus nerve stimulation) for the treatment of epilepsy that are NOT at stable doses, settings, or parameters for 1 month prior to Screening and are expected to make adjustments throughout the clinical trial.
- Currently taking any sodium channel-blocking medication.
- Any clinically significant abnormalities, medical, or psychiatric conditions identified by a detailed medical history, or physical examination, that, in the opinion of the investigator, would pose an additional safety risk to the participant or compromise the objectives of the study
- A history of cardiac disease(s)/cardiac conduction disorders/or cardiac structural abnormality(ies) (e.g., atrial or ventricular septal defects, valvular heart disease, coarctation of the aorta, left bundle branch block, arrhythmias, Brugada syndrome, congenital heart disease, familial short QT syndrome, or hypertrophic obstructive cardiomyopathy) or family history of sudden death or ventricular arrhythmias, including idiopathic ventricular fibrillation. Exception: atrioventricular block grade 1 will be allowed
- Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of drugs or which may jeopardize the participant in case of participation in the study. Examples of such conditions include (but are not limited to): a. History of inflammatory bowel syndrome, gastritis, gastrointestinal or rectal bleeding; b. History of major gastrointestinal tract surgery (ie, gastrectomy, gastroplasty for obesity, bowel resection, etc.); c. History or evidence of pancreatic injury or pancreatitis; d. History or presence of impaired renal function as indicated by abnormal renal function (estimated glomerular filtration rate [eGFR] <60 mL/min/1.73m2) or abnormal urinary constituents (eg, albuminuria).
- Abnormal vital signs after at least 5 minutes resting in the supine position: a. Systolic blood pressure ≤90 or ≥140 mmHg; b. Diastolic blood pressure ≤40 or ≥90 mmHg; c. Heart rate ≤40 or ≥100 beats per minute; d. Body temperature ≤35.5°C or ≥37.5°C.
- Abnormal standard 12-lead ECG after at least 5 minutes resting in the supine position: a. PR interval <120 ms with evidence of pre-excitation syndrome (e.g, delta wave) or >220 ms b. QRS >120 ms c. QTcF <350 ms or ≥450 ms if male or <360 ms or ≥460 ms if female
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 The Netherlands | Not Recruiting | 06 May 2023 | — |
| Netherlands | — | — | 12 |
Sites & Investigators
Research sites
Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
PRAX-628 | Test | CAPSULE | ORAL | 45 | 1 | PRD9990074 |
PRAX-628 | Test | CAPSULE | ORAL | 45 | 1 | PRD9990076 |
PRAX-628 | Test | CAPSULE | ORAL | 45 | 1 | PRD9990075 |
Placebo for PRAX-628 | Placebo | N/A | — | — | — | N/A |