Focal epilepsy
Conditions
Interventions
Part A (Single Ascending Dose) active PRAX-628 or placebo:
A1:5 mg, oral, fasted
A2:Up to 15 mg, oral, fasted
A3:Up to 45 mg, oral, fasted
A4:Up to 130 mg, oral, fasted
A5 and beyond: Maximum of 3-fo
Sponsors
Praxis Precision Medicines
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: 1. Willing and able to provide informed consent indicating that they understand the purpose of the clinical trial and the procedures that are required for the clinical trial, and that they are willing to comply with scheduled visits, and all studyrelated procedures. 2. Male or female between the ages of 18 and 55 years, inclusive. 3. Body mass index (BMI) of 18.0 to 32.0 kg/m2, inclusive, and a total body weight of at least 50 kg. 4. Females of childbearing potential are not pregnant or breast-feeding, 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. 5. 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.
Exclusion criteria
Exclusion criteria: 1. 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. 2. 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, or hypertrophic obstructive cardiomyopathy). 3. Has a history of any lifetime suicide attempt or active suicidal ideation as confirmed by C-SSRS Baseline Version (Part B only). 4. 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, 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] =140 mmHg b. Diastolic blood pressure =90 mmHg c. Heart rate =100 bpm d. Body temperature =37.5°C 6. Abnormal standard 12-lead ECG after at least 5 minutes resting in the supine position: a. PR interval 220 ms b. QRS >120 ms c. QTcF =450 ms if male or =470 ms if female 7. Any finding that, in the judgement 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). 8. An elevation of >=1.5× ULN for AST or ALT/ serum glutamic pyruvic transaminase (SGPT) or >=2×ULN for total bilirubin. 9. Positive test for HIV, hepatitis B (HBsAg), or hepatitis C. 10. History of drug or alcohol abuse. 11. Positive drug or alcohol test at Screening or Baseline. (Abnormal test results may be repeated for confirmation). 12. Smoker (use of tobacco or nicotine-containing products in the previous 3 months) or evidence of such use as indicated by cotinine testing at Screening and Baseline. 13. Use of an investigational drug or device within 90 days or 5 half-lives preceding the first dose of study drug, whichever is longer. 14. 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. 15. Inability to abstain from eating or drinking grapefruit or grapefruit-related citrus fruits (eg, Seville oranges, pomelos) from 7 days prior to the
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part A (SAD): • Incidence and severity of adverse events (AEs) • Changes in vital sign measurements • Changes in clinical laboratory results • Changes in electrocardiogram (ECG) parameters Part B (MAD): • Incidence and severity of AEs • Changes in vital sign measurements • Changes in clinical laboratory results • Changes in ECG parameters • Incidence of Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicidal ideation or behavior Part C (Food Effect): • Incidence and severity of AEs • Changes in vital sign measurements • Changes in clinical laboratory results • Changes in ECG parameters | — |
Secondary
| Measure | Time frame |
|---|---|
| Part A: • Plasma concentrations of PRAX-628 • Maximum observed concentration (Cmax) • Time to maximum observed concentration (tmax) • Area under the drug concentration-time curve from time zero to infinity (AUCinf) • Area under the concentration time curve from time zero to the last measurable concentration (AUClast) • Apparent terminal elimination half-life (t*) • Clearance (CL/F) • Volume of distribution (Vd/F) • Dose normalized Cmax • Dose normalized AUCinf Part B (MAD): • Plasma concentrations of PRAX-628 • Cmax • tmax • AUClast • AUCtau • t* • Accumulation ratio based on AUC (Rac(AUC)) • Accumulation ratio based on Cmax (Rac(Cmax)) Part C (Food Effect): • Plasma concentrations of PRAX-628 • Cmax • tmax • AUCinf • AUClast • AUC0-120 • CL/F • Vz/F • t* • %AUCex | — |
Countries
Netherlands
Outcome results
None listed