A Phase 1, Randomized, Double-blind, Placebo-controlled Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Ascending Doses of PRAX-628 in Healthy Participants.
- Conditions
- Focal epilepsy10039911
- Registration Number
- NL-OMON51482
- Lead Sponsor
- Praxis Precision Medicines
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 112
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.
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] <90 mL/min/1.73m2)
or abnormal urinary constituents (eg, albuminuria).
5. 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 bpm
d. Body temperature <=35.5°C or >=37.5°C
6. Abnormal standard 12-lead ECG after at least 5 minutes resting in the supine
position:
a. PR interval <120 with evidence of pre-excitation syndrome (e.g, delta wave)
or >220 ms
b. QRS >120 ms
c. QTcF <320 ms or >=450 ms if male or <320 ms 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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Part A (SAD):<br /><br>• Incidence and severity of adverse events (AEs)<br /><br>• Changes in vital sign measurements<br /><br>• Changes in clinical laboratory results<br /><br>• Changes in electrocardiogram (ECG) parameters<br /><br><br /><br>Part B (MAD):<br /><br>• Incidence and severity of AEs<br /><br>• Changes in vital sign measurements<br /><br>• Changes in clinical laboratory results<br /><br>• Changes in ECG parameters<br /><br>• Incidence of Columbia-Suicide Severity Rating Scale (C-SSRS) measured<br /><br>suicidal ideation or behavior<br /><br><br /><br>Part C (Food Effect):<br /><br>• Incidence and severity of AEs<br /><br>• Changes in vital sign measurements<br /><br>• Changes in clinical laboratory results<br /><br>• Changes in ECG parameters</p><br>
- Secondary Outcome Measures
Name Time Method <p>Part A:<br />• Plasma concentrations of PRAX-628<br />• Maximum observed concentration (Cmax)<br />• Time to maximum observed concentration (tmax)<br />• Area under the drug concentration-time curve from time zero to infinity<br />(AUCinf)<br />• Area under the concentration time curve from time zero to the last measurable<br />concentration (AUClast)<br />• Apparent terminal elimination half-life (t*)<br />• Clearance (CL/F)<br />• Volume of distribution (Vd/F)<br />• Dose normalized Cmax<br />• Dose normalized AUCinf<br /><br />Part B (MAD):<br />• Plasma concentrations of PRAX-628<br />• Cmax<br />• tmax<br />• AUClast<br />• AUCtau<br />• t*<br />• Accumulation ratio based on AUC (Rac(AUC))<br />• Accumulation ratio based on Cmax (Rac(Cmax))<br /><br />Part C (Food Effect):<br />• Plasma concentrations of PRAX-628<br />• Cmax<br />• tmax<br />• AUCinf<br />• AUClast<br />• AUC0-120<br />• CL/F<br />• Vz/F<br />• t*<br />• %AUCex</p>