Epilepsy, anxiety, spasticity or other CNS disorders Nervous System Diseases
Conditions
Interventions
This is a randomised, double-blind, placebo-controlled, SAD study in healthy volunteers. Each subject will be screened up to 28 days prior to Day 1. Eligible subjects will be admitted to the Clinical
Sponsors
Engrail Therapeutics, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Participants who are able to provide informed consent indicating they understand the purpose of, and procedures required, for the study and are willing to participate. 2. Healthy males/females aged 18 to 55 years at Screening. 3. Female subjects: a. Of non-childbearing potential, defined as either permanently sterilized (at least 4 months after surgical sterilization including bilateral salpingectomy, tubal ligation, or oophorectomy with or without hysterectomy) or post-menopausal (defined as amenorrhea for 12 consecutive months and documented plasma follicle-stimulating hormone [FSH] level >40 IU/mL; in the event a subject's menopausal status has been clearly established and yet serum FSH levels are not consistent with a post-menopausal status, determination of the subject’s eligibility to be included in the study will be at the Investigator’s discretion following consultation with the Sponsor); OR b. Of childbearing potential willing to use both a highly effective method of contraception and a condom with any partner or remain abstinent if abstaining from sexual intercourse is in line with the preferred and usual lifestyle of the participant, from the Day –1 until 3 months after Day 1; AND c. Of childbearing potential or non-childbearing potential with a negative pregnancy test at Screening and Day –1. 4. Male subjects who, if fertile (defined as post-pubertal and not permanently sterile by orchidectomy or vasectomy), are willing to use both a highly effective method of contraception and a condom with any partner of childbearing potential or remain abstinent if abstaining from sexual intercourse is in line with the preferred and usual lifestyle of the subject, from Day –1 until 3 months after Day 1. 5. Body mass index of 18 to 35 kg/m². 6. Willing and able to comply with all study-related restrictions.
Exclusion criteria
Exclusion criteria: 1. Clinically significant abnormality within 2 years of Screening that in the Investigator’s opinion may place the subject at risk or interfere with study outcome variables; this includes, but is not limited to, history of or current cardiac, renal, neurologic, gastrointestinal, pulmonary, endocrinologic, hematologic, or immunologic disease or history of malignancy. 2. History of convulsions (other than benign febrile convulsions of childhood) including epilepsy, or personal history of significant cerebral trauma or CNS infections (e.g.,meningitis). 3. History or evidence of any medical condition potentially altering the absorption, metabolism, or elimination of drugs; this includes a surgical history of the gastrointestinal tract affecting gastric motility or altering the gastrointestinal tract. 4. Any of the following cardiovascular conditions at Screening or Day –1: a. History or evidence of any of the following: i. Myocardial infarction ii. Cardiac valvulopathy iii. Cardiac surgery revascularization (coronary artery bypass grafting or percutaneous transluminal coronary angioplasty) iv. Unstable angina v. Cerebrovascular accident or stroke or transient ischemic attack vi. Pacemaker vii. Atrial fibrillation, flutter, or non-sustained or sustained ventricular tachycardia viii. Pulmonary arterial hypertension ix. Sick sinus syndrome, second- or third-degree atrioventricular block x. Uncontrolled hypertension xi. Congestive heart failure xii. Family history of sudden death or personal history of long QT syndrome xiii. Hypokalemia xiv. Unexplained syncope or syncope within the last 3 years regardless of etiology b. Electrographically and clinically significant abnormalities, as judged by the Investigator, that might interfere with ECG analysis at Screening and on Day –1, including evidence of a previous myocardial infarction, significant left ventricular hypertrophy, flat T-waves (particularly in the inferior leads), or more than minor non-specific ST-T wave changes. c. Rhythm other than sinus rhythm d. Heart rate 100 bpm e. Systolic blood pressure >140 mm Hg; mean diastolic blood pressure >90 mm Hg f. QT interval corrected using Fridericia’s formula (QTcF) >450 msec in males or >470 msec in females g. QRS interval =120 msec h. PR interval >220 msec 5. Self-reported or documented medical history of having experienced suicidal ideation within 30 days prior to Screening, any suicidal behaviour within 2 years prior to Screening, and/or the Investigator assesses the subject to be a safety risk to him/herself or others. 6. Diagnosis of any sleep disorder in the last 6 months or current complaints of sleep disturbance or daytime symptoms attributable to unsatisfactory sleep or shift worker whose routine work hours overlap with the typical sleep period. 7. History or evidence of moderate or severe substance use disorder as defined by the Diagnostic and Statistical Manual of Mental Disorders (5th Edition) or intake of more than14 units of alcohol weekly. 8. Is a smoker or has used nicotine or nicotine-containing products within 90 days of Screening and/or will not agree to abstain from nicotine use during the study from Screening through to the end of study visit; this includes cigarettes, e-cigarettes, and nicotine replacement or nicotine-containing products. 9. Has a positive qualitative drug or alcohol test at Screening or Day -1. 10. Has ingested any concomitant medication (excluding hormonal birth contr
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1.Adverse Events (AEs) including serious AEs (SAEs) and treatment emergent AEs (TEAEs) will be recorded from the point of informed consent up to final post-study follow up visit. 2.A full Physical examination (including weight measurement) at screening, Day -1 and end of study. A Symptom-directed physical examination will be performed on Day 1 and last day of treatment period (Day 4, Day 5 or Day 6). 3. Laboratory safety (biochemistry, haematology, coagulation and urinalysis) at screening, Day -1, last day of treatment period (Day 4, 5 or 6) & End of Study. 4.Vital signs (systolic/diastolic blood pressure, pulse, oral body temperature and respiratory rate) at screening, Day -1, Day 1 (pre-dose and 0.5, 1, 2, 4, 6, 8 and 12 hr post dose), Day 2 (24 hr & 36 hr post-dose), Day 3 (48 hr post-dose), Day 4 (72 hr post-dose), Day 5 (96 hr post-dose), Day 6 (120 hr post-dose) and End-of Study Visit. 5.12-lead ECG (heart rate, PR interval, QRS width, QT interval and QTcF interval) at screening, Day -1, Day 1 (pre-dose and 0.5, 1, 2, 4, 6, 8 and 12 hr post dose), Day 2 (24 hr & 36 hr post-dose), Day 3 (48 hr post-dose), Day 4 (72 hr post-dose), Day 5 (96 hr post-dose), Day 6 (120 hr post-dose) and End-of Study Visit. | — |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetic/pharmacodynamic parameters derived from analysis of plasma for concentrations of ENX-102. PK Endpoints are defined as follows: - Cmax - maximum observed concentration. - Tmax – Time taken to reach Cmax - AUC0-24 - area under the concentration-time curve from 0 to 24 hours. - AUC 0-t - the area under the concentration-time curve from dosing (time 0) to time t. - AUC0-Inf - Area under the plasma concentration time curve extrapolated to infinity. - t½ - half-life. Plasma samples for PK evaluation of ENX-102 will be taken at the following time points: Day 1: prior to dose, 15 mins, 30 mins, 45 mins, 1 hr, 1 hr 30 mins, 2 hr, 4 hr, 6 hr, 8 hr & 12 hr following dose Day 2: 24 hr & 36 hr post-dose Day 3: 48 hr post-dose Day 4: 72 hr post-dose Day 5: 96 hr post-dose Day 6: 120 hr post-dose End of Study | — |
Countries
United Kingdom, Wales
Contacts
Public ContactEve Taylor
Outcome results
None listed