Study to investigate the safety of ENX-101 and how well it works in healthy volunteers.

Phase 1

Completed

• Conditions: Epilepsy, spasticity and anxiety disorders; Not Applicable

• Registration Number: ISRCTN18262237
• Lead Sponsor: Engrail Therapeutics, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Completion: 2022-09-05
• Study Start: 2023-07-19
• Last Update Posted: 2 August 2023

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 53

Inclusion Criteria

1. Healthy male and female volunteers aged 18 to 55 years, inclusive, at Screening
2. Capable of giving written informed consent
3. Willing to give written consent to have data entered into Verified Clinical Trials
4. Female subjects
4.1. 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 level >40 IU/mL; in the event a subject's menopausal status has been clearly established and yet serum follicle-stimulating hormone 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), and with a negative pregnancy test at Screening and Day –2; OR
4.2. Of childbearing potential and willing to use two effective methods of contraception (i.e., established method of contraception + condom) or remain abstinent (where abstaining from sexual intercourse is in line with the preferred and usual lifestyle of the subject) from Day –2 through 3 months after the last dose of study drug, and with a negative pregnancy test at Screening and Day –2
5. Male subjects who, if fertile (defined as post-pubertal and not permanently sterile by orchidectomy or vasectomy) must be willing to use a condom or remain abstinent (where abstaining from sexual intercourse is in line with the preferred and usual lifestyle of the subject) from Day –2 through 3 months after the last dose of study drug
6. Body mass index of 18 to 35 kg/m2 at Screening
7. Willing and able to comply with all study requirements including the following:
7.1. Reside in the inpatient unit from Day –2 until discharge on Day 13
7.2. Refrain from strenuous exercise from Day –4 until Day 13
7.3. Abstain from grapefruit-, alcohol-, caffeine-, or xanthine-containing products from Day –4 through Day 13

Part 2 Subjects Only:
8. Subjects must have sleep pattern of going to bed between 10:00 pm and 12:00 am over the 4 weeks prior to Screening through to Day -29. Subjects must have been sleeping at least 6 to 8 hours per night over the 4 weeks prior to Screening through to Day -2

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 significant ophthalmologic or neurologic condition that would adversely affect the eye movement assessments.
4. 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.
5. Any of the following cardiovascular conditions at Screening or Day –1:
5.1. History or evidence of any of the following:
5.1.1. Myocardial infarction
5.1.2. Cardiac valvulopathy
5.1.3. Cardiac surgery revascularization (coronary artery bypass grafting or percutaneous transluminal coronary angioplasty)
5.1.4. Unstable angina
5.1.5. Cerebrovascular accident or stroke or transient ischemic attack
5.1.6. Pacemaker
5.1.7. Atrial fibrillation, flutter, or nonsustained or sustained ventricular tachycardia
5.1.8. Pulmonary arterial hypertension
5.1.9. Sick sinus syndrome, second- or third-degree atrioventricular block
5.1.10. Uncontrolled hypertension
5.1.11. Congestive heart failure
5.1.12. Family history of sudden death or personal history of long QT syndrome
5.1.13. Hypokalemia
5.1.14. Unexplained syncope or syncope within the last 3?years regardless of etiology
5.2. Electrographically and clinically significant abnormalities, as judged by the Investigator, that might interfere with ECG (electrocardiogram) analysis, including evidence of a previous myocardial infarction, significant left ventricular hypertrophy, flat T waves (particularly in the inferior leads), or more than minor nonspecific STT–wave changes.
5.2.1. Rhythm other than sinus rhythm
5.2.2. Mean HR <50 beats per minute (bpm) or >100 bpm
5.2.3. Mean systolic blood pressure >140 mmHg; mean diastolic blood pressure >90 mmHg
5.2.4. QTc interval using Fridericia’s formula (QTcF) >450 msec in males or >470 msec in females
5.2.5. QRS interval =120 msec
5.2.6. PR interval >200 msec
6. Reports having experienced suicidal ideation (Type 4 or 5 on the C-SSRS (Colombia-Suicide Severity Rating Scale)) within 30 days prior to Screening, any suicidal behavior within 2 years prior to Screening (any Yes” answers on the Suicidal Behavior section of C-SSRS) and/or the Investigator assesses the subject to be a safety risk to him/herself or others.
7. Diagnosis of any sleep disorder in the last 6 months or as judged significant by the Investigator or daytime symptoms attributable to unsatisfactory sleep or shift

Study & Design

• Study Type: Interventional
• Study Design: Not specified