A Multiple Ascending Dose Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ENX-101 at Plasma Steady State in Healthy Volunteers
- Conditions
- and anxiety disordersEpilepsyspasticity10029305
- Registration Number
- NL-OMON51175
- Lead Sponsor
- Engrail Therapeutics, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 53
Subjects must meet all the following criteria to be eligible for the study:
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
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 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
b. Of childbearing potential and willing to use 2 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:
a. Reside in the inpatient unit from Day *2 until discharge on Day 13
b. Refrain from strenuous exercise from Day *4 until Day 13
c. 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 -2
9. Subjects must have been sleeping at least 6 to 8 hours per night over the 4
weeks prior to Screening through to Day -2
Subjects meeting any of the following exclusion criteria will not be enrolled
in the study:
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
central nervous system 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 *2:
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, 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. Mean HR <50 beats per minute (bpm) or >100 bpm
e. Mean systolic blood pressure >140 mm Hg; mean diastolic blood pressure >90
mm Hg
f. QTc interval using Fridericia*s formula (QTcF) >450 msec in males or >470
msec in females
g. QRS interval *120 msec
h. PR interval >200 msec
6. Reports having experienced suicidal ideation (Type 4 or 5 on the C-SSRS)
within 30 days prior to Screening, any suicidal behavior within 2 years prior
to Screening (any *Yes* answers on 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 (including narcolepsy, central sleep apnea,
sleep related hypoventilation, circadian rhythm sleep-wake disorders,
substance/medication induced sleep disorder or parasomnias - NREM sleep arousal
disorders, nightmare disorder, REM sleep behavior disorder for Part 2) in the
last 6 months or current complaints of sleep disturbance or daytime symptoms
attributable to unsatisfactory sleep or shift worker whose routine
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The safety and tolerability of ENX-101 will be assessed by the following:<br /><br>- AEs<br /><br>- Vital signs (2-positional blood pressure and HR, respiratory rate, and<br /><br>tympanic body temperature)<br /><br>- 12-lead ECG<br /><br>- 24-hour continuous 12-lead ECG Holter monitoring (Part 1 only)<br /><br>- Clinical laboratory tests (hematology, serum chemistry, urinalysis)<br /><br>- Physical examination<br /><br>- Pregnancy test (where applicable)<br /><br>- C-SSRS<br /><br>- MOAA/S<br /><br>- LSEQ (Part 2 only)<br /><br>- CSD-Core (Part 2 only)</p><br>
- Secondary Outcome Measures
Name Time Method