| Eligibility |
Inclusion Criteria:
1. Age 18- 65 years at time of informed consent
2. The subject or designee is willing and able to keep an accurate study diary, the
subject is able to adhere to the protocol, the subject or the subject's legal
representative is able read, understand, and sign informed consent, as applicable.
3. Diagnosed with focal epilepsy according to ILAE (2017) criteria. Diagnosis to include
clinical history and an EEG consistent with focal epilepsy. A normal interictal EEG is
allowed when the clinical history is consistent with focal epilepsy.
4. Subject has no seizures that are not focal by the ILAE 2017 criteria
5. Subject must have 8 countable, observable focal seizures during the 8-week baseline
period prior to randomization, including at least 3 in each 4-week period with no
21-day seizure-free period. These seizures must be observable (focal aware with motor
component, focal impaired awareness, focal to bilateral tonic-clonic) and as such may
not include focal aware seizures without a detectable motor component, aphasia, or
other observable symptom.
6. Must have had a brain MRI or contrast-enhanced head CT scan with an available report
(images need not be available) that has been performed within the past 10 years and
that is negative for confounding conditions such as tumor, infection, demyelinating
disease, or other progressive neurological disease. Remote stroke that may represent
the etiology for epilepsy is allowed. If no such CT or MRI report is available, a
potential subject will be asked to undergo a head CT scan with intravenous contrast to
meet eligibility criteria prior to study enrollment.
7. Seizures uncontrolled after an adequate trial of at least 1 ASM within the last 2
years.
8. Currently receiving treatment with 1-3 ASMs with doses stable for at least 4 weeks
prior to screening. These medications must stay stable during the 8-week baseline
period and during the 16-week treatment period. In the case that the plasma level of a
concomitant ASM changes, the subject and their physician may then modify the dose to
maintain the plasma level that was present prior to beginning the study drug. and must
document the change in the EDC system.
9. If participant has a vagal nerve stimulator (VNS), responsive neurostimulator (RNS) or
deep brain stimulator (DBS), it must have been implanted and activated >1 year prior
to screening, and stimulation parameters that have been stable for >3 months, and
battery life of unit anticipated to extend for duration of trial.
10. Females of childbearing potential who are not sexually inactive (abstinent) for 30
days prior to the first dose, throughout the study, and then for 30 days following the
last dose, must agree to use of one of the following acceptable birth control methods
from 30 days prior to the first dose through 30 days after the last dose of study
drug:
i. Combined estrogen and progestogen containing hormonal contraception associated with
inhibition of ovulation (oral, intravaginal, transdermal) together with a condom or
other barrier method ii. Progestogen-only hormonal contraception associated with
inhibition of ovulation (oral, injectable, implantable) together with a condom or
other barrier method iii. Intrauterine device (IUD) together with a condom or other
barrier method iv. Intrauterine hormone releasing system (IUS) together with a condom
or other barrier method v. Bilateral tubal occlusion, hysterectomy, bilateral
oophorectomy vi. Vasectomized partner (vasectomy >6 months ago)
For this study, pre-menopausal is defined as not meeting the clinical criteria for post
menopausal, that is, no menstrual period for at least one year, in the absence of other
identifiable cause(s) of not having a period, together with the absence of typical symptoms
of menopause, such as hot flashes and mood instability. True abstinence is allowable when
in line with the preferred and usual lifestyle of the subject. Periodic abstinence (such as
calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not
acceptable methods of contraception.
Exclusion Criteria:
1. Pregnant or lactating
2. History of hypersensitivity to ivermectin or to any of the excipients in the EQU-001
gelcap
3. History of status epilepticus in the past 1 year from screening
4. History of pseudo- or nonepileptic seizures, or other nonepileptic events that could
be confused with epileptic seizures, within the past 5 years
5. History of traumatic brain injury within 30 days prior to screening
6. Resective epilepsy surgery within 1 year; epilepsy-related radiosurgery within 2 years
or Ventriculoperitoneal shunt placement within 1 year
7. Presence of progressive neurological disorder or other progressive disorder or
unstable medical condition(s) that may confound study results. History of long QT
syndrome, family history of sudden death of unknown cause.
8. Psychiatric disorder where changes in pharmacotherapy are needed or anticipated during
the study or which would interfere with the subject's ability to participate in the
trial
9. Active suicidal plan/intent in the past 6 months, a history of suicide attempt in the
last 2 years, or more than 1 lifetime suicide attempt as evidenced by a positive
response to C-SSRS questions 4 or 5
10. History of substance use disorder, including alcohol, within the past 2 years
11. Currently in another investigational drug study
12. Currently on felbamate for less than one year before visit 1 (aplastic anemia and
hepatic failure usually occur within 6 months to one year). If on felbamate,
documentation of stable hemogram and liver enzyme tests must be present.
13. Currently on vigabatrin for less than 2 years before visit 1, as most visual field
changes occur between 6 months and 2 years Subjects on vigabatrin should have
available, appropriate documentation of visual fields.
14. Currently taking retigabine/ezogabine
15. History of intermittent use of rescue benzodiazepines (i.e., 1 to 2 doses over a
24-hour period is considered a 1-time rescue) more than once in the 4 weeks prior to
the baseline visit or more than once per 4 weeks during the 8-week baseline period If
a subject is taking benzodiazepines for an indication other than epilepsy (e.g.,
anxiety, sleep), the dose should to be stable for at least 4 weeks prior to screening
and remain stable throughout screening and double blind periods of the study.
16. Currently taking ivermectin, or has taken it within the last 4 weeks prior to visit 1
17a. Use of the following medications within 4 weeks of the baseline visit and throughout
the study that may interfere with study drug metabolism (please note ASMs with CYP3A4
metabolism are not excluded from this study, as drug levels and safety are monitored
throughout the study):
i. CYP3A4 inducers: rifampin, lumacaftor, mitotane, enzalutamide, apalutamide, St. John's
wort, glucocorticoids
ii. Medications with PGP interactions: amiodarone, apalutamide, verapamil, lorlatinib,
rifampin, St. John's wort
17b. Use of the following medications/foods is not strictly prohibited but is discouraged.
Please make every attempt to refrain and to record each incidence of use of any of these
(along with all medications and supplements):
i. CYP3A4 inhibitors, including, but not limited to clarithromycin, ceritinib, idelalisib,
lonafarnib, tucatinib, erythromycin, telithromycin, diltiazem, dronedarone, posaconazole,
voriconazole, nefazodone, itraconazole, ketoconazole, anti-retroviral drugs (atazanavir,
darunavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, tipranavir), grapefruit
and grapefruit juice, pomegranate fruit and pomegranate juice
ii. Additional medications that may interact with CYP3A4, PGP, or Vitamin K: fluconazole,
isavuconazole, cyclosporine, dronedarone, imatinib, warfarin, acenocoumarol
18. Has any of the following laboratory or exam abnormalities: i. Positive urine drug
screen (methamphetamines, amphetamines, cocaine, PCP, opioids, barbiturates) at screening
without a therapy related explanation ii. Positive hCG (female participants) (at screening
or visit 2/enrollment) iii. QTcF > 450 msec at visit 2/enrollment
19. Subject is not approved for study inclusion by the Epilepsy Consortium based on the
diagnostic review form
20. Any condition that, in the opinion of the investigator, may impact a subject's safety
or ability to follow study procedures
21. History of 14 or more consecutive days in Angola, Equatorial Guinea, Gabon, Cameroon,
the Central African Republic, the Republic of Congo, the DR of Congo, Nigeria, Chad, and/or
South Sudan within the past 17 years and did not take diethylcarbamazine prophylaxis or has
not been evaluated for/found to be negative for or treated for loa loa and subsequently
evaluated as resolved since the most recent stay of at least 14 days.
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