| Eligibility |
Inclusion Criteria:
Potential subjects meeting all of the following criteria may be included in the study:
1. Subjects have a clinical diagnosis of epilepsy (GTC seizures or focal seizures with
impaired awareness) and were scheduled for admission to an Epilepsy Monitoring Unit
(EMU), General Clinical Research Center (GCRC), or similar facility for evaluation.
2. Male and female subjects between 2 and 16 years of age, inclusive.
3. Subjects had a body weight of at least 6 kg and less than or equal to 111 kg.
4. Subjects had an average frequency of at least 1 clinically apparent seizure every 3
days or =10 clinically apparent seizures per month, with alteration of consciousness
as documented by reliable subject report, personal seizure diary records, and/or by
seizure diaries dispensed at screening and verified prior to study entry.
5. Female subjects of childbearing potential (i.e., were having periods, were not
surgically sterile) must have had a negative serum pregnancy test (using Beta-hCG) at
Screening and a negative urine pregnancy test on Study Day I prior to drug dosing.
Female subjects of childbearing potential must have agreed to abstinence, have had a
partner who was sterile, or have been practicing double barrier contraception or have
been using an FDA-approved contraceptive (e.g., licensed hormonal or barrier methods)
for greater than 2 months prior to screening visit, and must have committed to an
acceptable form of birth control for the duration of the study and for 30 days after
participation in the study.
6. Male subjects with a female sexual partner of childbearing potential must have agreed
to abstinence or to practice adequate birth control during the study, including at
least 1 barrier method such a condom, diaphragm, or spermicide for more than 2 months
prior to the screening visit, and must have committed to an acceptable form of birth
control for the duration of the study and for 30 days after participation in the
study. Also, male subjects must have agreed not to donate sperm during the study and
for 90 days after the follow-up visit.
7. Subjects were currently receiving at least one antiepileptic medication.
8. Subject's parent or legally authorized representative must have been willing and able
to complete informed consent and HIPAA authorization. Subjects must have been willing
to give assent as required by the Institutional Review Board (IRB).
9. Subject must have agreed to be available or subject's parent(s) or legally authorized
representative(s) must have agreed to have the subject be available for both Treatment
Periods and the Follow-up Visit, and must have been willing to comply with all
required study procedures and adhere to all protocol requirements.
10. Subject or subject's parent(s) or legally authorized representative(s) must have been
able to comprehend and be informed of the nature of the study, as assessed by the
Investigator.
Exclusion Criteria:
Potential subjects meeting any of the following criteria were excluded from participating
in the study:
1. Subjects with a progressive neurological disorder such as a brain tumor, demyelinating
disease, or degenerative central nervous system (CNS) disease that was likely to
progress in the 12 months after screening.
2. Subjects with respiratory failure (or is at risk for respiratory failure) or other
severe cardiorespiratory disease with New York Heart Association Class Ill or IV
functional status, or who required supplemental oxygen.
3. Female subjects who were lactating, had a positive serum pregnancy test (ß-hCG) at
screening, or had a positive urine pregnancy test at Check-in for treatment periods.
4. Subjects with psychiatric disease that in the Investigator's judgment would prevent
the subject's successful completion of the study.
5. Subjects with recent history of suicide attempt (defined as an active, interrupted, or
aborted attempt within the previous 5 years) or reported suicidal ideation in the
previous 6 months as indicated by a positive response ("Yes") to either Question 4 or
Question 5 of the Columbia-Suicide Severity Rating Scale performed at the screening
visit.
6. Subjects with known history or presence of any clinically significant hepatic (e.g.,
hepatic impairment), renal/genitourinary (renal impairment, kidney stones),
psychiatric, dermatological, or hematological disease or condition, unless determined
as not clinically significant by the Investigator or designee and confirmed by Sponsor
via written communication prior to subject enrollment. Abnormal laboratory results
considered clinically significant by the Investigator or designee were to be evaluated
by the Investigator in consultation with the Medical Monitor.
7. Subjects with any clinically significant illness other than epilepsy within 30 days
prior to study drug administration, as determined by the Investigator.
8. Subjects with any significant physical or organ abnormality or other condition that
would interfere with study participation or constitute a safety risk in the judgment
of the Investigator.
9. Subjects with any significant lesion of the oral cavity or having oral prophylactic or
dental procedures within 30 days prior to study drug administration.
10. Subjects with a QT interval corrected by Fridericia's formula (QTcF) >450 ms for males
or QTcF >470 ms for females on screening ECG unless determined as not clinically
significant by the Investigator.
11. Subjects with a positive test result for any of the following drugs of abuse:
amphetamines, cocaine, opiates, phencyclidine, or a positive breath alcohol test.
Subjects who tested positive for tetrahydrocannabinol (THC) at screening were excluded
unless the Investigator was able to affirm in writing that the use of a medical
marijuana product was part of the subject's treatment plan as recommended by a
physician for treatment of a medical condition. In such case, the subject was to be
allowed to continue with screening, and the medical marijuana product was to be
recorded as a concomitant medication.
12. Subjects with a known history or presence of any of the following:
1. Substance abuse or dependence (including alcohol) within 1 year prior to first
study drug administration
2. Hypersensitivity or idiosyncratic reaction to diazepam, its excipients, sodium
phosphates, and/or related substances, e.g., benzodiazepines
3. Glaucoma (open or acute narrow angle)
4. Severe allergic reactions (e.g., anaphylactic reactions, angioedema) to
investigational product and excipients
13. Subjects who had participated in another clinical trial or who had received an
investigational drug within 30 days prior to study drug administration or 5 half-lives
of the investigational drug-whichever was the longer period.
14. Subjects with presence of mouth jewelry, dentures, oral implants, braces, or piercings
in the mouth or tongue that, in the opinion of the Investigator, would have been
likely to interfere with successful completion of the dosing procedure.
15. Subjects with a blood or plasma donation within 30 days prior to screening.
16. Subjects not willing or unable to tolerate blood draws.
17. Consumption of alcohol within 48 hours before dosing; or food or beverages containing
grapefruit, star fruit, Seville oranges, and/or pomelo, or their derived products
(e.g., fruit juice) within 10 days prior to study drug administration.
18. Use of any enzyme-modifying drugs, including strong inhibitors of cytochrome (CYP) 450
enzymes (e.g., cimetidine, fluoxetine, quinidine, erythromycin, ciprofloxacin,
fluconazole, ketoconazole, diltiazem, or HIV antivirals) and strong inducers of CYP
enzymes (e.g., glucocorticoids, St. John's Wort, or rifampicin), in the previous 30
days prior to study drug administration. (Barbiturates, carbamazepine, phenytoin, and
other enzyme-modifying antiepileptic drugs (AEDs) that were medically needed were
permitted.)
19. Use of any monoamine oxidase (MAO) inhibitors (e.g., phenelzine, tranylcypromine ),
and/or phenothiazines (chlorpromazine) within 30 days prior to first study drug
administration.
20. Employee or immediate relative of an employee of Aquestive Therapeutics, any of its
affiliates or partners, or Syneos Health.
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