Inclusion criteria:
1. Male or female between 18 and 75 years of age, inclusive, at the time of
consent.
2. Have a primary diagnosis of IH according to the ICSD-3-TR criteria.
NOTE: If documentation of diagnosis of IH is unavailable or the
Investigator deems it necessary to confirm diagnosis, diagnostic testing
may be conducted during the Screening Period to confirm the diagnosis of
IH according to ICSD-3-TR criteria. If the Investigator suspects a subject
with a previous clinical diagnosis of narcolepsy has IH, a screening
polysomnogram (PSG) and multiple sleep latency test (MSLT) may be
performed to confirm the diagnosis of IH.
3. At the Screening and Baseline visits, subjects who are not already taking
oxybate therapy must have Epworth Sleepiness Scale (ESS) scores >11.
NOTE: Any subject who will wash out of medications during the
Screening Period that could impact ESS score will only have to meet the
ESS score >11 requirement at Baseline visit, after they have washed out of
their medication.
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4. If currently treated with oxybate, must have documented clinical
improvement of excessive daytime sleepiness (EDS) after the initiation of
treatment per Investigator’s clinical judgement.
5. Average nightly total sleep time (TST) of >7 hours, per subject history and
confirmed by Screening Period sleep diary.
6. If currently treated with stimulants and/or alerting agents (see
APPENDIX 4), or nicotine replacement therapy, must have been using the
same dose and regimen for at least 2 months prior to Screening and must
agree to maintain the same dose and regimen leading up to and throughout
the Double-blind Randomized Withdrawal Period.
NOTE: WAKIX (pitolisant) may not be used during this study.
7. Females must be either:
a) postmenopausal defined as no menses for > 12 months without an
alternative cause or surgically sterile, or
b) a female of childbearing potential who has used a highly effective
contraceptive measure (see APPENDIX 3) for at least 2 months prior
to the first dose of study drug and consents to use a highly effective
contraceptive measure from the first dose of study drug, through 30
days after the last dose of study drug.
Male subjects who have not had a vasectomy and who are sexually active
with a female partner of childbearing potential must consent to using
condoms with their partner from Day 1 through 30 days after the last dose
of study drug.
8. Willing and able to provide written informed consent and comply with the
study schedule and other requirements.
 

 

Exclusion Criteria:
1. Pregnant, nursing, or lactating female.
NOTE: Females of childbearing potential will be tested for pregnancy at
Screening and throughout the study. A positive test will exclude
participation at Screening and result in study withdrawal at later visits.
2. Hypersomnia due to another medical, behavioral, sleep, or psychiatric
disorder or condition (e.g., narcolepsy, daytime hypoxemia, multiple
sclerosis, Parkinson’s disease, stroke).
3. Usual bedtime after 1 AM (0100 hours).
4. Untreated or incompletely treated sleep apnea in patients with an apnea-
hypopnea index (AHI) ≥ 15 by American Academy of Sleep Medicine
(AASM) 1A criteria. Adequate treatment is defined as follows:
a) Weight loss with subsequent evidence of AHI b) Neurostimulator treatment with evidence of AHI confirmation of regular use; or
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c) Oral appliance treatment with evidence of AHI confirmation of regular use; or
d) Positive airway pressure treatment with objective confirmation of use
for ≥ 4 hours per night on ≥ 70% of nights in the month leading up to
Screening; or
e) Surgical intervention with subsequent evidence of AHI 5. Clinically significant parasomnias (e.g., sleep-walking, rapid eye
movement [REMS] sleep behavior disorder, etc.) as determined by the
Investigator.
6. Oxygen (O2) saturation pulse oximetry on room air while fully awake; known obesity
hypoventilation syndrome or other known or suspected respiratory
difficulty or condition that may compromise a subject’s breathing or
ability to maintain adequate O2 saturation.
7. History or presence of any of the following clinical conditions:
a) Seizures, excluding childhood benign febrile seizures;
b) Head trauma associated with loss of consciousness in the past 5 years;
c) Head trauma that occurred more than 5 years ago but with ongoing
sequelae;
d) Succinic semialdehyde dehydrogenase deficiency;
e) Uncontrolled hypothyroidism.
8. History or presence of any of the following mental health disorders
according to DSM-5 criteria:
a) Bipolar and related disorders;
b) Schizophrenia, schizophrenia spectrum disorders, or other psychotic
disorders;
c) Current or past (within 1 year) major depressive episode;
NOTE: Subjects with depression that is well controlled with non-
sedating antidepressants or other therapy in the judgement of the
Investigator are allowed. Treatment must be stable for at least 6
months prior to Screening, and remain stable for the duration of the
study.
d) At risk for suicide as indicated by active suicidal ideation (confirmed
by positive response to item No. 4 or No. 5 on the Columbia Suicide
Severity Rating Scale (C-SSRS), or any history of suicide attempt.
9. Evidence of significant hepatic impairment during Screening including any
of the following:
a) Known acute hepatitis, including acute viral hepatitis;
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b) Aspartate aminotransferase (AST) or alanine aminotransferase (ALT)
level > 5 times the upper limit of normal (ULN);
c) Total bilirubin > 3 times the ULN (unless known Gilbert’s disease);
d) History of cirrhosis of the liver;
e) Manifestation of end-stage liver disease, such as ascites, esophageal
varices or hepatic encephalopathy;
f) Thrombocytopenia (10. Clinically significant laboratory test results or electrocardiogram (ECG)
abnormalities, or any acutely unstable clinical or mental health condition
that could place the subject at undue risk during study participation,
significantly alter study outcomes, or affect subject compliance with study
requirements for dosing and evaluation.
11. Treatment or planned treatment with any central nervous system (CNS)
sedating agents. See APPENDIX 4 for a representative list of excluded
medications and Section 8.19 for medication washout guidelines.
12. Current or past substance use disorder (including alcohol) according to
DSM-5 criteria or the subject is unwilling to refrain from consuming
alcohol, cannabinoids or prohibited medications during the study.
13. A positive breath alcohol test or urine drug screen, except for a prescribed
medication allowed by the study protocol (e.g., amphetamines) at a stable
dose. NOTE: Cannabinoids are not allowed during the study regardless of
prescription status.
14. Caffeine use > 600 mg/day within 1 week prior to Baseline, or anticipated
use > 600 mg/day during the Open-label Dose Titration, Stable Dose and
Double-blind Randomized Withdrawal Periods.
15. Occupation requiring nighttime shift work or variable shift work with early
work start times or other occupations that could place the subject at undue
risk.
16. Participation in another study of an investigational medicinal product
within 30 days prior to the Baseline, or within 5 half-lives of the last
investigational product received, whichever is greater.
17. Prior treatment with either FT218 or commercially available LUMRYZ.