FT218 for Idiopathic Hypersomnia

Recruiting at 6 trial locations

Overseen By Avadel Medical Information

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Avadel

Must not be taking: CNS sedating agents

Disqualifiers: Pregnancy, Sleep apnea, Seizures, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

150 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a double-blind, placebo-controlled, randomized withdrawal, multicenter study of the efficacy and safety of FT218. FT218 drug product is a once-nightly formulation of sodium oxybate for extended-release oral suspension. The study will enroll subjects who are diagnosed with idiopathic hypersomnia. Subjects will be eligible to enroll regardless of current treatment with oxybate therapy or stimulants/alerting agents at study entry. The estimated total duration of study for each subject is approximately 18 weeks, including the Screening period.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you can continue using stimulants or alerting agents if your dose and regimen have been stable for 2 months before the study and remain stable during the trial.

What data supports the effectiveness of the drug FT218 for idiopathic hypersomnia?

Research shows that a similar drug, lower-sodium oxybate, is effective in treating idiopathic hypersomnia, as well as excessive daytime sleepiness in narcolepsy. This suggests that FT218, which is a form of sodium oxybate, may also be effective for idiopathic hypersomnia. ^{1 2 3 4 5}

Is FT218 safe for humans?

FT218, a form of sodium oxybate, has been studied for safety in both healthy adults and those with idiopathic hypersomnia and narcolepsy. It is generally considered safe, with a lower sodium version being approved by the FDA for its reduced risk of high sodium intake, which is important for people with heart-related conditions. ^{1 2 6 7 8}

How is the drug FT218 different from other treatments for idiopathic hypersomnia?

FT218 is unique because it is a once-nightly formulation of sodium oxybate, unlike current treatments that require taking two doses each night. This makes it more convenient for patients, as they only need to take it once before bed. ^{1 3 5 6 9}

Eligibility Criteria

This trial is for individuals with idiopathic hypersomnia, which causes excessive daytime sleepiness. Participants can join whether or not they're currently using oxybate therapy or stimulants. Key exclusions aren't specified but typically would include those with other health conditions that could interfere with the study.

Inclusion Criteria

Willing and able to provide informed consent and comply with the requirements of the study

I am using or will use effective birth control before, during, and for 30 days after the study.

I have been on the same dose of medication for alertness for 2 months.

Exclusion Criteria

Pregnant, nursing or lactating females

I have excessive sleepiness not caused by another health issue.

I have not had seizures, serious head injuries, specific genetic disorders, uncontrolled thyroid issues, or severe liver problems.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive FT218 or placebo once nightly during the double-blind, randomized withdrawal phase

12 weeks

Randomized Withdrawal

Participants continue with FT218 or switch to placebo to assess withdrawal effects

2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• FT218

Trial Overview The trial is testing FT218, a once-nightly extended-release oral suspension of sodium oxybate, against a placebo to see if it's safe and effective for treating idiopathic hypersomnia. It's designed as a double-blind study where neither participants nor researchers know who gets the real drug versus placebo.

Participant Groups

Group I: FT218 Experimental Treatment 1 Intervention

FT218 at stable dose (selected during earlier titration) administered orally once nightly

Group II: Placebo Placebo Group 1 Intervention

Placebo equivalent administered orally once nightly

FT218 is already approved in United States for the following indications:

Approved in United States as LUMRYZ for:

• Excessive daytime sleepiness (EDS) or cataplexy in adults with narcolepsy
• Idiopathic hypersomnia

Who Is Running the Clinical Trial?

Avadel

Lead Sponsor

Trials

5

Recruited

660+

Findings from Research

Lower-sodium oxybate (LXB) significantly improved symptoms of idiopathic hypersomnia, with mean Epworth Sleepiness Scale scores decreasing from 15.7 to 6.1 and Idiopathic Hypersomnia Severity Scale scores from 31.6 to 15.3 during the treatment period.

The treatment was generally safe, with a decrease in treatment-emergent adverse events (TEAEs) over time; while 22.7% of participants discontinued treatment, the most common side effects like nausea and headache were less frequent as treatment continued.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Lower-Sodium Oxybate in an Open-Label Titration Period of a Phase 3 Clinical Study in Adults with Idiopathic Hypersomnia. Thorpy, MJ., Arnulf, I., Foldvary-Schaefer, N., et al.[2022]

In a 6-month open-label extension study involving 106 participants with idiopathic hypersomnia, low-sodium oxybate significantly improved sleepiness levels, as shown by a decrease in Epworth Sleepiness Scale (ESS) scores from 16.3 at baseline to 5.3 at the end of the study.

The treatment was found to be safe, with a decrease in newly reported adverse events over time, and the majority of participants reported feeling 'very much improved' by the end of the study, indicating sustained efficacy and safety for long-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term efficacy and safety of low-sodium oxybate in an open-label extension period of a placebo-controlled, double-blind, randomized withdrawal study in adults with idiopathic hypersomnia. Morse, AM., Dauvilliers, Y., Arnulf, I., et al.[2023]

Lower-sodium oxybate (LXB) is a new medication approved for treating cataplexy and excessive daytime sleepiness in narcolepsy patients aged 7 and older, containing 92% less sodium than its predecessor, sodium oxybate (SXB), which helps reduce cardiovascular risks associated with high sodium intake.

LXB works on the GABAB receptor in the brain, influencing noradrenergic and dopaminergic neurons, and has been shown to be effective and safe for both adults and children with narcolepsy, with its approval in the U.S. in August 2021 also extending to idiopathic hypersomnia in adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Calcium, Magnesium, Potassium, and Sodium Oxybates Oral Solution: A Lower-Sodium Alternative for Cataplexy or Excessive Daytime Sleepiness Associated with Narcolepsy. Dauvilliers, Y., Bogan, RK., Šonka, K., et al.[2022]

In a 12-month open-label trial involving 118 narcolepsy patients, nightly sodium oxybate (3 to 9 g) significantly reduced the frequency of cataplexy attacks and improved daytime sleepiness, with maximal benefits observed after 8 weeks.

The treatment was well-tolerated, with mostly mild adverse events reported, and no evidence of tolerance developed over the study period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A 12-month, open-label, multicenter extension trial of orally administered sodium oxybate for the treatment of narcolepsy. [2015]

In a multicenter trial involving 228 adults with narcolepsy, sodium oxybate significantly improved excessive daytime sleepiness, as evidenced by over 10 minutes increase in the Maintenance of Wakefulness Test for the 9 g dose after 8 weeks.

Sodium oxybate not only reduced daytime sleepiness but also showed significant improvements in overall disease severity, making it the first drug to effectively address both excessive daytime sleepiness and cataplexy in narcolepsy patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double-blind, placebo-controlled study demonstrates sodium oxybate is effective for the treatment of excessive daytime sleepiness in narcolepsy. [2015]

FT218, a once-nightly formulation of sodium oxybate, demonstrated a similar safety profile and tolerability to the current twice-nightly sodium oxybate formulations, with most adverse events being mild or moderate.

In pharmacokinetic studies, FT218 showed lower peak plasma concentrations (Cmax) and similar overall drug exposure (AUC) compared to twice-nightly sodium oxybate, suggesting it may provide effective treatment for narcolepsy with a more convenient dosing schedule.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of FT218, a Once-Nightly Sodium Oxybate Formulation in Healthy Adults. Seiden, D., Tyler, C., Dubow, J.[2021]

Lower-sodium oxybate (LXB) is FDA-approved for treating cataplexy and excessive daytime sleepiness in narcolepsy patients aged 7 and older, and it contains 92% less sodium than sodium oxybate (SXB), reducing the risk of hypertension and cardiovascular issues.

Clinical studies indicate that LXB is effective in managing symptoms of narcolepsy, and its lower sodium content may provide additional safety benefits for patients with existing cardiovascular conditions, although further long-term studies are necessary to confirm these advantages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Calcium, magnesium, potassium, and sodium oxybates oral solution for cataplexy or excessive daytime sleepiness associated with narcolepsy. Abad, VC.[2023]

In a study of 48 patients with obstructive sleep apnea syndrome (OSAS), sodium oxybate (SXB) significantly reduced the apnea-hypopnea index (AHI) and obstructive apnea index compared to placebo, indicating its potential efficacy in managing sleep apnea symptoms.

SXB treatment also increased the duration of slow wave sleep without causing respiratory depression, as there were no significant changes in oxygen saturation or central apneic events, suggesting it may be a safe option for OSAS patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A 2-week, polysomnographic, safety study of sodium oxybate in obstructive sleep apnea syndrome. George, CF., Feldman, N., Zheng, Y., et al.[2021]

Lower-sodium oxybate (LXB) was developed as a safer alternative to sodium oxybate (SXB), containing 92% less sodium, which helps reduce cardiovascular risks associated with high sodium intake in patients with narcolepsy and idiopathic hypersomnia.

Clinical trials demonstrated that LXB is equally effective as SXB in treating excessive daytime sleepiness and cataplexy, with similar side effects, making it a viable treatment option for patients aged 7 years and older.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of a lower-sodium oxybate formulation for the treatment of patients with narcolepsy and idiopathic hypersomnia. Junnarkar, G., Allphin, C., Profant, J., et al.[2022]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Lower-Sodium Oxybate in an Open-Label Titration Period of a Phase 3 Clinical Study in Adults with Idiopathic Hypersomnia. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Long-term efficacy and safety of low-sodium oxybate in an open-label extension period of a placebo-controlled, double-blind, randomized withdrawal study in adults with idiopathic hypersomnia. [2023]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Calcium, Magnesium, Potassium, and Sodium Oxybates Oral Solution: A Lower-Sodium Alternative for Cataplexy or Excessive Daytime Sleepiness Associated with Narcolepsy. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

A 12-month, open-label, multicenter extension trial of orally administered sodium oxybate for the treatment of narcolepsy. [2015]

5. United States pubmed.ncbi.nlm.nih.gov

A double-blind, placebo-controlled study demonstrates sodium oxybate is effective for the treatment of excessive daytime sleepiness in narcolepsy. [2015]

6. United States pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of FT218, a Once-Nightly Sodium Oxybate Formulation in Healthy Adults. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Calcium, magnesium, potassium, and sodium oxybates oral solution for cataplexy or excessive daytime sleepiness associated with narcolepsy. [2023]

8. Germany pubmed.ncbi.nlm.nih.gov

A 2-week, polysomnographic, safety study of sodium oxybate in obstructive sleep apnea syndrome. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Development of a lower-sodium oxybate formulation for the treatment of patients with narcolepsy and idiopathic hypersomnia. [2022]