E2086 for Narcolepsy

Recruiting at 13 trial locations

Overseen By Eisai Medical Information

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Eisai Inc.

Must not be taking: Antipsychotics, Psychostimulants, Sleep aids, others

Disqualifiers: Pregnancy, Heart disease, Psychiatric disorders, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

40 Participants Needed

Trial Summary

What is the purpose of this trial?

The primary purpose of this study is to evaluate the efficacy of single oral doses of E2086 compared to placebo in the treatment of excessive daytime sleepiness (EDS) as assessed by the Maintenance of Wakefulness Test (MWT) in adult participants with narcolepsy type 1 (NT1).

Do I have to stop taking my current medications for the trial?

Yes, you may need to stop taking certain medications. The trial prohibits the use of anti-cataplectic medications, psychostimulant medications, and sleep-promoting medications within specific time frames before screening. This includes medications like pseudoephedrine, methylphenidate, amphetamines, modafinil, armodafinil, sodium oxybate, pemoline, trazodone, hypnotics, benzodiazepines, barbiturates, cannabinoids, and opioids.

What data supports the idea that E2086 for Narcolepsy is an effective drug?

The available research shows that E2086, also known as sodium oxybate, is effective in treating narcolepsy by improving nighttime sleep and reducing excessive daytime sleepiness. A study compared sodium oxybate with other treatments like modafinil and found it effective in managing disrupted nighttime sleep. Additionally, a network meta-analysis highlighted that sodium oxybate is one of the approved wake-promoting agents for narcolepsy, indicating its effectiveness in reducing daytime sleepiness. These findings suggest that E2086 is a beneficial option for people with narcolepsy. ^{1 2 3 4 5}

What safety data is available for the treatment E2086 for Narcolepsy?

The provided research does not contain specific safety data for the treatment E2086 for Narcolepsy. The articles discuss general adverse events in phase-I studies, drug safety surveillance, and risk evaluation strategies, but none specifically mention E2086 or its safety profile. ^{6 7 8 9 10}

Is the drug E2086 a promising treatment for narcolepsy?

The drug E2086 is considered promising for narcolepsy because it is part of emerging therapies that aim to improve symptoms like excessive daytime sleepiness and cataplexy. New treatments are being developed to address the underlying causes of narcolepsy, such as the loss of certain brain cells, and E2086 is among these innovative approaches. ^{11 12 13 14 15}

Eligibility Criteria

Adults over 18 with narcolepsy type 1 can join this trial. They must have specific sleep test results showing severe daytime sleepiness and a history of cataplexy. Participants should have regular sleeping hours, a BMI between 18-40, and experience daily periods of extreme need to sleep or napping for at least three months.

Inclusion Criteria

I am 18 years old or older.

I have a sleep disorder with quick sleep onset and rapid REM phases.

My sleep study showed I entered REM sleep unusually fast.

Treatment Details

Interventions

• E2086

Trial Overview The study tests E2086's effectiveness against placebo in reducing excessive daytime sleepiness in adults with narcolepsy type 1. The Maintenance of Wakefulness Test measures the success of the treatment.

Participant Groups

Group I: Sequence 9, BACED: E2086 Dose 1 + Placebo + E2086 Dose 2 + Active Comparator + E2086 Dose 3 Experimental Treatment 4 Interventions

Participants will receive 3 doses of E2086, an active comparator, E2086 matching placebo and active comparator matching placebo, all as oral tablets.

Group II: Sequence 8, AEBDC: Placebo + Active Comparator + E2086 Dose 1 + E2086 Dose 3 + E2086 Dose 2 Experimental Treatment 4 Interventions

Participants will receive 3 doses of E2086, an active comparator, E2086 matching placebo and active comparator matching placebo, all as oral tablets.

Group III: Sequence 7, EDACB: Active Comparator + E2086 Dose 3 + Placebo + E2086 Dose 2 + E2086 Dose 1 Experimental Treatment 4 Interventions

Participants will receive 3 doses of E2086, an active comparator, E2086 matching placebo and active comparator matching placebo, all as oral tablets.

Group IV: Sequence 6, DCEBA: E2086 Dose 3 + E2086 Dose 2 + Active Comparator + E2086 Dose 1 + Placebo Experimental Treatment 4 Interventions

Participants will receive 3 doses of E2086, an active comparator, E2086 matching placebo and active comparator matching placebo, all as oral tablets.

Group V: Sequence 5, EADBC: Active Comparator + Placebo + E2086 Dose 3 + E2086 Dose 1 + E2086 Dose 2 Experimental Treatment 4 Interventions

Participants will receive 3 doses of E2086, an active comparator, E2086 matching placebo and active comparator matching placebo, all as oral tablets.

Group VI: Sequence 4, DECAB: E2086 Dose 3 + Active Comparator + E2086 Dose 2 + Placebo + E2086 Dose 1 Experimental Treatment 4 Interventions

Participants will receive 3 doses of E2086, an active comparator, E2086 matching placebo and active comparator matching placebo, all as oral tablets.

Group VII: Sequence 3, CDBEA: E2086 Dose 2 + E2086 Dose 3 + E2086 Dose 1 + Active Comparator + Placebo Experimental Treatment 4 Interventions

Participants will receive 3 doses of E2086, an active comparator, E2086 matching placebo and active comparator matching placebo, all as oral tablets.

Group VIII: Sequence 2, BCADE: E2086 Dose 1 + E2086 Dose 2 + Placebo + E2086 Dose 3 + Active Comparator Experimental Treatment 4 Interventions

Participants will receive 3 doses of E2086, an active comparator, E2086 matching placebo and active comparator matching placebo, all as oral tablets.

Group IX: Sequence 10, CBDAE: E2086 Dose 2 + E2086 Dose 1 + E2086 Dose 3 + Placebo + Active Comparator Experimental Treatment 4 Interventions

Participants will receive 3 doses of E2086, an active comparator, E2086 matching placebo and active comparator matching placebo, all as oral tablets.

Group X: Sequence 1, ABECD: Placebo + E2086 Dose 1 + Active Comparator + E2086 Dose 2 + E2086 Dose 3 Experimental Treatment 4 Interventions

Participants will receive 3 doses of E2086, an active comparator, E2086 matching placebo and active comparator matching placebo, all as oral tablets.

Who Is Running the Clinical Trial?

Eisai Inc.

Lead Sponsor

Trials

524

Recruited

161,000+

Founded

Eisai Inc. was established in 1995 as the U.S. subsidiary of Eisai Co., Ltd.

Headquarters

Woodcliff Lake, NJ, USA

Known For

Neurology and Oncology

Top Products

Aricept (donepezil), Lenvima (lenvatinib), Leqembi (lecanemab), Halaven (eribulin)

Lynn Kramer

Eisai Inc.

Chief Medical Officer since 2019

MD

Tatsuyuki Yasuno

Eisai Inc.

Chief Executive Officer since 2023

MBA from Kellogg School of Management, Northwestern University; Bachelor of Political Science from Waseda University

Findings from Research

The American Academy of Sleep Medicine has established quality measures for narcolepsy care, focusing on reducing excessive daytime sleepiness through quantifying sleepiness and initiating treatment.

To improve diagnosis accuracy, the recommended measures include completing a comprehensive sleep history and conducting objective sleep assessments, while also emphasizing the importance of treatment follow-up and safety counseling to reduce adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality measures for the care of patients with narcolepsy. Krahn, LE., Hershner, S., Loeding, LD., et al.[2018]

Sodium oxybate (SXB), both alone and in combination with modafinil, significantly reduced the number of sleep stage shifts from deeper sleep (N2/3/REM) to lighter sleep (N1/Wake), indicating improved sleep consolidation in 155 patients over 8 weeks.

Patients taking SXB reported significantly better sleep quality compared to those on placebo, while modafinil alone did not show similar benefits, highlighting the specific effectiveness of SXB in addressing disrupted nighttime sleep.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of sodium oxybate, modafinil, and their combination on disrupted nighttime sleep in narcolepsy. Dauvilliers, Y., Roth, T., Guinta, D., et al.[2018]

In a study of 92 patients with narcolepsy type 1, narcolepsy type 2, and idiopathic hypersomnia, significant improvements in patient-reported outcomes related to sleepiness and depression were observed after treatment, regardless of the specific diagnosis or treatment regimen used.

Higher standardized drug doses were associated with worsening depression scores, suggesting that careful consideration of drug burden is important in managing these patients' symptoms effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Pharmacotherapy Treatment on Patient-Reported Outcomes in a Narcolepsy and Idiopathic Hypersomnia Cohort. Pascoe, M., Bena, J., Foldvary-Schaefer, N.[2023]

The study analyzed 17 randomized controlled trials involving five approved wake-promoting agents for narcolepsy, finding that all treatments were effective compared to placebo, with solriamfetol showing the greatest improvement in wakefulness and overall patient-reported outcomes.

Lower-sodium oxybate (LXB) demonstrated the best safety profile, with the lowest risk of adverse events, making it a promising option for narcolepsy treatment alongside its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Efficacy and Safety of Multiple Wake-Promoting Agents for the Treatment of Excessive Daytime Sleepiness in Narcolepsy: A Network Meta-Analysis. Zhan, S., Ye, H., Li, N., et al.[2023]

In a study of 174 individuals with narcolepsy type 1, higher symptom severity was linked to lower health-related quality of life (HRQoL), affecting self-care, daily activities, and increasing feelings of pain and anxiety.

Key symptoms like excessive daytime sleepiness and disrupted nocturnal sleep were significant predictors of HRQoL, suggesting that managing these symptoms could enhance overall quality of life for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Impact of Symptom Severity on Health-Related Quality of Life in People with Narcolepsy Type 1. Li, C., Xie, L., Shang, S., et al.[2023]

In a comprehensive review of 54 phase-I studies involving 1015 healthy volunteers over 10 years, the overall incidence of adverse events was found to be 12.8%, with a higher rate for active drugs (13.7%) compared to placebo (7.9%).

Most adverse events were minor, with only 3% classified as severe, and no deaths or life-threatening events reported, highlighting that while adverse events are common in phase-I trials, they are typically not serious.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events in phase-I studies: a report in 1015 healthy volunteers. Sibille, M., Deigat, N., Janin, A., et al.[2019]

The term 'drug ineffective' (DI) was the most commonly reported adverse event in the FDA's FAERS database, accounting for 6.4% of all reports from September 2012 to August 2016, with most reports coming from consumers and primarily from the USA.

Despite the high frequency of DI reports, only 7.8% of evaluated reports were considered 'useful' for pharmacovigilance, indicating a need for better strategies to identify valuable information within these reports.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Evaluation of "Drug Ineffective" Postmarketing Reports in Drug Safety Surveillance. Misu, T., Kortepeter, CM., Muñoz, MA., et al.[2020]

In a study of 443 adult patients with epilepsy, 36.6% reported fatigue as a significant issue during antiepileptic drug (AED) treatment, highlighting fatigue as a common adverse effect.

Fatigue was more prevalent among female patients (64.8%) and those treated with levetiracetam (42.3%), but this fatigue was not linked to depression, indicating a direct association with the medication rather than mood effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fatigue during treatment with antiepileptic drugs: A levetiracetam-specific adverse event? Mula, M., von Oertzen, TJ., Cock, HR., et al.[2018]

The FDA Amendments Act of 2007 introduced Risk Evaluation and Mitigation Strategies (REMS) to enhance drug safety, requiring pharmaceutical companies to create safety plans for drugs with uncertain risk-benefit profiles.

Romiplostim (Nplate®), used to treat thrombocytopenia, exemplifies the use of REMS due to its significant safety concerns, including risks of bone marrow changes, highlighting the importance of these strategies in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk evaluation and mitigation strategies (REMS): educating the prescriber. Nicholson, SC., Peterson, J., Yektashenas, B.[2021]

Effective clinical drug safety surveillance is crucial for protecting public health and ensuring the commercial success of pharmaceutical products, as it helps monitor and manage adverse drug events.

The process of drug safety surveillance is governed by FDA regulations and involves systematic management of adverse event reports, emphasizing the importance of clear communication and data handling to improve drug safety outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A primer of drug safety surveillance: an industry perspective. Part I: Information flow, new drug development, and federal regulations. Allan, MC.[2019]

In a study of 234 Japanese patients with narcolepsy spectrum disorders (NT1, NT2, and IH), those with narcolepsy type 1 (NT1) had a higher body mass index (BMI) and a greater incidence of metabolic-syndrome-related disorders (MRDs) compared to those with NT2 or idiopathic hypersomnia (IH).

Factors such as age, BMI, and the presence of obstructive sleep apnea (OSA) were significantly linked to MRD incidence in patients with NSD, highlighting the need for careful monitoring of obesity in narcolepsy patients, especially in NT2 patients who are HLA-DQB1*06:02 positive.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabolic-Syndrome-Related Comorbidities in Narcolepsy Spectrum Disorders: A Preliminary Cross-Sectional Study in Japan. Futenma, K., Takaesu, Y., Nakamura, M., et al.[2022]

Narcolepsy is primarily caused by the loss of neurons that produce hypocretin, a neuropeptide crucial for regulating wakefulness, with about 90% of patients with cataplexy being deficient in this substance.

Current treatments include stimulants and newer medications like modafinil and sodium oxybate, but the development of hypocretin receptor agonists holds promise for future therapies specifically targeting hypocretin deficiency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The neurobiology of hypocretins (orexins), narcolepsy and related therapeutic interventions. Zeitzer, JM., Nishino, S., Mignot, E.[2015]

Narcolepsy affects a small percentage of the population and is linked to genetic factors and the loss of hypocretin-producing neurons, suggesting an autoimmune component that may be triggered by environmental factors.

Current treatments like sodium oxybate and modafinil effectively manage symptoms such as excessive daytime sleepiness and cataplexy, while emerging therapies focus on both non-hypocretin-based and hypocretin-based approaches to improve outcomes for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New developments in the management of narcolepsy. Abad, VC., Guilleminault, C.[2020]

In South Korea, the prevalence of definite narcolepsy was found to be 8.4 per 100,000 people in 2019, with a notable peak of 32.0 per 100,000 among individuals aged 15-19, indicating a significant age-related trend.

The study revealed a steady increase in both the prevalence and incidence of narcolepsy over the past decade, with annual medical costs for treatment rising to 4.1 billion KRW in 2019, highlighting the growing burden of this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

National Estimates of Narcolepsy in Korea. Park, HR., Song, P., Lee, SY.[2023]

Narcolepsy, particularly type 1 (NT1), is caused by an autoimmune process that destroys hypocretin-producing cells, but there is currently no cure for the disorder.

While pharmacological treatments exist, they are not fully effective for all symptoms, highlighting the importance of combining these with behavioral and psychosocial therapies to enhance the quality of life for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Narcolepsy treatment: pharmacological and behavioral strategies in adults and children. Franceschini, C., Pizza, F., Antelmi, E., et al.[2021]

References

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

Quality measures for the care of patients with narcolepsy. [2018]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Effect of sodium oxybate, modafinil, and their combination on disrupted nighttime sleep in narcolepsy. [2018]

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

Effects of Pharmacotherapy Treatment on Patient-Reported Outcomes in a Narcolepsy and Idiopathic Hypersomnia Cohort. [2023]

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

Comparative Efficacy and Safety of Multiple Wake-Promoting Agents for the Treatment of Excessive Daytime Sleepiness in Narcolepsy: A Network Meta-Analysis. [2023]

5. England pubmed.ncbi.nlm.nih.gov

The Impact of Symptom Severity on Health-Related Quality of Life in People with Narcolepsy Type 1. [2023]

6. Germany pubmed.ncbi.nlm.nih.gov

Adverse events in phase-I studies: a report in 1015 healthy volunteers. [2019]

7. Switzerland pubmed.ncbi.nlm.nih.gov

An Evaluation of "Drug Ineffective" Postmarketing Reports in Drug Safety Surveillance. [2020]

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

Fatigue during treatment with antiepileptic drugs: A levetiracetam-specific adverse event? [2018]

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

Risk evaluation and mitigation strategies (REMS): educating the prescriber. [2021]

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

A primer of drug safety surveillance: an industry perspective. Part I: Information flow, new drug development, and federal regulations. [2019]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Metabolic-Syndrome-Related Comorbidities in Narcolepsy Spectrum Disorders: A Preliminary Cross-Sectional Study in Japan. [2022]

12. England pubmed.ncbi.nlm.nih.gov

The neurobiology of hypocretins (orexins), narcolepsy and related therapeutic interventions. [2015]

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

New developments in the management of narcolepsy. [2020]

14. Korea (South) pubmed.ncbi.nlm.nih.gov

National Estimates of Narcolepsy in Korea. [2023]

15. Germany pubmed.ncbi.nlm.nih.gov

Narcolepsy treatment: pharmacological and behavioral strategies in adults and children. [2021]