Effect of Oral JZP-110 (ADX-N05) on Wakefulness and Sleepiness in Adults with Narcolepsy: A Phase 2b Study

Ruoff, Chad; Swick, Todd J.; Doekel, Robert C.; Emsellem, Hélène A.; Feldman, Neil T.; Rosenberg, Russell; Bream, Gary; Khayrallah, M.; Lü, Yuan; Black, Jed

doi:10.5665/sleep.5968

Cited by 68 publications

(74 citation statements)

References 27 publications

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“…The overall safety and tolerability in this study were consistent with other studies of solriamfetol, with the most common adverse events being headache, nausea, decreased appetite, nasopharyngitis, dry mouth, and anxiety; no serious adverse events were reported. Additionally, small increases in mean blood pressure and heart rate were observed, as previously reported with other wake‐promoting agents and psychostimulants …”

Section: Discussionsupporting

confidence: 88%

“…Importantly, improvements on both coprimary endpoints were observed at week 1, and these effects were maintained at the 150 and 300 mg doses over the study duration, indicating that there was no apparent tolerance over the 12 weeks of the study. Onset of efficacy at week 1 is consistent with what was observed previously in individuals with narcolepsy . Furthermore, on the MWT, significant effects were observed across all 5 of the individual MWT trials at the 150 and 300 mg doses, effects that were maintained over a 9‐hour duration following dosing at the 12‐week time point.…”

Section: Discussionsupporting

confidence: 87%

“…This sample size was based on an estimate of 54 patients per group to provide at least 80% power to detect a difference of 6 minutes in the mean sleep latency time as determined from the MWT (mean of the first 4 trials) and a difference of 4 points on the ESS changes from baseline to week 12 between each solriamfetol treatment dose group and placebo. These estimates were based on the effects observed at the 150 and 300 mg doses in 2 phase 2 studies . This calculation also assumed standard deviations (SDs) in the changes from baseline of 10 minutes for the MWT and 6 points for the ESS, and a 2‐sided significance level of 0.05 using a t test.…”

Section: Methodsmentioning

confidence: 99%

“…Together, these differences may account for the robust wake‐promoting effects and the lack of rebound hypersomnia that have been observed in rodent models of narcolepsy . In 2 phase 2 controlled clinical trials in adult patients with narcolepsy, solriamfetol reduced patient‐reported ES as measured on the Epworth Sleepiness Scale (ESS) and improved wakefulness as measured by the objective Maintenance of Wakefulness Test (MWT) …”

mentioning

confidence: 99%

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A randomized study of solriamfetol for excessive sleepiness in narcolepsy

Thorpy

Shapiro

Mayer³

et al. 2019

Annals of Neurology

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280

121

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Objective Solriamfetol (JZP‐110) is a selective dopamine and norepinephrine reuptake inhibitor with wake‐promoting effects. This phase 3 study (NCT02348593) evaluated the safety and efficacy of solriamfetol in narcolepsy. Methods Patients with narcolepsy with mean sleep latency <25 minutes on the Maintenance of Wakefulness Test (MWT), Epworth Sleepiness Scale (ESS) score ≥10, and usual nightly sleep ≥6 hours were randomized to solriamfetol 75, 150, or 300 mg, or placebo for 12 weeks. Coprimary endpoints were change from baseline to week 12 in MWT and ESS. Improvement on the Patient Global Impression of Change (PGI‐C) was the key secondary endpoint. Results Safety and modified intention‐to‐treat populations included 236 and 231 patients, respectively. Solriamfetol 300 and 150 mg were positive on both coprimary endpoints. Least squares mean (standard error [SE]) changes from baseline were 12.3 (SE = 1.4) and 9.8 (SE = 1.3) minutes for solriamfetol 300 and 150 mg on the MWT, respectively, versus 2.1 (SE = 1.3) minutes for placebo, and −6.4 (SE = 0.7) for 300 mg and −5.4 (SE = 0.7) for 150 mg on the ESS versus −1.6 (SE = 0.7) for placebo (all p < 0.0001). At week 12, higher percentages of patients treated with solriamfetol 150 mg (78.2%) and 300 mg (84.7%) reported PGI‐C improvement relative to placebo (39.7%; both p < 0.0001). Adverse events ≥5% across all solriamfetol doses included headache (21.5%), nausea (10.7%), decreased appetite (10.7%), nasopharyngitis (9.0%), dry mouth (7.3%), and anxiety (5.1%). Interpretation Solriamfetol has the potential to be an important therapeutic option for the treatment of impaired wakefulness and excessive sleepiness in patients with narcolepsy. ANN NEUROL 2019;85:359–370.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionsupporting

confidence: 87%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

A randomized study of solriamfetol for excessive sleepiness in narcolepsy

Thorpy

Shapiro

Mayer³

et al. 2019

Annals of Neurology

Self Cite

280

121

View full text Add to dashboard Cite

show abstract

“…A phase IIb, 12-week, randomised, double-blind, placebocontrolled trial evaluated the efficacy of solriamfetol in adults with narcolepsy with or without cataplexy [30]. Participants were randomly assigned to receive placebo or solriamfetol (150 mg/day for 4 weeks, then 300 mg/day for 8 weeks).…”

Section: Efficacymentioning

confidence: 99%

Recently Approved and Upcoming Treatments for Narcolepsy

Thorpy

2020

CNS Drugs

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Narcolepsy is a chronic, disabling neurologic disorder characterised by excessive daytime sleepiness (EDS) and, in up to 60% of patients, cataplexy. Treatments for narcolepsy are aimed at improving wakefulness (e.g. modafinil, armodafinil, stimulants), reducing cataplexy attacks (e.g. sodium oxybate, venlafaxine), and treating the symptoms of disturbed nocturnal sleep, sleep paralysis and sleep-related hallucinations (e.g. sodium oxybate). In general, medications that increase the release, or inhibit the reuptake, of norepinephrine or dopamine have wake-promoting effects and are useful in managing EDS, whereas medications that inhibit serotonin or norepinephrine reuptake have anticataplectic effects. Modulation of γ-aminobutyric acid B (GABA B) receptors or histamine H 3 receptors (H3Rs) has effects on both EDS and cataplexy. Pitolisant, an H3R antagonist, and solriamfetol, a dopamine and norepinephrine reuptake inhibitor, are the most recently approved treatments for EDS associated with narcolepsy in the European Union (pitolisant) and the USA (pitolisant and solriamfetol). Several new agents are being developed and tested as potential treatments for EDS and cataplexy associated with narcolepsy; these agents include novel oxybate formulations (once-nightly [FT218]; low sodium [JZP-258]), a selective norepinephrine reuptake inhibitor (AXS-12), and a product combining modafinil and an astroglial connexin inhibitor (THN102). This review summarises the mechanisms of action, pharmacokinetics, efficacy, and safety/tolerability of recently approved and emerging treatments for narcolepsy. Key Points Excessive daytime sleepiness and cataplexy are common and disabling symptoms associated with narcolepsy. Emerging treatments, including two recently approved medications (pitolisant and solriamfetol) and several medications still in development (FT218, JZP-258, AXS-12, THN102, SUVN-G3031, TAK-925), provide new options for the treatment of narcolepsy.

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Effects of solriamfetol on on‐the‐road driving performance in participants with excessive daytime sleepiness associated with obstructive sleep apnoea

Vinckenbosch

Asín

Vries

et al. 2022

Human Psychopharmacology

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Objective: To evaluate the impact of solriamfetol, a dopamine and norepinephrine reuptake inhibitor, on on-the-road driving in participants with excessive daytime sleepiness (EDS) associated with obstructive sleep apnoea (OSA). Methods: Eligible participants were aged 21-75 years with OSA and EDS (Maintenance of Wakefulness Test mean sleep latency <30 minutes and Epworth Sleepiness Scale score ≥10). Participants were randomised 1:1 to solriamfetol (150 mg/day [3 days], then 300 mg/day [4 days]) or placebo for 7 days, before crossover to the other treatment paradigm. On Day 7 of each period, standardised on-road driving tests occurred (2 and 6 hours postdose). Standard deviation of lateral position (SDLP) was the primary endpoint.

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Effect of Oral JZP-110 (ADX-N05) on Wakefulness and Sleepiness in Adults with Narcolepsy: A Phase 2b Study

Abstract: Clinicaltrials.gov identifier NCT01681121.

Cited by 68 publications

References 27 publications

A randomized study of solriamfetol for excessive sleepiness in narcolepsy

A randomized study of solriamfetol for excessive sleepiness in narcolepsy

Recently Approved and Upcoming Treatments for Narcolepsy

Effects of solriamfetol on on‐the‐road driving performance in participants with excessive daytime sleepiness associated with obstructive sleep apnoea

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