Effect of oral JZP-110 (ADX-N05) treatment on wakefulness and sleepiness in adults with narcolepsy

Bogan, Richard; Feldman, Neil T.; Emsellem, Hélène A.; Rosenberg, Russell; Lü, Yuan; Bream, Gary; Khayrallah, M.; Lankford, D. Alan

doi:10.1016/j.sleep.2015.05.013

Cited by 64 publications

(58 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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%

“…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%

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

279

121

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 88%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

A randomized study of solriamfetol for excessive sleepiness in narcolepsy

Thorpy

Shapiro

Mayer³

et al. 2019

Annals of Neurology

Self Cite

279

121

View full text Add to dashboard Cite

show abstract

“…After 4 weeks of JZP-110 at doses of 150 mg (weeks 1, 3) and 300 mg (weeks 2, 4), ESS decreased –6.7 in the treatment group (n=33) compared to –2.4 in the placebo group (n=33). MWT (40-minute test) mean-sleep-latency (MWT SL) after 2 weeks at the 300 mg dose was 12.7±10.6 minutes longer compared to placebo results of 0.9±6.0 minutes 50. A parallel group trial using 150 mg × 4 weeks and 300 mg × 8 weeks showed significant improvements in MWT SL, ESS, and CGIC in treated patients (n=44) compared to placebo (n=49).…”

Section: New Developments and Future Therapiesmentioning

confidence: 91%

“…It does not release monoamines nor does it inhibit serotonin reuptake; it also does not inhibit MAO-A enzymatic activity 50. In randomized, double-blind, placebo-controlled clinical trials, JZP-110 underwent Phase II (NCT01485770)50 and Phase II B (NCT01681121)51 testing in adults with narcolepsy with and without cataplexy 50,51. After 4 weeks of JZP-110 at doses of 150 mg (weeks 1, 3) and 300 mg (weeks 2, 4), ESS decreased –6.7 in the treatment group (n=33) compared to –2.4 in the placebo group (n=33).…”

Section: New Developments and Future Therapiesmentioning

confidence: 99%

New developments in the management of narcolepsy

Abad

Guilleminault

2017

NSS

View full text Add to dashboard Cite

Narcolepsy is a life-long, underrecognized sleep disorder that affects 0.02%–0.18% of the US and Western European populations. Genetic predisposition is suspected because of narcolepsy’s strong association with HLA DQB1*06-02, and genome-wide association studies have identified polymorphisms in T-cell receptor loci. Narcolepsy pathophysiology is linked to loss of signaling by hypocretin-producing neurons; an autoimmune etiology possibly triggered by some environmental agent may precipitate hypocretin neuronal loss. Current treatment modalities alleviate the main symptoms of excessive daytime somnolence (EDS) and cataplexy and, to a lesser extent, reduce nocturnal sleep disruption, hypnagogic hallucinations, and sleep paralysis. Sodium oxybate (SXB), a sodium salt of γ hydroxybutyric acid, is a first-line agent for cataplexy and EDS and may help sleep disruption, hypnagogic hallucinations, and sleep paralysis. Various antidepressant medications including norepinephrine serotonin reuptake inhibitors, selective serotonin reuptake inhibitors, and tricyclic antidepressants are second-line agents for treating cataplexy. In addition to SXB, modafinil and armodafinil are first-line agents to treat EDS. Second-line agents for EDS are stimulants such as methylphenidate and extended-release amphetamines. Emerging therapies include non-hypocretin-based therapy, hypocretin-based treatments, and immunotherapy to prevent hypocretin neuronal death. Non-hypocretin-based novel treatments for narcolepsy include pitolisant (BF2.649, tiprolisant); JZP-110 (ADX-N05) for EDS in adults; JZP 13-005 for children; JZP-386, a deuterated sodium oxybate oral suspension; FT 218 an extended-release formulation of SXB; and JNJ-17216498, a new formulation of modafinil. Clinical trials are investigating efficacy and safety of SXB, modafinil, and armodafinil in children. γ-amino butyric acid (GABA) modulation with GABAA receptor agonists clarithromycin and flumazenil may help daytime somnolence. Other drugs investigated include GABAB agonists (baclofen), melanin-concentrating hormone antagonist, and thyrotropin-releasing hormone agonists. Hypocretin-based therapies include hypocretin peptide replacement administered either through an intracerebroventricular route or intranasal route. Hypocretin neuronal transplant and transforming stem cells into hypothalamic neurons are also discussed in this article. Immunotherapy to prevent hypocretin neuronal death is reviewed.

show abstract

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

View full text Add to dashboard Cite

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.

show abstract

Effect of oral JZP-110 (ADX-N05) treatment on wakefulness and sleepiness in adults with narcolepsy

Abstract: The efficacy of JZP-110 for impaired wakefulness and excessive sleepiness was observed at 150-300 mg/day and as early as one week after initiating treatment (Clinicaltrials.gov identifier NCT01485770).

Cited by 64 publications

References 25 publications

A randomized study of solriamfetol for excessive sleepiness in narcolepsy

A randomized study of solriamfetol for excessive sleepiness in narcolepsy

New developments in the management of narcolepsy

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

Contact Info

Product

Resources

About