JZP-110 · program
Solriamfetol (Sunosi) for Excessive daytime sleepiness
Indications for JZP-110: Binge eating disorder · Phase 3 Excessive daytime sleepiness · Phase 3 Major depressive disorder · Phase 3 Attention-deficit/hyperactivity disorder · Phase 3
Axsome Therapeutics' investigational development of solriamfetol for excessive sleepiness associated with shift work disorder (SWD). The pivotal Phase 3 SUSTAIN trial (NCT06568367) -- a multicenter, randomized, double-blind, placebo-controlled, parallel-group study -- evaluates solriamfetol 150 mg and 300 mg once daily vs placebo over 12 weeks in adults with excessive sleepiness due to SWD, with co-primary endpoints of change from baseline to Week 12 in Maintenance of Wakefulness Test (MWT) mean sleep latency and in Clinician Global Impression of Severity (CGI-S) for sleepiness during the night shift. SUSTAIN was initiated in 2024 (announced in Axsome's August 5, 2024 Q2 business update) and is recruiting (CT.gov actual start August 2024; estimated primary completion December 2026). Per Axsome's February 23, 2026 business update, topline results are now anticipated in 2027 based on current enrollment trends (revised from the earlier 2026 expectation). Solriamfetol is separately approved as Sunosi for EDS in narcolepsy and obstructive sleep apnea; SWD is not an approved indication.
Development timeline
- UpcomingpendingSUSTAIN Phase 3 (solriamfetol for excessive sleepiness in shift work disorder) topline anticipated in 2027.↗
- Axsome initiated the SUSTAIN Phase 3 trial of solriamfetol (150 mg / 300 mg once daily) for excessive sleepiness associated with shift work disorder (NCT06568367); announced in the company's August 5, 2024 Q2 2024 business update. CT.gov registers an actual study start of August 2024; trial recruiting. At initiation the company anticipated topline results in 2026.↗
Readouts
- 2027AnticipatedTopline datapendingNCT06568367
SUSTAIN Phase 3 (solriamfetol for excessive sleepiness in shift work disorder) topline anticipated in 2027. ↗
Clinical trials in Excessive daytime sleepiness
NCT06568367SUSTAINPhase 3Recruitingn=520
A Multi-center, Randomized, Double-blind, Placebo-controlled Trial to Assess the Efficacy and Safety of Solriamfetol in Excessive Sleepiness Associated With Shift Work Disorder (SUSTAIN)
Formulations
| Formulation | Route | Regimen | Pharmacokinetics |
|---|---|---|---|
| Solriamfetol oral tablet (Sunosi) Film-coated tablets; administer once daily upon awakening. In excessive daytime sleepiness (narcolepsy/OSA), recommended dose 75-150 mg/day; initiate at 75 mg (OSA) or 37.5 mg (narcolepsy) and titrate; max 150 mg/day. Avoid administration within 9 hours of planned bedtime. | Oral | Once daily | t½ 7.1 h · Tmax 2 h · F 95% |
Mechanism of action
Selective dopamine and norepinephrine reuptake inhibitor (DNRI) with additional agonist activity at trace amine-associated receptor 1 (TAAR1). Inhibits dopamine and norepinephrine reuptake with IC50 values of ~2.9 uM and ~4.4 uM (binding Ki ~14.2 uM at DAT and ~3.7 uM at NET); negligible serotonin transporter activity (Ki ~81.5 uM). Acts as a human/rodent TAAR1 agonist (EC50 ~10-16 uM) at concentrations overlapping its transporter activity -- a mechanism not shared by modafinil or bupropion -- and is a weak 5-HT1A agonist. The combined monoaminergic/TAAR1 profile is hypothesized to drive wake-promotion and is being tested for antidepressant and pro-vigilance effects in MDD with excessive daytime sleepiness.
| Target | Action | Affinity |
|---|---|---|
| NETprimarySLC6A2 | Reuptake inhibitor | Ki 3700 nMⓘ |
| DATSLC6A3 | Reuptake inhibitor | Ki 14200 nMⓘ |
| TAAR1TAAR1 | Agonist | —ⓘ |
← Full JZP-110 compound page (identity, identifiers, all indications)
Sources
- Axsome Therapeutics Reports Fourth Quarter and Full Year 2025 Financial Results and Provides Business Update (smoking-cessation pivotal Phase 2/3 planned Q2 2026) — Axsome Therapeutics (GlobeNewswire)
- Axsome Therapeutics Reports Second Quarter 2024 Financial Results and Provides Business Update (SUSTAIN Phase 3 SWD trial initiated; topline then expected 2026) — Axsome Therapeutics (GlobeNewswire)
- Baladi et al. Characterization of the Neurochemical and Behavioral Effects of Solriamfetol (JZP-110), a Selective Dopamine and Norepinephrine Reuptake Inhibitor. J Pharmacol Exp Ther 2018;366(2):367-376 (PMID 29891587; DOI 10.1124/jpet.118.248120) — Journal of Pharmacology and Experimental Therapeutics (PubMed)
- SUNOSI (solriamfetol) tablets, for oral use, CIV — Full Prescribing Information — FDA / DailyMed (NLM)
- SUSTAIN: A Phase 3 Trial of Solriamfetol in Excessive Sleepiness Associated With Shift Work Disorder (NCT06568367) — ClinicalTrials.gov