JZP-110 · program
Solriamfetol (Sunosi) for Major depressive disorder
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's MDD development of solriamfetol. The broad Phase 3 proof-of-concept PARADIGM trial (NCT06360419; n=346; 300 mg once daily) did NOT meet its primary MADRS endpoint in the overall MDD population (topline 1 Apr 2025), but the prespecified subgroup of patients with severe excessive daytime sleepiness (EDS; ESS >=16, n=51) showed clinically meaningful, numerically greater improvements vs placebo across MADRS and global measures. Axsome therefore narrowed the program to MDD-with-EDS and initiated the Phase 3 CLARITY randomized-withdrawal trial (NCT07484217; 150 mg; primary endpoint time-to-relapse), first patient dosed late February 2026 (recruiting). Solriamfetol remains approved as Sunosi for EDS in narcolepsy/OSA (a separate indication).
Development timeline
- UpcomingpendingCLARITY Phase 3 (MDD with EDS) topline anticipated after a ~December 2028 primary completion.↗
- Axsome initiated the CLARITY Phase 3 randomized-withdrawal trial (NCT07484217) of solriamfetol 150 mg in MDD with EDS symptoms; first patient dosed. MDD program continues, focused on the EDS subpopulation.↗
- missedPARADIGM Phase 3 missed its primary MADRS endpoint in the overall MDD population; signal seen in the severe-EDS subgroup.↗
- Axsome initiated the PARADIGM Phase 3 trial of solriamfetol 300 mg in MDD (NCT06360419), primary endpoint MADRS at Week 6.↗
Readouts
- 2029AnticipatedTopline datapendingNCT07484217
CLARITY Phase 3 (MDD with EDS) topline anticipated after a ~December 2028 primary completion. ↗
- 2025-04-01ReportedTopline datamissedNCT06360419
PARADIGM Phase 3 missed its primary MADRS endpoint in the overall MDD population; signal seen in the severe-EDS subgroup. ↗
Clinical trials in Major depressive disorder
NCT07484217CLARITYPhase 3Recruitingn=508
A Multicenter, Double-blind, Placebo-controlled, Randomized Withdrawal Study of Solriamfetol in Subjects With Major Depressive Disorder With Excessive Daytime Sleepiness Symptoms (CLARITY)
NCT06360419PARADIGMPhase 3Completedn=346
A Randomized, Double-Blind, Placebo-Controlled Trial of Solriamfetol in Subjects With Major Depressive Disorder (PARADIGM)
mixedsecondaryMADRS and global measures in the severe-EDS subgroup (ESS >=16, n=51) at Week 6
In the prespecified severe-EDS subgroup, solriamfetol produced clinically meaningful and numerically greater improvements vs placebo on MADRS total score, MADRS anhedonia subscale, MADRS remission, CGI-S, CGI-I, and PGI-I; numbers/significance not detailed in the topline PR. This signal motivated the CLARITY MDD-with-EDS program.
missedprimaryMADRS total score change from baseline at Week 6 (overall MDD population)
Solriamfetol 300 mg once daily did not produce a statistically significant change in MADRS total score vs placebo in the overall population (MDD patients with [n=51] and without [n=295] severe EDS). Exact effect size and p-value not disclosed in the company topline release.
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 Announces Topline Results of PARADIGM Phase 3 Proof-of-Concept Trial of Solriamfetol in MDD with and without Excessive Daytime Sleepiness — Axsome Therapeutics (GlobeNewswire)
- Axsome Therapeutics Initiates CLARITY Phase 3 Trial of Solriamfetol in Adults with Major Depressive Disorder with Excessive Daytime Sleepiness Symptoms — Axsome Therapeutics (GlobeNewswire)
- Axsome Therapeutics Initiates PARADIGM Phase 3 Trial of Solriamfetol for the Treatment of Major Depressive Disorder — 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)
- CLARITY: Phase 3 randomized-withdrawal trial of solriamfetol in MDD with EDS (NCT07484217) — ClinicalTrials.gov
- PARADIGM: Phase 3 trial of solriamfetol in MDD (NCT06360419) — ClinicalTrials.gov
- SUNOSI (solriamfetol) tablets, for oral use, CIV — Full Prescribing Information — FDA / DailyMed (NLM)