S-071031B · program
Ammoxetine (S-071031B) for Major depressive disorder
MDD development by CSPC ZhongQi. Phase 2 (NCT05762458; 239 patients, 15 China sites) met its primary endpoint: both ammoxetine 40 mg/day (MADRS difference vs placebo −3.3, p=0.02) and 60 mg/day (−3.1, p=0.02) at Week 8, published in JAMA Network Open (Sept 2025). A multicenter, randomized, double-blind, double-dummy, placebo-controlled and sertraline active-controlled Phase 3 study (NCT06827431; est. 770 participants; primary endpoint MADRS change at Week 8) is registered with an estimated start of 14 Feb 2025 and primary-completion estimate of 30 Jun 2026. No Phase 3 topline data yet. Provenance for ongoing Phase 3 status is registry + the published Phase 2 paper; flag for reviewer.
Development timeline
- UpcomingpendingSertraline-controlled Phase 3 MDD topline anticipated; primary-completion estimate 30 Jun 2026.
- Phase 3 sertraline-controlled study (NCT06827431) registered with an estimated start date of 14 Feb 2025; registry overall status NOT_YET_RECRUITING at research time. Phase advanced to Phase 3 in MDD.
- Phase 2 MDD study (NCT05762458, n=239, 15 China sites) completed; primary MADRS endpoint met for both 40 mg/day and 60 mg/day vs placebo at Week 8. Estimated study completion 15 Oct 2024; results published in JAMA Network Open September 2025.
Readouts
- 1H 2026AnticipatedTopline datapendingNCT06827431
Sertraline-controlled Phase 3 MDD topline anticipated; primary-completion estimate 30 Jun 2026.
- 2025-09-01ReportedFull resultsmetNCT05762458
Phase 2 MDD trial positive: ammoxetine 40 and 60 mg/day beat placebo on MADRS at Week 8. ↗
Clinical trials in Major depressive disorder
NCT06827431Phase 3Activen=770
Efficacy and Safety of Ammoxetine Hydrochloride Enteric-coated Tablets in Subjects With Depression: A Multicenter, Randomized, Double-blind, Double-Dummy, Placebo-controlled and Sertraline Active-controlled, Parallel-group, Phase III Study
NCT05762458Phase 2Completedn=239
Efficacy and Safety of Ammoxetine Hydrochloride Enteric-coated Tablets in Subjects With Depression: A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, Phase II Study
metprimaryMADRS total score change from baseline to Week 8 (40 mg/day) — LS mean change −16.7 (SE 1.3); difference vs placebo −3.3 (0.02)
Ammoxetine 40 mg/day significantly reduced MADRS vs placebo (placebo LS mean change −13.5) at Week 8. Published JAMA Network Open 2025;8(9):e2532650.
metprimaryMADRS total score change from baseline to Week 8 (60 mg/day) — LS mean change −16.6 (SE 1.3); difference vs placebo −3.1 (0.02)
Ammoxetine 60 mg/day significantly reduced MADRS vs placebo (placebo LS mean change −13.5) at Week 8. Both doses statistically superior to placebo; treatment generally well tolerated (TEAEs 78.8% at 40 mg/day, 85.0% at 60 mg/day, 60.8% placebo; common: dry mouth, nausea, dizziness).
Formulations
| Formulation | Route | Regimen | Pharmacokinetics |
|---|---|---|---|
| Ammoxetine oral tablet 40 mg or 60 mg once daily (Phase 2 MDD) | Oral | Once daily | — |
Mechanism of action
Potent, balanced serotonin–norepinephrine reuptake inhibitor (SNRI). Ammoxetine inhibits the serotonin transporter (SERT / SLC6A4) and the norepinephrine transporter (NET / SLC6A2) with weak affinity for the dopamine transporter (DAT / SLC6A3) and negligible activity at monoamine oxidase and a panel of GPCRs/opioid receptors. Preclinical work reports it as more potent than its parent duloxetine at the two transporters with lower hepatotoxicity; precise human SERT/NET binding constants remain unpublished.
| Target | Action | Affinity |
|---|---|---|
| Serotonin transporter (SERT)primarySLC6A4 | Inhibitor | —ⓘ |
| DATSLC6A3 | Inhibitor | —ⓘ |
| Norepinephrine transporter (NET)SLC6A2 | Inhibitor | —ⓘ |
← Full S-071031B compound page (identity, identifiers, all indications)
Sources
- Efficacy and Safety of Ammoxetine in Major Depressive Disorder: A Randomized Clinical Trial — JAMA Network Open (PMC)
- Evaluation of the analgesic effects of ammoxetine, a novel potent serotonin and norepinephrine reuptake inhibitor — Acta Pharmacologica Sinica (PMC)
- Phase 2 study of ammoxetine hydrochloride enteric-coated tablets in depression (NCT05762458) — ClinicalTrials.gov
- The Research of Ammoxetine Hydrochloride Enteric-coated Tablets in Subjects With Depression — ClinicalTrials.gov