Small Molecule · S-071031B

Ammoxetine (S-071031B)

Phase 3CSPC ZhongQi Pharmaceutical Technology (Shijiazhuang) Co., Ltd. (1093.HK)

Oral, once-daily serotonin–norepinephrine reuptake inhibitor (SNRI). Ammoxetine is the S-(−) enantiomer of 071031B, a chiral benzodioxole analog of duloxetine designed by replacing duloxetine's naphthyl ring with a 1,3-benzodioxole to reduce hepatotoxicity while retaining potent, balanced SERT/NET inhibition. Originated at the Beijing Institute of Pharmacology and Toxicology (Academy of Military Medical Sciences) and developed for MDD by CSPC ZhongQi Pharmaceutical Technology (CSPC Pharmaceutical Group). Phase 2 in MDD (NCT05762458) was positive on MADRS at 40 and 60 mg/day; a sertraline-controlled Phase 3 (NCT06827431) is registered.

Also known as: S-071031B, 071031B, Ammoxetine hydrochloride, ammoxetine, S-(−) isomer of 3-(benzo[d][1,3]dioxol-4-yloxy)-N-methyl-3-(thiophen-2-yl)propan-1-amine

Data current as of

Modality
Small molecule
Chemical class
aryloxypropanamine, Benzodioxole, thiophene
Chemistry
Single enantiomer
Mechanism
Serotonin transporter (SERT) inhibitor
Highest phase
Phase 3
Lead indication
Major depressive disorder
Developer
CSPC ZhongQi Pharmaceutical Technology (Shijiazhuang) Co., Ltd. (1093.HK)
Trials
2 tracked
Next catalyst
1H 2026 — Topline data (Major depressive disorder)

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parent duloxetine at the two transporters with lower hepatotoxicity; precise human SERT/NET binding constants remain unpublished.

TargetActionAffinity
Serotonin transporter (SERT)primarySLC6A4Inhibitor—ⓘ
DATSLC6A3Inhibitor—ⓘ
Norepinephrine transporter (NET)SLC6A2Inhibitor—ⓘ

Formulations

FormulationRouteRegimenPharmacokinetics
Ammoxetine oral tablet
40 mg or 60 mg once daily (Phase 2 MDD)
OralOnce daily—

Development timeline

Phase 3Feb 2025 – Jun 2026
  1. UpcomingpendingSertraline-controlled Phase 3 MDD topline anticipated; primary-completion estimate 30 Jun 2026.
  2. metPhase 2 MDD trial positive: ammoxetine 40 and 60 mg/day beat placebo on MADRS at Week 8.↗
  3. 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 2Oct 2024
  1. 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.

Ammoxetine (S-071031B) for Major depressive disorder

Phase 3ActiveMajor depressive disorder indication →

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.

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

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

Started Feb 2025· Primary completion Jun 2026

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

Started Feb 2023· Primary completion May 2024

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).

Identifiers

    Sources

    1. Efficacy and Safety of Ammoxetine in Major Depressive Disorder: A Randomized Clinical Trial — JAMA Network Open (PMC)
    2. Evaluation of the analgesic effects of ammoxetine, a novel potent serotonin and norepinephrine reuptake inhibitor — Acta Pharmacologica Sinica (PMC)
    3. Phase 2 study of ammoxetine hydrochloride enteric-coated tablets in depression (NCT05762458) — ClinicalTrials.gov
    4. The Research of Ammoxetine Hydrochloride Enteric-coated Tablets in Subjects With Depression — ClinicalTrials.gov