XEN1101 · program

Azetukalner (XEN1101) for Bipolar depression

Phase 3RecruitingXenon Pharmaceuticals Inc. (XENE)

Indications for XEN1101: Epilepsy · Phase 3 Major depressive disorder · Phase 3 Bipolar depression · Phase 3

Azetukalner for depressive episodes associated with bipolar I or II disorder (X-CEED Phase 3 program). 20 mg azetukalner administered orally with food as monotherapy over a 6-week double-blind period; primary efficacy endpoint is change from baseline in MADRS total score at Week 6. The Phase 3 BPD program comprises two planned randomized, double-blind, placebo-controlled trials (~400 patients each); the first, X-CEED (NCT07172516), began enrolling August 2025 (primary completion estimated June 2028). A long-term open-label extension, X-CEED-OLE (NCT07217860), opened October 2025 (enrolling by invitation). The second pivotal efficacy trial is planned but not yet registered. No direct Phase 2 study in bipolar depression preceded X-CEED; the program leverages the MDD/X-NOVA and epilepsy clinical experience.

Data current as of

Development timeline

Phase 3Aug 2025 – Jun 2028
  1. UpcomingX-CEED Phase 3 topline in bipolar I/II depression (MADRS at Week 6) anticipated
  2. Phase 3 bipolar depression program initiated; X-CEED (NCT07172516) began enrolling (actual study start 2025-08-08). X-CEED is the first of two planned Phase 3 BPD efficacy trials.

Readouts

  • 2028AnticipatedTopline dataNCT07172516

    X-CEED Phase 3 topline in bipolar I/II depression (MADRS at Week 6) anticipated

Clinical trials in Bipolar depression

NCT07217860X-CEED-OLEPhase 3Activen=400

A Multicenter, Long-term, Open-Label, Safety, Tolerability, and Efficacy Study of Azetukalner in Bipolar I or II Depression (X-CEED-OLE)

Started Oct 2025· 📍 15 sites across 1 country (United States)

NCT07172516X-CEEDPhase 3Recruitingn=400

A Phase 3, Randomized, Double-blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Azetukalner in Depressive Episodes Associated With Bipolar I or II Disorder (Bipolar Depression) (X-CEED)

Started Aug 2025· 📍 28 sites across 1 country (United States)

Formulations

FormulationRouteRegimenPharmacokinetics
Azetukalner oral once-dailypowder-in-capsule
10-25 mg once daily with food, no titration; effective half-life >24 h supports once-daily dosing. Phase 1 used a powder-in-capsule formulation; Phase 2b/3 (X-TOLE, X-TOLE2) used 10/15/20/25 mg once daily with food.
OralOnce daily—

Mechanism of action (compound-wide)

Selective opener of neuronal Kv7.2/Kv7.3 (KCNQ2/3) channels; increases K+ flux, hyperpolarizes the membrane and dampens hyperexcitability. EC50 ~27 nM at the Kv7.2/7.3 heteromer.

TargetActionAffinity
Kv7.2primaryKCNQ2ActivatorEC50 27 nMⓘ
Kv7.3KCNQ3Activator—ⓘ

← Full XEN1101 compound page (identity, identifiers, all indications)

Sources

  1. medchemexpress.com — Reference
  2. X-CEED — Phase 3 Azetukalner in Bipolar I/II Depression (NCT07172516) — ClinicalTrials.gov
  3. X-CEED-OLE — Open-label Azetukalner in Bipolar I/II Depression (NCT07217860) — ClinicalTrials.gov
  4. Xenon Announces Final Results of XEN1101 Phase 1 Clinical Trial (powder-in-capsule formulation, effective half-life >24 h, once-per-day dosing) — Xenon Pharmaceuticals / GlobeNewswire