NBI-1117568 · program

Direclidine (NBI-1117568) for Bipolar disorder

Phase 2RecruitingNeurocrine Biosciences, Inc. (NBIX)

Indications for NBI-1117568: Schizophrenia · Phase 3 Bipolar disorder · Phase 2

Bipolar I disorder with current mania is a secondary indication for NBI-1117568 (direclidine), Neurocrine's oral, once-daily, M4-selective orthosteric muscarinic agonist (lead indication: schizophrenia). Building on the muscarinic-agonist antipsychotic rationale, Neurocrine is running a single Phase 2, multicenter, randomized, double-blind, placebo-controlled study (NCT07288320 / NBI-1117568-BPD2036, ~150 adults aged 18-65) evaluating NBI-1117568 vs. placebo for the acute treatment of a manic episode (with or without mixed features) in adults with bipolar I disorder. The primary endpoint is the change from baseline in the Young Mania Rating Scale (YMRS) total score at Day 21. Neurocrine had previously guided (via partner Nxera Pharma, Jan 2025) to initiate this study in 2H 2025; the trial began dosing on 24 Dec 2025 and is recruiting, with an estimated primary completion in February 2028. No topline data have been reported yet.

Data current as of

Development timeline

Phase 2Jan 2025 – Feb 2028
  1. UpcomingAnticipated topline from the Phase 2 bipolar I mania study (NBI-1117568-BPD2036): change from baseline in YMRS total score at Day 21.
  2. Phase 2 bipolar I mania study (NCT07288320 / NBI-1117568-BPD2036, n~150) started (actual start date 2025-12-24 per ClinicalTrials.gov); status RECRUITING. Primary endpoint: change from baseline in YMRS total score at Day 21; estimated primary completion Feb 2028.
  3. Neurocrine guided (via partner Nxera Pharma portfolio update) that it expected to initiate a Phase 2 study of NBI-1117568 ('NBI-'568') in bipolar mania in 2H 2025.↗

Readouts

  • 1H 2028AnticipatedTopline dataNCT07288320

    Anticipated topline from the Phase 2 bipolar I mania study (NBI-1117568-BPD2036): change from baseline in YMRS total score at Day 21.

Clinical trials in Bipolar disorder

NCT07288320NBI-1117568-BPD2036Phase 2Recruitingn=150

A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy, Safety, and Pharmacokinetics of NBI-1117568 in Adults With Bipolar I Disorder With Current Mania

Started Dec 2025· Primary completion Feb 2028· 📍 6 sites across 1 country (United States)

Mechanism of action (compound-wide)

Selective orthosteric agonist at the muscarinic acetylcholine M4 receptor (CHRM4 / Gi/o-coupled GPCR), with very low affinity at the M1, M2, M3 and M5 muscarinic subtypes. M4 agonism in striatal and cortical circuits is hypothesized to reduce dopaminergic hyperactivity and produce antipsychotic effects via a non-D2 mechanism. As an orthosteric agonist (binding the acetylcholine site, competitive, non-covalent) it does not require the presence of endogenous acetylcholine for activity, distinguishing it from allosteric M4 PAMs. The molecule's M4 selectivity is intended to deliver antipsychotic efficacy while limiting the peripheral cholinergic (GI/cardiovascular) burden seen with non-selective muscarinic agonists, so no co-administered peripheral muscarinic antagonist is needed.

TargetActionAffinity
M4primaryCHRM4Agonist—ⓘ

← Full NBI-1117568 compound page (identity, identifiers, all indications)

Sources

  1. An Assessment of Efficacy, Safety, and Pharmacokinetics of NBI-1117568 in Adults With Bipolar I Disorder With Current Mania (NCT07288320) — ClinicalTrials.gov
  2. M4 receptor (CHRM4), GtoPdb object 16 — IUPHAR/BPS Guide to Pharmacology
  3. Nxera Pharma provides update on Neurocrine's progress with its partnered muscarinic agonist portfolio — Nxera Pharma (via BioIndustry Association)