NBI-1117568 · program
Direclidine (NBI-1117568) for Schizophrenia
Indications for NBI-1117568: Schizophrenia · Phase 3 Bipolar disorder · Phase 2
Schizophrenia is the lead indication for NBI-1117568 (direclidine). A Phase 2, randomized, double-blind, placebo-controlled inpatient study (NCT05545111, n=210) met its primary endpoint: the once-daily 20 mg dose produced a placebo-adjusted PANSS total reduction of 7.5 points at Week 6 (p=0.011, effect size 0.61) with an 18.2-point reduction from baseline, plus significant improvement on CGI-S and Marder positive- and negative-symptom factors; the drug was generally safe and well tolerated with minimal GI/cardiovascular adverse events (reported 28 Aug 2024). On 30 Apr 2025 Neurocrine initiated a global Phase 3 registrational program comprising replicate acute-exacerbation inpatient studies (SCZ3029 / NCT06963034 and SCZ3030 / NCT07105098, ~284 each; primary endpoint PANSS change, key secondary CGI-S), a long-term safety study (SCZ3032 / NCT07114874, ~600), and a relapse-prevention study (NCT07227818, ~560). As of mid-2026 the program is active and recruiting in Phase 3.
Development timeline
- UpcomingAnticipated topline from Phase 3 acute study SCZ3030 (PANSS at Week 6).
- UpcomingAnticipated topline from Phase 3 acute study SCZ3029 (PANSS at Week 6).
- Phase 3 registrational program initiated (acute studies SCZ3029/SCZ3030, long-term SCZ3032, relapse-prevention) following positive Phase 2 data.↗
Readouts
- Q4 2027AnticipatedTopline dataNCT07105098
Anticipated topline from Phase 3 acute study SCZ3030 (PANSS at Week 6).
- Q4 2027AnticipatedTopline dataNCT06963034
Anticipated topline from Phase 3 acute study SCZ3029 (PANSS at Week 6).
- 2024-08-28ReportedTopline datametNCT05545111
Phase 2 met its primary endpoint: 20 mg QD gave placebo-adjusted PANSS -7.5 at Week 6 (p=0.011, ES 0.61). ↗
Clinical trials in Schizophrenia
NCT07227818Phase 3Recruitingn=560
Efficacy of NBI-1117568 in Preventing Relapse in Adults With Schizophrenia
NCT07105098NBI-1117568-SCZ3030Phase 3Recruitingn=284
NBI-1117568-SCZ3030: Evaluation of NBI-1117568 in Inpatient Adults With Schizophrenia
NCT07114874NBI-1117568-SCZ3032Phase 3Recruitingn=600
NBI-1117568-SCZ3032: Long-Term Evaluation of NBI-1117568 in Adults With Schizophrenia
NCT06963034NBI-1117568-SCZ3029Phase 3Recruitingn=284
NBI-1117568-SCZ3029: Evaluation of NBI-1117568 in Inpatient Adults With Schizophrenia
NCT05545111NBI-1117568-SCZ2027Phase 2Completedn=210
A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy, Safety, Tolerability, and Pharmacokinetics of NBI-1117568 in Adults With Schizophrenia Who Warrant Inpatient Hospitalization
metsecondaryCGI-S and Marder Positive / Negative symptom factor scores (Week 6)
Statistically significant improvement across several secondary endpoints, including CGI-S and the Marder Factor Score for positive- and negative-symptom change. Generally safe and well tolerated at all doses with minimal GI and cardiovascular adverse events.
metprimaryPANSS total change from baseline at Week 6 (20 mg once-daily dose) — Placebo-adjusted mean reduction 7.5 points; effect size 0.61; 18.2-point reduction from baseline (0.011)
Primary endpoint met for the 20 mg QD arm: clinically meaningful and statistically significant placebo-adjusted reduction in PANSS total at Week 6. Reported 28 Aug 2024.
Formulations
| Formulation | Route | Regimen | Pharmacokinetics |
|---|---|---|---|
| Direclidine oral tablet 20 mg once daily (dose that met the Phase 2 primary endpoint and advanced into the Phase 3 registrational program); additional Phase 2 arms evaluated 40 mg once daily, 60 mg once daily, and 30 mg twice daily | Oral | Once daily | — |
Mechanism of action
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.
| Target | Action | Affinity |
|---|---|---|
| M4primaryCHRM4 | Agonist | —ⓘ |
← Full NBI-1117568 compound page (identity, identifiers, all indications)
Sources
- M4 receptor (CHRM4), GtoPdb object 16 — IUPHAR/BPS Guide to Pharmacology
- NBI-1117568-SCZ3029 Phase 3 inpatient schizophrenia study (NCT06963034) — ClinicalTrials.gov
- NBI-1117568-SCZ3030 Phase 3 inpatient schizophrenia study (NCT07105098) — ClinicalTrials.gov
- NBI-1117568-SCZ3032 long-term Phase 3 schizophrenia study (NCT07114874) — ClinicalTrials.gov
- Neurocrine Biosciences Initiates Phase 3 Registrational Program for NBI-1117568 as Potential Treatment for Adults with Schizophrenia — Neurocrine Biosciences / IR
- Neurocrine Biosciences Initiates Phase 3 Registrational Program for NBI-1117568 as Potential Treatment for Adults with Schizophrenia — Neurocrine Biosciences (via PR Newswire)
- Neurocrine Biosciences Reports Positive Phase 2 Data for NBI-1117568 in Adults with Schizophrenia — Neurocrine Biosciences / IR
- Phase 2 study of NBI-1117568 in adults with schizophrenia (NCT05545111) — ClinicalTrials.gov
- Phase 3 relapse-prevention study of NBI-1117568 in schizophrenia (NCT07227818) — ClinicalTrials.gov
- Sosei Heptares' Partner Neurocrine Biosciences Initiates Phase 2 Clinical Study Evaluating NBI-1117568 in Adults with Schizophrenia — Sosei Heptares (Nxera Pharma) / GlobeNewswire