Efficacy and Safety of Direclidine (NBI-1117568) in Hospitalized Adults with Schizophrenia: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study

The primary objective is to assess the efficacy of NBI‑1117568 compared with placebo in improving behavioral and psychological symptoms of schizophrenia in adult in‑patients, thereby addressing a critical need for rapid symptom reduction during acute hospitalization. The secondary objective is to evaluate the safety and tolerability profile of NBI‑1117568 in the same patient population.

The trial enrolled 143 adult participants, both female and male, ranging from 18 to 65 years of age, all of whom were diagnosed with schizophrenia and were experiencing an acute worsening or relapse of symptoms that began less than two months before screening, necessitating hospitalization. Subjects were selected on the basis of a primary diagnosis of the disorder, age criteria, and the recent onset of a relapse requiring inpatient care. No specific dietary, physical activity, or habit restrictions were imposed beyond the clinical requirements related to the acute episode. Inclusion criteria emphasized the recent relapse and hospitalization status, while general health status was limited to individuals capable of providing informed consent and meeting the acute clinical presentation outlined above.

The study is a global, Phase 3, multicenter, randomized, double‑blind, placebo‑controlled trial evaluating NBI‑1117568 (oral hard capsule) versus matching placebo in adults aged 18–65 years with a primary diagnosis of schizophrenia experiencing an acute relapse that warrants inpatient hospitalization. After an initial screening visit to confirm eligibility, participants receive the first dose of study medication and constitute the baseline (Day 0) visit. Subsequent study visits occur weekly for five weeks, during which efficacy is assessed by the change from baseline in PANSS total score (primary endpoint) and CGI‑S score (secondary endpoint) at Week 5, and safety is monitored. The final visit at Week 5 serves as the end‑of‑study assessment. Overall participant involvement spans approximately six weeks, encompassing screening, five weekly evaluations, and the concluding visit. The trial period for recruitment extends from October 2025 to February 2028.

The investigational product, identified as NBI-1117568, is supplied as a hard gelatin capsule intended for oral administration. Each capsule contains 00 mg of the active moiety direclidine. The capsule is to be taken by the participant according to the dosing schedule defined in the protocol, with the route of administration recorded as oral.

The comparator in the study is the NBI-1117568 Placebo Capsule, which contains no active pharmaceutical ingredient and is formulated to be indistinguishable from the active capsule in appearance and administration. The placebo is also administered orally in accordance with the same schedule as the investigational product.

Both the active and placebo capsules are provided in identical packaging to preserve blinding. Participant compliance with the dosing regimen is monitored by accounting of dispensed and returned capsules and by documenting administration times in the trial records. The study evaluates the efficacy and safety of NBI-1117568 in adults hospitalized for schizophrenia compared with placebo.

Efficacy will be evaluated by measuring the change from baseline in the PANSS total score at Week 5. The Positive and Negative Syndrome Scale, a validated clinician‑rated instrument, will be administered at screening to establish baseline values and repeated at the Week 5 visit to assess symptom improvement.

A secondary efficacy endpoint is the change from baseline in the CGI‑S score at Week 5. The Clinical Global Impressions – Severity scale, also a validated clinician‑rated tool, will be completed at baseline and at the Week 5 assessment to capture overall clinical severity.