Trial Outcomes & Findings for A Study to Evaluate Safety and Tolerability of CVL-231 (Emraclidine) in Adult Participants With Schizophrenia (NCT NCT05443724)

Two groups of participants were included in the study: rollover (who completed treatment in the double-blind, placebo-controlled, Phase 2 efficacy Study CVL-231-2001 or Study CVL-231-2002) and de novo participants (who had stable schizophrenia and were not enrolled in either Phase 2 efficacy study). The study included an up to 15-day Screening Period (de novo participants only), a 52-week Treatment Period, and a 28-day Follow-up Period.

The Intent-to-treat (ITT) population included all participants who were enrolled in this trial and was used for the Participant Flow, Demographic and Baseline Characteristics, and safety analysis. The Safety Analysis Set included all participants who received at least 1 dose of emraclidine in Study CVL-231-2003 and was used for efficacy evaluations.

A Study to Evaluate Safety and Tolerability of CVL-231 (Emraclidine) in Adult Participants With Schizophrenia

An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study drug. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent adverse events/treatment-emergent serious adverse events (TEAEs/TESAEs) are defined as any event that began or worsened in severity on or after the first dose of study drug.

Vital signs were obtained after the participant had been supine and at rest for 3 minutes and included systolic and diastolic blood pressure, heart rate, temperature, and respiratory rate.

Participants' body weights were measured and recorded.

The number of participants with clinically significant changes in physical and neurological examination results post-treatment was documented.

12-lead electrocardiogram (ECG) recordings were obtained after the participant had been supine and at rest for at least 3 minutes.

Clinical laboratory tests were performed at scheduled study visits, and the investigator recorded any clinically significant changes.

Clinical laboratory tests were performed at scheduled study visits, and the investigator recorded any clinically significant changes in metabolic parameter values.

The C-SSRS rates an individual's degree of suicidal ideation (SI) on a scale, ranging from "wish to be dead" to "active suicidal ideation with specific plan and intent." The scale identifies SI severity and intensity, which may be indicative of an individual's intent to commit suicide. C-SSRS SI severity subscale ranges from 0 (no SI) to 5 (active SI with plan and intent).

The SAS consists of a list of 10 symptoms of parkinsonism. Each item is rated on a 5-point scale, with a score of 0 representing absence of symptoms and a score of 4 representing a severe condition. The SAS total score is the sum of the scores for all 10 items. Baseline was defined as the last value obtained prior to initiation of study drug. Change from baseline for a given endpoint was defined as the value on a given Study Day (Time Point) minus the Baseline Value. Negative changes from Baseline indicate an improvement in symptoms.

The Abnormal Involuntary Movement Scale assessment consists of 10 items describing symptoms of dyskinesia. Facial and oral movements (items 1-4), extremity movements (items 5 and 6), and trunk movements (item 7) are observed unobtrusively while the participant is at rest, and the investigator also makes global judgments on the participant's dyskinesias (items 8-10). Each item is rated on a 5-point scale, with a score of 0 representing absence of symptoms (for item 10, no awareness), and a score of 4 indicating a severe condition (for item 10, awareness, severe distress). In addition, the AIMS includes 2 yes/no questions that address the participant's dental status. The AIMS Movement Rating Score is defined as the sum of individual scores from items 1-7, ranging from 0 to 28. A lower score indicates less severe or absent abnormal movements. A negative change in the mean from Baseline indicates improvement in the severity of abnormal involuntary movements.

The BARS consists of 4 items related to akathisia. The fourth item, reported here, is the Global Clinical Evaluation Score. The Global Clinical Evaluation Score is evaluated using a 6-point scale, ranging from 0 to 5, with 0 representing absence of symptoms and a score of 5 representing severe akathisia. A negative change from baseline indicates an improvement in symptoms.