A Phase 1B Trial To Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Multiple Ascending Doses of CVL-231 in Subjects With Schizophrenia

Change from Baseline of Simpson-Angus Scale (SAS) Results

Time Frame: Up to Day 72

Evaluating Extrapyramidal symptoms using the SAS. The SAS consists of a list of 10 symptoms of parkinsonism (gait, arm dropping, shoulder shaking, elbow rigidity, wrist rigidity, head rotation, glabella tap, tremor, salivation, and akathisia). 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.

Incidence of Treatment Emergent Adverse Events (TEAEs)

Time Frame: Up to Day 72

Includes Incidence of Significant ECG Abnormalities Occurring Post-Baseline, significant changes in Vital signs (Systolic and Diastolic blood pressures, heart rate, respiratory rate and body temperature), and changes in laboratory measures (hematology, serum chemistry and urinalysis)

Change from Baseline of Abnormal Involuntary Movement Scale (AIMS) Results

Time Frame: Up to Day 72

The AIMS assessment consists of 10 items describing symptoms of dyskinesia. Facial and oral movements (items 1 through 4), extremity movements (items 5 and 6), and trunk movements (item 7) are observed unobtrusively while the subject is at rest, and the investigator also makes global judgments on the subject's dyskinesias (items 8 through 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 subject's dental status. The AIMS Movement Rating Score is defined as the sum of items 1 through 7 (ie, items 1 through 4, facial and oral movements; items 5 and 6, extremity movements; and item 7, trunk movements).

Incidence of suicidality as assessed by Columbia-Suicide Severity Rating Scale(C-SSRS)

Time Frame: Up to Day 72

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).

Change from Baseline of Barnes Akathisia Rating Scale (BARS) Results

Time Frame: Up to Day 72

Evaluating Extrapyramidal symptoms using the BARS. The BARS consists of 4 items related to akathisia: objective observation of akathisia by the investigator, subjective feelings of restlessness by the subject, subjective distress due to akathisia, and global clinical assessment of akathisia. The first 3 items are rated on a 4-point scale, with a score of 0 representing absence of symptoms and a score of 3 representing a severe condition. The global clinical evaluation is made on a 6-point scale, with a score of 0 representing absence of symptom and a score of 5 representing severe akathisia.