Schizophrenia
Conditions
Keywords
Schizophrenia, Schizophrenia Spectrum and Other Psychotic Disorders, Mental Disorders
Brief summary
This is a Phase 2, multicenter, randomized, double-blind, placebo-controlled, parallel-group, 6-week trial to evaluate the efficacy, safety, and tolerability of 2 fixed doses of CVL-231 (Emraclidine) (15 mg QD and 30 mg QD) in male and female adult participants who have schizophrenia and are experiencing an acute exacerbation of psychosis.
Detailed description
The trial included up to a 15-day Screening Period (up to a maximum of 21 days allowed with approval of the medical monitor), a 45-day Inpatient Treatment Period, and a 28-day Follow-up Period. Each participant participated in the trial for up to approximately 13 weeks.
Interventions
DRUGEmraclidine 15 mg
Emraclidine 15 mg, oral (tablet), once per day (QD) for 6 weeks
Emraclidine 30 mg, oral (tablet), QD for 6 weeks
DRUGPlacebo
Matching placebo, oral (tablet), QD for 6 weeks
Sponsors
AbbVie
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Intervention model description
Placebo-controlled
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Primary diagnosis of schizophrenia per DSM-5, as confirmed by the MINI for Psychotic Disorders. * CGI-S ≥4 (moderately to severely ill) at the time of signing the ICF and Baseline. * PANSS Total Score between 85 and 120, inclusive, at the time of signing the ICF and at Baseline. * Experiencing an acute exacerbation or relapse of psychotic symptoms, with onset less than 60 days prior to signing the ICF. * Willing to discontinue all prohibited medications to meet protocol-required washouts prior to and during the trial period. * Body mass index of 18.0 to 40.0 kg/m2 and a total body weight ≥50 kg (110 lbs). * Ability, in the opinion of the investigator, to understand the nature of the trial, participate in trial visits, and comply with protocol requirements.
Exclusion criteria
* Current DSM-5 diagnosis other than schizophrenia (note: anxiety symptoms secondary to schizophrenia are allowed); Acute depressive symptoms within 30 days prior to signing the ICF that require treatment with an antidepressant are exclusory. Acute manic symptoms within 30 days prior to signing the ICF that require treatment with a mood stabilizer are exclusory. * Any of the following: * Schizophrenia considered resistant/refractory to antipsychotic treatment by history (failure to respond to 2 or more courses of adequate pharmacological treatment defined as an adequate dose per label and a treatment duration of at least 4 weeks) * History of response to clozapine treatment only or failure to respond to clozapine treatment * Any of the following regarding history of schizophrenia: * Time from initial onset of schizophrenia \<2 years based on prior records or participant self-report * Presenting with an initial diagnosis of schizophrenia * Presenting for the first time with an acute psychotic episode requiring treatment * Reduction (improvement) in PANSS total score of ≥20% between Screening and Baseline. * Current or past history of significant cardiovascular, pulmonary, gastrointestinal, renal, hepatic, metabolic, genitourinary, endocrine (including diabetes mellitus), malignancy (except for basal cell carcinoma of the skin and cervical carcinoma in situ, at the discretion of the investigator), hematological, immunological, neurological, or psychiatric disease that, in the opinion of the investigator or medical monitor, could compromise either participant safety or the results of the trial. * Active central nervous system infection, demyelinating disease, degenerative neurological disease, brain tumor, prior hospitalization for severe head trauma, seizures (excluding febrile seizures in childhood), or any central nervous system disease deemed to be progressive during the course of the trial that may confound the interpretation of the trial results * Diagnosis of moderate to severe substance or alcohol-use disorder (excluding nicotine or caffeine) as per DSM-5 criteria within 12 months prior to signing the ICF. * Risk for suicidal behavior as assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) and investigator's clinical assessment. * Any condition that could possibly affect drug absorption. * Use of prohibited medications prior to randomization within the required wash-out period or likely to require prohibited concomitant therapy during the trial. * Clinically significant abnormal findings on the physical examination, medical history review, ECG, or clinical laboratory results at screening. * Positive pregnancy test result prior to receiving IMP. Note: female participants who are pregnant, breastfeeding, or planning to become pregnant during IMP treatment or within 7 days after the last dose of IMP are also excluded.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline at Week 6 in the Positive and Negative Syndrome Scale (PANSS) Total Score | Baseline through Week 6 | The PANSS measures symptom severity of participants with schizophrenia and contains 7 positive symptom scales, 7 negative system scales, and 16 general psychopathology symptom scales. Participants are rated from 1 to 7 on each symptom scale with a total minimum score of 30 and a maximum score of 210. Baseline was defined as the last value obtained prior to initiation of investigational medicinal product (IMP). Change from baseline for a given endpoint was defined as the value on a given Study Day (Time Point) minus the Baseline Value. A decrease in PANSS total score correlates with an improvement in schizophrenia symptoms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline at All Time Points in Positive and Negative Syndrome Scale (PANSS) Total Score | Baseline; Weeks 1, 2, 3, 4, 5, and 6 | The PANSS measures symptom severity of participants with schizophrenia and contains 7 positive symptom scales, 7 negative system scales, and 16 general psychopathology symptom scales. Participants are rated from 1 to 7 on each symptom scale with a total minimum score of 30 and a maximum score of 210. Baseline was defined as the last value obtained prior to initiation of investigational medicinal product (IMP). Change from baseline for a given endpoint was defined as the value on a given Study Day (Time Point) minus the Baseline Value. A decrease in PANSS total score correlates with an improvement in schizophrenia symptoms. |
| Change From Baseline at All Time Points in the Clinical Global Impression - Severity (CGI-S) Score | Baseline; Weeks 1, 2, 3, 4, 5, and 6 | The CGI-S captures clinician's response to: Considering your total clinical experience, how mentally ill is the participant at this time? The clinician's answer rated on the following 7-point scale: 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; 7 = among the most extremely ill participants. Baseline was defined as the last value obtained prior to initiation of Emraclidine. 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 less mental illness. |
| Percentage of Responders at Week 6 (Responders Defined as ≥30% Reduction From Baseline in PANSS Total Score) | Baseline through Week 6 | The PANSS measures symptom severity of participants with schizophrenia and contains 7 positive symptom scales, 7 negative system scales, and 16 general psychopathology symptom scales. Participants are rated from 1 to 7 on each symptom scale with a total minimum score of 30 and a maximum score of 210. A PANSS responder is defined as a participant with at least a 30% change in PANSS total score compared to baseline at Week 6 or the early termination visit. If a subject discontinued and did not have an early termination visit, the subject's last assessment was considered. |
| Number of Participants With Treatment Emergent Adverse Event (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | From first dose of study drug until 28 days following last dose of study drug (up to Week 10) | 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. |
| Number of Participants With Clinically Significant Changes in Electrocardiogram (ECGs) | Baseline; from first dose of study drug up to Week 6 | Assessment of clinically significant changes in electrocardiogram measures measured by 12-lead ECG recording after the participant has been supine and at rest for at least 3 minutes. |
| Number of Participants With Clinically Significant Changes in Clinical Laboratory Assessments | Baseline; from first dose of study drug up to Week 6 | Clinical laboratory tests were performed at scheduled study visits, and the investigator recorded any clinically significant changes. |
| Change From Baseline at Week 6 in the Clinical Global Impression - Severity (CGI-S Score) | Baseline through Week 6 | The CGI-S captures clinician's response to: Considering your total clinical experience, how mentally ill is the participant at this time? The clinician's answer rated on the following 7-point scale: 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; 7 = among the most extremely ill participants. Baseline was defined as the last value obtained prior to initiation of investigational medicinal product (IMP). 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 less mental illness. |
| Number of Participants With Clinically Significant Changes in Physical and Neurological Examination Results | Baseline; from first dose of study drug up to Week 6 | The number of participants with clinically significant changes in physical and neurological examination results was documented. |
| Number of Participants With Suicide-Related Treatment-Emergent Events Assessed Using the Columbia Suicide-Severity Rating Scale (C-SSRS) | Baseline; from first dose of study drug up to Week 6 | 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 in Simpson Angus Scale (SAS) Total Score | Baseline; Weeks 3 and 6 | 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. |
| Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Movement Rating Score | Baseline; Weeks 3 and 6 | 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. |
| Change From Baseline in Barnes Akathisia Rating Scale (BARS) Global Clinical Evaluation Score | Baseline; Weeks 3 and 6 | The BARS consists of 4 items related to 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 fourth item, reported here, is the Global Clinical Evaluation Score. The Global Clinical Evaluation Score is evaluated using a 6-point scale, with a score of 0 representing the absence of symptoms and a score of 5 representing severe akathisia. A negative change from baseline indicates an improvement in symptoms. |
| Number of Participants With Clinically Significant Changes in Vital Sign Measurements | Baseline; from first dose of study drug up to Week 6 | Vital signs were obtained after the participant had been supine and at rest for 3 minutes and included temperature, systolic and diastolic blood pressure, respiratory rate, and heart rate. Participants' body weights were also measured and recorded. |
Countries
Bulgaria, Hungary, United States
Participant flow
Recruitment details
Participants were randomly assigned at a ratio of 1:1:1 to one of three treatment groups (Emraclidine 15 mg QD, Emraclidine 30 mg QD, or Placebo). Randomization was stratified by geographic region (United States or all other countries).
Pre-assignment details
The ITT population included all randomized participants and was used for the Demographic and Baseline Characteristics. The modified ITT (mITT) population included all randomized participants who received at least one dose of study drug, had a baseline assessment, and had at least 1 postbaseline PANSS assessment. The mITT population was used for the efficacy evaluations. The FAS included all randomized participants who receive at least one dose of study drug and was used for the safety analysis.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received a single daily oral dose of Placebo each morning from Day 1 (baseline) through Day 45. Participants (completers and early withdrawals) were followed for safety up to approximately 28 days after the last dose. | 130 |
| Emraclidine 15 mg QD Participants received a single daily oral dose of Emraclidine 15 mg each morning from Day 1 (baseline) through Day 45. Participants (completers and early withdrawals) were followed for safety up to approximately 28 days after the last dose. | 130 |
| Emraclidine 30 mg QD Participants received a single daily oral dose of Emraclidine 30 mg each morning from Day 1 (baseline) through Day 45. Participants (completers and early withdrawals) were followed for safety up to approximately 28 days after the last dose. | 131 |
| Total | 391 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 6 | 4 |
| Overall Study | Lack of Efficacy | 4 | 0 | 1 |
| Overall Study | Non-Compliance with Study Schedule | 0 | 1 | 0 |
| Overall Study | Other | 1 | 1 | 0 |
| Overall Study | Physician Decision | 2 | 2 | 1 |
| Overall Study | Protocol Violation | 2 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 17 | 26 | 32 |
Baseline characteristics
| Characteristic | Placebo | Emraclidine 15 mg QD | Emraclidine 30 mg QD | Total |
|---|---|---|---|---|
| Age, Continuous | 42.1 years STANDARD_DEVIATION 12.18 | 42.7 years STANDARD_DEVIATION 11.51 | 41.5 years STANDARD_DEVIATION 10.76 | 42.1 years STANDARD_DEVIATION 11.48 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 30 Participants | 25 Participants | 25 Participants | 80 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 100 Participants | 105 Participants | 106 Participants | 311 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 76 Participants | 83 Participants | 85 Participants | 244 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 53 Participants | 44 Participants | 44 Participants | 141 Participants |
| Sex: Female, Male Female | 27 Participants | 34 Participants | 25 Participants | 86 Participants |
| Sex: Female, Male Male | 103 Participants | 96 Participants | 106 Participants | 305 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 130 | 0 / 130 | 0 / 131 |
| other Total, other adverse events | 47 / 130 | 47 / 130 | 50 / 131 |
| serious Total, serious adverse events | 1 / 130 | 3 / 130 | 1 / 131 |
Outcome results
Primary
Change From Baseline at Week 6 in the Positive and Negative Syndrome Scale (PANSS) Total Score
The PANSS measures symptom severity of participants with schizophrenia and contains 7 positive symptom scales, 7 negative system scales, and 16 general psychopathology symptom scales. Participants are rated from 1 to 7 on each symptom scale with a total minimum score of 30 and a maximum score of 210. Baseline was defined as the last value obtained prior to initiation of investigational medicinal product (IMP). Change from baseline for a given endpoint was defined as the value on a given Study Day (Time Point) minus the Baseline Value. A decrease in PANSS total score correlates with an improvement in schizophrenia symptoms.
Time frame: Baseline through Week 6
Population: Modified Intent-to-Treat population (mITT): All randomized participants who receive at least 1 dose of investigational medicinal product (IMP) and have both a baseline and at least 1 postbaseline PANSS assessment. Overall Number of Participants Analyzed includes participants with a non-missing value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Change From Baseline at Week 6 in the Positive and Negative Syndrome Scale (PANSS) Total Score | -16.1 score on a scale |
| Emraclidine 15mg QD | Change From Baseline at Week 6 in the Positive and Negative Syndrome Scale (PANSS) Total Score | -18.5 score on a scale |
| Emraclidine 30mg QD | Change From Baseline at Week 6 in the Positive and Negative Syndrome Scale (PANSS) Total Score | -14.2 score on a scale |
p-value: 0.292595% CI: [-7, 2.1]Mixed Model for Repeated Measures (MMRM)
Comparison: Emraclidine 30 mg versus Placebop-value: 0.391495% CI: [-2.5, 6.4]Mixed Model for Repeated Measures (MMRM)
Secondary
Change From Baseline at All Time Points in Positive and Negative Syndrome Scale (PANSS) Total Score
The PANSS measures symptom severity of participants with schizophrenia and contains 7 positive symptom scales, 7 negative system scales, and 16 general psychopathology symptom scales. Participants are rated from 1 to 7 on each symptom scale with a total minimum score of 30 and a maximum score of 210. Baseline was defined as the last value obtained prior to initiation of investigational medicinal product (IMP). Change from baseline for a given endpoint was defined as the value on a given Study Day (Time Point) minus the Baseline Value. A decrease in PANSS total score correlates with an improvement in schizophrenia symptoms.
Time frame: Baseline; Weeks 1, 2, 3, 4, 5, and 6
Population: mITT: All randomized participants who receive at least 1 dose of investigational medicinal product (IMP) and have both a baseline and at least 1 postbaseline PANSS assessment. Overall Number of Participants Analyzed includes participants with available data.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Placebo | Change From Baseline at All Time Points in Positive and Negative Syndrome Scale (PANSS) Total Score | Week 1 | -5.0 score on a scale |
| Placebo | Change From Baseline at All Time Points in Positive and Negative Syndrome Scale (PANSS) Total Score | Week 2 | -8.5 score on a scale |
| Placebo | Change From Baseline at All Time Points in Positive and Negative Syndrome Scale (PANSS) Total Score | Week 3 | -11.2 score on a scale |
| Placebo | Change From Baseline at All Time Points in Positive and Negative Syndrome Scale (PANSS) Total Score | Week 4 | -12.8 score on a scale |
| Placebo | Change From Baseline at All Time Points in Positive and Negative Syndrome Scale (PANSS) Total Score | Week 5 | -14.7 score on a scale |
| Placebo | Change From Baseline at All Time Points in Positive and Negative Syndrome Scale (PANSS) Total Score | Week 6 | -16.1 score on a scale |
| Emraclidine 15mg QD | Change From Baseline at All Time Points in Positive and Negative Syndrome Scale (PANSS) Total Score | Week 6 | -18.5 score on a scale |
| Emraclidine 15mg QD | Change From Baseline at All Time Points in Positive and Negative Syndrome Scale (PANSS) Total Score | Week 1 | -6.8 score on a scale |
| Emraclidine 15mg QD | Change From Baseline at All Time Points in Positive and Negative Syndrome Scale (PANSS) Total Score | Week 4 | -13.4 score on a scale |
| Emraclidine 15mg QD | Change From Baseline at All Time Points in Positive and Negative Syndrome Scale (PANSS) Total Score | Week 5 | -16.5 score on a scale |
| Emraclidine 15mg QD | Change From Baseline at All Time Points in Positive and Negative Syndrome Scale (PANSS) Total Score | Week 2 | -8.7 score on a scale |
| Emraclidine 15mg QD | Change From Baseline at All Time Points in Positive and Negative Syndrome Scale (PANSS) Total Score | Week 3 | -12.5 score on a scale |
| Emraclidine 30mg QD | Change From Baseline at All Time Points in Positive and Negative Syndrome Scale (PANSS) Total Score | Week 2 | -7.5 score on a scale |
| Emraclidine 30mg QD | Change From Baseline at All Time Points in Positive and Negative Syndrome Scale (PANSS) Total Score | Week 3 | -10.0 score on a scale |
| Emraclidine 30mg QD | Change From Baseline at All Time Points in Positive and Negative Syndrome Scale (PANSS) Total Score | Week 6 | -14.2 score on a scale |
| Emraclidine 30mg QD | Change From Baseline at All Time Points in Positive and Negative Syndrome Scale (PANSS) Total Score | Week 4 | -12.0 score on a scale |
| Emraclidine 30mg QD | Change From Baseline at All Time Points in Positive and Negative Syndrome Scale (PANSS) Total Score | Week 1 | -4.9 score on a scale |
| Emraclidine 30mg QD | Change From Baseline at All Time Points in Positive and Negative Syndrome Scale (PANSS) Total Score | Week 5 | -12.9 score on a scale |
Comparison: Week 1-- Emraclidine 15 mg versus Placebop-value: 0.116795% CI: [-4, 0.5]Mixed Model for Repeated Measures (MMRM)
Comparison: Week 1-- Emraclidine 30 mg versus Placebop-value: 0.925495% CI: [-2.1, 2.3]Mixed Model for Repeated Measures (MMRM)
Comparison: Week 2-- Emraclidine 15 mg versus Placebop-value: 0.879295% CI: [-3.3, 2.8]Mixed Model for Repeated Measures (MMRM)
Comparison: Week 2-- Emraclidine 30 mg versus Placebop-value: 0.509495% CI: [-2, 4]Mixed Model for Repeated Measures (MMRM)
Comparison: Week 3-- Emraclidine 15 mg versus Placebop-value: 0.448795% CI: [-4.8, 2.1]Mixed Model for Repeated Measures (MMRM)
Comparison: Week 3-- Emraclidine 30 mg versus Placebop-value: 0.485295% CI: [-2.2, 4.6]Mixed Model for Repeated Measures (MMRM)
Comparison: Week 4-- Emraclidine 15 mg versus Placebop-value: 0.759395% CI: [-4.2, 3.1]Mixed Model for Repeated Measures (MMRM)
Comparison: Week 4-- Emraclidine 30 mg versus Placebop-value: 0.679295% CI: [-2.8, 4.3]Mixed Model for Repeated Measures (MMRM)
Comparison: Week 5-- Emraclidine 15 mg versus Placebop-value: 0.398395% CI: [-5.9, 2.4]Mixed Model for Repeated Measures (MMRM)
Comparison: Week 5-- Emraclidine 30 mg versus Placebop-value: 0.385995% CI: [-2.3, 5.9]Mixed Model for Repeated Measures (MMRM)
Comparison: Week 6-- Emraclidine 15 mg versus Placebop-value: 0.292595% CI: [-7, 2.1]Mixed Model for Repeated Measures (MMRM)
Comparison: Week 6-- Emraclidine 30 mg versus Placebop-value: 0.391495% CI: [-2.5, 6.4]Mixed Model for Repeated Measures (MMRM)
Secondary
Change From Baseline at All Time Points in the Clinical Global Impression - Severity (CGI-S) Score
The CGI-S captures clinician's response to: Considering your total clinical experience, how mentally ill is the participant at this time? The clinician's answer rated on the following 7-point scale: 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; 7 = among the most extremely ill participants. Baseline was defined as the last value obtained prior to initiation of Emraclidine. 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 less mental illness.
Time frame: Baseline; Weeks 1, 2, 3, 4, 5, and 6
Population: mITT: All randomized participants who receive at least 1 dose of investigational medicinal product (IMP) and have both a baseline and at least 1 postbaseline PANSS assessment. Overall Number of Participants Analyzed includes participants with available data.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Placebo | Change From Baseline at All Time Points in the Clinical Global Impression - Severity (CGI-S) Score | Week 1 | -0.21 score on a scale |
| Placebo | Change From Baseline at All Time Points in the Clinical Global Impression - Severity (CGI-S) Score | Week 2 | -0.42 score on a scale |
| Placebo | Change From Baseline at All Time Points in the Clinical Global Impression - Severity (CGI-S) Score | Week 3 | -0.55 score on a scale |
| Placebo | Change From Baseline at All Time Points in the Clinical Global Impression - Severity (CGI-S) Score | Week 4 | -0.72 score on a scale |
| Placebo | Change From Baseline at All Time Points in the Clinical Global Impression - Severity (CGI-S) Score | Week 5 | -0.78 score on a scale |
| Placebo | Change From Baseline at All Time Points in the Clinical Global Impression - Severity (CGI-S) Score | Week 6 | -0.83 score on a scale |
| Emraclidine 15mg QD | Change From Baseline at All Time Points in the Clinical Global Impression - Severity (CGI-S) Score | Week 6 | -1.05 score on a scale |
| Emraclidine 15mg QD | Change From Baseline at All Time Points in the Clinical Global Impression - Severity (CGI-S) Score | Week 1 | -0.33 score on a scale |
| Emraclidine 15mg QD | Change From Baseline at All Time Points in the Clinical Global Impression - Severity (CGI-S) Score | Week 4 | -0.74 score on a scale |
| Emraclidine 15mg QD | Change From Baseline at All Time Points in the Clinical Global Impression - Severity (CGI-S) Score | Week 5 | -0.91 score on a scale |
| Emraclidine 15mg QD | Change From Baseline at All Time Points in the Clinical Global Impression - Severity (CGI-S) Score | Week 2 | -0.42 score on a scale |
| Emraclidine 15mg QD | Change From Baseline at All Time Points in the Clinical Global Impression - Severity (CGI-S) Score | Week 3 | -0.64 score on a scale |
| Emraclidine 30mg QD | Change From Baseline at All Time Points in the Clinical Global Impression - Severity (CGI-S) Score | Week 2 | -0.38 score on a scale |
| Emraclidine 30mg QD | Change From Baseline at All Time Points in the Clinical Global Impression - Severity (CGI-S) Score | Week 3 | -0.49 score on a scale |
| Emraclidine 30mg QD | Change From Baseline at All Time Points in the Clinical Global Impression - Severity (CGI-S) Score | Week 6 | -0.80 score on a scale |
| Emraclidine 30mg QD | Change From Baseline at All Time Points in the Clinical Global Impression - Severity (CGI-S) Score | Week 4 | -0.62 score on a scale |
| Emraclidine 30mg QD | Change From Baseline at All Time Points in the Clinical Global Impression - Severity (CGI-S) Score | Week 1 | -0.21 score on a scale |
| Emraclidine 30mg QD | Change From Baseline at All Time Points in the Clinical Global Impression - Severity (CGI-S) Score | Week 5 | -0.69 score on a scale |
Comparison: Week 1-- Emraclidine 15 mg versus Placebop-value: 0.086595% CI: [-0.27, 0.02]Mixed Model for Repeated Measures (MMRM)
Comparison: Week 1-- Emraclidine 30 mg versus Placebop-value: 0.992195% CI: [-0.14, 0.14]Mixed Model for Repeated Measures (MMRM)
Comparison: Week 2-- Emraclidine 15 mg versus Placebop-value: 0.97295% CI: [-0.18, 0.18]Mixed Model for Repeated Measures (MMRM)
Comparison: Week 2-- Emraclidine 30 mg versus Placebop-value: 0.662195% CI: [-0.14, 0.21]Mixed Model for Repeated Measures (MMRM)
Comparison: Week 3-- Emraclidine 15 mg versus Placebop-value: 0.361795% CI: [-0.29, 0.11]Mixed Model for Repeated Measures (MMRM)
Comparison: Week 3-- Emraclidine 30 mg versus Placebop-value: 0.545695% CI: [-0.13, 0.25]Mixed Model for Repeated Measures (MMRM)
Comparison: Week 4-- Emraclidine 15 mg versus Placebop-value: 0.845995% CI: [-0.24, 0.19]Mixed Model for Repeated Measures (MMRM)
Comparison: Week 4-- Emraclidine 30 mg versus Placebop-value: 0.392295% CI: [-0.12, 0.3]Mixed Model for Repeated Measures (MMRM)
Comparison: Week 5-- Emraclidine 15 mg versus Placebop-value: 0.291595% CI: [-0.37, 0.11]Mixed Model for Repeated Measures (MMRM)
Comparison: Week 5-- Emraclidine 30 mg versus Placebop-value: 0.442595% CI: [-0.14, 0.33]Mixed Model for Repeated Measures (MMRM)
Comparison: Week 6-- Emraclidine 15 mg versus Placebop-value: 0.116595% CI: [-0.48, 0.05]Mixed Model for Repeated Measures (MMRM)
Comparison: Week 6-- Emraclidine 30 mg versus Placebop-value: 0.826595% CI: [-0.23, 0.29]Mixed Model for Repeated Measures (MMRM)
Secondary
Change From Baseline at Week 6 in the Clinical Global Impression - Severity (CGI-S Score)
The CGI-S captures clinician's response to: Considering your total clinical experience, how mentally ill is the participant at this time? The clinician's answer rated on the following 7-point scale: 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; 7 = among the most extremely ill participants. Baseline was defined as the last value obtained prior to initiation of investigational medicinal product (IMP). 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 less mental illness.
Time frame: Baseline through Week 6
Population: mITT: All randomized participants who receive at least 1 dose of investigational medicinal product (IMP) and have both a baseline and at least 1 postbaseline PANSS assessment. Overall Number of Participants Analyzed includes participants with available data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Change From Baseline at Week 6 in the Clinical Global Impression - Severity (CGI-S Score) | -0.83 score on a scale |
| Emraclidine 15mg QD | Change From Baseline at Week 6 in the Clinical Global Impression - Severity (CGI-S Score) | -1.05 score on a scale |
| Emraclidine 30mg QD | Change From Baseline at Week 6 in the Clinical Global Impression - Severity (CGI-S Score) | -0.80 score on a scale |
Comparison: Emraclidine 15 mg versus Placebop-value: 0.116595% CI: [-0.48, 0.05]Mixed Model for Repeated Measures (MMRM)
Comparison: Emraclidine 30 mg versus Placebop-value: 0.826595% CI: [-0.23, 0.29]Mixed Model for Repeated Measures (MMRM)
Secondary
Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Movement Rating Score
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.
Time frame: Baseline; Weeks 3 and 6
Population: Full analysis set: All randomized participants who received at least 1 dose of investigational medicinal product (IMP); participants with available data
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Placebo | Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Movement Rating Score | Week 3 | 0.0 score on a scale |
| Placebo | Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Movement Rating Score | Week 6 | 0.0 score on a scale |
| Emraclidine 15mg QD | Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Movement Rating Score | Week 3 | 0.0 score on a scale |
| Emraclidine 15mg QD | Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Movement Rating Score | Week 6 | 0.0 score on a scale |
| Emraclidine 30mg QD | Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Movement Rating Score | Week 3 | 0.0 score on a scale |
| Emraclidine 30mg QD | Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Movement Rating Score | Week 6 | 0.0 score on a scale |
Comparison: Week 3-- Emraclidine 15 mg versus Placebop-value: 0.507395% CI: [-0.1, 0.1]Mixed Model for Repeated Measures (MMRM)
Comparison: Week 3-- Emraclidine 30 mg versus Placebop-value: 0.46595% CI: [-0.1, 0.1]Mixed Model for Repeated Measures (MMRM)
Comparison: Week 6-- Emraclidine 15 mg versus Placebop-value: 0.067295% CI: [-0.1, 0]Mixed Model for Repeated Measures (MMRM)
Comparison: Week 6-- Emraclidine 30 mg versus Placebop-value: 0.80395% CI: [-0.1, 0.1]Mixed Model for Repeated Measures (MMRM)
Secondary
Change From Baseline in Barnes Akathisia Rating Scale (BARS) Global Clinical Evaluation Score
The BARS consists of 4 items related to 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 fourth item, reported here, is the Global Clinical Evaluation Score. The Global Clinical Evaluation Score is evaluated using a 6-point scale, with a score of 0 representing the absence of symptoms and a score of 5 representing severe akathisia. A negative change from baseline indicates an improvement in symptoms.
Time frame: Baseline; Weeks 3 and 6
Population: Full analysis set: All randomized participants who received at least 1 dose of investigational medicinal product (IMP); participants with available data.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Placebo | Change From Baseline in Barnes Akathisia Rating Scale (BARS) Global Clinical Evaluation Score | Week 6 | -0.1 score on a scale |
| Placebo | Change From Baseline in Barnes Akathisia Rating Scale (BARS) Global Clinical Evaluation Score | Week 3 | 0.0 score on a scale |
| Emraclidine 15mg QD | Change From Baseline in Barnes Akathisia Rating Scale (BARS) Global Clinical Evaluation Score | Week 3 | 0.0 score on a scale |
| Emraclidine 15mg QD | Change From Baseline in Barnes Akathisia Rating Scale (BARS) Global Clinical Evaluation Score | Week 6 | 0.0 score on a scale |
| Emraclidine 30mg QD | Change From Baseline in Barnes Akathisia Rating Scale (BARS) Global Clinical Evaluation Score | Week 3 | 0.0 score on a scale |
| Emraclidine 30mg QD | Change From Baseline in Barnes Akathisia Rating Scale (BARS) Global Clinical Evaluation Score | Week 6 | 0.0 score on a scale |
Comparison: Week 3-- Emraclidine 15 mg versus Placebop-value: 0.825995% CI: [-0.1, 0.1]Mixed Model for Repeated Measures (MMRM)
Comparison: Week 3-- Emraclidine 30 mg versus Placebop-value: 0.593695% CI: [-0.1, 0]Mixed Model for Repeated Measures (MMRM)
Comparison: Week 6-- Emraclidine 15 mg versus Placebop-value: 0.025395% CI: [0, 0.1]Mixed Model for Repeated Measures (MMRM)
Comparison: Week 6-- Emraclidine 30 mg versus Placebop-value: 0.27195% CI: [0, 0.1]Mixed Model for Repeated Measures (MMRM)
Secondary
Change From Baseline in Simpson Angus Scale (SAS) Total Score
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.
Time frame: Baseline; Weeks 3 and 6
Population: Full analysis set: All randomized participants who received at least 1 dose of investigational medicinal product (IMP); participants with available data
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Placebo | Change From Baseline in Simpson Angus Scale (SAS) Total Score | Week 3 | -0.1 score on a scale |
| Placebo | Change From Baseline in Simpson Angus Scale (SAS) Total Score | Week 6 | 0.0 score on a scale |
| Emraclidine 15mg QD | Change From Baseline in Simpson Angus Scale (SAS) Total Score | Week 3 | 0.0 score on a scale |
| Emraclidine 15mg QD | Change From Baseline in Simpson Angus Scale (SAS) Total Score | Week 6 | 0.0 score on a scale |
| Emraclidine 30mg QD | Change From Baseline in Simpson Angus Scale (SAS) Total Score | Week 3 | 0.0 score on a scale |
| Emraclidine 30mg QD | Change From Baseline in Simpson Angus Scale (SAS) Total Score | Week 6 | 0.0 score on a scale |
Comparison: Week 3-- Emraclidine 15 mg versus Placebop-value: 0.049395% CI: [0, 0.2]Mixed Model for Repeated Measures (MMRM)
Comparison: Week 3-- Emraclidine 30 mg versus Placebop-value: 0.022695% CI: [0, 0.2]Mixed Model for Repeated Measures (MMRM)
Comparison: Week 6-- Emraclidine 15 mg versus Placebop-value: 0.684595% CI: [-0.1, 0.1]Mixed Model for Repeated Measures (MMRM)
Comparison: Week 6-- Emraclidine 30 mg versus Placebop-value: 0.89595% CI: [-0.1, 0.1]Mixed Model for Repeated Measures (MMRM)
Secondary
Number of Participants With Clinically Significant Changes in Clinical Laboratory Assessments
Clinical laboratory tests were performed at scheduled study visits, and the investigator recorded any clinically significant changes.
Time frame: Baseline; from first dose of study drug up to Week 6
Population: Full analysis set: All randomized participants who received at least 1 dose of investigational medicinal product (IMP)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Clinically Significant Changes in Clinical Laboratory Assessments | 3 Participants |
| Emraclidine 15mg QD | Number of Participants With Clinically Significant Changes in Clinical Laboratory Assessments | 4 Participants |
| Emraclidine 30mg QD | Number of Participants With Clinically Significant Changes in Clinical Laboratory Assessments | 3 Participants |
Secondary
Number of Participants With Clinically Significant Changes in Electrocardiogram (ECGs)
Assessment of clinically significant changes in electrocardiogram measures measured by 12-lead ECG recording after the participant has been supine and at rest for at least 3 minutes.
Time frame: Baseline; from first dose of study drug up to Week 6
Population: Full analysis set: All randomized participants who received at least 1 dose of investigational medicinal product (IMP)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Clinically Significant Changes in Electrocardiogram (ECGs) | QTcF increase from baseline: > 60 msec | 1 Participants |
| Placebo | Number of Participants With Clinically Significant Changes in Electrocardiogram (ECGs) | QTcF value: > 500 msec | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Changes in Electrocardiogram (ECGs) | QTcF value: > 450 - 480 msec | 3 Participants |
| Placebo | Number of Participants With Clinically Significant Changes in Electrocardiogram (ECGs) | QTcF value: > 480 - 500 msec | 1 Participants |
| Placebo | Number of Participants With Clinically Significant Changes in Electrocardiogram (ECGs) | QTcF increase from baseline: > 30 - 60 msec | 7 Participants |
| Emraclidine 15mg QD | Number of Participants With Clinically Significant Changes in Electrocardiogram (ECGs) | QTcF value: > 480 - 500 msec | 0 Participants |
| Emraclidine 15mg QD | Number of Participants With Clinically Significant Changes in Electrocardiogram (ECGs) | QTcF increase from baseline: > 60 msec | 1 Participants |
| Emraclidine 15mg QD | Number of Participants With Clinically Significant Changes in Electrocardiogram (ECGs) | QTcF increase from baseline: > 30 - 60 msec | 10 Participants |
| Emraclidine 15mg QD | Number of Participants With Clinically Significant Changes in Electrocardiogram (ECGs) | QTcF value: > 500 msec | 0 Participants |
| Emraclidine 15mg QD | Number of Participants With Clinically Significant Changes in Electrocardiogram (ECGs) | QTcF value: > 450 - 480 msec | 1 Participants |
| Emraclidine 30mg QD | Number of Participants With Clinically Significant Changes in Electrocardiogram (ECGs) | QTcF increase from baseline: > 60 msec | 1 Participants |
| Emraclidine 30mg QD | Number of Participants With Clinically Significant Changes in Electrocardiogram (ECGs) | QTcF value: > 450 - 480 msec | 3 Participants |
| Emraclidine 30mg QD | Number of Participants With Clinically Significant Changes in Electrocardiogram (ECGs) | QTcF value: > 500 msec | 0 Participants |
| Emraclidine 30mg QD | Number of Participants With Clinically Significant Changes in Electrocardiogram (ECGs) | QTcF increase from baseline: > 30 - 60 msec | 10 Participants |
| Emraclidine 30mg QD | Number of Participants With Clinically Significant Changes in Electrocardiogram (ECGs) | QTcF value: > 480 - 500 msec | 0 Participants |
Secondary
Number of Participants With Clinically Significant Changes in Physical and Neurological Examination Results
The number of participants with clinically significant changes in physical and neurological examination results was documented.
Time frame: Baseline; from first dose of study drug up to Week 6
Population: Full analysis set: All randomized participants who received at least 1 dose of investigational medicinal product (IMP)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Clinically Significant Changes in Physical and Neurological Examination Results | Clinically Significant Changes in Physical Examination | 1 Participants |
| Placebo | Number of Participants With Clinically Significant Changes in Physical and Neurological Examination Results | Clinically Significant Changes in Neurological Examination | 3 Participants |
| Emraclidine 15mg QD | Number of Participants With Clinically Significant Changes in Physical and Neurological Examination Results | Clinically Significant Changes in Physical Examination | 1 Participants |
| Emraclidine 15mg QD | Number of Participants With Clinically Significant Changes in Physical and Neurological Examination Results | Clinically Significant Changes in Neurological Examination | 3 Participants |
| Emraclidine 30mg QD | Number of Participants With Clinically Significant Changes in Physical and Neurological Examination Results | Clinically Significant Changes in Physical Examination | 0 Participants |
| Emraclidine 30mg QD | Number of Participants With Clinically Significant Changes in Physical and Neurological Examination Results | Clinically Significant Changes in Neurological Examination | 0 Participants |
Secondary
Number of Participants With Clinically Significant Changes in Vital Sign Measurements
Vital signs were obtained after the participant had been supine and at rest for 3 minutes and included temperature, systolic and diastolic blood pressure, respiratory rate, and heart rate. Participants' body weights were also measured and recorded.
Time frame: Baseline; from first dose of study drug up to Week 6
Population: Full analysis set: All randomized participants who received at least 1 dose of investigational medicinal product (IMP)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Clinically Significant Changes in Vital Sign Measurements | Weight: ≥ 7% decrease | 6 Participants |
| Placebo | Number of Participants With Clinically Significant Changes in Vital Sign Measurements | Temperature: < 36 °C | 2 Participants |
| Placebo | Number of Participants With Clinically Significant Changes in Vital Sign Measurements | Orthostatic Change in Systolic Blood Pressure: ≥ 20 mmHg decrease | 4 Participants |
| Placebo | Number of Participants With Clinically Significant Changes in Vital Sign Measurements | Supine Heart Rate: > 120 bpm | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Changes in Vital Sign Measurements | Supine Diastolic Blood Pressure: > 120 mmHg | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Changes in Vital Sign Measurements | Supine Diastolic Blood Pressure: > 90 mmHg and ≤ 100 mmHg | 5 Participants |
| Placebo | Number of Participants With Clinically Significant Changes in Vital Sign Measurements | Supine Heart Rate: > 100 bpm and ≤ 120 bpm | 5 Participants |
| Placebo | Number of Participants With Clinically Significant Changes in Vital Sign Measurements | Orthostatic Change in Diastolic Blood Pressure: ≥ 10 mmHg decrease | 3 Participants |
| Placebo | Number of Participants With Clinically Significant Changes in Vital Sign Measurements | Respiratory Rate: > 20 breaths/min | 3 Participants |
| Placebo | Number of Participants With Clinically Significant Changes in Vital Sign Measurements | Supine Heart Rate: ≥ 50 bpm and < 60 bpm | 19 Participants |
| Placebo | Number of Participants With Clinically Significant Changes in Vital Sign Measurements | Supine Heart Rate: < 50 bpm | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Changes in Vital Sign Measurements | Supine Diastolic Blood Pressure: < 50 mmHg | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Changes in Vital Sign Measurements | Weight: ≥ 7% increase | 8 Participants |
| Placebo | Number of Participants With Clinically Significant Changes in Vital Sign Measurements | Supine Systolic Blood Pressure: > 200 mmHg | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Changes in Vital Sign Measurements | Respiratory Rate: < 12 breaths/min | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Changes in Vital Sign Measurements | Supine Diastolic Blood Pressure: > 100 mmHg and ≤ 120 mmHg | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Changes in Vital Sign Measurements | Supine Systolic Blood Pressure: < 90 mmHg | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Changes in Vital Sign Measurements | Supine Systolic Blood Pressure: 160 mmHg and ≤ 200 mmHg | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Changes in Vital Sign Measurements | Temperature: > 38 °C | 2 Participants |
| Placebo | Number of Participants With Clinically Significant Changes in Vital Sign Measurements | Supine Systolic Blood Pressure: > 140 mmHg and ≤ 160 mmHg | 10 Participants |
| Emraclidine 15mg QD | Number of Participants With Clinically Significant Changes in Vital Sign Measurements | Respiratory Rate: > 20 breaths/min | 1 Participants |
| Emraclidine 15mg QD | Number of Participants With Clinically Significant Changes in Vital Sign Measurements | Supine Systolic Blood Pressure: 160 mmHg and ≤ 200 mmHg | 0 Participants |
| Emraclidine 15mg QD | Number of Participants With Clinically Significant Changes in Vital Sign Measurements | Supine Systolic Blood Pressure: > 200 mmHg | 0 Participants |
| Emraclidine 15mg QD | Number of Participants With Clinically Significant Changes in Vital Sign Measurements | Orthostatic Change in Systolic Blood Pressure: ≥ 20 mmHg decrease | 1 Participants |
| Emraclidine 15mg QD | Number of Participants With Clinically Significant Changes in Vital Sign Measurements | Supine Diastolic Blood Pressure: < 50 mmHg | 0 Participants |
| Emraclidine 15mg QD | Number of Participants With Clinically Significant Changes in Vital Sign Measurements | Supine Diastolic Blood Pressure: > 90 mmHg and ≤ 100 mmHg | 12 Participants |
| Emraclidine 15mg QD | Number of Participants With Clinically Significant Changes in Vital Sign Measurements | Supine Systolic Blood Pressure: < 90 mmHg | 0 Participants |
| Emraclidine 15mg QD | Number of Participants With Clinically Significant Changes in Vital Sign Measurements | Supine Systolic Blood Pressure: > 140 mmHg and ≤ 160 mmHg | 10 Participants |
| Emraclidine 15mg QD | Number of Participants With Clinically Significant Changes in Vital Sign Measurements | Supine Diastolic Blood Pressure: > 100 mmHg and ≤ 120 mmHg | 1 Participants |
| Emraclidine 15mg QD | Number of Participants With Clinically Significant Changes in Vital Sign Measurements | Supine Diastolic Blood Pressure: > 120 mmHg | 0 Participants |
| Emraclidine 15mg QD | Number of Participants With Clinically Significant Changes in Vital Sign Measurements | Orthostatic Change in Diastolic Blood Pressure: ≥ 10 mmHg decrease | 12 Participants |
| Emraclidine 15mg QD | Number of Participants With Clinically Significant Changes in Vital Sign Measurements | Supine Heart Rate: < 50 bpm | 2 Participants |
| Emraclidine 15mg QD | Number of Participants With Clinically Significant Changes in Vital Sign Measurements | Supine Heart Rate: ≥ 50 bpm and < 60 bpm | 12 Participants |
| Emraclidine 15mg QD | Number of Participants With Clinically Significant Changes in Vital Sign Measurements | Supine Heart Rate: > 100 bpm and ≤ 120 bpm | 20 Participants |
| Emraclidine 15mg QD | Number of Participants With Clinically Significant Changes in Vital Sign Measurements | Supine Heart Rate: > 120 bpm | 0 Participants |
| Emraclidine 15mg QD | Number of Participants With Clinically Significant Changes in Vital Sign Measurements | Temperature: < 36 °C | 5 Participants |
| Emraclidine 15mg QD | Number of Participants With Clinically Significant Changes in Vital Sign Measurements | Temperature: > 38 °C | 0 Participants |
| Emraclidine 15mg QD | Number of Participants With Clinically Significant Changes in Vital Sign Measurements | Respiratory Rate: < 12 breaths/min | 1 Participants |
| Emraclidine 15mg QD | Number of Participants With Clinically Significant Changes in Vital Sign Measurements | Weight: ≥ 7% decrease | 0 Participants |
| Emraclidine 15mg QD | Number of Participants With Clinically Significant Changes in Vital Sign Measurements | Weight: ≥ 7% increase | 13 Participants |
| Emraclidine 30mg QD | Number of Participants With Clinically Significant Changes in Vital Sign Measurements | Supine Systolic Blood Pressure: > 200 mmHg | 0 Participants |
| Emraclidine 30mg QD | Number of Participants With Clinically Significant Changes in Vital Sign Measurements | Supine Heart Rate: > 120 bpm | 1 Participants |
| Emraclidine 30mg QD | Number of Participants With Clinically Significant Changes in Vital Sign Measurements | Supine Systolic Blood Pressure: > 140 mmHg and ≤ 160 mmHg | 19 Participants |
| Emraclidine 30mg QD | Number of Participants With Clinically Significant Changes in Vital Sign Measurements | Weight: ≥ 7% increase | 13 Participants |
| Emraclidine 30mg QD | Number of Participants With Clinically Significant Changes in Vital Sign Measurements | Temperature: < 36 °C | 4 Participants |
| Emraclidine 30mg QD | Number of Participants With Clinically Significant Changes in Vital Sign Measurements | Supine Systolic Blood Pressure: < 90 mmHg | 0 Participants |
| Emraclidine 30mg QD | Number of Participants With Clinically Significant Changes in Vital Sign Measurements | Weight: ≥ 7% decrease | 4 Participants |
| Emraclidine 30mg QD | Number of Participants With Clinically Significant Changes in Vital Sign Measurements | Temperature: > 38 °C | 0 Participants |
| Emraclidine 30mg QD | Number of Participants With Clinically Significant Changes in Vital Sign Measurements | Supine Diastolic Blood Pressure: > 90 mmHg and ≤ 100 mmHg | 19 Participants |
| Emraclidine 30mg QD | Number of Participants With Clinically Significant Changes in Vital Sign Measurements | Supine Systolic Blood Pressure: 160 mmHg and ≤ 200 mmHg | 0 Participants |
| Emraclidine 30mg QD | Number of Participants With Clinically Significant Changes in Vital Sign Measurements | Respiratory Rate: < 12 breaths/min | 0 Participants |
| Emraclidine 30mg QD | Number of Participants With Clinically Significant Changes in Vital Sign Measurements | Orthostatic Change in Systolic Blood Pressure: ≥ 20 mmHg decrease | 2 Participants |
| Emraclidine 30mg QD | Number of Participants With Clinically Significant Changes in Vital Sign Measurements | Supine Heart Rate: < 50 bpm | 0 Participants |
| Emraclidine 30mg QD | Number of Participants With Clinically Significant Changes in Vital Sign Measurements | Orthostatic Change in Diastolic Blood Pressure: ≥ 10 mmHg decrease | 5 Participants |
| Emraclidine 30mg QD | Number of Participants With Clinically Significant Changes in Vital Sign Measurements | Supine Diastolic Blood Pressure: < 50 mmHg | 0 Participants |
| Emraclidine 30mg QD | Number of Participants With Clinically Significant Changes in Vital Sign Measurements | Supine Heart Rate: ≥ 50 bpm and < 60 bpm | 8 Participants |
| Emraclidine 30mg QD | Number of Participants With Clinically Significant Changes in Vital Sign Measurements | Supine Diastolic Blood Pressure: > 120 mmHg | 0 Participants |
| Emraclidine 30mg QD | Number of Participants With Clinically Significant Changes in Vital Sign Measurements | Respiratory Rate: > 20 breaths/min | 3 Participants |
| Emraclidine 30mg QD | Number of Participants With Clinically Significant Changes in Vital Sign Measurements | Supine Heart Rate: > 100 bpm and ≤ 120 bpm | 16 Participants |
| Emraclidine 30mg QD | Number of Participants With Clinically Significant Changes in Vital Sign Measurements | Supine Diastolic Blood Pressure: > 100 mmHg and ≤ 120 mmHg | 1 Participants |
Secondary
Number of Participants With Suicide-Related Treatment-Emergent Events Assessed Using the Columbia Suicide-Severity Rating Scale (C-SSRS)
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).
Time frame: Baseline; from first dose of study drug up to Week 6
Population: Full analysis set: All randomized participants who received at least 1 dose of investigational medicinal product (IMP)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Suicide-Related Treatment-Emergent Events Assessed Using the Columbia Suicide-Severity Rating Scale (C-SSRS) | Treatment-Emergent Suicidal Ideation Compared to Recent History | 3 Participants |
| Placebo | Number of Participants With Suicide-Related Treatment-Emergent Events Assessed Using the Columbia Suicide-Severity Rating Scale (C-SSRS) | Treatment-Emergent Serious Suicidal Ideation Compared to Recent History | 0 Participants |
| Placebo | Number of Participants With Suicide-Related Treatment-Emergent Events Assessed Using the Columbia Suicide-Severity Rating Scale (C-SSRS) | Emergence of Serious Suicidal Ideation Compared to Recent History | 0 Participants |
| Placebo | Number of Participants With Suicide-Related Treatment-Emergent Events Assessed Using the Columbia Suicide-Severity Rating Scale (C-SSRS) | Emergence of Suicidal Behavior Compared to all Prior History | 0 Participants |
| Emraclidine 15mg QD | Number of Participants With Suicide-Related Treatment-Emergent Events Assessed Using the Columbia Suicide-Severity Rating Scale (C-SSRS) | Emergence of Suicidal Behavior Compared to all Prior History | 0 Participants |
| Emraclidine 15mg QD | Number of Participants With Suicide-Related Treatment-Emergent Events Assessed Using the Columbia Suicide-Severity Rating Scale (C-SSRS) | Treatment-Emergent Suicidal Ideation Compared to Recent History | 5 Participants |
| Emraclidine 15mg QD | Number of Participants With Suicide-Related Treatment-Emergent Events Assessed Using the Columbia Suicide-Severity Rating Scale (C-SSRS) | Emergence of Serious Suicidal Ideation Compared to Recent History | 0 Participants |
| Emraclidine 15mg QD | Number of Participants With Suicide-Related Treatment-Emergent Events Assessed Using the Columbia Suicide-Severity Rating Scale (C-SSRS) | Treatment-Emergent Serious Suicidal Ideation Compared to Recent History | 0 Participants |
| Emraclidine 30mg QD | Number of Participants With Suicide-Related Treatment-Emergent Events Assessed Using the Columbia Suicide-Severity Rating Scale (C-SSRS) | Emergence of Suicidal Behavior Compared to all Prior History | 0 Participants |
| Emraclidine 30mg QD | Number of Participants With Suicide-Related Treatment-Emergent Events Assessed Using the Columbia Suicide-Severity Rating Scale (C-SSRS) | Treatment-Emergent Serious Suicidal Ideation Compared to Recent History | 0 Participants |
| Emraclidine 30mg QD | Number of Participants With Suicide-Related Treatment-Emergent Events Assessed Using the Columbia Suicide-Severity Rating Scale (C-SSRS) | Emergence of Serious Suicidal Ideation Compared to Recent History | 0 Participants |
| Emraclidine 30mg QD | Number of Participants With Suicide-Related Treatment-Emergent Events Assessed Using the Columbia Suicide-Severity Rating Scale (C-SSRS) | Treatment-Emergent Suicidal Ideation Compared to Recent History | 2 Participants |
Secondary
Number of Participants With Treatment Emergent Adverse Event (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
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.
Time frame: From first dose of study drug until 28 days following last dose of study drug (up to Week 10)
Population: Full analysis set: All randomized participants who received at least 1 dose of investigational medicinal product (IMP).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Treatment Emergent Adverse Event (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TEAE | 69 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Event (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TESAE | 1 Participants |
| Emraclidine 15mg QD | Number of Participants With Treatment Emergent Adverse Event (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TEAE | 65 Participants |
| Emraclidine 15mg QD | Number of Participants With Treatment Emergent Adverse Event (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TESAE | 3 Participants |
| Emraclidine 30mg QD | Number of Participants With Treatment Emergent Adverse Event (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TEAE | 65 Participants |
| Emraclidine 30mg QD | Number of Participants With Treatment Emergent Adverse Event (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TESAE | 1 Participants |
Secondary
Percentage of Responders at Week 6 (Responders Defined as ≥30% Reduction From Baseline in PANSS Total Score)
The PANSS measures symptom severity of participants with schizophrenia and contains 7 positive symptom scales, 7 negative system scales, and 16 general psychopathology symptom scales. Participants are rated from 1 to 7 on each symptom scale with a total minimum score of 30 and a maximum score of 210. A PANSS responder is defined as a participant with at least a 30% change in PANSS total score compared to baseline at Week 6 or the early termination visit. If a subject discontinued and did not have an early termination visit, the subject's last assessment was considered.
Time frame: Baseline through Week 6
Population: mITT: All randomized participants who receive at least 1 dose of Emraclidine and have both a baseline and at least 1 postbaseline PANSS assessment. Overall Number of Participants Analyzed includes participants with a non-missing value.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Responders at Week 6 (Responders Defined as ≥30% Reduction From Baseline in PANSS Total Score) | 19.5 percentage of participants |
| Emraclidine 15mg QD | Percentage of Responders at Week 6 (Responders Defined as ≥30% Reduction From Baseline in PANSS Total Score) | 23.8 percentage of participants |
| Emraclidine 30mg QD | Percentage of Responders at Week 6 (Responders Defined as ≥30% Reduction From Baseline in PANSS Total Score) | 12.2 percentage of participants |
Comparison: Emraclidine 15 mg versus Placebop-value: 0.459795% CI: [0.68, 2.33]Regression, Logistic
Comparison: Emraclidine 30 mg versus Placebop-value: 0.120595% CI: [0.28, 1.16]Regression, Logistic