Trial Outcomes & Findings for A Trial of 15 and 30 mg Doses of CVL-231 (Emraclidine) in Participants With Schizophrenia (NCT NCT05227703)

NCT ID: NCT05227703

Last Updated: 2025-10-28

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 391 participants
• Primary outcome timeframe: Baseline through Week 6
• Results posted on: 2025-10-28

Participant Flow

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).

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.

Participant milestones

Measure	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.	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.	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.
Overall Study STARTED	130	130	131
Overall Study COMPLETED	102	93	93
Overall Study NOT COMPLETED	28	37	38

Reasons for withdrawal

Measure	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.	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.	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.
Overall Study Adverse Event	2	6	4
Overall Study Lack of Efficacy	4	0	1
Overall Study Physician Decision	2	2	1
Overall Study Protocol Violation	2	1	0
Overall Study Withdrawal by Subject	17	26	32
Overall Study Non-Compliance with Study Schedule	0	1	0
Overall Study Other	1	1	0

Baseline Characteristics

A Trial of 15 and 30 mg Doses of CVL-231 (Emraclidine) in Participants With Schizophrenia

Baseline characteristics by cohort

Measure	Placebo n=130 Participants 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.	Emraclidine 15 mg QD n=130 Participants 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.	Emraclidine 30 mg QD n=131 Participants 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.	Total n=391 Participants Total of all reporting groups
Age, Continuous	42.1 years STANDARD_DEVIATION 12.18 • n=5 Participants	42.7 years STANDARD_DEVIATION 11.51 • n=7 Participants	41.5 years STANDARD_DEVIATION 10.76 • n=5 Participants	42.1 years STANDARD_DEVIATION 11.48 • n=4 Participants
Sex: Female, Male Female	27 Participants n=5 Participants	34 Participants n=7 Participants	25 Participants n=5 Participants	86 Participants n=4 Participants
Sex: Female, Male Male	103 Participants n=5 Participants	96 Participants n=7 Participants	106 Participants n=5 Participants	305 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	30 Participants n=5 Participants	25 Participants n=7 Participants	25 Participants n=5 Participants	80 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	100 Participants n=5 Participants	105 Participants n=7 Participants	106 Participants n=5 Participants	311 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Black or African American	76 Participants n=5 Participants	83 Participants n=7 Participants	85 Participants n=5 Participants	244 Participants n=4 Participants
Race (NIH/OMB) White	53 Participants n=5 Participants	44 Participants n=7 Participants	44 Participants n=5 Participants	141 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Placebo n=104 Participants Participants received a single daily oral dose of Placebo QD 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.	Emraclidine 15mg QD n=94 Participants Participants received a single daily oral dose of Emraclidine 15 mg QD 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.	Emraclidine 30mg QD n=96 Participants Participants received a single daily oral dose of Emraclidine 30 mg QD 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.
Change From Baseline at Week 6 in the Positive and Negative Syndrome Scale (PANSS) Total Score	-16.1 score on a scale Interval -19.4 to -12.8	-18.5 score on a scale Interval -22.0 to -15.0	-14.2 score on a scale Interval -17.5 to -10.8

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Placebo n=104 Participants Participants received a single daily oral dose of Placebo QD 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.	Emraclidine 15mg QD n=94 Participants Participants received a single daily oral dose of Emraclidine 15 mg QD 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.	Emraclidine 30mg QD n=96 Participants Participants received a single daily oral dose of Emraclidine 30 mg QD 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.
Change From Baseline at Week 6 in the Clinical Global Impression - Severity (CGI-S Score)	-0.83 score on a scale Interval -1.03 to -0.64	-1.05 score on a scale Interval -1.25 to -0.84	-0.80 score on a scale Interval -1.0 to -0.6

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Placebo n=128 Participants Participants received a single daily oral dose of Placebo QD 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.	Emraclidine 15mg QD n=122 Participants Participants received a single daily oral dose of Emraclidine 15 mg QD 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.	Emraclidine 30mg QD n=123 Participants Participants received a single daily oral dose of Emraclidine 30 mg QD 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.
Change From Baseline at All Time Points in Positive and Negative Syndrome Scale (PANSS) Total Score Week 1	-5.0 score on a scale Interval -6.9 to -3.1	-6.8 score on a scale Interval -8.8 to -4.8	-4.9 score on a scale Interval -6.8 to -2.9
Change From Baseline at All Time Points in Positive and Negative Syndrome Scale (PANSS) Total Score Week 2	-8.5 score on a scale Interval -10.9 to -6.1	-8.7 score on a scale Interval -11.2 to -6.3	-7.5 score on a scale Interval -9.9 to -5.1
Change From Baseline at All Time Points in Positive and Negative Syndrome Scale (PANSS) Total Score Week 3	-11.2 score on a scale Interval -13.8 to -8.5	-12.5 score on a scale Interval -15.3 to -9.7	-10.0 score on a scale Interval -12.6 to -7.3
Change From Baseline at All Time Points in Positive and Negative Syndrome Scale (PANSS) Total Score Week 4	-12.8 score on a scale Interval -15.5 to -10.1	-13.4 score on a scale Interval -16.3 to -10.5	-12.0 score on a scale Interval -14.8 to -9.2
Change From Baseline at All Time Points in Positive and Negative Syndrome Scale (PANSS) Total Score Week 5	-14.7 score on a scale Interval -17.7 to -11.6	-16.5 score on a scale Interval -19.7 to -13.2	-12.9 score on a scale Interval -16.0 to -9.8
Change From Baseline at All Time Points in Positive and Negative Syndrome Scale (PANSS) Total Score Week 6	-16.1 score on a scale Interval -19.4 to -12.8	-18.5 score on a scale Interval -22.0 to -15.0	-14.2 score on a scale Interval -17.5 to -10.8

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Placebo n=128 Participants Participants received a single daily oral dose of Placebo QD 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.	Emraclidine 15mg QD n=122 Participants Participants received a single daily oral dose of Emraclidine 15 mg QD 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.	Emraclidine 30mg QD n=123 Participants Participants received a single daily oral dose of Emraclidine 30 mg QD 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.
Change From Baseline at All Time Points in the Clinical Global Impression - Severity (CGI-S) Score Week 1	-0.21 score on a scale Interval -0.33 to -0.09	-0.33 score on a scale Interval -0.46 to -0.21	-0.21 score on a scale Interval -0.33 to -0.09
Change From Baseline at All Time Points in the Clinical Global Impression - Severity (CGI-S) Score Week 2	-0.42 score on a scale Interval -0.56 to -0.28	-0.42 score on a scale Interval -0.56 to -0.27	-0.38 score on a scale Interval -0.52 to -0.24
Change From Baseline at All Time Points in the Clinical Global Impression - Severity (CGI-S) Score Week 3	-0.55 score on a scale Interval -0.7 to -0.4	-0.64 score on a scale Interval -0.8 to -0.48	-0.49 score on a scale Interval -0.64 to -0.34
Change From Baseline at All Time Points in the Clinical Global Impression - Severity (CGI-S) Score Week 4	-0.72 score on a scale Interval -0.88 to -0.55	-0.74 score on a scale Interval -0.91 to -0.57	-0.62 score on a scale Interval -0.79 to -0.46
Change From Baseline at All Time Points in the Clinical Global Impression - Severity (CGI-S) Score Week 5	-0.78 score on a scale Interval -0.96 to -0.6	-0.91 score on a scale Interval -1.1 to -0.72	-0.69 score on a scale Interval -0.87 to -0.51
Change From Baseline at All Time Points in the Clinical Global Impression - Severity (CGI-S) Score Week 6	-0.83 score on a scale Interval -1.03 to -0.64	-1.05 score on a scale Interval -1.25 to -0.084	-0.80 score on a scale Interval -1.0 to -0.6

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Placebo n=128 Participants Participants received a single daily oral dose of Placebo QD 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.	Emraclidine 15mg QD n=122 Participants Participants received a single daily oral dose of Emraclidine 15 mg QD 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.	Emraclidine 30mg QD n=123 Participants Participants received a single daily oral dose of Emraclidine 30 mg QD 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.
Percentage of Responders at Week 6 (Responders Defined as ≥30% Reduction From Baseline in PANSS Total Score)	19.5 percentage of participants	23.8 percentage of participants	12.2 percentage of participants

SECONDARY outcome

Timeframe: 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).

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.

Outcome measures

Measure	Placebo n=130 Participants Participants received a single daily oral dose of Placebo QD 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.	Emraclidine 15mg QD n=130 Participants Participants received a single daily oral dose of Emraclidine 15 mg QD 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.	Emraclidine 30mg QD n=131 Participants Participants received a single daily oral dose of Emraclidine 30 mg QD 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.
Number of Participants With Treatment Emergent Adverse Event (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) Any TEAE	69 Participants	65 Participants	65 Participants
Number of Participants With Treatment Emergent Adverse Event (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) TESAE	1 Participants	3 Participants	1 Participants

SECONDARY outcome

Timeframe: 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)

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.

Outcome measures

Measure	Placebo n=130 Participants Participants received a single daily oral dose of Placebo QD 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.	Emraclidine 15mg QD n=130 Participants Participants received a single daily oral dose of Emraclidine 15 mg QD 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.	Emraclidine 30mg QD n=131 Participants Participants received a single daily oral dose of Emraclidine 30 mg QD 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.
Number of Participants With Clinically Significant Changes in Electrocardiogram (ECGs) QTcF value: > 450 - 480 msec	3 Participants	1 Participants	3 Participants
Number of Participants With Clinically Significant Changes in Electrocardiogram (ECGs) QTcF value: > 480 - 500 msec	1 Participants	0 Participants	0 Participants
Number of Participants With Clinically Significant Changes in Electrocardiogram (ECGs) QTcF value: > 500 msec	0 Participants	0 Participants	0 Participants
Number of Participants With Clinically Significant Changes in Electrocardiogram (ECGs) QTcF increase from baseline: > 30 - 60 msec	7 Participants	10 Participants	10 Participants
Number of Participants With Clinically Significant Changes in Electrocardiogram (ECGs) QTcF increase from baseline: > 60 msec	1 Participants	1 Participants	1 Participants

SECONDARY outcome

Timeframe: 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)

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

Outcome measures

Measure	Placebo n=130 Participants Participants received a single daily oral dose of Placebo QD 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.	Emraclidine 15mg QD n=130 Participants Participants received a single daily oral dose of Emraclidine 15 mg QD 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.	Emraclidine 30mg QD n=131 Participants Participants received a single daily oral dose of Emraclidine 30 mg QD 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.
Number of Participants With Clinically Significant Changes in Clinical Laboratory Assessments	3 Participants	4 Participants	3 Participants

SECONDARY outcome

Timeframe: 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)

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.

Outcome measures

Measure	Placebo n=130 Participants Participants received a single daily oral dose of Placebo QD 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.	Emraclidine 15mg QD n=130 Participants Participants received a single daily oral dose of Emraclidine 15 mg QD 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.	Emraclidine 30mg QD n=131 Participants Participants received a single daily oral dose of Emraclidine 30 mg QD 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.
Number of Participants With Clinically Significant Changes in Vital Sign Measurements Supine Systolic Blood Pressure: < 90 mmHg	0 Participants	0 Participants	0 Participants
Number of Participants With Clinically Significant Changes in Vital Sign Measurements Supine Systolic Blood Pressure: > 140 mmHg and ≤ 160 mmHg	10 Participants	10 Participants	19 Participants
Number of Participants With Clinically Significant Changes in Vital Sign Measurements Supine Systolic Blood Pressure: 160 mmHg and ≤ 200 mmHg	0 Participants	0 Participants	0 Participants
Number of Participants With Clinically Significant Changes in Vital Sign Measurements Supine Systolic Blood Pressure: > 200 mmHg	0 Participants	0 Participants	0 Participants
Number of Participants With Clinically Significant Changes in Vital Sign Measurements Orthostatic Change in Systolic Blood Pressure: ≥ 20 mmHg decrease	4 Participants	1 Participants	2 Participants
Number of Participants With Clinically Significant Changes in Vital Sign Measurements Supine Diastolic Blood Pressure: < 50 mmHg	0 Participants	0 Participants	0 Participants
Number of Participants With Clinically Significant Changes in Vital Sign Measurements Supine Diastolic Blood Pressure: > 90 mmHg and ≤ 100 mmHg	5 Participants	12 Participants	19 Participants
Number of Participants With Clinically Significant Changes in Vital Sign Measurements Supine Diastolic Blood Pressure: > 100 mmHg and ≤ 120 mmHg	0 Participants	1 Participants	1 Participants
Number of Participants With Clinically Significant Changes in Vital Sign Measurements Supine Diastolic Blood Pressure: > 120 mmHg	0 Participants	0 Participants	0 Participants
Number of Participants With Clinically Significant Changes in Vital Sign Measurements Orthostatic Change in Diastolic Blood Pressure: ≥ 10 mmHg decrease	3 Participants	12 Participants	5 Participants
Number of Participants With Clinically Significant Changes in Vital Sign Measurements Supine Heart Rate: < 50 bpm	0 Participants	2 Participants	0 Participants
Number of Participants With Clinically Significant Changes in Vital Sign Measurements Supine Heart Rate: ≥ 50 bpm and < 60 bpm	19 Participants	12 Participants	8 Participants
Number of Participants With Clinically Significant Changes in Vital Sign Measurements Supine Heart Rate: > 100 bpm and ≤ 120 bpm	5 Participants	20 Participants	16 Participants
Number of Participants With Clinically Significant Changes in Vital Sign Measurements Supine Heart Rate: > 120 bpm	0 Participants	0 Participants	1 Participants
Number of Participants With Clinically Significant Changes in Vital Sign Measurements Temperature: < 36 °C	2 Participants	5 Participants	4 Participants
Number of Participants With Clinically Significant Changes in Vital Sign Measurements Respiratory Rate: < 12 breaths/min	0 Participants	1 Participants	0 Participants
Number of Participants With Clinically Significant Changes in Vital Sign Measurements Respiratory Rate: > 20 breaths/min	3 Participants	1 Participants	3 Participants
Number of Participants With Clinically Significant Changes in Vital Sign Measurements Weight: ≥ 7% decrease	6 Participants	0 Participants	4 Participants
Number of Participants With Clinically Significant Changes in Vital Sign Measurements Weight: ≥ 7% increase	8 Participants	13 Participants	13 Participants
Number of Participants With Clinically Significant Changes in Vital Sign Measurements Temperature: > 38 °C	2 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 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)

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

Outcome measures

Measure	Placebo n=130 Participants Participants received a single daily oral dose of Placebo QD 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.	Emraclidine 15mg QD n=130 Participants Participants received a single daily oral dose of Emraclidine 15 mg QD 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.	Emraclidine 30mg QD n=131 Participants Participants received a single daily oral dose of Emraclidine 30 mg QD 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.
Number of Participants With Clinically Significant Changes in Physical and Neurological Examination Results Clinically Significant Changes in Physical Examination	1 Participants	1 Participants	0 Participants
Number of Participants With Clinically Significant Changes in Physical and Neurological Examination Results Clinically Significant Changes in Neurological Examination	3 Participants	3 Participants	0 Participants

SECONDARY outcome

Timeframe: 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)

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).

Outcome measures

Measure	Placebo n=130 Participants Participants received a single daily oral dose of Placebo QD 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.	Emraclidine 15mg QD n=130 Participants Participants received a single daily oral dose of Emraclidine 15 mg QD 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.	Emraclidine 30mg QD n=131 Participants Participants received a single daily oral dose of Emraclidine 30 mg QD 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.
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	5 Participants	2 Participants
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	0 Participants	0 Participants
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	0 Participants	0 Participants
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	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Measure	Placebo n=130 Participants Participants received a single daily oral dose of Placebo QD 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.	Emraclidine 15mg QD n=130 Participants Participants received a single daily oral dose of Emraclidine 15 mg QD 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.	Emraclidine 30mg QD n=131 Participants Participants received a single daily oral dose of Emraclidine 30 mg QD 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.
Change From Baseline in Simpson Angus Scale (SAS) Total Score Week 3	-0.1 score on a scale Interval -0.1 to 0.0	0.0 score on a scale Interval -0.1 to 0.1	0.0 score on a scale Interval 0.0 to 0.1
Change From Baseline in Simpson Angus Scale (SAS) Total Score Week 6	0.0 score on a scale Interval -0.1 to 0.1	0.0 score on a scale Interval 0.0 to 0.1	0.0 score on a scale Interval -0.1 to 0.1

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Measure	Placebo n=130 Participants Participants received a single daily oral dose of Placebo QD 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.	Emraclidine 15mg QD n=130 Participants Participants received a single daily oral dose of Emraclidine 15 mg QD 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.	Emraclidine 30mg QD n=131 Participants Participants received a single daily oral dose of Emraclidine 30 mg QD 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.
Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Movement Rating Score Week 3	0.0 score on a scale Interval 0.0 to 0.1	0.0 score on a scale Interval -0.1 to 0.1	0.0 score on a scale Interval -0.1 to 0.1
Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Movement Rating Score Week 6	0.0 score on a scale Interval 0.0 to 0.1	0.0 score on a scale Interval -0.1 to 0.0	0.0 score on a scale Interval 0.0 to 0.1

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Placebo n=130 Participants Participants received a single daily oral dose of Placebo QD 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.	Emraclidine 15mg QD n=130 Participants Participants received a single daily oral dose of Emraclidine 15 mg QD 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.	Emraclidine 30mg QD n=131 Participants Participants received a single daily oral dose of Emraclidine 30 mg QD 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.
Change From Baseline in Barnes Akathisia Rating Scale (BARS) Global Clinical Evaluation Score Week 3	0.0 score on a scale Interval -0.1 to 0.0	0.0 score on a scale Interval -0.1 to 0.0	0.0 score on a scale Interval -0.1 to 0.0
Change From Baseline in Barnes Akathisia Rating Scale (BARS) Global Clinical Evaluation Score Week 6	-0.1 score on a scale Interval -0.1 to 0.0	0.0 score on a scale Interval 0.0 to 0.1	0.0 score on a scale Interval -0.1 to 0.0

Adverse Events

Placebo

Serious events: 1 serious events

Other events: 47 other events

Deaths: 0 deaths

Emraclidine 15mg QD

Serious events: 3 serious events

Other events: 47 other events

Deaths: 0 deaths

Emraclidine 30mg QD

Serious events: 1 serious events

Other events: 50 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=130 participants at risk 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.	Emraclidine 15mg QD n=130 participants at risk 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.	Emraclidine 30mg QD n=131 participants at risk 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.
Eye disorders VISION BLURRED	0.00% 0/130 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.	0.77% 1/130 • Number of events 1 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.	0.00% 0/131 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.
Nervous system disorders HEADACHE	0.00% 0/130 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.	0.77% 1/130 • Number of events 1 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.	0.00% 0/131 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.
Nervous system disorders NEUROLEPTIC MALIGNANT SYNDROME	0.77% 1/130 • Number of events 1 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.	0.00% 0/130 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.	0.00% 0/131 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.
Psychiatric disorders ACUTE PSYCHOSIS	0.00% 0/130 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.	0.77% 1/130 • Number of events 1 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.	0.00% 0/131 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.
Psychiatric disorders AGITATION	0.00% 0/130 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.	0.00% 0/130 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.	0.76% 1/131 • Number of events 1 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.
Psychiatric disorders PSYCHOTIC DISORDER	0.00% 0/130 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.	0.77% 1/130 • Number of events 1 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.	0.00% 0/131 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.
Psychiatric disorders SCHIZOPHRENIA	0.00% 0/130 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.	0.77% 1/130 • Number of events 1 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.	0.00% 0/131 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.

Other adverse events

Measure	Placebo n=130 participants at risk 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.	Emraclidine 15mg QD n=130 participants at risk 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.	Emraclidine 30mg QD n=131 participants at risk 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.
Cardiac disorders SINUS TACHYCARDIA	0.00% 0/130 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.	3.1% 4/130 • Number of events 5 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.	0.00% 0/131 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.
Gastrointestinal disorders ABDOMINAL DISCOMFORT	2.3% 3/130 • Number of events 4 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.	3.1% 4/130 • Number of events 4 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.	0.00% 0/131 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.
Gastrointestinal disorders CONSTIPATION	1.5% 2/130 • Number of events 2 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.	4.6% 6/130 • Number of events 6 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.	2.3% 3/131 • Number of events 3 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.
Gastrointestinal disorders DRY MOUTH	0.77% 1/130 • Number of events 1 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.	0.77% 1/130 • Number of events 1 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.	5.3% 7/131 • Number of events 7 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.
Gastrointestinal disorders DYSPEPSIA	1.5% 2/130 • Number of events 2 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.	3.1% 4/130 • Number of events 4 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.	2.3% 3/131 • Number of events 3 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.
Gastrointestinal disorders GASTROOESOPHAGEAL REFLUX DISEASE	0.00% 0/130 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.	0.77% 1/130 • Number of events 1 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.	2.3% 3/131 • Number of events 3 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.
Gastrointestinal disorders NAUSEA	3.8% 5/130 • Number of events 5 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.	4.6% 6/130 • Number of events 6 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.	3.1% 4/131 • Number of events 4 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.
Gastrointestinal disorders TOOTHACHE	4.6% 6/130 • Number of events 6 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.	2.3% 3/130 • Number of events 3 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.	1.5% 2/131 • Number of events 2 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.
Infections and infestations TINEA PEDIS	0.00% 0/130 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.	0.00% 0/130 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.	2.3% 3/131 • Number of events 3 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.
Infections and infestations TOOTH ABSCESS	1.5% 2/130 • Number of events 2 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.	0.00% 0/130 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.	2.3% 3/131 • Number of events 3 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.
Investigations BLOOD PRESSURE INCREASED	0.00% 0/130 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.	2.3% 3/130 • Number of events 3 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.	0.76% 1/131 • Number of events 1 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.
Investigations WEIGHT INCREASED	3.8% 5/130 • Number of events 5 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.	8.5% 11/130 • Number of events 11 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.	3.1% 4/131 • Number of events 4 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.
Musculoskeletal and connective tissue disorders BACK PAIN	2.3% 3/130 • Number of events 3 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.	0.00% 0/130 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.	2.3% 3/131 • Number of events 3 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.
Musculoskeletal and connective tissue disorders PAIN IN EXTREMITY	0.00% 0/130 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.	2.3% 3/130 • Number of events 3 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.	0.76% 1/131 • Number of events 1 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.
Nervous system disorders DIZZINESS	0.00% 0/130 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.	1.5% 2/130 • Number of events 3 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.	2.3% 3/131 • Number of events 3 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.
Nervous system disorders HEADACHE	10.8% 14/130 • Number of events 17 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.	13.8% 18/130 • Number of events 19 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.	13.0% 17/131 • Number of events 19 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.
Nervous system disorders SOMNOLENCE	4.6% 6/130 • Number of events 6 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.	3.1% 4/130 • Number of events 4 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.	3.1% 4/131 • Number of events 4 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.
Psychiatric disorders ANXIETY	3.1% 4/130 • Number of events 4 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.	3.1% 4/130 • Number of events 4 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.	3.1% 4/131 • Number of events 4 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.
Psychiatric disorders INSOMNIA	3.1% 4/130 • Number of events 4 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.	1.5% 2/130 • Number of events 2 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.	3.1% 4/131 • Number of events 4 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.
Psychiatric disorders SUICIDAL IDEATION	2.3% 3/130 • Number of events 3 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.	0.00% 0/130 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.	2.3% 3/131 • Number of events 3 • All-cause mortality and adverse event tables include events reported from the time informed consent was signed to the end of the study. The median time on follow-up was 80 days for the Placebo group, 67.5 days for the Emraclidine 15 mg group, and 64.0 days for the Emraclidine 30 mg group.

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