Trial Outcomes & Findings for A Study of LY2140023 in Schizophrenia Patients With Prominent Negative Symptoms (NCT NCT01052103)

NCT ID: NCT01052103

Last Updated: 2022-09-07

Results Overview

The NSA-16 scale is used to help clinicians rate behaviors (not psychopathology) commonly associated with negative symptoms of schizophrenia. The scale rates participants on 16 "anchors". Each item ("anchor") is rated from 1 (better) to 6 (worse). The total score is the sum of the 16 specific items and ranges from 16 to 96. Higher scores indicate greater severity of illness. The Mixed Model Repeated Measure (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values are controlled for visit, pooled investigative site, treatment, standard of care (SOC) type, baseline positive symptom stratum, treatment\*visit, baseline NSA-16 total score, and baseline NSA-16 total score\*visit.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 167 participants
• Primary outcome timeframe: Baseline, randomization treatment Week 16
• Results posted on: 2022-09-07

Participant Flow

This study consisted of a 1-week placebo lead-in period and a 16-week randomization treatment period.

Participant milestones

Measure	LY2140023 + SOC 1 week placebo lead-in period followed by 20 milligrams (mg) LY2140023 orally, twice daily for 16 weeks (40 mg/day) treatment period. The dose was allowed to adjust to a minimum of 20 mg/day or a maximum of 80 mg/day plus one of the following Standard of Care (SOC) Antipsychotics (aripiprazole, olanzapine, risperidone, quetiapine) taken per label (United States labeling).	Placebo + SOC 1 week placebo lead-in period followed by placebo orally, twice daily for 16 weeks (40 mg/day) plus one of the following SOC Antipsychotics (aripiprazole, olanzapine, risperidone, quetiapine) taken per label (United States labeling) during the treatment period.
Overall Study STARTED	84	83
Overall Study Received at Least 1 Dose of Study Drug	82	82
Overall Study COMPLETED	50	60
Overall Study NOT COMPLETED	34	23

Reasons for withdrawal

Measure	LY2140023 + SOC 1 week placebo lead-in period followed by 20 milligrams (mg) LY2140023 orally, twice daily for 16 weeks (40 mg/day) treatment period. The dose was allowed to adjust to a minimum of 20 mg/day or a maximum of 80 mg/day plus one of the following Standard of Care (SOC) Antipsychotics (aripiprazole, olanzapine, risperidone, quetiapine) taken per label (United States labeling).	Placebo + SOC 1 week placebo lead-in period followed by placebo orally, twice daily for 16 weeks (40 mg/day) plus one of the following SOC Antipsychotics (aripiprazole, olanzapine, risperidone, quetiapine) taken per label (United States labeling) during the treatment period.
Overall Study Adverse Event	10	6
Overall Study Entry Criteria Not Met	3	1
Overall Study Lost to Follow-up	3	5
Overall Study Protocol Violation	10	4
Overall Study Scheduling conflict	2	1
Overall Study Sponsor Decision	2	0
Overall Study Withdrawal by Subject	3	6
Overall Study Perceived Lack of Efficacy	1	0

Baseline Characteristics

A Study of LY2140023 in Schizophrenia Patients With Prominent Negative Symptoms

Baseline characteristics by cohort

Measure	LY2140023 + SOC n=82 Participants 1 week placebo lead-in period followed by 20 milligrams (mg) LY2140023 orally, twice daily for 16 weeks (40 mg/day) treatment period. The dose was allowed to adjust to a minimum of 20 mg/day or a maximum of 80 mg/day plus one of the following Standard of Care (SOC) Antipsychotics (aripiprazole, olanzapine, risperidone, quetiapine) taken per label (United States labeling).	Placebo + SOC n=82 Participants 1 week placebo lead-in period followed by placebo orally, twice daily for 16 weeks (40 mg/day) plus one of the following SOC Antipsychotics (aripiprazole, olanzapine, risperidone, quetiapine) taken per label (United States labeling) during the treatment period.	Total n=164 Participants Total of all reporting groups
Age, Continuous	43.7 years STANDARD_DEVIATION 11.22 • n=5 Participants	42.8 years STANDARD_DEVIATION 10.23 • n=7 Participants	43.3 years STANDARD_DEVIATION 10.71 • n=5 Participants
Sex: Female, Male Female	19 Participants n=5 Participants	18 Participants n=7 Participants	37 Participants n=5 Participants
Sex: Female, Male Male	63 Participants n=5 Participants	64 Participants n=7 Participants	127 Participants n=5 Participants
Race/Ethnicity, Customized Asian	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Race/Ethnicity, Customized Black or African American	41 participants n=5 Participants	43 participants n=7 Participants	84 participants n=5 Participants
Race/Ethnicity, Customized Multiple	0 participants n=5 Participants	2 participants n=7 Participants	2 participants n=5 Participants
Race/Ethnicity, Customized White	41 participants n=5 Participants	35 participants n=7 Participants	76 participants n=5 Participants
Race/Ethnicity, Customized Missing	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Region of Enrollment United States	58 participants n=5 Participants	61 participants n=7 Participants	119 participants n=5 Participants
Region of Enrollment Spain	9 participants n=5 Participants	7 participants n=7 Participants	16 participants n=5 Participants
Region of Enrollment Israel	11 participants n=5 Participants	9 participants n=7 Participants	20 participants n=5 Participants
Region of Enrollment Italy	2 participants n=5 Participants	2 participants n=7 Participants	4 participants n=5 Participants
Region of Enrollment Puerto Rico	2 participants n=5 Participants	3 participants n=7 Participants	5 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, randomization treatment Week 16

Population: All randomized participants who received at least one dose of study drug, had a baseline and at least one post-baseline NSA-16 total score measurement.

The NSA-16 scale is used to help clinicians rate behaviors (not psychopathology) commonly associated with negative symptoms of schizophrenia. The scale rates participants on 16 "anchors". Each item ("anchor") is rated from 1 (better) to 6 (worse). The total score is the sum of the 16 specific items and ranges from 16 to 96. Higher scores indicate greater severity of illness. The Mixed Model Repeated Measure (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values are controlled for visit, pooled investigative site, treatment, standard of care (SOC) type, baseline positive symptom stratum, treatment*visit, baseline NSA-16 total score, and baseline NSA-16 total score*visit.

Outcome measures

Measure	LY2140023 + SOC n=81 Participants 1 week placebo lead-in period followed by 20 milligrams (mg) LY2140023 orally, twice daily for 16 weeks (40 mg/day) treatment period. The dose was allowed to adjust to a minimum of 20 mg/day or a maximum of 80 mg/day plus one of the following Standard of Care (SOC) Antipsychotics (aripiprazole, olanzapine, risperidone, quetiapine) taken per label (United States labeling).	Placebo + SOC n=82 Participants 1 week placebo lead-in period followed by placebo orally, twice daily for 16 weeks (40 mg/day) plus one of the following SOC Antipsychotics (aripiprazole, olanzapine, risperidone, quetiapine) taken per label (United States labeling) during the treatment period.
Change From Baseline in the 16-Item Negative Symptoms Assessment (NSA-16)	-2.7 units on a scale Standard Error 1.2	-3.6 units on a scale Standard Error 1.2

SECONDARY outcome

Timeframe: Baseline, randomization treatment Week 16

Population: All randomized participants who received at least one dose of study drug, had a baseline and at least one post-baseline PANSS total score measurement.

The PANSS Scale consists of 30 items and is designed to measure the severity of psychopathology in schizophrenia. Each item is rated from 1 (symptom not present) to 7 (symptom extremely severe). The PANSS total score is the sum of the 30 items and has a score ranging from 30 to 210. Higher scores indicate greater severity of illness. The Mixed Model Repeated Measure (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values are controlled for visit, pooled investigative site, treatment, standard of care (SOC) type, baseline positive symptom stratum, treatment*visit, baseline PANSS total score, and baseline PANSS total score*visit.

Outcome measures

Measure	LY2140023 + SOC n=81 Participants 1 week placebo lead-in period followed by 20 milligrams (mg) LY2140023 orally, twice daily for 16 weeks (40 mg/day) treatment period. The dose was allowed to adjust to a minimum of 20 mg/day or a maximum of 80 mg/day plus one of the following Standard of Care (SOC) Antipsychotics (aripiprazole, olanzapine, risperidone, quetiapine) taken per label (United States labeling).	Placebo + SOC n=82 Participants 1 week placebo lead-in period followed by placebo orally, twice daily for 16 weeks (40 mg/day) plus one of the following SOC Antipsychotics (aripiprazole, olanzapine, risperidone, quetiapine) taken per label (United States labeling) during the treatment period.
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score	-4.4 units on a scale Standard Error 1.62	-6.6 units on a scale Standard Error 1.55

SECONDARY outcome

Timeframe: Baseline, randomization treatment Week 16

Population: All randomized participants who received at least one dose of study drug, had a baseline and at least one post-baseline CGI-S measurement.

The CGI-S instrument is used to record the severity of mental illness at the time of assessment. The score ranges from 1 (normal, not at all ill) to 7 (among the most extremely ill). Higher scores indicate greater severity of illness. The Mixed Model Repeated Measure (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values are controlled for visit, pooled investigative site, treatment, standard of care (SOC) type, baseline positive symptom stratum, treatment*visit, baseline CGI-S score, and baseline CGI-S score*visit.

Outcome measures

Measure	LY2140023 + SOC n=82 Participants 1 week placebo lead-in period followed by 20 milligrams (mg) LY2140023 orally, twice daily for 16 weeks (40 mg/day) treatment period. The dose was allowed to adjust to a minimum of 20 mg/day or a maximum of 80 mg/day plus one of the following Standard of Care (SOC) Antipsychotics (aripiprazole, olanzapine, risperidone, quetiapine) taken per label (United States labeling).	Placebo + SOC n=82 Participants 1 week placebo lead-in period followed by placebo orally, twice daily for 16 weeks (40 mg/day) plus one of the following SOC Antipsychotics (aripiprazole, olanzapine, risperidone, quetiapine) taken per label (United States labeling) during the treatment period.
Change From Baseline in Clinical Global Impression Severity (CGI-S) Scale	-0.4 units on a scale Standard Error 0.1	-0.3 units on a scale Standard Error 0.1

SECONDARY outcome

Timeframe: Baseline, randomization treatment Week 16

Population: All randomized participants who received at least one dose of study drug, had a baseline and at least one post-baseline MCCB overall composite T-score measurement.

MCCB is an instrument that contains 10 tests to measure cognitive performance in 7 cognitive domains: speed processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition. The MCCB overall composite T-score combines the individual scores of the 10 tests and scores them on a normative scale to derive a T-score, where the mean is 50 and a standard deviation is 10 for the MCCB overall composite T-score. Higher scores indicate better cognition. The Mixed Model Repeated Measure (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values are controlled for visit, pooled investigative site, treatment, standard of care (SOC) type, baseline positive symptom stratum, treatment*visit, baseline MCCB overall composite T-score, and baseline MCCB overall composite T-score*visit.

Outcome measures

Measure	LY2140023 + SOC n=58 Participants 1 week placebo lead-in period followed by 20 milligrams (mg) LY2140023 orally, twice daily for 16 weeks (40 mg/day) treatment period. The dose was allowed to adjust to a minimum of 20 mg/day or a maximum of 80 mg/day plus one of the following Standard of Care (SOC) Antipsychotics (aripiprazole, olanzapine, risperidone, quetiapine) taken per label (United States labeling).	Placebo + SOC n=56 Participants 1 week placebo lead-in period followed by placebo orally, twice daily for 16 weeks (40 mg/day) plus one of the following SOC Antipsychotics (aripiprazole, olanzapine, risperidone, quetiapine) taken per label (United States labeling) during the treatment period.
Change From Baseline in Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB) Overall Composite T-Score	3.2 T-scores Standard Error 1.0	1.8 T-scores Standard Error 1.0

SECONDARY outcome

Timeframe: Baseline, randomization treatment Week 16

Population: All randomized participants who received at least one dose of study drug, had a baseline and at least one post-baseline UPSA-B total score measurement.

The UPSA-B is a performance-based assessment of improvement in functional capacity. Participants are asked to role-play tasks in 2 areas of functioning: communication and finances. Raw scores for the 2 subscales are converted into an UPSA-B Total Score (range = 0-100) with higher scores indicating a greater level of functional capacity. Scores of 75 or higher are associated with independent living. The Mixed Model Repeated Measure (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values are controlled for visit, pooled investigative site, treatment, standard of care (SOC) type, baseline positive symptom stratum, treatment*visit, baseline UPSA-B total score, and baseline UPSA-B total score*visit.

Outcome measures

Measure	LY2140023 + SOC n=62 Participants 1 week placebo lead-in period followed by 20 milligrams (mg) LY2140023 orally, twice daily for 16 weeks (40 mg/day) treatment period. The dose was allowed to adjust to a minimum of 20 mg/day or a maximum of 80 mg/day plus one of the following Standard of Care (SOC) Antipsychotics (aripiprazole, olanzapine, risperidone, quetiapine) taken per label (United States labeling).	Placebo + SOC n=65 Participants 1 week placebo lead-in period followed by placebo orally, twice daily for 16 weeks (40 mg/day) plus one of the following SOC Antipsychotics (aripiprazole, olanzapine, risperidone, quetiapine) taken per label (United States labeling) during the treatment period.
Change From Baseline in University of California at San Diego Performance-Based Skills Assessment-Brief Version (UPSA-B) Total Score	6.5 units on a scale Standard Error 1.9	4.9 units on a scale Standard Error 1.8

SECONDARY outcome

Timeframe: Baseline, randomization treatment Week 16

Population: All randomized participants who received at least one dose of study drug, had a baseline and at least one post-baseline BAS global score measurement.

The BAS is a 4-item instrument that evaluates akathisia associated with use of antipsychotic medications. Item 4 is the Global Clinical Assessment and is rated 0 to 5 (0 = absent, 5 = severe). The Mixed Model Repeated Measure (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values are controlled for visit, pooled investigative site, treatment, standard of care (SOC) type, baseline positive symptom stratum, treatment*visit, baseline BAS global score, and baseline BAS global score*visit.

Outcome measures

Measure	LY2140023 + SOC n=82 Participants 1 week placebo lead-in period followed by 20 milligrams (mg) LY2140023 orally, twice daily for 16 weeks (40 mg/day) treatment period. The dose was allowed to adjust to a minimum of 20 mg/day or a maximum of 80 mg/day plus one of the following Standard of Care (SOC) Antipsychotics (aripiprazole, olanzapine, risperidone, quetiapine) taken per label (United States labeling).	Placebo + SOC n=82 Participants 1 week placebo lead-in period followed by placebo orally, twice daily for 16 weeks (40 mg/day) plus one of the following SOC Antipsychotics (aripiprazole, olanzapine, risperidone, quetiapine) taken per label (United States labeling) during the treatment period.
Change From Baseline in Barnes-Akathisia Scale (BAS) Global Score	-0.1 units on a scale Standard Error 0.0	0.0 units on a scale Standard Error 0.0

SECONDARY outcome

Timeframe: Baseline, randomization treatment Week 16

Population: All randomized participants who received at least one dose of study drug, had a baseline and at least one post-baseline SAS total score measurement.

The SAS is used to measure Parkinsonian-type symptoms in participants exposed to antipsychotics. SAS consists of 10 items; each rated on a 5-point scale, with 0 meaning complete absence of the condition and 4 meaning the presence of the condition in extreme form. The total score is obtained by adding the ten items, and ranges from 0 to 40. Higher scores indicate greater severity of illness. The Mixed Model Repeated Measure (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values are controlled for visit, pooled investigative site, treatment, standard of care (SOC) type, baseline positive symptom stratum, treatment*visit, baseline SAS total score, and baseline SAS total score*visit.

Outcome measures

Measure	LY2140023 + SOC n=82 Participants 1 week placebo lead-in period followed by 20 milligrams (mg) LY2140023 orally, twice daily for 16 weeks (40 mg/day) treatment period. The dose was allowed to adjust to a minimum of 20 mg/day or a maximum of 80 mg/day plus one of the following Standard of Care (SOC) Antipsychotics (aripiprazole, olanzapine, risperidone, quetiapine) taken per label (United States labeling).	Placebo + SOC n=82 Participants 1 week placebo lead-in period followed by placebo orally, twice daily for 16 weeks (40 mg/day) plus one of the following SOC Antipsychotics (aripiprazole, olanzapine, risperidone, quetiapine) taken per label (United States labeling) during the treatment period.
Change From Baseline in Simpson Angus Scale (SAS) Total Score	-0.2 units on a scale Standard Error 0.2	-0.1 units on a scale Standard Error 0.1

SECONDARY outcome

Timeframe: Baseline, randomization treatment Week 16

Population: All randomized participants who received at least one dose of study drug, had a baseline and at least one post-baseline AIMS 1-7 total score measurement.

The AIMS is a 12-item scale designed to record the occurrence of dyskinetic movements. Items 1 to 10 are rated on a 5- point scale, with 0 being no dyskinetic movements and 4 being severe dyskinetic movements. Items 11 and 12 are yes/no questions regarding the dental condition of a subject. The AIMS 1-7 total score is the total of items 1 through 7 of the AIMS, and ranges from 0 to 28. Higher scores indicate greater severity of illness. The Mixed Model Repeated Measure (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values are controlled for visit, pooled investigative site, treatment, standard of care (SOC) type, baseline positive symptom stratum, treatment*visit, baseline AIMS 1-7 total score, and baseline AIMS 1-7 total score*visit.

Outcome measures

Measure	LY2140023 + SOC n=82 Participants 1 week placebo lead-in period followed by 20 milligrams (mg) LY2140023 orally, twice daily for 16 weeks (40 mg/day) treatment period. The dose was allowed to adjust to a minimum of 20 mg/day or a maximum of 80 mg/day plus one of the following Standard of Care (SOC) Antipsychotics (aripiprazole, olanzapine, risperidone, quetiapine) taken per label (United States labeling).	Placebo + SOC n=82 Participants 1 week placebo lead-in period followed by placebo orally, twice daily for 16 weeks (40 mg/day) plus one of the following SOC Antipsychotics (aripiprazole, olanzapine, risperidone, quetiapine) taken per label (United States labeling) during the treatment period.
Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score	0.0 units on a scale Standard Error 0.2	0.1 units on a scale Standard Error 0.2

SECONDARY outcome

Timeframe: Baseline to randomization treatment Week 16

Population: All randomized participants who received at least one dose of study drug, had a baseline and at least one post-baseline EEG measurement.

Incidence of epileptiform activity outside of normal range in EEGs is based on the changes from normal (E0) or within normal range (E1) at baseline to questionably epileptiform (E2) or clearly epileptiform (E3) or seizure (E4) post-baseline. E0 = Normal; E1 (within normal range) = fewer than 3 focal abnormalities or non-epileptiform abnormalities; E2 (questionably epileptiform) = 3 to 10 focal discharges and/or 1 to 10 multifocal or generalized discharges; E3 (clearly epileptiform) = Sharp/slow complex, runs of epileptiform abnormalities, greater than 10 total epileptiform discharges; and E4 = seizure.

Outcome measures

Measure	LY2140023 + SOC n=80 Participants 1 week placebo lead-in period followed by 20 milligrams (mg) LY2140023 orally, twice daily for 16 weeks (40 mg/day) treatment period. The dose was allowed to adjust to a minimum of 20 mg/day or a maximum of 80 mg/day plus one of the following Standard of Care (SOC) Antipsychotics (aripiprazole, olanzapine, risperidone, quetiapine) taken per label (United States labeling).	Placebo + SOC n=82 Participants 1 week placebo lead-in period followed by placebo orally, twice daily for 16 weeks (40 mg/day) plus one of the following SOC Antipsychotics (aripiprazole, olanzapine, risperidone, quetiapine) taken per label (United States labeling) during the treatment period.
Number of Participants With Incidence of Epileptiform Activity Outside of Normal Range in Electroencephalograms (EEGs)	1 participants	0 participants

SECONDARY outcome

Timeframe: Baseline to randomization treatment Week 16

Population: All randomized participants who received at least one dose of study drug, had a baseline and at least one post-baseline ECG QTcF measurement.

QT interval is a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle. QTcF is the QT interval corrected for heart rate using the Fridericia formula. A potentially clinically significant change in QTcF is defined as >450 milliseconds (ms) for male and >470 ms for female.

Outcome measures

Measure	LY2140023 + SOC n=81 Participants 1 week placebo lead-in period followed by 20 milligrams (mg) LY2140023 orally, twice daily for 16 weeks (40 mg/day) treatment period. The dose was allowed to adjust to a minimum of 20 mg/day or a maximum of 80 mg/day plus one of the following Standard of Care (SOC) Antipsychotics (aripiprazole, olanzapine, risperidone, quetiapine) taken per label (United States labeling).	Placebo + SOC n=82 Participants 1 week placebo lead-in period followed by placebo orally, twice daily for 16 weeks (40 mg/day) plus one of the following SOC Antipsychotics (aripiprazole, olanzapine, risperidone, quetiapine) taken per label (United States labeling) during the treatment period.
Number of Participants With Incidence of Potentially Clinically Significant Changes in Corrected (for Rate) Cardiac QT Interval Using Fridericia's Formula (QTcF) Electrocardiograms (ECGs)	3 participants	1 participants

SECONDARY outcome

Timeframe: Baseline to randomization treatment Week 16

Population: All randomized participants who received at least one dose of study drug, had a baseline and at least one post-baseline neurological examination.

Neurological change from baseline was assessed using a 17-item neurological examination and defined as treatment-emergent tremor [increased score on any Item 1- 5; each ranged from 0 (absent) to 3 (interferes with motor function)], nystagmus [increased score for Item 6 or 7; each ranged 0 (absent) to 3 (present on forward gaze)], increased reflexes [increased score and absolute score >2 on any Item 8-11; each ranged 0 (absent) to 4 (clonic)], decreased reflexes [decreased score and absolute score <2 on any Item 8-11; each ranged 0 (absent) to 4 (clonic)], abnormal finger-nose test (Item 12; normal to abnormal), Romberg's sign (Item 13; absent to present), abnormal gait (Item 14; normal to abnormal), decreased muscle strength [decreased score for Item 15 or 16; each ranged 0 (no muscle contraction) to 5 (full and normal power against resistance)], myoclonic jerks [increased score for Item 17; ranged from 0 (absent) to 3 (frequent and across several body regions)].

Outcome measures

Measure	LY2140023 + SOC n=82 Participants 1 week placebo lead-in period followed by 20 milligrams (mg) LY2140023 orally, twice daily for 16 weeks (40 mg/day) treatment period. The dose was allowed to adjust to a minimum of 20 mg/day or a maximum of 80 mg/day plus one of the following Standard of Care (SOC) Antipsychotics (aripiprazole, olanzapine, risperidone, quetiapine) taken per label (United States labeling).	Placebo + SOC n=82 Participants 1 week placebo lead-in period followed by placebo orally, twice daily for 16 weeks (40 mg/day) plus one of the following SOC Antipsychotics (aripiprazole, olanzapine, risperidone, quetiapine) taken per label (United States labeling) during the treatment period.
Percentage of Participants With a Worsening of Neurological Symptoms From Baseline to Endpoint on the Neurological Examination Tremor	11.0 percentage of participants	12.2 percentage of participants
Percentage of Participants With a Worsening of Neurological Symptoms From Baseline to Endpoint on the Neurological Examination Nystagmus	2.4 percentage of participants	2.4 percentage of participants
Percentage of Participants With a Worsening of Neurological Symptoms From Baseline to Endpoint on the Neurological Examination Increased Reflexes	3.7 percentage of participants	4.9 percentage of participants
Percentage of Participants With a Worsening of Neurological Symptoms From Baseline to Endpoint on the Neurological Examination Decreased Reflexes	7.3 percentage of participants	8.5 percentage of participants
Percentage of Participants With a Worsening of Neurological Symptoms From Baseline to Endpoint on the Neurological Examination Abnormal Finger-Nose Test	1.2 percentage of participants	3.7 percentage of participants
Percentage of Participants With a Worsening of Neurological Symptoms From Baseline to Endpoint on the Neurological Examination Romberg's Sign	1.2 percentage of participants	0.0 percentage of participants
Percentage of Participants With a Worsening of Neurological Symptoms From Baseline to Endpoint on the Neurological Examination Abnormal Gait	2.4 percentage of participants	2.4 percentage of participants
Percentage of Participants With a Worsening of Neurological Symptoms From Baseline to Endpoint on the Neurological Examination Decreased Muscle Strength	3.7 percentage of participants	4.9 percentage of participants
Percentage of Participants With a Worsening of Neurological Symptoms From Baseline to Endpoint on the Neurological Examination Myoclonus Jerks	4.9 percentage of participants	2.4 percentage of participants

SECONDARY outcome

Timeframe: Baseline, randomization treatment Week 16

Population: All randomized participants who received at least one dose of study drug, had a baseline and at least one post-baseline standing BP measurement.

The Mixed Model Repeated Measure (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values are controlled for visit, pooled investigative site, treatment, standard of care (SOC) type, baseline positive symptom stratum, treatment*visit, baseline standing BP, and baseline standing BP*visit.

Outcome measures

Measure	LY2140023 + SOC n=82 Participants 1 week placebo lead-in period followed by 20 milligrams (mg) LY2140023 orally, twice daily for 16 weeks (40 mg/day) treatment period. The dose was allowed to adjust to a minimum of 20 mg/day or a maximum of 80 mg/day plus one of the following Standard of Care (SOC) Antipsychotics (aripiprazole, olanzapine, risperidone, quetiapine) taken per label (United States labeling).	Placebo + SOC n=82 Participants 1 week placebo lead-in period followed by placebo orally, twice daily for 16 weeks (40 mg/day) plus one of the following SOC Antipsychotics (aripiprazole, olanzapine, risperidone, quetiapine) taken per label (United States labeling) during the treatment period.
Change From Baseline in Standing Blood Pressure (BP) Standing Systolic BP	-2.0 millimeters of mercury (mmHg) Standard Error 1.6	-2.0 millimeters of mercury (mmHg) Standard Error 1.6
Change From Baseline in Standing Blood Pressure (BP) Standing Diastolic BP	1.4 millimeters of mercury (mmHg) Standard Error 1.1	-2.4 millimeters of mercury (mmHg) Standard Error 1.1

SECONDARY outcome

Timeframe: Baseline, randomization treatment Week 16

Population: All randomized participants who received at least one dose of study drug, had a baseline and at least one post-baseline standing pulse rate measurement.

The Mixed Model Repeated Measure (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values are controlled for visit, pooled investigative site, treatment, standard of care (SOC) type, baseline positive symptom stratum, treatment*visit, baseline standing pulse rate, and baseline standing pulse rate*visit.

Outcome measures

Measure	LY2140023 + SOC n=82 Participants 1 week placebo lead-in period followed by 20 milligrams (mg) LY2140023 orally, twice daily for 16 weeks (40 mg/day) treatment period. The dose was allowed to adjust to a minimum of 20 mg/day or a maximum of 80 mg/day plus one of the following Standard of Care (SOC) Antipsychotics (aripiprazole, olanzapine, risperidone, quetiapine) taken per label (United States labeling).	Placebo + SOC n=82 Participants 1 week placebo lead-in period followed by placebo orally, twice daily for 16 weeks (40 mg/day) plus one of the following SOC Antipsychotics (aripiprazole, olanzapine, risperidone, quetiapine) taken per label (United States labeling) during the treatment period.
Change From Baseline in Standing Pulse Rate	-2.3 beats per minute (bpm) Standard Error 1.7	-1.8 beats per minute (bpm) Standard Error 1.6

SECONDARY outcome

Timeframe: Baseline, randomization treatment Week 16

Population: All randomized participants who received at least one dose of study drug, had a baseline and at least one post-baseline weight measurement.

The Mixed Model Repeated Measure (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values are controlled for visit, pooled investigative site, treatment, standard of care (SOC) type, baseline positive symptom stratum, treatment*visit, baseline weight, and baseline weight*visit.

Outcome measures

Measure	LY2140023 + SOC n=81 Participants 1 week placebo lead-in period followed by 20 milligrams (mg) LY2140023 orally, twice daily for 16 weeks (40 mg/day) treatment period. The dose was allowed to adjust to a minimum of 20 mg/day or a maximum of 80 mg/day plus one of the following Standard of Care (SOC) Antipsychotics (aripiprazole, olanzapine, risperidone, quetiapine) taken per label (United States labeling).	Placebo + SOC n=81 Participants 1 week placebo lead-in period followed by placebo orally, twice daily for 16 weeks (40 mg/day) plus one of the following SOC Antipsychotics (aripiprazole, olanzapine, risperidone, quetiapine) taken per label (United States labeling) during the treatment period.
Change From Baseline in Weight	-1.25 kilograms (kg) Standard Error 0.56	-0.81 kilograms (kg) Standard Error 0.55

SECONDARY outcome

Timeframe: Baseline to randomization treatment Week 16

Population: All randomized participants who received at least one dose of study drug and had at least one post-baseline laboratory measurement.

PCS change in laboratory values were defined as a laboratory value which reached a predefined alert level at any time post-baseline. PCS change in liver function: alanine transaminase (ALT) or aspartate aminotransferase (AST) ≥2* the upper limit of normal (ULN) or total bilirubin ≥1.5*ULN any time post-baseline regardless of the baseline value. Hy's rule: ALT ≥3*ULN, total bilirubin ≥1.5*ULN and alkaline phosphatase <2*ULN at the same time any time post-baseline regardless of the baseline value. PCS change in eosinophil counts: >1.5*10³ cells/microliter any time post-baseline regardless of the baseline value. PCS change in blood creatine phosphokinase: ≥5*ULN any time post-baseline regardless of the baseline value.

Outcome measures

Measure	LY2140023 + SOC n=82 Participants 1 week placebo lead-in period followed by 20 milligrams (mg) LY2140023 orally, twice daily for 16 weeks (40 mg/day) treatment period. The dose was allowed to adjust to a minimum of 20 mg/day or a maximum of 80 mg/day plus one of the following Standard of Care (SOC) Antipsychotics (aripiprazole, olanzapine, risperidone, quetiapine) taken per label (United States labeling).	Placebo + SOC n=82 Participants 1 week placebo lead-in period followed by placebo orally, twice daily for 16 weeks (40 mg/day) plus one of the following SOC Antipsychotics (aripiprazole, olanzapine, risperidone, quetiapine) taken per label (United States labeling) during the treatment period.
Number of Participants With Incidence of Potentially Clinically Significant (PCS) Change in Laboratory Values Any Time Post-Baseline - General ALT	4 participants	5 participants
Number of Participants With Incidence of Potentially Clinically Significant (PCS) Change in Laboratory Values Any Time Post-Baseline - General AST	1 participants	3 participants
Number of Participants With Incidence of Potentially Clinically Significant (PCS) Change in Laboratory Values Any Time Post-Baseline - General Total bilirubin	2 participants	0 participants
Number of Participants With Incidence of Potentially Clinically Significant (PCS) Change in Laboratory Values Any Time Post-Baseline - General Hy's rule	0 participants	0 participants
Number of Participants With Incidence of Potentially Clinically Significant (PCS) Change in Laboratory Values Any Time Post-Baseline - General Eosinophil counts	0 participants	0 participants
Number of Participants With Incidence of Potentially Clinically Significant (PCS) Change in Laboratory Values Any Time Post-Baseline - General Blood creatine phosphokinase	7 participants	7 participants

SECONDARY outcome

Timeframe: Baseline to randomization treatment Week 16

Population: All randomized participants who received at least one dose of study drug, had normal or borderline cholesterol level at baseline and at least one post-baseline cholesterol measurement. "Number" represents number of participants with an incidence of potentially clinically significant (PCS) change in laboratory values

PCS change in laboratory values were defined as a laboratory value which reached a predefined alert level at any time post-baseline. PCS change in total cholesterol: Normal (N) to High (H) <200 milligrams/deciliter (mg/dL) at baseline and ≥240 mg/dL post-baseline; Borderline (B) to H ≥200 mg/dL and <240 mg/dL at baseline and ≥240 mg/dL post-baseline; N/B to H <240 mg/dL at baseline and ≥240 mg/dL post-baseline; N to B/H <200 mg/dL at baseline, ≥200 mg/dL post-baseline. PCS change in low-density lipoprotein (LDL) cholesterol: N to H <100 mg/dL at baseline and ≥160 mg/dL post-baseline; B to H ≥100 mg/dL and <160 mg/dL at baseline and ≥160 mg/dL post-baseline; N/B to H <160 mg/dL at baseline and ≥160 mg/dL post-baseline; N to B/H <100 mg/dL at baseline, ≥100 mg/dL post-baseline. PCS change in high-density lipoprotein (HDL) cholesterol: ≥40 mg/dL at baseline and <40 mg/dL post-baseline.

Outcome measures

Measure	LY2140023 + SOC n=73 Participants 1 week placebo lead-in period followed by 20 milligrams (mg) LY2140023 orally, twice daily for 16 weeks (40 mg/day) treatment period. The dose was allowed to adjust to a minimum of 20 mg/day or a maximum of 80 mg/day plus one of the following Standard of Care (SOC) Antipsychotics (aripiprazole, olanzapine, risperidone, quetiapine) taken per label (United States labeling).	Placebo + SOC n=68 Participants 1 week placebo lead-in period followed by placebo orally, twice daily for 16 weeks (40 mg/day) plus one of the following SOC Antipsychotics (aripiprazole, olanzapine, risperidone, quetiapine) taken per label (United States labeling) during the treatment period.
Number of Participants With Incidence of Potentially Clinically Significant (PCS) Change in Laboratory Values Any Time Post-Baseline - Fasting Cholesterol Total Cholesterol N to H	1 participants	0 participants
Number of Participants With Incidence of Potentially Clinically Significant (PCS) Change in Laboratory Values Any Time Post-Baseline - Fasting Cholesterol Total Cholesterol B to H	8 participants	7 participants
Number of Participants With Incidence of Potentially Clinically Significant (PCS) Change in Laboratory Values Any Time Post-Baseline - Fasting Cholesterol Total Cholesterol N/B to H	9 participants	7 participants
Number of Participants With Incidence of Potentially Clinically Significant (PCS) Change in Laboratory Values Any Time Post-Baseline - Fasting Cholesterol Total Cholesterol N to B/H	9 participants	9 participants
Number of Participants With Incidence of Potentially Clinically Significant (PCS) Change in Laboratory Values Any Time Post-Baseline - Fasting Cholesterol LDL Cholesterol N to H	0 participants	0 participants
Number of Participants With Incidence of Potentially Clinically Significant (PCS) Change in Laboratory Values Any Time Post-Baseline - Fasting Cholesterol LDL Cholesterol B to H	13 participants	13 participants
Number of Participants With Incidence of Potentially Clinically Significant (PCS) Change in Laboratory Values Any Time Post-Baseline - Fasting Cholesterol LDL Cholesterol N/B to H	13 participants	13 participants
Number of Participants With Incidence of Potentially Clinically Significant (PCS) Change in Laboratory Values Any Time Post-Baseline - Fasting Cholesterol LDL Cholesterol N to B/H	9 participants	2 participants
Number of Participants With Incidence of Potentially Clinically Significant (PCS) Change in Laboratory Values Any Time Post-Baseline - Fasting Cholesterol HDL Cholesterol N to Low	24 participants	24 participants

SECONDARY outcome

Timeframe: Baseline to randomization treatment Week 16

Population: All randomized participants who received at least one dose of study drug, had normal or borderline triglycerides level at baseline and at least one post-baseline triglycerides measurement. "Number" represents number of participants with an incidence of potentially clinically significant (PCS) change in laboratory values

PCS change in laboratory values were defined as a laboratory value which reached a predefined alert level at any time post-baseline. PCS change for Normal (N) to High (H) <150 milligrams/deciliter (mg/dL) at baseline and ≥200 mg/dL post-baseline; N/Borderline (B) to H <200 mg/dL at baseline and ≥200 mg/dL post-baseline; N to very H <150 mg/dL at baseline and ≥500 mg/dL post-baseline; B to H >150 and <200 mg/dL at baseline and ≥200 mg/dL post-baseline; B to very H >150 and <200 mg/dL at baseline and ≥500 mg/dL post-baseline; N/B to very H <200 mg/dL at baseline and ≥500 mg/dL post-baseline; N to B/H/very H <150 mg/dL at baseline and ≥150 mg/dL post-baseline.

Outcome measures

Measure	LY2140023 + SOC n=67 Participants 1 week placebo lead-in period followed by 20 milligrams (mg) LY2140023 orally, twice daily for 16 weeks (40 mg/day) treatment period. The dose was allowed to adjust to a minimum of 20 mg/day or a maximum of 80 mg/day plus one of the following Standard of Care (SOC) Antipsychotics (aripiprazole, olanzapine, risperidone, quetiapine) taken per label (United States labeling).	Placebo + SOC n=59 Participants 1 week placebo lead-in period followed by placebo orally, twice daily for 16 weeks (40 mg/day) plus one of the following SOC Antipsychotics (aripiprazole, olanzapine, risperidone, quetiapine) taken per label (United States labeling) during the treatment period.
Number of Participants With Incidence of Potentially Clinically Significant (PCS) Change in Laboratory Values Any Time Post-Baseline - Fasting Triglycerides N to H	10 participants	7 participants
Number of Participants With Incidence of Potentially Clinically Significant (PCS) Change in Laboratory Values Any Time Post-Baseline - Fasting Triglycerides N/B to H	20 participants	13 participants
Number of Participants With Incidence of Potentially Clinically Significant (PCS) Change in Laboratory Values Any Time Post-Baseline - Fasting Triglycerides N to very H	0 participants	0 participants
Number of Participants With Incidence of Potentially Clinically Significant (PCS) Change in Laboratory Values Any Time Post-Baseline - Fasting Triglycerides B to H	10 participants	6 participants
Number of Participants With Incidence of Potentially Clinically Significant (PCS) Change in Laboratory Values Any Time Post-Baseline - Fasting Triglycerides B to very H	0 participants	0 participants
Number of Participants With Incidence of Potentially Clinically Significant (PCS) Change in Laboratory Values Any Time Post-Baseline - Fasting Triglycerides N/B to very H	0 participants	0 participants
Number of Participants With Incidence of Potentially Clinically Significant (PCS) Change in Laboratory Values Any Time Post-Baseline - Fasting Triglycerides N to B/H/very H	18 participants	17 participants

SECONDARY outcome

Timeframe: Baseline to randomization treatment Week 16

Population: All randomized participants who received at least one dose of study drug, had normal or impaired glucose level at baseline and at least 1 post-baseline glucose measurement. "Number" represents number of participants with an incidence of potentially clinically significant (PCS) change in laboratory values

PCS change in laboratory values were defined as a laboratory value which reached a predefined alert level at any time post-baseline. PCS change for Normal to High: <100 milligrams/deciliter (mg/dL) at baseline and ≥126 mg/dL post-baseline; Impaired to High ≥100 mg/dL and <126 mg/dL at baseline and ≥126 mg/dL any time post-baseline; Normal/Impaired to High <126 mg/dL at baseline and ≥126 mg/dL any time post-baseline.

Outcome measures

Measure	LY2140023 + SOC n=74 Participants 1 week placebo lead-in period followed by 20 milligrams (mg) LY2140023 orally, twice daily for 16 weeks (40 mg/day) treatment period. The dose was allowed to adjust to a minimum of 20 mg/day or a maximum of 80 mg/day plus one of the following Standard of Care (SOC) Antipsychotics (aripiprazole, olanzapine, risperidone, quetiapine) taken per label (United States labeling).	Placebo + SOC n=76 Participants 1 week placebo lead-in period followed by placebo orally, twice daily for 16 weeks (40 mg/day) plus one of the following SOC Antipsychotics (aripiprazole, olanzapine, risperidone, quetiapine) taken per label (United States labeling) during the treatment period.
Number of Participants With Incidence of Potentially Clinically Significant (PCS) Change in Laboratory Values Any Time Post-Baseline - Fasting Glucose Normal to High	2 participants	8 participants
Number of Participants With Incidence of Potentially Clinically Significant (PCS) Change in Laboratory Values Any Time Post-Baseline - Fasting Glucose Impaired to High	10 participants	5 participants
Number of Participants With Incidence of Potentially Clinically Significant (PCS) Change in Laboratory Values Any Time Post-Baseline - Fasting Glucose Normal/Impaired to High	12 participants	13 participants

SECONDARY outcome

Timeframe: Baseline to randomization treatment Week 16

Population: All randomized participants who received at least one dose of study drug, had a baseline and at least one post-baseline C-SSRS measurement.

Columbia Suicide Rating Scale (C-SSRS) captures occurrence, severity, and frequency of suicide-related thoughts and behaviors. Suicidal ideation: a "yes" answer to any one of 5 suicidal ideation questions: wish to be dead, and 4 different categories of active suicidal ideation. Suicidal behavior: a "yes" answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Percentage of participants with incidence of potentially clinically significant change of the C-SSRS was calculated as the number of participants with an increase in suicidal behavior or ideation over baseline, divided by the total number of participants multiplied by 100.

Outcome measures

Measure	LY2140023 + SOC n=82 Participants 1 week placebo lead-in period followed by 20 milligrams (mg) LY2140023 orally, twice daily for 16 weeks (40 mg/day) treatment period. The dose was allowed to adjust to a minimum of 20 mg/day or a maximum of 80 mg/day plus one of the following Standard of Care (SOC) Antipsychotics (aripiprazole, olanzapine, risperidone, quetiapine) taken per label (United States labeling).	Placebo + SOC n=82 Participants 1 week placebo lead-in period followed by placebo orally, twice daily for 16 weeks (40 mg/day) plus one of the following SOC Antipsychotics (aripiprazole, olanzapine, risperidone, quetiapine) taken per label (United States labeling) during the treatment period.
Percentage of Participants With Incidence of Potentially Clinically Significant Change of Columbia-Suicide Severity Rating Scale (C-SSRS) Treatment-Emergent Suicidal Ideation	2.4 percentage of participants	4.9 percentage of participants
Percentage of Participants With Incidence of Potentially Clinically Significant Change of Columbia-Suicide Severity Rating Scale (C-SSRS) Treatment-Emergent Suicidal Behavior	0.0 percentage of participants	1.2 percentage of participants

SECONDARY outcome

Timeframe: Baseline, randomization treatment Week 16

Population: All randomized participants who received at least one dose of study drug, had a baseline and at least one post-baseline PSP measurement.

The PSP scale is a 100-point, single item, clinician-rated scale to assess a participant's overall functioning, including personal and social relationships, socially useful activities, self-care, and disturbing and aggressive behaviors. The higher scores indicate a higher level of functioning. The Mixed Model Repeated Measure (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values are controlled for visit, pooled investigative site, treatment, standard of care (SOC) type, baseline positive symptom stratum, treatment*visit, baseline PSP score, and baseline PSP score*visit.

Outcome measures

Measure	LY2140023 + SOC n=75 Participants 1 week placebo lead-in period followed by 20 milligrams (mg) LY2140023 orally, twice daily for 16 weeks (40 mg/day) treatment period. The dose was allowed to adjust to a minimum of 20 mg/day or a maximum of 80 mg/day plus one of the following Standard of Care (SOC) Antipsychotics (aripiprazole, olanzapine, risperidone, quetiapine) taken per label (United States labeling).	Placebo + SOC n=77 Participants 1 week placebo lead-in period followed by placebo orally, twice daily for 16 weeks (40 mg/day) plus one of the following SOC Antipsychotics (aripiprazole, olanzapine, risperidone, quetiapine) taken per label (United States labeling) during the treatment period.
Change From Baseline to Endpoint in Personal and Social Performance (PSP) Scale	8.9 units on a scale Standard Error 1.3	7.9 units on a scale Standard Error 1.3

SECONDARY outcome

Timeframe: First dose to randomization treatment Week 16

Population: All randomized participants who received at least one dose of study drug. Participants who completed the study were considered censored: 50 for LY2140023 + SOC group and 60 for placebo + SOC group.

The time to discontinuation due to any reason was defined as the total number of days between the date of first dose and discontinuation date. The time to discontinuation was analyzed using Kaplan-Meier estimated survival curves. Participants who completed the study were considered censored. Less than 50% of participants discontinued from study at randomization treatment Week 16 endpoint, therefore median values were not calculated.

Outcome measures

Measure	LY2140023 + SOC n=82 Participants 1 week placebo lead-in period followed by 20 milligrams (mg) LY2140023 orally, twice daily for 16 weeks (40 mg/day) treatment period. The dose was allowed to adjust to a minimum of 20 mg/day or a maximum of 80 mg/day plus one of the following Standard of Care (SOC) Antipsychotics (aripiprazole, olanzapine, risperidone, quetiapine) taken per label (United States labeling).	Placebo + SOC n=82 Participants 1 week placebo lead-in period followed by placebo orally, twice daily for 16 weeks (40 mg/day) plus one of the following SOC Antipsychotics (aripiprazole, olanzapine, risperidone, quetiapine) taken per label (United States labeling) during the treatment period.
Time to Discontinuation From the Study Due to Any Reason	NA months The median (full range) was not calculated because an insufficient number of participants reached the event at the final time point (randomization treatment Week 16).	NA months The median (full range) was not calculated because an insufficient number of participants reached the event at the final time point (randomization treatment Week 16).

SECONDARY outcome

Timeframe: Baseline to randomization treatment Week 16

Population: All randomized participants who received at least one dose of study drug and had S-RUM assessment.

The S-RUM is a 31-item questionnaire to assess the participant's occupation (work and home), living arrangements, encounters with law enforcement, victimization, ER visits, and outpatient medical visits for a specified period of time. Item 1 asks about the number of ER or equivalent facility visits a participant had for psychiatric (psych) illness. Item 2 asks about the number of ER or equivalent facility visits a participant had for non-psychiatric (non-psych) illness or injury. Item 5 asks about the number of outpatient visits to other physicians (not psychiatrists or dentists).

Outcome measures

Measure	LY2140023 + SOC n=80 Participants 1 week placebo lead-in period followed by 20 milligrams (mg) LY2140023 orally, twice daily for 16 weeks (40 mg/day) treatment period. The dose was allowed to adjust to a minimum of 20 mg/day or a maximum of 80 mg/day plus one of the following Standard of Care (SOC) Antipsychotics (aripiprazole, olanzapine, risperidone, quetiapine) taken per label (United States labeling).	Placebo + SOC n=80 Participants 1 week placebo lead-in period followed by placebo orally, twice daily for 16 weeks (40 mg/day) plus one of the following SOC Antipsychotics (aripiprazole, olanzapine, risperidone, quetiapine) taken per label (United States labeling) during the treatment period.
Schizophrenia Resource Use Module (S-RUM) - Number of Emergency Room (ER) or Equivalent Facility Visits and Outpatient Medical Visits ER/Facility (Psych) visits	0.6 visits Standard Deviation 4.11	0.2 visits Standard Deviation 1.79
Schizophrenia Resource Use Module (S-RUM) - Number of Emergency Room (ER) or Equivalent Facility Visits and Outpatient Medical Visits ER/Facility (Non-Psych) visits	0.2 visits Standard Deviation 0.43	0.1 visits Standard Deviation 0.56
Schizophrenia Resource Use Module (S-RUM) - Number of Emergency Room (ER) or Equivalent Facility Visits and Outpatient Medical Visits Outpatient (Non-Psych or Dentist) visits	0.7 visits Standard Deviation 1.33	1.2 visits Standard Deviation 2.99

SECONDARY outcome

Timeframe: Baseline to randomization treatment Week 16

Population: All randomized participants who received at least one dose of study drug and had S-RUM assessment.

The S-RUM is a 31-item questionnaire to assess the participant's occupation (work and home), living arrangements, encounters with law enforcement, victimization, Emergency Room (ER) visits, and outpatient medical visits for a specified period of time. Item 4 asks about the number of sessions with a psychiatrist a participant had.

Outcome measures

Measure	LY2140023 + SOC n=80 Participants 1 week placebo lead-in period followed by 20 milligrams (mg) LY2140023 orally, twice daily for 16 weeks (40 mg/day) treatment period. The dose was allowed to adjust to a minimum of 20 mg/day or a maximum of 80 mg/day plus one of the following Standard of Care (SOC) Antipsychotics (aripiprazole, olanzapine, risperidone, quetiapine) taken per label (United States labeling).	Placebo + SOC n=80 Participants 1 week placebo lead-in period followed by placebo orally, twice daily for 16 weeks (40 mg/day) plus one of the following SOC Antipsychotics (aripiprazole, olanzapine, risperidone, quetiapine) taken per label (United States labeling) during the treatment period.
Schizophrenia Resource Use Module (S-RUM) - Number of Sessions With a Psychiatrist	3.4 sessions Standard Deviation 17.49	1.5 sessions Standard Deviation 2.76

SECONDARY outcome

Timeframe: Baseline, randomization treatment Week 16

Population: All randomized participants who received at least one dose of study drug, had a baseline and at least one post-baseline VAS health state measurement.

The EQ-5D is a generic, multidimensional, health-related, quality-of-life instrument that contains 2 parts: a health status profile and a visual analog scale (VAS) to rate global health-related quality of life. VAS health state scores range from 0 (worst imaginable health state) to 100 (best imaginable health state). The Mixed Model Repeated Measure (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values are controlled for visit, pooled investigative site, treatment, standard of care (SOC) type, baseline positive symptom stratum, treatment*visit, baseline VAS health state score, and baseline VAS health state score*visit.

Outcome measures

Measure	LY2140023 + SOC n=74 Participants 1 week placebo lead-in period followed by 20 milligrams (mg) LY2140023 orally, twice daily for 16 weeks (40 mg/day) treatment period. The dose was allowed to adjust to a minimum of 20 mg/day or a maximum of 80 mg/day plus one of the following Standard of Care (SOC) Antipsychotics (aripiprazole, olanzapine, risperidone, quetiapine) taken per label (United States labeling).	Placebo + SOC n=77 Participants 1 week placebo lead-in period followed by placebo orally, twice daily for 16 weeks (40 mg/day) plus one of the following SOC Antipsychotics (aripiprazole, olanzapine, risperidone, quetiapine) taken per label (United States labeling) during the treatment period.
Change From Baseline to Endpoint in the EuroQol Questionnaire-5 Dimension (EQ-5D) Visual Analog Scale (VAS) Health State Score	3.7 units on a scale Standard Error 2.6	5.4 units on a scale Standard Error 2.4

SECONDARY outcome

Timeframe: Baseline, randomization treatment Week 16

Population: All randomized participants who received at least one dose of study drug, had a baseline and at least one post-baseline SWN-SF total score measurement.

The SWN-SF measures subjective well-being for the previous 7 days. The 20-item scale covers 5 health domains (subscales; 4 items each): emotional regulation, self-control, mental functioning, social integration, and physical functioning. Individual scores range from 1 (not at all) to 6 (very much). Each of the 5 subscale scores range from 4 to 24. SWN-SF total scores range from 20 to 120. Higher scores indicate greater well-being. The Mixed Model Repeated Measure (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values are controlled for visit, pooled investigative site, treatment, standard of care (SOC) type, baseline positive symptom stratum, treatment*visit, baseline SWN-SF total score, and baseline SWN-SF total score*visit.

Outcome measures

Measure	LY2140023 + SOC n=73 Participants 1 week placebo lead-in period followed by 20 milligrams (mg) LY2140023 orally, twice daily for 16 weeks (40 mg/day) treatment period. The dose was allowed to adjust to a minimum of 20 mg/day or a maximum of 80 mg/day plus one of the following Standard of Care (SOC) Antipsychotics (aripiprazole, olanzapine, risperidone, quetiapine) taken per label (United States labeling).	Placebo + SOC n=75 Participants 1 week placebo lead-in period followed by placebo orally, twice daily for 16 weeks (40 mg/day) plus one of the following SOC Antipsychotics (aripiprazole, olanzapine, risperidone, quetiapine) taken per label (United States labeling) during the treatment period.
Change From Baseline to Endpoint in the Subjective Well-Being Under Neuroleptic Treatment-Short Form (SWN-SF) Total Score	3.9 units on a scale Standard Error 2.0	4.4 units on a scale Standard Error 1.9

Adverse Events

LY2140023 + SOC

Serious events: 8 serious events

Other events: 54 other events

Deaths: 0 deaths

Placebo + SOC

Serious events: 4 serious events

Other events: 51 other events

Deaths: 0 deaths

Serious adverse events

Measure	LY2140023 + SOC n=82 participants at risk 1 week placebo lead-in period followed by 20 milligrams (mg) LY2140023 orally, twice daily for 16 weeks (40 mg/day) treatment period. The dose was allowed to adjust to a minimum of 20 mg/day or a maximum of 80 mg/day plus one of the following Standard of Care (SOC) Antipsychotics (aripiprazole, olanzapine, risperidone, quetiapine) taken per label (United States labeling).	Placebo + SOC n=82 participants at risk 1 week placebo lead-in period followed by placebo orally, twice daily for 16 weeks (40 mg/day) plus one of the following SOC Antipsychotics (aripiprazole, olanzapine, risperidone, quetiapine) taken per label (United States labeling) during the treatment period.
Hepatobiliary disorders Cholangitis	1.2% 1/82 • Number of events 1	0.00% 0/82
Infections and infestations Cellulitis	1.2% 1/82 • Number of events 1	0.00% 0/82
Nervous system disorders Ischaemic stroke	0.00% 0/82	1.2% 1/82 • Number of events 1
Psychiatric disorders Psychotic disorder	3.7% 3/82 • Number of events 3	1.2% 1/82 • Number of events 1
Psychiatric disorders Schizophrenia	3.7% 3/82 • Number of events 3	1.2% 1/82 • Number of events 1
Psychiatric disorders Suicidal ideation	0.00% 0/82	1.2% 1/82 • Number of events 1
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/82	1.2% 1/82 • Number of events 1

Other adverse events

Measure	LY2140023 + SOC n=82 participants at risk 1 week placebo lead-in period followed by 20 milligrams (mg) LY2140023 orally, twice daily for 16 weeks (40 mg/day) treatment period. The dose was allowed to adjust to a minimum of 20 mg/day or a maximum of 80 mg/day plus one of the following Standard of Care (SOC) Antipsychotics (aripiprazole, olanzapine, risperidone, quetiapine) taken per label (United States labeling).	Placebo + SOC n=82 participants at risk 1 week placebo lead-in period followed by placebo orally, twice daily for 16 weeks (40 mg/day) plus one of the following SOC Antipsychotics (aripiprazole, olanzapine, risperidone, quetiapine) taken per label (United States labeling) during the treatment period.
Gastrointestinal disorders Abdominal discomfort	3.7% 3/82 • Number of events 3	0.00% 0/82
Gastrointestinal disorders Diarrhoea	6.1% 5/82 • Number of events 5	2.4% 2/82 • Number of events 3
Gastrointestinal disorders Dry mouth	2.4% 2/82 • Number of events 2	11.0% 9/82 • Number of events 9
Gastrointestinal disorders Nausea	13.4% 11/82 • Number of events 12	4.9% 4/82 • Number of events 4
Gastrointestinal disorders Toothache	1.2% 1/82 • Number of events 1	3.7% 3/82 • Number of events 3
Gastrointestinal disorders Vomiting	12.2% 10/82 • Number of events 13	2.4% 2/82 • Number of events 7
General disorders Fatigue	1.2% 1/82 • Number of events 1	4.9% 4/82 • Number of events 4
General disorders Pain	3.7% 3/82 • Number of events 3	0.00% 0/82
Infections and infestations Nasopharyngitis	3.7% 3/82 • Number of events 3	4.9% 4/82 • Number of events 4
Infections and infestations Upper respiratory tract infection	1.2% 1/82 • Number of events 1	3.7% 3/82 • Number of events 5
Infections and infestations Vulvovaginal mycotic infection	5.3% 1/19 • Number of events 1	0.00% 0/18
Investigations Blood creatine phosphokinase increased	7.3% 6/82 • Number of events 6	8.5% 7/82 • Number of events 7
Investigations Weight increased	3.7% 3/82 • Number of events 3	1.2% 1/82 • Number of events 1
Musculoskeletal and connective tissue disorders Arthralgia	2.4% 2/82 • Number of events 2	6.1% 5/82 • Number of events 5
Musculoskeletal and connective tissue disorders Back pain	2.4% 2/82 • Number of events 2	3.7% 3/82 • Number of events 3
Nervous system disorders Akathisia	1.2% 1/82 • Number of events 1	4.9% 4/82 • Number of events 5
Nervous system disorders Dizziness	3.7% 3/82 • Number of events 4	3.7% 3/82 • Number of events 3
Nervous system disorders Headache	13.4% 11/82 • Number of events 12	13.4% 11/82 • Number of events 12
Nervous system disorders Somnolence	0.00% 0/82	3.7% 3/82 • Number of events 3
Psychiatric disorders Anxiety	3.7% 3/82 • Number of events 4	2.4% 2/82 • Number of events 2
Psychiatric disorders Insomnia	3.7% 3/82 • Number of events 3	3.7% 3/82 • Number of events 4
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/82	3.7% 3/82 • Number of events 3

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: GT60