A Study of LY2140023 in Patients With Schizophrenia

The PANSS scale assessed participants for positive symptoms, negative symptoms, and general psychopathology specifically associated with schizophrenia. The scale consisted of 30 items. Each item was rated from 1 (absence of symptoms) to 7 (symptoms extremely severe). The sum of the 30 items was defined as the PANSS total score and ranged from 30 to 210. The least squares (LS) mean was estimated using a mixed-effects model with repeated measures (MMRM) that included the fixed categorical effects of treatment, pooled investigative site, visit, treatment-by-visit interaction, and gender, as well as the continuous fixed covariates of baseline score, and baseline score-by-visit interaction.

The PSP scale was a 100-point, single item scale that assessed 4 domains of functioning (personal and social relationships, socially useful activities, self-care, and disturbing and aggressive behaviors). PSP scores ranged from 1 (risk of death) to 100 (excellent functioning) in all 4 domain areas. A higher score indicated a better health state. The least squares (LS) mean was estimated using a mixed-effects model with repeated measures (MMRM) that included the fixed, categorical effects of treatment, pooled investigative site, visit, treatment-by-visit interaction, gender, and predefined subpopulation ('yes/no'), as well as the continuous, fixed covariates of baseline score and baseline score-by-visit interaction.

The PSP scale was a 100-point, single item scale that assessed 4 domains of functioning (personal and social relationships, socially useful activities, self-care, and disturbing and aggressive behaviors). PSP scores ranged from 1 (risk of death) to 100 (excellent functioning) in all 4 domain areas. A higher score indicated a better health state. The least squares (LS) mean was estimated using a mixed-effects model with repeated measures (MMRM) that included the fixed, categorical effects of treatment, pooled investigative site, visit, treatment-by-visit interaction, and gender, as well as the continuous, fixed covariates of baseline score and baseline score-by-visit interaction.

The PANSS scale assessed participants for positive symptoms, negative symptoms, and general psychopathology specifically associated with schizophrenia. The scale consisted of 30 items. Each item was rated from 1 (absence of symptoms) to 7 (symptoms extremely severe). The sum of the 30 items was defined as the PANSS total score and ranged from 30 to 210. The least squares (LS) mean was estimated using a mixed-effects model with repeated measures (MMRM) that included the fixed, categorical effects of treatment, pooled investigative site, visit, treatment-by-visit interaction, and predefined subpopulation ('yes/no'), as well as the continuous, fixed covariates of baseline score and baseline score-by-visit interaction.

PANSS subscales included the positive, negative, and general psychopathology subscales. PANSS positive and negative subscales assessed participants for 7 symptoms (positive or negative) associated with schizophrenia. Each item was rated from 1 (absence of symptoms) to 7 (symptoms extremely severe). Scores for both subscales ranged from 7 to 49. PANSS general psychopathology subscale assessed participants for 16 items of general psychopathology associated with schizophrenia. Each item was rated from 1 (absence of symptom) to 7 (symptom extremely severe). General psychopathology scores ranged from 16 to 112. The least squares (LS) mean was estimated using a mixed-effects model with repeated measures (MMRM) that included the fixed, categorical effects of treatment, pooled investigative site, visit, treatment-by-visit interaction, gender, and predefined subpopulation ('yes/no'), as well as the continuous, fixed covariates of baseline score and baseline score-by-visit interaction.

Response during the treatment period was defined as a ≥30% decrease from baseline in Positive and Negative Syndrome Scale (PANSS) total score. The PANSS scale assessed participants for positive symptoms, negative symptoms, and general psychopathology specifically associated with schizophrenia. The scale consisted of 30 items. Each item was rated from 1 (absence of symptoms) to 7 (symptoms extremely severe). The sum of the 30 items was defined as the PANSS total score and ranged from 30 to 210.

Time to response is the number of days from randomization until a ≥30% decrease from lead-in baseline in Positive and Negative Syndrome Scale (PANSS) total score. Participants who did not have a response were censored. The PANSS scale assessed participants for positive symptoms, negative symptoms, and general psychopathology specifically associated with schizophrenia. The scale consisted of 30 items. Each item was rated from 1 (absence of symptoms) to 7 (symptoms extremely severe). The sum of the 30 items was defined as the PANSS total score and ranged from 30 to 210.

The CGI-S was a single item scale that measured severity of illness at the time of assessment. Scores ranged from 1 (normal, not at all ill) to 7 (among the most extremely ill participants). The least squares (LS) mean was estimated using a mixed-effects model with repeated measures (MMRM) that included the fixed, categorical effects of treatment, pooled investigative site, visit, treatment-by-visit interaction, gender, and predefined subpopulation ('yes/no'), as well as the continuous, fixed covariates of baseline score and baseline score-by-visit interaction.

The NSA-16 scale was used to help clinicians rate behaviors (not psychopathology) commonly associated with negative symptoms of schizophrenia. The scale contained 16 items and each item was rated from 1 (normal behavior) to 6 (extreme, abnormal behavior). The sum of the 16 items was defined as the NSA-16 total score and ranged from 16 to 96. Higher scores indicated a greater severity of illness. The least squares (LS) mean was estimated using a mixed-effects model with repeated measures (MMRM) that included the fixed, categorical effects of treatment, pooled investigative site, visit, treatment-by-visit interaction, gender, and predefined subpopulation ('yes/no'), as well as the continuous, fixed covariates of baseline score and baseline score-by-visit interaction.

The EQ-5D was a generic, multidimensional, health-related, quality-of-life instrument. The overall health state score was self-reported using a visual analogue scale (VAS) from 0 (worst imaginable health state) to 100 (best imaginable health state). The least squares (LS) mean was estimated using an analysis of covariance (ANCOVA) model that included terms for treatment, pooled investigative site, gender, baseline score and predefined subpopulation ('yes/no').

The S-RUM was 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 asked about the number of ER or equivalent facility visits a participant had for psychiatric (psych) illness during the last year [baseline (BL) assessment] or since the last assessment (post-baseline assessment). Item 2 asked about the number of ER or equivalent facility visits a participant had for non-psychiatric (non-psych) illness or injury during the last year (BL assessment) or since the last assessment (post-BL assessment). Item 5 asked about the number of outpatient visits to other physicians (not psychiatrists or dentists) a participant had during the last year (BL assessment) or since the last assessment (post-BL assessment).

The S-RUM was 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 asked about the number of sessions with a psychiatrist a participant had, that were not part of this study, during the last year (baseline assessment) or since the last assessment (post-baseline assessment).

The SWN-S was a self-rated scale that measured subjective well-being for the previous 7 days. The SWN-S consisted of 20 items each rated using a 6-point scale from 1 (not at all) to 6 (very much). The sum of the 20 items was defined as the SWN-S total score and ranged from 20 to 120, with higher scores indicating better subjective well-being. The least squares (LS) mean was estimated using a mixed-effects model with repeated measures (MMRM) that included the fixed, categorical effects of treatment, pooled investigative site, visit, treatment-by-visit interaction, gender, and predefined subpopulation ('yes/no'), as well as the continuous, fixed covariates of baseline score and baseline score-by-visit interaction.

The BAS was a 4-item instrument that evaluated akathisia associated with the use of antipsychotic medications. Item 4 was the Global Clinical Assessment (global score) and was rated from 0 (absent) to 5 (severe). The least squares (LS) mean was estimated using a mixed-effects model with repeated measures (MMRM) that included the fixed, categorical effects of treatment, pooled investigative site, visit, treatment-by-visit interaction, gender, and predefined subpopulation ('yes/no'), as well as the continuous, fixed covariates of baseline score and baseline score-by-visit interaction.

The SAS was used to measure Parkinsonian-type symptoms in participants exposed to antipsychotics. The scale consisted of 10 items and each item was rated on a 5-point scale from 0 (complete absence of the condition) to 4 (the presence of the condition in extreme form). The sum of the 10 items was defined as the SAS total score and ranged from 0 to 40. Higher scores indicated a greater severity of illness. The least squares (LS) mean was estimated using a mixed-effects model with repeated measures (MMRM) that included the fixed, categorical effects of treatment, pooled investigative site, visit, treatment-by-visit interaction, gender, and predefined subpopulation ('yes/no'), as well as the continuous, fixed covariates of baseline score and baseline score-by-visit interaction.

The AIMS was a 12-item scale designed to record the occurrence of abnormal involuntary (dyskinetic) movements. Items 1 to 10 were rated on a 5-point scale from 0 (no dyskinetic movements) to 4 (severe dyskinetic movements). Items 11 and 12 were 'yes/no' questions regarding the dental condition of a participant. The sum of Items 1 through 7 was defined as the AIMS 1-7 total score and ranged from 0 to 28. Higher scores indicated a greater severity of illness. The least squares (LS) mean was estimated using a mixed-effects model with repeated measures (MMRM) that included the fixed, categorical effects of treatment, pooled investigative site, visit, treatment-by-visit interaction, gender, and predefined subpopulation ('yes/no'), as well as the continuous, fixed covariates of baseline score and baseline score-by-visit interaction.

The C-SSRS captured the occurrence, severity, and frequency of suicide-related thoughts and behaviors during the assessment period. Suicidal behavior: a "yes" answer to any 1 of 5 suicidal behavior questions (preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide). Suicidal ideation: a "yes" answer to any 1 of 5 suicidal ideation questions (wish to be dead, and 4 different categories of active suicidal ideation). The percentage of participants with treatment-emergent suicidal ideation or behavior (with a change from baseline in C-SSRS) was calculated as the number of participants with an increase in suicidal behavior or ideation over lead-in baseline, divided by the total number of participants multiplied by 100.

The reasons for study discontinuation are located in the Participant Flow.

The time to discontinuation, due to any reason, was defined as the total number of days between the randomization date and discontinuation date. Participants who completed the study period were censored. The time to discontinuation was analyzed using Kaplan-Meier estimated survival curves.

The least squares (LS) mean was estimated using a mixed-effects model with repeated measures (MMRM) that included the fixed, categorical effects of treatment, pooled investigative site, visit, treatment-by-visit interaction, gender, and predefined subpopulation ('yes/no'), as well as the continuous, fixed covariates of baseline score and baseline score-by-visit interaction.