Trial Outcomes & Findings for A Comparison Study of LY2140023 and Aripiprazole in Schizophrenia Patients (NCT NCT01328093)

This study consisted of a 24-week Double-Blind Active Treatment Phase and was followed by a 28-week Open-Label Active Treatment Phase. Modified intent-to-treat (mITT) is all randomized participants who received at least 1 dose of study drug, excluding participants from a Good Clinical Practice (GCP) noncompliant study site.

A Comparison Study of LY2140023 and Aripiprazole in Schizophrenia Patients

Mixed model repeated measures (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values were adjusted for baseline, treatment, gender, pooled investigator, visit, prior olanzapine use, treatment-by-visit interaction and baseline-by-visit interaction.

Clinically significant change in body weight is defined as either an increase or decrease in weight of ≥7% from baseline.

The BAS is a 4-item instrument that evaluates akathisia associated with use of antipsychotic medications. Item 4 Global Clinical Assessment of Akathisia is rated on a 6- point scale, with scores range from 0 (no symptoms) to 5 (increased severity of symptoms); Only Item 4 was analyzed and presented. The Mixed Model Repeated Measures (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values were adjusted for baseline, treatment, gender, pooled investigative site, visit, predefined subpopulation, treatment-by-visit interaction and baseline-by-visit interaction.

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: 0 (complete absence of the condition) to 4 (presence of the condition in extreme form). The SAS 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 Measures (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values were adjusted for baseline, treatment, gender, pooled investigative site, visit, predefined subpopulation, treatment by-visit-interaction and baseline-by-visit interaction.

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: 0 (no dyskinetic movements) to 4 (severe dyskinetic movements). Items 11 and 12 are yes/no questions regarding the dental condition of a participant. The AIMS 1-7 Total Score is the sum of Items 1 through 7 of the AIMS, and ranges from 0 to 28. Higher scores indicate greater severity of illness. Only AIMS 1-7 Total Score was analyzed and presented. The Mixed Model Repeated Measures (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values were adjusted for baseline, treatment, gender, pooled investigative site, visit, predefined subpopulation, treatment-by-visit interaction and baseline-by-visit interaction.

The PANSS consists of 30 items and 3 subscales and is designed to measure severity of psychopathology in schizophrenia. The PANSS Positive Subscale and the PANSS Negative Subscale each contain 7 items, and the remaining 16 items make up the PANSS General Psychopathology Subscale. 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, with scores range from 30 to 210. The PANSS Positive Subscale and PANSS Negative Subscale scores each range from 7 to 49. The PANSS General Psychopathology subscale score ranges from 16 to 112. Higher scores indicate greater severity of illness. The Mixed Model Repeated Measures (MMRM) analysis was used to calculate Least Squares (LS) mean and 95% confidence interval. LS mean values were adjusted for baseline, treatment, gender, pooled investigative site, visit, predefined subpopulation, treatment-by-visit interaction and baseline-by-visit interaction.

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 Measures (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values were adjusted for baseline, treatment, gender, pooled investigative site, visit, predefined subpopulation, treatment-by-visit interaction and baseline-by-visit interaction.

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). Analysis of variance (ANOVA) was used to calculate Least Squares (LS) mean and standard error. LS mean values were adjusted for pooled investigator, gender and treatment.

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. Analysis of variance (ANOVA) was used to calculate Least Squares (LS) mean and standard error. LS mean values were adjusted for pooled investigator, gender and treatment.

The SWN-SF measures subjective well-being of the participant 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 Measures (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values were adjusted for baseline, treatment, gender, pooled investigative site, visit, predefined subpopulation, treatment-by-visit interaction and baseline-by-visit interaction.

The PSP scale is a 100-point (minimum 1, maximum 100), 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. Higher scores indicate a higher level of functioning. The Mixed Model Repeated Measures (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values were adjusted for baseline, treatment, gender, pooled investigative site, visit, predefined subpopulation, treatment-by-visit interaction and baseline-by-visit interaction.

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 Measures (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values were adjusted for baseline, treatment, gender, pooled investigative site, visit, predefined subpopulation, treatment-by-visit interaction and baseline-by-visit interaction.

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 NSA-16 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 Measures (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values were adjusted for baseline, treatment, gender, pooled investigative site, visit, predefined subpopulation, treatment-by-visit interaction and baseline-by-visit interaction.

The PANSS assesses the positive symptoms, negative symptoms, and general psychopathology specifically associated with schizophrenia. The scale consists of 30 items. Each item is rated on a scale from 1 (absence of symptoms) to 7 (symptoms extremely severe). The sum of the 30 items is defined as the PANSS Total Score and ranges from 30 to 210. Higher scores indicate greater severity of illness. Data presented are the number of participants with 30% or greater decrease from baseline in PANSS Total score.

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. Data presented are the number of participants with treatment-emergent suicidal ideation or behavior during the treatment period (with a change from lead-in baseline in C-SSRS).

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