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| ID | Type | Description | Link |
|---|---|---|---|
| H8Y-MC-HBBN | Other Identifier | Eli Lilly and Company |
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The decision to stop the trial was based on efficacy results in the overall schizophrenia participant population.
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The purpose of this study is to determine whether at least 1 dose level of LY2140023 given to acutely ill patients with schizophrenia will demonstrate significantly greater efficacy as compared to placebo.
The primary objective of this study was to test the hypothesis that at least 1 dose level of LY2140023, given orally to patients with schizophrenia at doses of 80 mg twice daily (BID), 40 mg BID, or 10 mg BID, would demonstrate significantly greater efficacy than placebo at Visit 9, as measured by the change from baseline in the Positive and Negative Syndrome Scale (PANSS) total score.
This was a multicenter, randomized, double-blind, parallel, fixed-dose, Phase 3 study in patients with schizophrenia. The study consisted of 3 periods: a screening and antipsychotic taper phase, a 7-day placebo lead-in phase that was blinded to investigators and patients, and a 6-week active treatment phase.
Eligible patients were those for whom a modification of antipsychotic medication was acutely indicated, in the opinion of the investigator. To be included in the study, patients must have experienced an exacerbation of their illness within the 2 weeks prior to study entry, leading to an intensification of the level of psychiatric care.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 80 milligrams (mg) LY2140023, BID | Experimental | An 80-mg LY2140023 tablet administered orally, twice daily (BID) for 6 weeks. Prior to randomization, participants will complete a 1-week placebo lead-in period, during which time placebo tablets identical to LY2140023 are administered orally, BID. |
|
| 40 mg LY2140023, BID | Experimental | A 40-mg LY2140023 tablet administered orally, BID for 6 weeks. Prior to randomization, participants will complete a 1-week placebo lead-in period, during which time, placebo tablets identical to LY2140023 are administered orally, BID. |
|
| 10 mg LY2140023, BID | Experimental | A 10-mg LY2140023 tablet administered orally, BID for 6 weeks. Prior to randomization, participants will complete a 1-week placebo lead-in period, during which time, placebo tablets identical to LY2140023 are administered orally, BID. |
|
| Placebo | Placebo Comparator | A placebo tablet administered orally, BID for 7 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| LY2140023 | Drug | Administered orally |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score | The PANSS scale assessed participants (pts) 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, gender, and predefined subpopulation ('yes/no'), as well as the continuous, fixed covariates of baseline score and baseline score-by-visit interaction. | Baseline, Week 6 |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score in a Predefined Subpopulation of Schizophrenia Participants | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Serious Adverse Events (SAEs) Which Occurred During 30 Days After Last Dose of Study Drug | SAEs occurring AFTER a participant's last dose of study drug were to be followed for 30 days, regardless of the investigator's opinion of causation. An SAE was any adverse event (AE) that resulted in death, an initial or prolonged inpatient hospitalization (other than that required by protocol), a life-threatening experience with the immediate risk of dying, a persistent or significant disability/incapacity, a congenital anomaly/birth defect, the occurrence of a seizure or seizure-like event, or an event considered significant by the investigator for any reason. SAEs were reported per Medical Dictionary for Regulatory Activities (MedDRA version 15.1) preferred terms. A summary of serious and all other non-serious AEs reported from Baseline up to Week 6 is located in the Reported Adverse Events module. |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern Time (UTC/GMT - 5 hours, EST) | Eli Lilly and Company | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Wichita | Kansas | 67207 |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25890643 | Derived | Kinon BJ, Millen BA, Zhang L, McKinzie DL. Exploratory analysis for a targeted patient population responsive to the metabotropic glutamate 2/3 receptor agonist pomaglumetad methionil in schizophrenia. Biol Psychiatry. 2015 Dec 1;78(11):754-62. doi: 10.1016/j.biopsych.2015.03.016. Epub 2015 Mar 19. |
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Prior to randomization, participants completed a 1-week placebo lead-in period, during which time placebo tablets were administered orally, twice daily (BID). The Participant Flow and results are based on participants, post-randomization.
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| ID | Title | Description |
|---|---|---|
| FG000 | 80 mg LY2140023, BID | 160 milligrams per day (mg/day) LY2140023: An 80-mg LY2140023 tablet, administered orally, BID for 6 weeks, post-randomization with the exception of the first 3 days of treatment, post-randomization, when a 40-mg LY2140023 tablet was administered orally, BID. |
| FG001 | 40 mg LY2140023, BID | 80 mg/day LY2140023: A 40-mg LY2140023 tablet, administered orally, BID for 6 weeks, post-randomization. |
| FG002 | 10 mg LY2140023, BID | 20 mg/day LY2140023: A 10-mg LY2140023 tablet, administered orally, BID for 6 weeks, post-randomization. |
| FG003 | Placebo | Placebo tablets, identical to LY2140023, administered orally, BID for 6 weeks, post-randomization. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Intent-to-treat (ITT) population: Participants who received at least 1 dose of study drug according to the treatment group to which they were randomized.
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| ID | Title | Description |
|---|---|---|
| BG000 | 80 mg LY2140023, BID | 160 milligrams per day (mg/day) LY2140023: An 80-mg LY2140023 tablet, administered orally, BID for 6 weeks, post-randomization with the exception of the first 3 days of treatment, post-randomization, when a 40-mg LY2140023 tablet was administered orally, BID. |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score | The PANSS scale assessed participants (pts) 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, gender, and predefined subpopulation ('yes/no'), as well as the continuous, fixed covariates of baseline score and baseline score-by-visit interaction. | Pts in efficacy-evaluable intent-to-treat (EE-ITT) population (received at least 1 dose of study drug and not placebo lead-in responders) who had baseline and at least 1 post-baseline PANSS total score. Excluded were pts with missing predefined subpopulation data. Placebo lead-in responder had ≥25% PANSS total score improvement in lead-in period. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline, Week 6 |
Baseline to 30 Days After Last Dose of Study Drug
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 80 mg LY2140023, BID | 160 milligrams per day (mg/day) LY2140023: An 80-mg LY2140023 tablet, administered orally, BID for 6 weeks, post-randomization with the exception of the first 3 days of treatment, post-randomization, when a 40-mg LY2140023 tablet was administered orally, BID. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Atrial flutter | Cardiac disorders | MedDRA 15.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal discomfort | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
An interim analysis for futility was planned and conducted, using a pre-defined threshold. Since probability of trial meeting primary efficacy objectives, given available interim data, was below pre-defined level, trial was stopped early.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Chief Medical Officer | Eli Lilly and Company | 800-545-5979 |
| ID | Term |
|---|---|
| D012559 | Schizophrenia |
| ID | Term |
|---|---|
| D019967 | Schizophrenia Spectrum and Other Psychotic Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| C534551 | LY 2140023 |
| C000626254 | pomaglumetad methionil |
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| Placebo | Drug | Administered orally |
|
| Baseline, Week 6 |
| Change From Baseline in the Personal and Social Performance (PSP) Score | 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. | Baseline, Week 6 |
| Change From Baseline in the Personal and Social Performance (PSP) Score in a Predefined Subpopulation | 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. | Baseline, Week 6 |
| Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score in Females | 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. | Baseline, Week 6 |
| Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Subscores | 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. | Baseline, Week 6 |
| Percentage of Participants Who Are Responders | 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. | Baseline, Week 6 |
| Time to Response | 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. | Baseline up to Week 6 |
| Change From Baseline in the Clinical Global Impression-Severity (CGI-S) Scale | 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. | Baseline, Week 6 |
| Change From Baseline in the 16-Item Negative Symptoms Assessment (NSA-16) Total Score | 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. | Baseline, Week 6 |
| Change From Baseline on the European Quality of Life-5 Dimension (EQ-5D) Questionnaire | 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'). | Baseline, Week 6 |
| Change From Baseline on Schizophrenia Resource Utilization Module (S-RUM): Emergency Room (ER) Visits and Outpatient Visits | 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). | Baseline and Week (Wk) 6 |
| Change From Baseline on Schizophrenia Resource Utilization Module (S-RUM): Sessions With a Psychiatrist | 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). | Baseline and Week 6 |
| Change From Baseline on Subjective Well-Being Under Neuroleptic Treatment Scale - Short Form (SWN-S) Total Score | 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. | Baseline, Week 6 |
| Change From Baseline in Barnes Akathisia Scale (BAS) Global Score | 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. | Baseline, Week 6 |
| Change From Baseline in Simpson-Angus Scale (SAS) Total Score | 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. | Baseline, Week 6 |
| Change From Baseline in Abnormal Involuntary Movement Scales (AIMS) 1-7 Total Score | 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. | Baseline, Week 6 |
| Percentage of Participants With a Change From Baseline in Suicidal Behaviors and Ideations Measured by the Columbia-Suicide Severity Rating Scale (C-SSRS) | 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. | Baseline up to Week 6 |
| Number of Participants Who Discontinued | The reasons for study discontinuation are located in the Participant Flow. | Randomization up to Week 6 |
| Time to Discontinuation | 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. | Randomization up to Week 6 |
| Change From Baseline in Prolactin | Baseline, Week 6 |
| Change From Baseline in Weight | 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. | Baseline, Week 6 |
| Last dose (either early discontinuation or Week 6) through 30-day follow-up period |
| United States |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Guadalajara | 44340 | Mexico |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Monterrey | 64060 | Mexico |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | San Juan | 00926 | Puerto Rico |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Lipetsk | 399007 | Russia |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Moscow | 109559 | Russia |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Saint Petersburg | 190005 | Russia |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Saratov | 410060 | Russia |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Voronezh | 394071 | Russia |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Donetsk | 83037 | Ukraine |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Kiev | 2660 | Ukraine |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Lviv | 79021 | Ukraine |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Vinnytsia | 21005 | Ukraine |
| Entry Criteria Not Met |
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| Lost to Follow-up |
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| Perceived Lack of Efficacy |
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| Protocol Violation |
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| Schedule Conflict Prevented Continuation |
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| Sponsor Decision |
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| Withdrawal by Subject |
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| Participant Moved |
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| 40 mg LY2140023, BID |
80 mg/day LY2140023: A 40-mg LY2140023 tablet, administered orally, BID for 6 weeks, post-randomization. |
| BG002 | 10 mg LY2140023, BID | 20 mg/day LY2140023: A 10-mg LY2140023 tablet, administered orally, BID for 6 weeks, post-randomization. |
| BG003 | Placebo | Placebo tablets, identical to LY2140023, administered orally, BID for 6 weeks, post-randomization. |
| BG004 | Total | Total of all reporting groups |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| ID | Title | Description |
|---|---|---|
| OG000 | 80 mg LY2140023, BID | 160 milligrams per day (mg/day) LY2140023: An 80-mg LY2140023 tablet, administered orally, BID for 6 weeks, post-randomization with the exception of the first 3 days of treatment, post-randomization, when a 40-mg LY2140023 tablet was administered orally, BID. |
| OG001 | 40 mg LY2140023, BID | 80 mg/day LY2140023: A 40-mg LY2140023 tablet, administered orally, BID for 6 weeks, post-randomization. |
| OG002 | 10 mg LY2140023, BID | 20 mg/day LY2140023: A 10-mg LY2140023 tablet, administered orally, BID for 6 weeks, post-randomization. |
| OG003 | Placebo | Placebo tablets, identical to LY2140023, administered orally, BID for 6 weeks, post-randomization. |
|
|
|
| Secondary | Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score in a Predefined Subpopulation of Schizophrenia Participants | 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. | EE-ITT participants (see Outcome Measure 1 for population definition) in the predefined subpopulation who had a baseline and at least 1 post-baseline PANSS total score. The predefined subpopulation excluded non-Hispanic whites (self-reported) who had A/A genotype at the serotonin 2A receptor (HTR2A) single nucleotide polymorphism (SNP), rs7330461. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline, Week 6 |
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| Secondary | Change From Baseline in the Personal and Social Performance (PSP) Score | 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. | Participants (pts) in the EE-ITT population (pts who received at least 1 dose of study drug and were not placebo lead-in responders) who had a baseline and at least 1 post-baseline PSP score. Excluded were pts with missing predefined subpopulation data. Placebo lead-in responders had a ≥25% PANSS total score improvement in the lead-in period. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline, Week 6 |
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| Secondary | Change From Baseline in the Personal and Social Performance (PSP) Score in a Predefined Subpopulation | 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. | EE-ITT participants (see Outcome Measure 1 for population definition) in the predefined subpopulation who had a baseline and at least 1 post-baseline PSP score. The predefined subpopulation excluded non-Hispanic whites (self-reported) who had A/A genotype at the serotonin 2A receptor (HTR2A) single nucleotide polymorphism (SNP), rs7330461. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline, Week 6 |
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| Secondary | Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score in Females | 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. | Female participants (pts) in EE-ITT population (pts who received at least 1 dose of study drug and were not placebo lead-in responders) who had baseline and at least 1 post-baseline PANSS total score. Excluded were pts with missing predefined subpopulation data. Placebo lead-in responders had ≥25% PANSS total score improvement in lead-in period. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline, Week 6 |
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| Secondary | Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Subscores | 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. | Participants (pts) in the EE-ITT population (pts who received at least 1 dose of study drug and were not placebo lead-in responders) who had a baseline and at least 1 post-baseline PANSS subscore. Excluded were pts with missing predefined subpopulation data. Placebo lead-in responders had a ≥25% PANSS total score improvement in the lead-in period. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline, Week 6 |
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| Secondary | Percentage of Participants Who Are Responders | 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. | Participants in the EE-ITT population (participants who received at least 1 dose of study drug and were not placebo lead-in responders) who had a baseline and at least 1 post-baseline PANSS total score. Placebo lead-in responders had a ≥25% PANSS total score improvement in the lead-in period; Last observation carried forward (LOCF). | Posted | Number | percentage of participants | Baseline, Week 6 |
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| Secondary | Time to Response | 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. | Participants (pts) in the EE-ITT population (pts who received at least 1 dose of study drug and were not placebo lead-in responders) who had a baseline and at least 1 post-baseline PANSS total score. Number of pts censored: 80 mg LY2140023, BID = 88 pts, 40 mg LY2140023, BID = 90 pts, 10 mg LY2140023, BID = 99 pts, and placebo = 189 pts. | Posted | Median | Full Range | days | Baseline up to Week 6 |
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| Secondary | Change From Baseline in the Clinical Global Impression-Severity (CGI-S) Scale | 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. | Participants (pts) in the EE-ITT population (pts who received at least 1 dose of study drug and were not placebo lead-in responders) who had a baseline and at least 1 post-baseline CGI-S score. Excluded were pts with missing predefined subpopulation data. Placebo lead-in responders had a ≥25% PANSS total score improvement in the lead-in period. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline, Week 6 |
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| Secondary | Change From Baseline in the 16-Item Negative Symptoms Assessment (NSA-16) Total Score | 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. | Participants (pts) in the EE-ITT population (pts who received at least 1 dose of study drug and were not placebo lead-in responders) who had baseline and at least 1 post-baseline NSA-16 total score. Excluded were pts with missing predefined subpopulation data. Placebo lead-in responders had ≥25% PANSS total score improvement in the lead-in period. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline, Week 6 |
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| Secondary | Change From Baseline on the European Quality of Life-5 Dimension (EQ-5D) Questionnaire | 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'). | Participants in the EE-ITT population (participants who received at least 1 dose of study drug and were not placebo lead-in responders) who had a baseline and at least 1 post-baseline EQ-5D VAS health state score. Excluded were participants with missing predefined subpopulation data; Last observation carried forward (LOCF). | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline, Week 6 |
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| Secondary | Change From Baseline on Schizophrenia Resource Utilization Module (S-RUM): Emergency Room (ER) Visits and Outpatient Visits | 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). | Participants (pts) in EE-ITT population (pts who received at least 1 dose of study drug and were not placebo lead-in responders) who had a baseline S-RUM score for ER/facility visits or outpatient visits. Placebo lead-in responders had a ≥25% PANSS total score improvement in the lead-in period; Last observation carried forward (LOCF). | Posted | Mean | Standard Deviation | visits | Baseline and Week (Wk) 6 |
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| Secondary | Change From Baseline on Schizophrenia Resource Utilization Module (S-RUM): Sessions With a Psychiatrist | 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). | Participants (pts) in EE-ITT population (pts who received at least 1 dose of study drug and were not placebo lead-in responders) who had a baseline S-RUM score for sessions with a psychiatrist. Placebo lead-in responders had a ≥25% PANSS total score improvement in the lead-in period; Last observation carried forward (LOCF). | Posted | Mean | Standard Deviation | sessions | Baseline and Week 6 |
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| Secondary | Change From Baseline on Subjective Well-Being Under Neuroleptic Treatment Scale - Short Form (SWN-S) Total Score | 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. | Participants (pts) in the EE-ITT population (pts who received at least 1 dose of study drug and were not placebo lead-in responders) who had a baseline and at least 1 post-baseline SWN-S total score. Excluded were pts with missing predefined subpopulation data. Placebo lead-in responders had ≥25% PANSS total score improvement in the lead-in period. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline, Week 6 |
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| Secondary | Change From Baseline in Barnes Akathisia Scale (BAS) Global Score | 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. | Participants in the ITT population (participants who received at least 1 dose of study drug according to the treatment group to which they were randomized) who had a baseline and at least 1 post-baseline BAS global score. Excluded were participants with missing predefined subpopulation data. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline, Week 6 |
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| Secondary | Change From Baseline in Simpson-Angus Scale (SAS) Total Score | 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. | Participants in the ITT population (participants who received at least 1 dose of study drug according to the treatment group to which they were randomized) who had a baseline and at least 1 post-baseline SAS total score. Excluded were participants with missing predefined subpopulation data. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline, Week 6 |
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| Secondary | Change From Baseline in Abnormal Involuntary Movement Scales (AIMS) 1-7 Total Score | 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. | Participants in the ITT population (participants who received at least 1 dose of study drug according to the treatment group to which they were randomized) who had a baseline and at least 1 post-baseline AIMS 1-7 total score. Excluded were participants with missing predefined subpopulation data. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline, Week 6 |
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| Secondary | Percentage of Participants With a Change From Baseline in Suicidal Behaviors and Ideations Measured by the Columbia-Suicide Severity Rating Scale (C-SSRS) | 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. | Participants in the ITT population (participants who received at least 1 dose of study drug according to the treatment group to which they were randomized) who had a baseline and at least 1 post-baseline C-SSRS assessment. | Posted | Number | percentage of participants | Baseline up to Week 6 |
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| Secondary | Number of Participants Who Discontinued | The reasons for study discontinuation are located in the Participant Flow. | All randomized participants. | Posted | Number | participants | Randomization up to Week 6 |
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| Secondary | Time to Discontinuation | 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. | Participants (pts) in the ITT population (pts who received at least 1 dose of study drug according to the treatment group to which they were randomized). Number of pts censored: 80 mg LY2140023, BID = 57 pts, 40 mg LY2140023, BID = 45 pts, 10 mg LY2140023, BID = 60 pts, and placebo = 118 pts. | Posted | Median | Full Range | days | Randomization up to Week 6 |
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| Secondary | Change From Baseline in Prolactin | Participants in the ITT population (participants who received at least 1 dose of study drug according to the treatment group to which they were randomized) who had a baseline and at least 1 post-baseline prolactin lab result; Last observation carried forward (LOCF). | Posted | Mean | Standard Deviation | micrograms per Liter (mcg/L) | Baseline, Week 6 |
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| Secondary | Change From Baseline in Weight | 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. | Participants in the ITT population (participants who received at least 1 dose of study drug according to the treatment group to which they were randomized) who had their weight measured at baseline and at least 1 post-baseline visit. Excluded were participants with missing predefined subpopulation data. | Posted | Least Squares Mean | Standard Error | kilograms (kg) | Baseline, Week 6 |
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| Other Pre-specified | Serious Adverse Events (SAEs) Which Occurred During 30 Days After Last Dose of Study Drug | SAEs occurring AFTER a participant's last dose of study drug were to be followed for 30 days, regardless of the investigator's opinion of causation. An SAE was any adverse event (AE) that resulted in death, an initial or prolonged inpatient hospitalization (other than that required by protocol), a life-threatening experience with the immediate risk of dying, a persistent or significant disability/incapacity, a congenital anomaly/birth defect, the occurrence of a seizure or seizure-like event, or an event considered significant by the investigator for any reason. SAEs were reported per Medical Dictionary for Regulatory Activities (MedDRA version 15.1) preferred terms. A summary of serious and all other non-serious AEs reported from Baseline up to Week 6 is located in the Reported Adverse Events module. | Participants who received at least 1 dose of study drug according to the treatment group to which they were randomized. | Posted | Number | participants | Last dose (either early discontinuation or Week 6) through 30-day follow-up period |
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| 4 |
| 111 |
| 70 |
| 111 |
| EG001 | 40 mg LY2140023, BID | 80 mg/day LY2140023: A 40-mg LY2140023 tablet, administered orally, BID for 6 weeks, post-randomization. | 6 | 110 | 70 | 110 |
| EG002 | 10 mg LY2140023, BID | 20 mg/day LY2140023: A 10-mg LY2140023 tablet, administered orally, BID for 6 weeks, post-randomization. | 5 | 118 | 75 | 118 |
| EG003 | Placebo | Placebo tablets, identical to LY2140023, administered orally, BID for 6 weeks, post-randomization. | 11 | 228 | 129 | 228 |
| Gastritis | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
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| Bronchitis | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
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| Upper limb fracture | Injury, poisoning and procedural complications | MedDRA 15.1 | Systematic Assessment |
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| Stupor | Nervous system disorders | MedDRA 15.1 | Systematic Assessment |
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| Syncope | Nervous system disorders | MedDRA 15.1 | Systematic Assessment |
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| Delusion | Psychiatric disorders | MedDRA 15.1 | Systematic Assessment |
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| Psychotic disorder | Psychiatric disorders | MedDRA 15.1 | Systematic Assessment |
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| Schizophrenia | Psychiatric disorders | MedDRA 15.1 | Systematic Assessment |
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| Suicidal behaviour | Psychiatric disorders | MedDRA 15.1 | Systematic Assessment |
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| Suicidal ideation | Psychiatric disorders | MedDRA 15.1 | Systematic Assessment |
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| Irritability | Nervous system disorders | MedDRA 15.1 | Systematic Assessment |
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| Homocidal ideation | Nervous system disorders | MedDRA 15.1 | Systematic Assessment |
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| Acute myocardial infarction | Cardiac disorders | MedDRA 15.1 | Systematic Assessment |
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| Abdominal pain upper | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
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| Toothache | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
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| Irritability | General disorders | MedDRA 15.1 | Systematic Assessment |
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| Pain | General disorders | MedDRA 15.1 | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
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| Vulvovaginal mycotic infection | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
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| Blood creatine phosphokinase increased | Investigations | MedDRA 15.1 | Systematic Assessment |
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| Decreased appetite | Metabolism and nutrition disorders | MedDRA 15.1 | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 15.1 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 15.1 | Systematic Assessment |
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| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 15.1 | Systematic Assessment |
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| Akathisia | Nervous system disorders | MedDRA 15.1 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 15.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 15.1 | Systematic Assessment |
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| Somnolence | Nervous system disorders | MedDRA 15.1 | Systematic Assessment |
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| Tremor | Nervous system disorders | MedDRA 15.1 | Systematic Assessment |
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| Anxiety | Psychiatric disorders | MedDRA 15.1 | Systematic Assessment |
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| Insomnia | Psychiatric disorders | MedDRA 15.1 | Systematic Assessment |
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| Psychotic disorder | Psychiatric disorders | MedDRA 15.1 | Systematic Assessment |
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| Schizophrenia | Psychiatric disorders | MedDRA 15.1 | Systematic Assessment |
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| Dysmenorrhoea | Reproductive system and breast disorders | MedDRA 15.1 | Systematic Assessment |
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| Menorrhagia | Reproductive system and breast disorders | MedDRA 15.1 | Systematic Assessment |
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| Vaginal haemorrhage | Reproductive system and breast disorders | MedDRA 15.1 | Systematic Assessment |
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| Vulvovaginal pruritus | Reproductive system and breast disorders | MedDRA 15.1 | Systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 15.1 | Systematic Assessment |
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| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
Not provided
| 0.912 |
The p-value was 1-sided without adjustment for multiplicity. |
| LS mean difference |
| 3.4 |
| Standard Error of the Mean |
| 2.5 |
| 2-Sided |
| 95 |
| -1.6 |
| 8.4 |
| Superiority or Other (legacy) |
| Mixed Models Analysis | 0.223 | The p-value was 1-sided without adjustment for multiplicity. | LS mean difference | 2.9 | Standard Error of the Mean | 2.4 | 2-Sided | 95 | -1.8 | 7.7 | Superiority or Other (legacy) |
| 0.223 |
The p-value was 1-sided without adjustment for multiplicity. |
| LS mean difference |
| 1.3 |
| Standard Error of the Mean |
| 1.7 |
| 2-Sided |
| 95 |
| -2.0 |
| 4.6 |
| Superiority or Other (legacy) |
| Mixed Models Analysis | 0.414 | The p-value was 2-sided without adjustment for multiplicity. | LS mean difference | -1.2 | Standard Error of the Mean | 1.5 | 2-Sided | 95 | -4.2 | 1.7 | Superiority or Other (legacy) |
| 0.192 |
The p-value was 1-sided without adjustment for multiplicity. |
| LS mean difference |
| 1.5 |
| Standard Error of the Mean |
| 1.7 |
| 2-Sided |
| 95 |
| -1.9 |
| 4.8 |
| Superiority or Other (legacy) |
| Mixed Models Analysis | 0.619 | The p-value was 2-sided without adjustment for multiplicity. | LS mean difference | -0.8 | Standard Error of the Mean | 1.6 | 2-Sided | 95 | -3.9 | 2.3 | Superiority or Other (legacy) |
| 0.061 |
The p-value was 2-sided without adjustment for multiplicity. |
| LS mean difference |
| 8.7 |
| Standard Error of the Mean |
| 4.6 |
| 2-Sided |
| 95 |
| -0.4 |
| 17.8 |
| Superiority or Other (legacy) |
| Mixed Models Analysis | 0.304 | The p-value was 2-sided without adjustment for multiplicity. | LS mean difference | 4.2 | Standard Error of the Mean | 4.1 | 2-Sided | 95 | -3.9 | 12.3 | Superiority or Other (legacy) |
| PANSS Negative Subscore |
|
| PANSS General Psychopathology Subscore |
|
| Mixed Models Analysis |
| 0.616 |
The comparison between 40 mg LY2140023, BID and placebo for change from baseline in PANSS positive subscores was 2-sided without adjustment for multiplicity. |
| LS mean difference |
| 0.4 |
| Standard Error of the Mean |
| 0.8 |
| 2-Sided |
| 95 |
| -1.2 |
| 2.0 |
| Superiority or Other (legacy) |
| Mixed Models Analysis | 0.307 | The comparison between 10 mg LY2140023, BID and placebo for change from baseline in PANSS positive subscores was 2-sided without adjustment for multiplicity. | LS mean difference | 0.7 | Standard Error of the Mean | 0.7 | 2-Sided | 95 | -0.7 | 2.2 | Superiority or Other (legacy) |
| Mixed Models Analysis | 0.382 | The comparison between 80 mg LY2140023, BID and placebo for the change from baseline in PANSS negative subscores was 2-sided without adjustment for multiplicity. | LS mean difference | 0.7 | Standard Error of the Mean | 0.7 | 2-Sided | 95 | -0.8 | 2.1 | Superiority or Other (legacy) |
| Mixed Models Analysis | 0.107 | The comparison between 40 mg LY2140023, BID and placebo for the change from baseline in PANSS negative subscores was 2-sided without adjustment for multiplicity. | LS mean difference | 1.3 | Standard Error of the Mean | 0.8 | 2-Sided | 95 | -0.3 | 2.8 | Superiority or Other (legacy) |
| Mixed Models Analysis | 0.436 | The comparison between 10 mg LY2140023, BID and placebo for the change from baseline in PANSS negative subscores was 2-sided without adjustment for multiplicity. | LS mean difference | 0.6 | Standard Error of the Mean | 0.7 | 2-Sided | 95 | -0.9 | 2.0 | Superiority or Other (legacy) |
| Mixed Models Analysis | 0.073 | The comparison between 80 mg LY2140023, BID and placebo for the change from baseline in PANSS general psychopathology subscores was 2-sided without adjustment for multiplicity. | LS mean difference | 2.3 | Standard Error of the Mean | 1.3 | 2-Sided | 95 | -0.2 | 4.9 | Superiority or Other (legacy) |
| Mixed Models Analysis | 0.280 | The comparison between 40 mg LY2140023, BID and placebo for the change from baseline in PANSS general psychopathology subscores was 2-sided without adjustment for multiplicity. | LS mean difference | 1.5 | Standard Error of the Mean | 1.4 | 2-Sided | 95 | -1.2 | 4.2 | Superiority or Other (legacy) |
| Mixed Models Analysis | 0.209 | The comparison between 10 mg LY2140023, BID and placebo for the change from baseline in PANSS general psychopathology subscores was 2-sided without adjustment for multiplicity. | LS mean difference | 1.6 | Standard Error of the Mean | 1.3 | 2-Sided | 95 | -0.9 | 4.0 | Superiority or Other (legacy) |
| 0.824 |
The p-value was 2-sided without adjustment for multiplicity. |
| 95 |
| Superiority or Other (legacy) |
| Fisher Exact | >0.999 | The p-value was 2-sided without adjustment for multiplicity. | 95 | Superiority or Other (legacy) |
| 0.659 |
The p-value was 2-sided without adjustment for multiplicity. |
| LS mean difference |
| -0.06 |
| Standard Error of the Mean |
| 0.14 |
| 2-Sided |
| 95 |
| -0.33 |
| 0.21 |
| Superiority or Other (legacy) |
| Mixed Models Analysis | 0.413 | The p-value was 2-sided without adjustment for multiplicity. | LS mean difference | 0.10 | Standard Error of the Mean | 0.12 | 2-Sided | 95 | -0.14 | 0.35 | Superiority or Other (legacy) |
| 0.265 |
The p-value was 2-sided without adjustment for multiplicity. |
| LS mean difference |
| -1.8 |
| Standard Error of the Mean |
| 1.6 |
| 2-Sided |
| 95 |
| -4.9 |
| 1.3 |
| Superiority or Other (legacy) |
| Mixed Models Analysis | 0.531 | The p-value was 2-sided without adjustment for multiplicity. | LS mean difference | -0.9 | Standard Error of the Mean | 1.4 | 2-Sided | 95 | -3.7 | 1.9 | Superiority or Other (legacy) |
| ANCOVA |
| 0.351 |
The comparison between 40 mg LY2140023, BID and placebo for the change from baseline in EQ-5D Questionnaire (VAS) was 2-sided without adjustment for multiplicity. |
| LS mean difference |
| -2.56 |
| Standard Error of the Mean |
| 2.74 |
| 2-Sided |
| 95 |
| -7.94 |
| 2.83 |
| Superiority or Other (legacy) |
| ANCOVA | 0.403 | The comparison between 10 mg LY2140023, BID and placebo for the change from baseline in EQ-5D Questionnaire (VAS) was 2-sided without adjustment for multiplicity. | LS mean difference | 2.12 | Standard Error of the Mean | 2.54 | 2-Sided | 95 | -2.86 | 7.11 | Superiority or Other (legacy) |
| ER/Facility (Psych), Wk 6 |
|
| ER/Facility (Non-Psych), BL |
|
| ER/Facility (Non-Psych), Wk 6 |
|
| Outpatient, BL |
|
| Outpatient, Wk 6 |
|
| Sessions at Week 6 |
|
| 0.487 |
The p-value was 2-sided without adjustment for multiplicity. |
| LS mean difference |
| 1.8 |
| Standard Error of the Mean |
| 2.6 |
| 2-Sided |
| 95 |
| -3.3 |
| 6.9 |
| Superiority or Other (legacy) |
| Mixed Models Analysis | 0.693 | The p-value was 2-sided without adjustment for multiplicity. | LS mean difference | -0.9 | Standard Error of the Mean | 2.4 | 2-Sided | 95 | -5.6 | 3.7 | Superiority or Other (legacy) |
| Mixed Models Analysis |
| 0.201 |
The comparison between 40 mg LY2140023, BID and placebo was conducted at a 2-sided alpha level of 0.05 without adjustment for multiplicity. |
| LS mean difference |
| -0.06 |
| Standard Error of the Mean |
| 0.04 |
| 2-Sided |
| 95 |
| -0.14 |
| 0.03 |
| Superiority or Other (legacy) |
| Mixed Models Analysis | 0.697 | The comparison between 10 mg LY2140023, BID and placebo was conducted at a 2-sided alpha level of 0.05 without adjustment for multiplicity. | LS mean difference | -0.02 | Standard Error of the Mean | 0.04 | 2-Sided | 95 | -0.09 | 0.06 | Superiority or Other (legacy) |
| Mixed Models Analysis |
| 0.596 |
The comparison between 40 mg LY2140023, BID and placebo was conducted at a 2-sided alpha level of 0.05 without adjustment for multiplicity. |
| LS mean difference |
| -0.07 |
| Standard Error of the Mean |
| 0.14 |
| 2-Sided |
| 95 |
| -0.34 |
| 0.20 |
| Superiority or Other (legacy) |
| Mixed Models Analysis | 0.055 | The comparison between 10 mg LY2140023, BID and placebo was conducted at a 2-sided alpha level of 0.05 without adjustment for multiplicity. | LS mean difference | 0.24 | Standard Error of the Mean | 0.13 | 2-Sided | 95 | 0.00 | 0.49 | Superiority or Other (legacy) |
| Mixed Models Analysis |
| 0.519 |
The comparison between 40 mg LY2140023, BID and placebo was conducted at a 2-sided alpha level of 0.05 without adjustment for multiplicity. |
| LS mean difference |
| 0.09 |
| Standard Error of the Mean |
| 0.15 |
| 2-Sided |
| 95 |
| -0.19 |
| 0.38 |
| Superiority or Other (legacy) |
| Mixed Models Analysis | 0.323 | The comparison between 10 mg LY2140023, BID and placebo was conducted at a 2-sided alpha level of 0.05 without adjustment for multiplicity. | LS mean difference | 0.13 | Standard Error of the Mean | 0.14 | 2-Sided | 95 | -0.13 | 0.40 | Superiority or Other (legacy) |
| Treatment-Emergent Suicidal Behavior |
|
| Fisher Exact |
| 0.576 |
The comparison between 40 mg LY2140023, BID and placebo in the percentage of participants with a change from baseline in C-SSRS suicidal ideation was conducted at a 2-sided alpha level of 0.05 without adjustment for multiplicity. |
| 95 |
| Superiority or Other (legacy) |
| Fisher Exact | 0.425 | The comparison between 10 mg LY2140023, BID and placebo in the percentage of participants with a change from baseline in C-SSRS suicidal ideation was conducted at a 2-sided alpha level of 0.05 without adjustment for multiplicity. | 95 | Superiority or Other (legacy) |
| ANOVA |
ANOVA model on rank-transformed change. |
| 0.799 |
The comparison between 40 mg LY2140023, BID and placebo was conducted at a 2-sided alpha level of 0.05 without adjustment for multiplicity. |
| 95 |
| Superiority or Other (legacy) |
| ANOVA | ANOVA model on rank-transformed change. | 0.073 | The comparison between 10 mg LY2140023, BID and placebo was conducted at a 2-sided alpha level of 0.05 without adjustment for multiplicity. | 95 | Superiority or Other (legacy) |
| Mixed Models Analysis |
| 0.761 |
The comparison between 40 mg LY2140023, BID and placebo was conducted at a 2-sided alpha level of 0.05 without adjustment for multiplicity. |
| LS mean difference |
| 0.14 |
| Standard Error of the Mean |
| 0.47 |
| 2-Sided |
| 95 |
| -0.78 |
| 1.06 |
| Superiority or Other (legacy) |
| Mixed Models Analysis | 0.489 | The comparison between 10 mg LY2140023, BID and placebo was conducted at a 2-sided alpha level of 0.05 without adjustment for multiplicity. | LS mean difference | -0.31 | Standard Error of the Mean | 0.44 | 2-Sided | 95 | -1.17 | 0.56 | Superiority or Other (legacy) |
| Suicidal ideation |
|
| Homicidal ideation |
|
| Acute myocardial infarction (resulted in death) |
|
| Schizophrenia |
|