Schizophrenia
Conditions
Brief summary
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.
Detailed description
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.
Interventions
DRUGLY2140023
Administered orally
DRUGPlacebo
Administered orally
Sponsors
Denovo Biopharma LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of schizophrenia as defined in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR); and confirmed by the Structured Clinical Interview for DSM-IV-TR (SCID) * Non pregnant female patients who agree to use acceptable birth control * Participants must be considered moderately ill in the opinion of the investigator * Patients in whom a modification of antipsychotic medication or initiation of antipsychotic medication is acutely indicated in the opinion of the investigator * Willing to participate in a minimum of 2 weeks of inpatient hospitalization * One year history of Schizophrenia prior to entering the study * At study entry patients with a history of antipsychotic treatment must have a lifetime history of at least one hospitalization for the treatment of schizophrenia, not including the hospitalization required for study. Patients who have never taken antipsychotic treatment may enter the study even without a history of hospitalization. * At study entry patients with a history of antipsychotic treatment must have a history of at least one episode of illness exacerbation requiring an intensification of treatment intervention or care in the last 2 years, not including the present episode of illness. Patients who have never taken antipsychotic treatment may enter the study without a past history of illness exacerbation and intensification of treatment in the last 2 years. * At study entry patients must have experienced an exacerbation of illness within the 2 weeks prior to entering the study, leading to an intensification of psychiatric care in the opinion of the investigator. If exacerbation occurs in patients who are presently hospitalized, the patient must not have been hospitalized longer than 60 days at entry of the study. * Patients must be considered reliable and have a level of understanding sufficient to perform all tests and examinations required by the protocol, and be willing to perform all study procedures
Exclusion criteria
* Patients who have a history of inadequate clinical response to antipsychotic treatment for schizophrenia * Diagnosis of substance dependence or substance abuse within 6 month of study entry * Diagnosis of substance-induced psychosis within 7 days of study entry * Currently enrolled in, or discontinued within 6 months from a clinical trial involving an investigational product or unapproved use of a drug or device * Participated in any clinical trial with any pharmacological treatment intervention for which they received a study-related medication in the 6 months prior to study entry * Previously completed or withdrawn from this study, or any other study investigating LY2140023 or any predecessor molecules with glutamatergic activity * Treatment with clozapine at doses greater than 200 mg daily within 12 months prior to entering the study, or who have received any clozapine at all during the month before study entry * Patients currently receiving treatment (within 1 dosing interval, minimum of 4 weeks, prior entering the study) with a depot formulation of an antipsychotic medication * Patients who are currently suicidal * Females who are pregnant, nursing, or who intend to become pregnant within 30 days of completing the study * Patients with uncorrected narrow-angle glaucoma, uncontrolled diabetes, certain diseases of the liver, renal insufficiency, uncontrolled thyroid condition or other serious or unstable illnesses * Have a history of one or more seizures * Electroconvulsive therapy (ECT) within 3 months of entering the study or who will have ECT at any time during the study * History of low white blood cell count * Medical history of Human Immunodeficiency Virus positive (HIV+) status. * Higher than normal blood prolactin levels * Abnormal electrocardiogram results
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score | Baseline, Week 6 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Prolactin | Baseline, Week 6 | — |
| Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score in a Predefined Subpopulation of Schizophrenia Participants | Baseline, Week 6 | 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. |
| Change From Baseline in the Personal and Social Performance (PSP) Score | Baseline, Week 6 | 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. |
| Change From Baseline in the Personal and Social Performance (PSP) Score in a Predefined Subpopulation | Baseline, Week 6 | 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. |
| Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score in Females | Baseline, Week 6 | 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. |
| Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Subscores | Baseline, Week 6 | 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. |
| Percentage of Participants Who Are Responders | Baseline, Week 6 | 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 | Baseline up to Week 6 | 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. |
| Change From Baseline in the Clinical Global Impression-Severity (CGI-S) Scale | Baseline, Week 6 | 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. |
| Change From Baseline in the 16-Item Negative Symptoms Assessment (NSA-16) Total Score | Baseline, Week 6 | 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. |
| Change From Baseline on Schizophrenia Resource Utilization Module (S-RUM): Emergency Room (ER) Visits and Outpatient Visits | Baseline and Week (Wk) 6 | 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). |
| Change From Baseline on Schizophrenia Resource Utilization Module (S-RUM): Sessions With a Psychiatrist | Baseline and Week 6 | 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). |
| Change From Baseline on Subjective Well-Being Under Neuroleptic Treatment Scale - Short Form (SWN-S) Total Score | Baseline, Week 6 | 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. |
| Change From Baseline in Barnes Akathisia Scale (BAS) Global Score | Baseline, Week 6 | 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. |
| Change From Baseline in Simpson-Angus Scale (SAS) Total Score | Baseline, Week 6 | 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. |
| Change From Baseline in Abnormal Involuntary Movement Scales (AIMS) 1-7 Total Score | Baseline, Week 6 | 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. |
| Percentage of Participants With a Change From Baseline in Suicidal Behaviors and Ideations Measured by the Columbia-Suicide Severity Rating Scale (C-SSRS) | Baseline up to Week 6 | 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. |
| Number of Participants Who Discontinued | Randomization up to Week 6 | The reasons for study discontinuation are located in the Participant Flow. |
| Time to Discontinuation | Randomization up to Week 6 | 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. |
| Change From Baseline in Weight | Baseline, Week 6 | 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. |
| Change From Baseline on the European Quality of Life-5 Dimension (EQ-5D) Questionnaire | Baseline, Week 6 | 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'). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Serious Adverse Events (SAEs) Which Occurred During 30 Days After Last Dose of Study Drug | Last dose (either early discontinuation or Week 6) through 30-day follow-up period | 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. |
Countries
Mexico, Puerto Rico, Russia, Ukraine, United States
Participant flow
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 111 |
| 40 mg LY2140023, BID 80 mg/day LY2140023: A 40-mg LY2140023 tablet, administered orally, BID for 6 weeks, post-randomization. | 110 |
| 10 mg LY2140023, BID 20 mg/day LY2140023: A 10-mg LY2140023 tablet, administered orally, BID for 6 weeks, post-randomization. | 118 |
| Placebo Placebo tablets, identical to LY2140023, administered orally, BID for 6 weeks, post-randomization. | 228 |
| Total | 567 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 9 | 8 | 10 | 14 |
| Overall Study | Entry Criteria Not Met | 0 | 0 | 0 | 2 |
| Overall Study | Lost to Follow-up | 5 | 6 | 2 | 8 |
| Overall Study | Participant Moved | 0 | 2 | 1 | 3 |
| Overall Study | Perceived Lack of Efficacy | 24 | 23 | 20 | 33 |
| Overall Study | Protocol Violation | 0 | 3 | 4 | 5 |
| Overall Study | Schedule Conflict Prevented Continuation | 0 | 3 | 1 | 2 |
| Overall Study | Sponsor Decision | 6 | 9 | 12 | 28 |
| Overall Study | Withdrawal by Subject | 10 | 11 | 8 | 15 |
Baseline characteristics
| Characteristic | 80 mg LY2140023, BID | 40 mg LY2140023, BID | 10 mg LY2140023, BID | Placebo | Total |
|---|---|---|---|---|---|
| Age, Continuous | 41.15 years STANDARD_DEVIATION 11.43 | 40.23 years STANDARD_DEVIATION 11.39 | 39.80 years STANDARD_DEVIATION 10.45 | 40.83 years STANDARD_DEVIATION 11.19 | 40.56 years STANDARD_DEVIATION 11.11 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 11 Participants | 18 Participants | 18 Participants | 35 Participants | 82 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 99 Participants | 92 Participants | 99 Participants | 191 Participants | 481 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 2 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 2 Participants | 4 Participants | 7 Participants |
| Race (NIH/OMB) Black or African American | 57 Participants | 54 Participants | 59 Participants | 115 Participants | 285 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 4 Participants | 2 Participants | 5 Participants | 12 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 51 Participants | 50 Participants | 52 Participants | 103 Participants | 256 Participants |
| Region of Enrollment Mexico | 3 participants | 3 participants | 4 participants | 9 participants | 19 participants |
| Region of Enrollment Puerto Rico | 2 participants | 2 participants | 1 participants | 2 participants | 7 participants |
| Region of Enrollment Romania | 3 participants | 4 participants | 5 participants | 9 participants | 21 participants |
| Region of Enrollment Russian Federation | 15 participants | 13 participants | 17 participants | 29 participants | 74 participants |
| Region of Enrollment Ukraine | 0 participants | 0 participants | 2 participants | 1 participants | 3 participants |
| Region of Enrollment United States | 88 participants | 88 participants | 89 participants | 178 participants | 443 participants |
| Sex: Female, Male Female | 33 Participants | 28 Participants | 30 Participants | 66 Participants | 157 Participants |
| Sex: Female, Male Male | 78 Participants | 82 Participants | 88 Participants | 162 Participants | 410 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 70 / 111 | 70 / 110 | 75 / 118 | 129 / 228 |
| serious Total, serious adverse events | 4 / 111 | 6 / 110 | 5 / 118 | 11 / 228 |
Outcome results
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.
Time frame: Baseline, Week 6
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 80 mg LY2140023, BID | Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score | -3.7 units on a scale | Standard Error 2.1 |
| 40 mg LY2140023, BID | Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score | -4.8 units on a scale | Standard Error 2.3 |
| 10 mg LY2140023, BID | Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score | -5.0 units on a scale | Standard Error 2 |
| Placebo | Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score | -7.8 units on a scale | Standard Error 1.6 |
p-value: 0.99495% CI: [-0.5, 8.8]Mixed Models Analysis
p-value: 0.97395% CI: [-1.9, 7.9]Mixed Models Analysis
p-value: 0.89695% CI: [-1.6, 7.2]Mixed Models Analysis
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.
Time frame: Baseline, Week 6
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 80 mg LY2140023, BID | Change From Baseline in Abnormal Involuntary Movement Scales (AIMS) 1-7 Total Score | -0.09 units on a scale | Standard Error 0.12 |
| 40 mg LY2140023, BID | Change From Baseline in Abnormal Involuntary Movement Scales (AIMS) 1-7 Total Score | -0.01 units on a scale | Standard Error 0.13 |
| 10 mg LY2140023, BID | Change From Baseline in Abnormal Involuntary Movement Scales (AIMS) 1-7 Total Score | 0.03 units on a scale | Standard Error 0.11 |
| Placebo | Change From Baseline in Abnormal Involuntary Movement Scales (AIMS) 1-7 Total Score | -0.10 units on a scale | Standard Error 0.09 |
p-value: 0.92995% CI: [-0.27, 0.29]Mixed Models Analysis
p-value: 0.51995% CI: [-0.19, 0.38]Mixed Models Analysis
p-value: 0.32395% CI: [-0.13, 0.4]Mixed Models Analysis
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.
Time frame: Baseline, Week 6
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 80 mg LY2140023, BID | Change From Baseline in Barnes Akathisia Scale (BAS) Global Score | -0.01 units on a scale | Standard Error 0.04 |
| 40 mg LY2140023, BID | Change From Baseline in Barnes Akathisia Scale (BAS) Global Score | -0.4 units on a scale | Standard Error 0.04 |
| 10 mg LY2140023, BID | Change From Baseline in Barnes Akathisia Scale (BAS) Global Score | 0.0 units on a scale | Standard Error 0.04 |
| Placebo | Change From Baseline in Barnes Akathisia Scale (BAS) Global Score | 0.01 units on a scale | Standard Error 0.03 |
p-value: 0.66195% CI: [-0.1, 0.06]Mixed Models Analysis
p-value: 0.20195% CI: [-0.14, 0.03]Mixed Models Analysis
p-value: 0.69795% CI: [-0.09, 0.06]Mixed Models Analysis
Secondary
Change From Baseline in Prolactin
Time frame: Baseline, Week 6
Population: 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).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 80 mg LY2140023, BID | Change From Baseline in Prolactin | 0.6 micrograms per Liter (mcg/L) | Standard Deviation 15.4 |
| 40 mg LY2140023, BID | Change From Baseline in Prolactin | -0.1 micrograms per Liter (mcg/L) | Standard Deviation 15.1 |
| 10 mg LY2140023, BID | Change From Baseline in Prolactin | 1.9 micrograms per Liter (mcg/L) | Standard Deviation 12.2 |
| Placebo | Change From Baseline in Prolactin | -0.8 micrograms per Liter (mcg/L) | Standard Deviation 13 |
p-value: 0.444ANOVA
p-value: 0.799ANOVA
p-value: 0.073ANOVA
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.
Time frame: Baseline, Week 6
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 80 mg LY2140023, BID | Change From Baseline in Simpson-Angus Scale (SAS) Total Score | -0.06 units on a scale | Standard Error 0.11 |
| 40 mg LY2140023, BID | Change From Baseline in Simpson-Angus Scale (SAS) Total Score | -0.18 units on a scale | Standard Error 0.12 |
| 10 mg LY2140023, BID | Change From Baseline in Simpson-Angus Scale (SAS) Total Score | 0.13 units on a scale | Standard Error 0.11 |
| Placebo | Change From Baseline in Simpson-Angus Scale (SAS) Total Score | -0.11 units on a scale | Standard Error 0.08 |
p-value: 0.69495% CI: [-0.2, 0.31]Mixed Models Analysis
p-value: 0.59695% CI: [-0.34, 0.2]Mixed Models Analysis
p-value: 0.05595% CI: [0, 0.49]Mixed Models Analysis
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.
Time frame: Baseline, Week 6
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 80 mg LY2140023, BID | Change From Baseline in the 16-Item Negative Symptoms Assessment (NSA-16) Total Score | -5.5 units on a scale | Standard Error 1.4 |
| 40 mg LY2140023, BID | Change From Baseline in the 16-Item Negative Symptoms Assessment (NSA-16) Total Score | -7.1 units on a scale | Standard Error 1.5 |
| 10 mg LY2140023, BID | Change From Baseline in the 16-Item Negative Symptoms Assessment (NSA-16) Total Score | -6.3 units on a scale | Standard Error 1.3 |
| Placebo | Change From Baseline in the 16-Item Negative Symptoms Assessment (NSA-16) Total Score | -5.4 units on a scale | Standard Error 1.1 |
p-value: 0.9195% CI: [-3.1, 2.7]Mixed Models Analysis
p-value: 0.26595% CI: [-4.9, 1.3]Mixed Models Analysis
p-value: 0.53195% CI: [-3.7, 1.9]Mixed Models Analysis
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.
Time frame: Baseline, Week 6
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 80 mg LY2140023, BID | Change From Baseline in the Clinical Global Impression-Severity (CGI-S) Scale | -0.5 units on a scale | Standard Error 0.1 |
| 40 mg LY2140023, BID | Change From Baseline in the Clinical Global Impression-Severity (CGI-S) Scale | -0.6 units on a scale | Standard Error 0.1 |
| 10 mg LY2140023, BID | Change From Baseline in the Clinical Global Impression-Severity (CGI-S) Scale | -0.5 units on a scale | Standard Error 0.1 |
| Placebo | Change From Baseline in the Clinical Global Impression-Severity (CGI-S) Scale | -0.6 units on a scale | Standard Error 0.1 |
p-value: 0.3495% CI: [-0.13, 0.38]Mixed Models Analysis
p-value: 0.65995% CI: [-0.33, 0.21]Mixed Models Analysis
p-value: 0.41395% CI: [-0.14, 0.35]Mixed Models Analysis
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.
Time frame: Baseline, Week 6
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 80 mg LY2140023, BID | Change From Baseline in the Personal and Social Performance (PSP) Score | 7.9 units on a scale | Standard Error 1.4 |
| 40 mg LY2140023, BID | Change From Baseline in the Personal and Social Performance (PSP) Score | 9.6 units on a scale | Standard Error 1.6 |
| 10 mg LY2140023, BID | Change From Baseline in the Personal and Social Performance (PSP) Score | 7.1 units on a scale | Standard Error 1.4 |
| Placebo | Change From Baseline in the Personal and Social Performance (PSP) Score | 8.4 units on a scale | Standard Error 1.1 |
p-value: 0.6195% CI: [-3.5, 2.6]Mixed Models Analysis
p-value: 0.22395% CI: [-2, 4.6]Mixed Models Analysis
p-value: 0.41495% CI: [-4.2, 1.7]Mixed Models Analysis
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.
Time frame: Baseline, Week 6
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 80 mg LY2140023, BID | Change From Baseline in the Personal and Social Performance (PSP) Score in a Predefined Subpopulation | 6.7 units on a scale | Standard Error 1.4 |
| 40 mg LY2140023, BID | Change From Baseline in the Personal and Social Performance (PSP) Score in a Predefined Subpopulation | 8.6 units on a scale | Standard Error 1.4 |
| 10 mg LY2140023, BID | Change From Baseline in the Personal and Social Performance (PSP) Score in a Predefined Subpopulation | 6.3 units on a scale | Standard Error 1.3 |
| Placebo | Change From Baseline in the Personal and Social Performance (PSP) Score in a Predefined Subpopulation | 7.1 units on a scale | Standard Error 1 |
p-value: 0.60395% CI: [-3.7, 2.8]Mixed Models Analysis
p-value: 0.19295% CI: [-1.9, 4.8]Mixed Models Analysis
p-value: 0.61995% CI: [-3.9, 2.3]Mixed Models Analysis
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.
Time frame: Baseline, Week 6
Population: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 80 mg LY2140023, BID | Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Subscores | PANSS Positive Subscore | -1.2 units on a scale | Standard Error 0.7 |
| 80 mg LY2140023, BID | Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Subscores | PANSS Negative Subscore | -0.5 units on a scale | Standard Error 0.7 |
| 80 mg LY2140023, BID | Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Subscores | PANSS General Psychopathology Subscore | -1.9 units on a scale | Standard Error 1.1 |
| 40 mg LY2140023, BID | Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Subscores | PANSS Positive Subscore | -2.3 units on a scale | Standard Error 0.7 |
| 40 mg LY2140023, BID | Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Subscores | PANSS Negative Subscore | 0.2 units on a scale | Standard Error 0.7 |
| 40 mg LY2140023, BID | Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Subscores | PANSS General Psychopathology Subscore | -2.8 units on a scale | Standard Error 1.2 |
| 10 mg LY2140023, BID | Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Subscores | PANSS General Psychopathology Subscore | -2.7 units on a scale | Standard Error 1.1 |
| 10 mg LY2140023, BID | Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Subscores | PANSS Positive Subscore | -2.0 units on a scale | Standard Error 0.6 |
| 10 mg LY2140023, BID | Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Subscores | PANSS Negative Subscore | -0.6 units on a scale | Standard Error 0.6 |
| Placebo | Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Subscores | PANSS Negative Subscore | -1.1 units on a scale | Standard Error 0.5 |
| Placebo | Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Subscores | PANSS General Psychopathology Subscore | -4.2 units on a scale | Standard Error 0.8 |
| Placebo | Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Subscores | PANSS Positive Subscore | -2.8 units on a scale | Standard Error 0.5 |
p-value: 0.03695% CI: [0.1, 3.1]Mixed Models Analysis
p-value: 0.61695% CI: [-1.2, 2]Mixed Models Analysis
p-value: 0.30795% CI: [-0.7, 2.2]Mixed Models Analysis
p-value: 0.38295% CI: [-0.8, 2.1]Mixed Models Analysis
p-value: 0.10795% CI: [-0.3, 2.8]Mixed Models Analysis
p-value: 0.43695% CI: [-0.9, 2]Mixed Models Analysis
p-value: 0.07395% CI: [-0.2, 4.9]Mixed Models Analysis
p-value: 0.2895% CI: [-1.2, 4.2]Mixed Models Analysis
p-value: 0.20995% CI: [-0.9, 4]Mixed Models Analysis
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.
Time frame: Baseline, Week 6
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 80 mg LY2140023, BID | Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score in a Predefined Subpopulation of Schizophrenia Participants | -3.4 units on a scale | Standard Error 2.2 |
| 40 mg LY2140023, BID | Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score in a Predefined Subpopulation of Schizophrenia Participants | -4.3 units on a scale | Standard Error 2.2 |
| 10 mg LY2140023, BID | Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score in a Predefined Subpopulation of Schizophrenia Participants | -4.8 units on a scale | Standard Error 2 |
| Placebo | Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score in a Predefined Subpopulation of Schizophrenia Participants | -7.7 units on a scale | Standard Error 1.5 |
p-value: 0.95595% CI: [-0.7, 9.3]Mixed Models Analysis
p-value: 0.91295% CI: [-1.6, 8.4]Mixed Models Analysis
p-value: 0.22395% CI: [-1.8, 7.7]Mixed Models Analysis
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.
Time frame: Baseline, Week 6
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 80 mg LY2140023, BID | Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score in Females | 0.8 units on a scale | Standard Error 3.8 |
| 40 mg LY2140023, BID | Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score in Females | 0.0 units on a scale | Standard Error 4.3 |
| 10 mg LY2140023, BID | Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score in Females | -4.5 units on a scale | Standard Error 3.5 |
| Placebo | Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score in Females | -8.7 units on a scale | Standard Error 2.7 |
p-value: 0.02295% CI: [1.4, 17.6]Mixed Models Analysis
p-value: 0.06195% CI: [-0.4, 17.8]Mixed Models Analysis
p-value: 0.30495% CI: [-3.9, 12.3]Mixed Models Analysis
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.
Time frame: Baseline, Week 6
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 80 mg LY2140023, BID | Change From Baseline in Weight | 0.6 kilograms (kg) | Standard Error 0.4 |
| 40 mg LY2140023, BID | Change From Baseline in Weight | 0.6 kilograms (kg) | Standard Error 0.4 |
| 10 mg LY2140023, BID | Change From Baseline in Weight | 0.2 kilograms (kg) | Standard Error 0.4 |
| Placebo | Change From Baseline in Weight | 0.5 kilograms (kg) | Standard Error 0.3 |
p-value: 0.76195% CI: [-0.76, 1.04]Mixed Models Analysis
p-value: 0.76195% CI: [-0.78, 1.06]Mixed Models Analysis
p-value: 0.48995% CI: [-1.17, 0.56]Mixed Models Analysis
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).
Time frame: Baseline and Week (Wk) 6
Population: 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).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 80 mg LY2140023, BID | Change From Baseline on Schizophrenia Resource Utilization Module (S-RUM): Emergency Room (ER) Visits and Outpatient Visits | Outpatient, Wk 6 | 0.1 visits | Standard Deviation 0.7 |
| 80 mg LY2140023, BID | Change From Baseline on Schizophrenia Resource Utilization Module (S-RUM): Emergency Room (ER) Visits and Outpatient Visits | Outpatient, BL | 2.3 visits | Standard Deviation 10 |
| 80 mg LY2140023, BID | Change From Baseline on Schizophrenia Resource Utilization Module (S-RUM): Emergency Room (ER) Visits and Outpatient Visits | ER/Facility (Non-Psych), Wk 6 | 0.0 visits | Standard Deviation 0.2 |
| 80 mg LY2140023, BID | Change From Baseline on Schizophrenia Resource Utilization Module (S-RUM): Emergency Room (ER) Visits and Outpatient Visits | ER/Facility (Psych), Wk 6 | 0.1 visits | Standard Deviation 0.6 |
| 80 mg LY2140023, BID | Change From Baseline on Schizophrenia Resource Utilization Module (S-RUM): Emergency Room (ER) Visits and Outpatient Visits | ER/Facility (Psych), BL | 1.4 visits | Standard Deviation 1.8 |
| 80 mg LY2140023, BID | Change From Baseline on Schizophrenia Resource Utilization Module (S-RUM): Emergency Room (ER) Visits and Outpatient Visits | ER/Facility (Non-Psych), BL | 0.4 visits | Standard Deviation 0.9 |
| 40 mg LY2140023, BID | Change From Baseline on Schizophrenia Resource Utilization Module (S-RUM): Emergency Room (ER) Visits and Outpatient Visits | Outpatient, Wk 6 | 0.1 visits | Standard Deviation 0.3 |
| 40 mg LY2140023, BID | Change From Baseline on Schizophrenia Resource Utilization Module (S-RUM): Emergency Room (ER) Visits and Outpatient Visits | ER/Facility (Psych), BL | 1.1 visits | Standard Deviation 1.6 |
| 40 mg LY2140023, BID | Change From Baseline on Schizophrenia Resource Utilization Module (S-RUM): Emergency Room (ER) Visits and Outpatient Visits | ER/Facility (Psych), Wk 6 | 0.0 visits | Standard Deviation 0.2 |
| 40 mg LY2140023, BID | Change From Baseline on Schizophrenia Resource Utilization Module (S-RUM): Emergency Room (ER) Visits and Outpatient Visits | ER/Facility (Non-Psych), BL | 0.3 visits | Standard Deviation 0.8 |
| 40 mg LY2140023, BID | Change From Baseline on Schizophrenia Resource Utilization Module (S-RUM): Emergency Room (ER) Visits and Outpatient Visits | Outpatient, BL | 1.6 visits | Standard Deviation 3.2 |
| 40 mg LY2140023, BID | Change From Baseline on Schizophrenia Resource Utilization Module (S-RUM): Emergency Room (ER) Visits and Outpatient Visits | ER/Facility (Non-Psych), Wk 6 | 0.0 visits | Standard Deviation 0.1 |
| 10 mg LY2140023, BID | Change From Baseline on Schizophrenia Resource Utilization Module (S-RUM): Emergency Room (ER) Visits and Outpatient Visits | Outpatient, Wk 6 | 0.1 visits | Standard Deviation 0.5 |
| 10 mg LY2140023, BID | Change From Baseline on Schizophrenia Resource Utilization Module (S-RUM): Emergency Room (ER) Visits and Outpatient Visits | ER/Facility (Non-Psych), Wk 6 | 0.0 visits | Standard Deviation 0.2 |
| 10 mg LY2140023, BID | Change From Baseline on Schizophrenia Resource Utilization Module (S-RUM): Emergency Room (ER) Visits and Outpatient Visits | ER/Facility (Psych), Wk 6 | 0.1 visits | Standard Deviation 0.5 |
| 10 mg LY2140023, BID | Change From Baseline on Schizophrenia Resource Utilization Module (S-RUM): Emergency Room (ER) Visits and Outpatient Visits | ER/Facility (Psych), BL | 1.1 visits | Standard Deviation 1.8 |
| 10 mg LY2140023, BID | Change From Baseline on Schizophrenia Resource Utilization Module (S-RUM): Emergency Room (ER) Visits and Outpatient Visits | ER/Facility (Non-Psych), BL | 0.5 visits | Standard Deviation 1.3 |
| 10 mg LY2140023, BID | Change From Baseline on Schizophrenia Resource Utilization Module (S-RUM): Emergency Room (ER) Visits and Outpatient Visits | Outpatient, BL | 1.6 visits | Standard Deviation 3.3 |
| Placebo | Change From Baseline on Schizophrenia Resource Utilization Module (S-RUM): Emergency Room (ER) Visits and Outpatient Visits | Outpatient, BL | 1.6 visits | Standard Deviation 2.9 |
| Placebo | Change From Baseline on Schizophrenia Resource Utilization Module (S-RUM): Emergency Room (ER) Visits and Outpatient Visits | Outpatient, Wk 6 | 0.2 visits | Standard Deviation 0.8 |
| Placebo | Change From Baseline on Schizophrenia Resource Utilization Module (S-RUM): Emergency Room (ER) Visits and Outpatient Visits | ER/Facility (Non-Psych), Wk 6 | 0.0 visits | Standard Deviation 0.3 |
| Placebo | Change From Baseline on Schizophrenia Resource Utilization Module (S-RUM): Emergency Room (ER) Visits and Outpatient Visits | ER/Facility (Psych), BL | 1.3 visits | Standard Deviation 2.4 |
| Placebo | Change From Baseline on Schizophrenia Resource Utilization Module (S-RUM): Emergency Room (ER) Visits and Outpatient Visits | ER/Facility (Psych), Wk 6 | 0.0 visits | Standard Deviation 0.3 |
| Placebo | Change From Baseline on Schizophrenia Resource Utilization Module (S-RUM): Emergency Room (ER) Visits and Outpatient Visits | ER/Facility (Non-Psych), BL | 0.4 visits | Standard Deviation 0.9 |
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).
Time frame: Baseline and Week 6
Population: 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).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 80 mg LY2140023, BID | Change From Baseline on Schizophrenia Resource Utilization Module (S-RUM): Sessions With a Psychiatrist | Sessions at Baseline | 6.7 sessions | Standard Deviation 6.8 |
| 80 mg LY2140023, BID | Change From Baseline on Schizophrenia Resource Utilization Module (S-RUM): Sessions With a Psychiatrist | Sessions at Week 6 | 0.6 sessions | Standard Deviation 2.5 |
| 40 mg LY2140023, BID | Change From Baseline on Schizophrenia Resource Utilization Module (S-RUM): Sessions With a Psychiatrist | Sessions at Baseline | 7.1 sessions | Standard Deviation 7.4 |
| 40 mg LY2140023, BID | Change From Baseline on Schizophrenia Resource Utilization Module (S-RUM): Sessions With a Psychiatrist | Sessions at Week 6 | 0.5 sessions | Standard Deviation 2.1 |
| 10 mg LY2140023, BID | Change From Baseline on Schizophrenia Resource Utilization Module (S-RUM): Sessions With a Psychiatrist | Sessions at Baseline | 7.0 sessions | Standard Deviation 8.3 |
| 10 mg LY2140023, BID | Change From Baseline on Schizophrenia Resource Utilization Module (S-RUM): Sessions With a Psychiatrist | Sessions at Week 6 | 0.6 sessions | Standard Deviation 2.6 |
| Placebo | Change From Baseline on Schizophrenia Resource Utilization Module (S-RUM): Sessions With a Psychiatrist | Sessions at Baseline | 6.7 sessions | Standard Deviation 9.4 |
| Placebo | Change From Baseline on Schizophrenia Resource Utilization Module (S-RUM): Sessions With a Psychiatrist | Sessions at Week 6 | 0.2 sessions | Standard Deviation 0.8 |
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.
Time frame: Baseline, Week 6
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 80 mg LY2140023, BID | Change From Baseline on Subjective Well-Being Under Neuroleptic Treatment Scale - Short Form (SWN-S) Total Score | 1.2 units on a scale | Standard Error 2.3 |
| 40 mg LY2140023, BID | Change From Baseline on Subjective Well-Being Under Neuroleptic Treatment Scale - Short Form (SWN-S) Total Score | 8.6 units on a scale | Standard Error 2.5 |
| 10 mg LY2140023, BID | Change From Baseline on Subjective Well-Being Under Neuroleptic Treatment Scale - Short Form (SWN-S) Total Score | 5.9 units on a scale | Standard Error 2.2 |
| Placebo | Change From Baseline on Subjective Well-Being Under Neuroleptic Treatment Scale - Short Form (SWN-S) Total Score | 6.8 units on a scale | Standard Error 1.7 |
p-value: 0.02195% CI: [-10.4, -0.8]Mixed Models Analysis
p-value: 0.48795% CI: [-3.3, 6.9]Mixed Models Analysis
p-value: 0.69395% CI: [-5.6, 3.7]Mixed Models Analysis
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').
Time frame: Baseline, Week 6
Population: 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).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 80 mg LY2140023, BID | Change From Baseline on the European Quality of Life-5 Dimension (EQ-5D) Questionnaire | 6.0 units on a scale | Standard Error 2.5 |
| 40 mg LY2140023, BID | Change From Baseline on the European Quality of Life-5 Dimension (EQ-5D) Questionnaire | 3.5 units on a scale | Standard Error 2.8 |
| 10 mg LY2140023, BID | Change From Baseline on the European Quality of Life-5 Dimension (EQ-5D) Questionnaire | 8.2 units on a scale | Standard Error 2.4 |
| Placebo | Change From Baseline on the European Quality of Life-5 Dimension (EQ-5D) Questionnaire | 6.1 units on a scale | Standard Error 2 |
p-value: 0.98395% CI: [-5.21, 5.1]ANCOVA
p-value: 0.35195% CI: [-7.94, 2.83]ANCOVA
p-value: 0.40395% CI: [-2.86, 7.11]ANCOVA
Secondary
Number of Participants Who Discontinued
The reasons for study discontinuation are located in the Participant Flow.
Time frame: Randomization up to Week 6
Population: All randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 80 mg LY2140023, BID | Number of Participants Who Discontinued | 54 participants |
| 40 mg LY2140023, BID | Number of Participants Who Discontinued | 65 participants |
| 10 mg LY2140023, BID | Number of Participants Who Discontinued | 58 participants |
| Placebo | Number of Participants Who Discontinued | 110 participants |
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.
Time frame: Baseline, Week 6
Population: 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).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 80 mg LY2140023, BID | Percentage of Participants Who Are Responders | 3.3 percentage of participants |
| 40 mg LY2140023, BID | Percentage of Participants Who Are Responders | 7.2 percentage of participants |
| 10 mg LY2140023, BID | Percentage of Participants Who Are Responders | 7.5 percentage of participants |
| Placebo | Percentage of Participants Who Are Responders | 8.3 percentage of participants |
p-value: 0.137Fisher Exact
p-value: 0.824Fisher Exact
p-value: >0.999Fisher Exact
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.
Time frame: Baseline up to Week 6
Population: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 80 mg LY2140023, BID | Percentage of Participants With a Change From Baseline in Suicidal Behaviors and Ideations Measured by the Columbia-Suicide Severity Rating Scale (C-SSRS) | Treatment-Emergent Suicidal Behavior | 0.0 percentage of participants |
| 80 mg LY2140023, BID | Percentage of Participants With a Change From Baseline in Suicidal Behaviors and Ideations Measured by the Columbia-Suicide Severity Rating Scale (C-SSRS) | Treatment-Emergent Suicidal Ideation | 2.8 percentage of participants |
| 40 mg LY2140023, BID | Percentage of Participants With a Change From Baseline in Suicidal Behaviors and Ideations Measured by the Columbia-Suicide Severity Rating Scale (C-SSRS) | Treatment-Emergent Suicidal Behavior | 0.0 percentage of participants |
| 40 mg LY2140023, BID | Percentage of Participants With a Change From Baseline in Suicidal Behaviors and Ideations Measured by the Columbia-Suicide Severity Rating Scale (C-SSRS) | Treatment-Emergent Suicidal Ideation | 5.6 percentage of participants |
| 10 mg LY2140023, BID | Percentage of Participants With a Change From Baseline in Suicidal Behaviors and Ideations Measured by the Columbia-Suicide Severity Rating Scale (C-SSRS) | Treatment-Emergent Suicidal Ideation | 6.0 percentage of participants |
| 10 mg LY2140023, BID | Percentage of Participants With a Change From Baseline in Suicidal Behaviors and Ideations Measured by the Columbia-Suicide Severity Rating Scale (C-SSRS) | Treatment-Emergent Suicidal Behavior | 0.0 percentage of participants |
| Placebo | Percentage of Participants With a Change From Baseline in Suicidal Behaviors and Ideations Measured by the Columbia-Suicide Severity Rating Scale (C-SSRS) | Treatment-Emergent Suicidal Behavior | 0.9 percentage of participants |
| Placebo | Percentage of Participants With a Change From Baseline in Suicidal Behaviors and Ideations Measured by the Columbia-Suicide Severity Rating Scale (C-SSRS) | Treatment-Emergent Suicidal Ideation | 4.0 percentage of participants |
p-value: 0.758Fisher Exact
p-value: 0.576Fisher Exact
p-value: 0.425Fisher Exact
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.
Time frame: Randomization up to Week 6
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 80 mg LY2140023, BID | Time to Discontinuation | NA days |
| 40 mg LY2140023, BID | Time to Discontinuation | NA days |
| 10 mg LY2140023, BID | Time to Discontinuation | NA days |
| Placebo | Time to Discontinuation | NA days |
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.
Time frame: Baseline up to Week 6
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 80 mg LY2140023, BID | Time to Response | NA days |
| 40 mg LY2140023, BID | Time to Response | NA days |
| 10 mg LY2140023, BID | Time to Response | NA days |
| Placebo | Time to Response | NA days |
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.
Time frame: Last dose (either early discontinuation or Week 6) through 30-day follow-up period
Population: Participants who received at least 1 dose of study drug according to the treatment group to which they were randomized.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 80 mg LY2140023, BID | Serious Adverse Events (SAEs) Which Occurred During 30 Days After Last Dose of Study Drug | Suicidal ideation | 1 participants |
| 80 mg LY2140023, BID | Serious Adverse Events (SAEs) Which Occurred During 30 Days After Last Dose of Study Drug | Schizophrenia | 0 participants |
| 80 mg LY2140023, BID | Serious Adverse Events (SAEs) Which Occurred During 30 Days After Last Dose of Study Drug | Acute myocardial infarction (resulted in death) | 0 participants |
| 80 mg LY2140023, BID | Serious Adverse Events (SAEs) Which Occurred During 30 Days After Last Dose of Study Drug | Irritability | 0 participants |
| 80 mg LY2140023, BID | Serious Adverse Events (SAEs) Which Occurred During 30 Days After Last Dose of Study Drug | Homicidal ideation | 1 participants |
| 40 mg LY2140023, BID | Serious Adverse Events (SAEs) Which Occurred During 30 Days After Last Dose of Study Drug | Schizophrenia | 0 participants |
| 40 mg LY2140023, BID | Serious Adverse Events (SAEs) Which Occurred During 30 Days After Last Dose of Study Drug | Acute myocardial infarction (resulted in death) | 0 participants |
| 40 mg LY2140023, BID | Serious Adverse Events (SAEs) Which Occurred During 30 Days After Last Dose of Study Drug | Irritability | 0 participants |
| 40 mg LY2140023, BID | Serious Adverse Events (SAEs) Which Occurred During 30 Days After Last Dose of Study Drug | Homicidal ideation | 0 participants |
| 40 mg LY2140023, BID | Serious Adverse Events (SAEs) Which Occurred During 30 Days After Last Dose of Study Drug | Suicidal ideation | 0 participants |
| 10 mg LY2140023, BID | Serious Adverse Events (SAEs) Which Occurred During 30 Days After Last Dose of Study Drug | Suicidal ideation | 0 participants |
| 10 mg LY2140023, BID | Serious Adverse Events (SAEs) Which Occurred During 30 Days After Last Dose of Study Drug | Homicidal ideation | 0 participants |
| 10 mg LY2140023, BID | Serious Adverse Events (SAEs) Which Occurred During 30 Days After Last Dose of Study Drug | Acute myocardial infarction (resulted in death) | 0 participants |
| 10 mg LY2140023, BID | Serious Adverse Events (SAEs) Which Occurred During 30 Days After Last Dose of Study Drug | Schizophrenia | 0 participants |
| 10 mg LY2140023, BID | Serious Adverse Events (SAEs) Which Occurred During 30 Days After Last Dose of Study Drug | Irritability | 1 participants |
| Placebo | Serious Adverse Events (SAEs) Which Occurred During 30 Days After Last Dose of Study Drug | Schizophrenia | 2 participants |
| Placebo | Serious Adverse Events (SAEs) Which Occurred During 30 Days After Last Dose of Study Drug | Homicidal ideation | 0 participants |
| Placebo | Serious Adverse Events (SAEs) Which Occurred During 30 Days After Last Dose of Study Drug | Acute myocardial infarction (resulted in death) | 1 participants |
| Placebo | Serious Adverse Events (SAEs) Which Occurred During 30 Days After Last Dose of Study Drug | Irritability | 0 participants |
| Placebo | Serious Adverse Events (SAEs) Which Occurred During 30 Days After Last Dose of Study Drug | Suicidal ideation | 0 participants |