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| ID | Type | Description | Link |
|---|---|---|---|
| H8Y-MC-HBDE | 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 weight gain will be significantly less in LY2140023 than aripiprazole in patients with schizophrenia.
The primary objective of this study was to test the hypothesis that mean weight gain, as assessed by change from baseline, would be statistically significantly less for flexibly dosed LY2140023 (20, 40, or 80 mg twice daily [BID]) than for flexibly dosed aripiprazole (10, 15, or 30 mg/day) in patients with schizophrenia after 24 weeks of double-blind treatment.
This was a multicenter, randomized, double-blind, Phase 3 study to assess the safety and efficacy of LY2140023 (flexibly dosed between 20 and 80 mg BID) in patients with schizophrenia. An active control, aripiprazole (flexibly dosed between 10 and 30 mg/day), was included for comparison.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| LY2140023 | Experimental | Double Blind Phase: 40 milligrams (mg) administered orally, given twice daily for 24 weeks. Dose may be adjusted to a minimum of 20 mg or a maximum of 80 mg. Open Label Phase: 40 mg administered orally, given twice daily for an additional 28 weeks. |
|
| Aripiprazole | Active Comparator | Double Blind Phase: 15 mg administered orally, given once daily for 24 weeks. Dose can be adjusted to a minimum of 10 mg or a maximum of 30 mg. Open Label Phase: LY2140023, 40 mg administered orally, given twice daily for an additional 28 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| LY2140023 | Drug | Administered orally |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline to 24 Weeks in Body Weight | Mixed model repeated measures (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values were adjusted for baseline, treatment, gender, pooled investigator, visit, prior olanzapine use, treatment-by-visit interaction and baseline-by-visit interaction. | Baseline, 24 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Clinically Significant Weight Change | Clinically significant change in body weight is defined as either an increase or decrease in weight of ≥7% from baseline. | Baseline up to 24 weeks |
| Change From Baseline up to 24 Weeks in Barnes Akathisia Scale (BAS) |
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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. | Cerritos | California | 90703 |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24772351 | Derived | Adams DH, Zhang L, Millen BA, Kinon BJ, Gomez JC. Pomaglumetad Methionil (LY2140023 Monohydrate) and Aripiprazole in Patients with Schizophrenia: A Phase 3, Multicenter, Double-Blind Comparison. Schizophr Res Treatment. 2014;2014:758212. doi: 10.1155/2014/758212. Epub 2014 Mar 19. |
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This study consisted of a 24-week Double-Blind Active Treatment Phase and was followed by a 28-week Open-Label Active Treatment Phase. Modified intent-to-treat (mITT) is all randomized participants who received at least 1 dose of study drug, excluding participants from a Good Clinical Practice (GCP) noncompliant study site.
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| ID | Title | Description |
|---|---|---|
| FG000 | LY2140023-DB / LY2140023-OL | 40 milligrams (mg) LY2140023 administered orally, twice daily for 24 weeks during the Double-Blind (DB) Phase. Dose was adjustable to 20 mg twice daily or 80 mg twice daily. 40mg LY2140023 administered orally, twice daily for 28 weeks during the Open -Label (OL) Phase. Dose was adjustable to 20 mg twice daily or 80 mg twice daily. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Double-Blind Phase |
|
Not provided
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| Aripiprazole |
| Drug |
Administered orally |
|
The BAS is a 4-item instrument that evaluates akathisia associated with use of antipsychotic medications. Item 4 Global Clinical Assessment of Akathisia is rated on a 6- point scale, with scores range from 0 (no symptoms) to 5 (increased severity of symptoms); Only Item 4 was analyzed and presented. The Mixed Model Repeated Measures (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values were adjusted for baseline, treatment, gender, pooled investigative site, visit, predefined subpopulation, treatment-by-visit interaction and baseline-by-visit interaction. |
| Baseline, 24 weeks |
| Change From Baseline up to 24 Weeks in Simpson-Angus Scale (SAS) | The SAS is used to measure Parkinsonian-type symptoms in participants exposed to antipsychotics. SAS consists of 10 items, each rated on a 5-point scale: 0 (complete absence of the condition) to 4 (presence of the condition in extreme form). The SAS Total Score is obtained by adding the ten items, and ranges from 0 to 40. Higher scores indicate greater severity of illness. The Mixed Model Repeated Measures (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values were adjusted for baseline, treatment, gender, pooled investigative site, visit, predefined subpopulation, treatment by-visit-interaction and baseline-by-visit interaction. | Baseline, 24 weeks |
| Change From Baseline up to 24 Weeks in Abnormal Involuntary Movement Scale (AIMS) | AIMS is a 12-item scale designed to record the occurrence of dyskinetic movements. Items 1 to 10 are rated on a 5- point scale: 0 (no dyskinetic movements) to 4 (severe dyskinetic movements). Items 11 and 12 are yes/no questions regarding the dental condition of a participant. The AIMS 1-7 Total Score is the sum of Items 1 through 7 of the AIMS, and ranges from 0 to 28. Higher scores indicate greater severity of illness. Only AIMS 1-7 Total Score was analyzed and presented. The Mixed Model Repeated Measures (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values were adjusted for baseline, treatment, gender, pooled investigative site, visit, predefined subpopulation, treatment-by-visit interaction and baseline-by-visit interaction. | Baseline, 24 weeks |
| Change From Baseline up to 24 Weeks in Positive and Negative Syndrome Scale (PANSS) Total and Subscale Scores | The PANSS consists of 30 items and 3 subscales and is designed to measure severity of psychopathology in schizophrenia. The PANSS Positive Subscale and the PANSS Negative Subscale each contain 7 items, and the remaining 16 items make up the PANSS General Psychopathology Subscale. Each item is rated from 1 (symptom not present) to 7 (symptom extremely severe). The PANSS Total Score is the sum of the 30 items, with scores range from 30 to 210. The PANSS Positive Subscale and PANSS Negative Subscale scores each range from 7 to 49. The PANSS General Psychopathology subscale score ranges from 16 to 112. Higher scores indicate greater severity of illness. The Mixed Model Repeated Measures (MMRM) analysis was used to calculate Least Squares (LS) mean and 95% confidence interval. LS mean values were adjusted for baseline, treatment, gender, pooled investigative site, visit, predefined subpopulation, treatment-by-visit interaction and baseline-by-visit interaction. | Baseline, 24 weeks |
| Change From Baseline up to 24 Weeks in EuroQol-5 Dimensions Questionnaire (EQ-5D) Visual Analog Scale (VAS) Health State Score | The EQ-5D is a generic, multidimensional, health-related, quality-of-life instrument that contains 2 parts: a health status profile and a visual analog scale (VAS) to rate global health-related quality of life. VAS health state scores range from 0 (worst imaginable health state) to 100 (best imaginable health state). The Mixed Model Repeated Measures (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values were adjusted for baseline, treatment, gender, pooled investigative site, visit, predefined subpopulation, treatment-by-visit interaction and baseline-by-visit interaction. | Baseline, 24 weeks |
| Schizophrenia Resource Utilization Module (S-RUM) - Number of Emergency Room (ER) or Equivalent Facility Visits and Outpatient Medical Visits | The S-RUM is a 31-item questionnaire to assess the participant's occupation (work and home), living arrangements, encounters with law enforcement, victimization, ER visits, and outpatient medical visits for a specified period of time. Item 1 asks about the number of ER or equivalent facility visits a participant had for psychiatric (psych) illness. Item 2 asks about the number of ER or equivalent facility visits a participant had for non-psychiatric (non-psych) illness or injury. Item 5 asks about the number of outpatient visits to other physicians (not psychiatrists or dentists). Analysis of variance (ANOVA) was used to calculate Least Squares (LS) mean and standard error. LS mean values were adjusted for pooled investigator, gender and treatment. | Baseline to 24 weeks |
| Schizophrenia Resource Use Module (S-RUM) - Number of Sessions With a Psychiatrist | The S-RUM is a 31-item questionnaire to assess the participant's occupation (work and home), living arrangements, encounters with law enforcement, victimization, emergency room (ER) visits, and outpatient medical visits for a specified period of time. Item 4 asks about the number of sessions with a psychiatrist a participant had. Analysis of variance (ANOVA) was used to calculate Least Squares (LS) mean and standard error. LS mean values were adjusted for pooled investigator, gender and treatment. | Baseline to 24 weeks |
| Change From Baseline up to 24 Weeks in Subjective Well-Being Under Neuroleptic Treatment Scale- Short Form (SWN-SF) Total Score | The SWN-SF measures subjective well-being of the participant for the previous 7 days. The 20-item scale covers 5 health domains (subscales; 4 items each): emotional regulation, self-control, mental functioning, social integration, and physical functioning. Individual scores range from 1 (not at all) to 6 (very much). Each of the 5 subscale scores range from 4 to 24. SWN-SF Total Scores range from 20 to 120. Higher scores indicate greater well-being. The Mixed Model Repeated Measures (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values were adjusted for baseline, treatment, gender, pooled investigative site, visit, predefined subpopulation, treatment-by-visit interaction and baseline-by-visit interaction. | Baseline, 24 weeks |
| Change From Baseline up to 24 Weeks in Personal and Social Performance (PSP) Score | The PSP scale is a 100-point (minimum 1, maximum 100), single item, clinician-rated scale to assess a participant's overall functioning, including personal and social relationships, socially useful activities, self-care, and disturbing and aggressive behaviors. Higher scores indicate a higher level of functioning. The Mixed Model Repeated Measures (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values were adjusted for baseline, treatment, gender, pooled investigative site, visit, predefined subpopulation, treatment-by-visit interaction and baseline-by-visit interaction. | Baseline, 24 weeks |
| Change From Baseline up to 24 Weeks in Clinical Global Impression-Severity Scale (CGI-S) | The CGI-S instrument is used to record the severity of mental illness at the time of assessment. The score ranges from 1 (normal, not at all ill) to 7 (among the most extremely ill). Higher scores indicate greater severity of illness. The Mixed Model Repeated Measures (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values were adjusted for baseline, treatment, gender, pooled investigative site, visit, predefined subpopulation, treatment-by-visit interaction and baseline-by-visit interaction. | Baseline, 24 weeks |
| Change From Baseline up to 24 Weeks in 16-Item Negative Symptom Assessment (NSA-16) | The NSA-16 scale is used to help clinicians rate behaviors (not psychopathology) commonly associated with negative symptoms of schizophrenia. The scale rates participants on 16 "anchors". Each item ("anchor") is rated from 1 (better) to 6 (worse). The NSA-16 Total Score is the sum of the 16 specific items and ranges from 16 to 96. Higher scores indicate greater severity of illness. The Mixed Model Repeated Measures (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values were adjusted for baseline, treatment, gender, pooled investigative site, visit, predefined subpopulation, treatment-by-visit interaction and baseline-by-visit interaction. | Baseline, 24 weeks |
| Number of Participants With 30% or Greater Decrease in Positive and Negative Syndrome Scale (PANSS) Total Score | The PANSS assesses the positive symptoms, negative symptoms, and general psychopathology specifically associated with schizophrenia. The scale consists of 30 items. Each item is rated on a scale from 1 (absence of symptoms) to 7 (symptoms extremely severe). The sum of the 30 items is defined as the PANSS Total Score and ranges from 30 to 210. Higher scores indicate greater severity of illness. Data presented are the number of participants with 30% or greater decrease from baseline in PANSS Total score. | Baseline up to 24 weeks |
| Number of Participants With Suicidal Behaviors and Ideations Measured by Columbia Suicide Severity Rating Scale (C-SSRS) | Columbia Suicide Rating Scale (C-SSRS) captures occurrence, severity, and frequency of suicide-related thoughts and behaviors. Suicidal ideation: a "yes" answer to any one of 5 suicidal ideation questions: wish to be dead, and 4 different categories of active suicidal ideation. Suicidal behavior: a "yes" answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Data presented are the number of participants with treatment-emergent suicidal ideation or behavior during the treatment period (with a change from lead-in baseline in C-SSRS). | Baseline to 24 weeks |
| Time to Discontinuation | The time to discontinuation due to any reason was defined as the total number of days between randomization and discontinuation date. The time to discontinuation was analyzed using Kaplan-Meier estimated survival curves. Participants who completed the study were considered censored. | Randomization up to 24 weeks |
| 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. | Escondido | California | 92025 | 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. | Garden Grove | California | 92845 | 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. | Long Beach | California | 90813 | 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. | Oakland | California | 94612 | 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. | Sherman Oaks | California | 91403 | 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. | Coral Gables | Florida | 33145 | 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. | Maitland | Florida | 32751 | 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. | North Miami | Florida | 33161 | 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. | Sanford | Florida | 32771 | 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. | Chicago | Illinois | 60640 | United States |
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| FG001 |
| Aripiprazole-DB / LY2140023-OL |
15 mg aripiprazole administered orally, once daily for 24 weeks during the Double-Blind (DB) Phase. Dose was adjustable to 10 mg once daily or 30 mg once daily. 40mg LY2140023 administered orally, twice daily for 28 weeks during the Open -Label (OL) Phase. Dose was adjustable to 20 mg twice daily or 80 mg twice daily. |
| Received at Least 1 Dose of Study Drug |
|
| Modified Intent-To-Treat (mITT) |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
| Open-Label Phase |
|
|
Modified intention-to-treat (mITT) population: All randomized participants who received at least 1 dose of study drug, excluding participants from the excluded study site.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | LY2140023-DB | 40 milligrams (mg) LY2140023 administered orally, twice daily for 24 weeks during the Double-Blind (DB) Phase. Dose was adjustable to 20 mg twice daily or 80 mg twice daily. |
| BG001 | Aripiprazole-DB | 15 mg aripiprazole administered orally, once daily for 24 weeks during the Double-Blind (DB) Phase. Dose was adjustable to 10 mg once daily or 30 mg once daily. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| 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 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | Change From Baseline to 24 Weeks in Body Weight | Mixed model repeated measures (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values were adjusted for baseline, treatment, gender, pooled investigator, visit, prior olanzapine use, treatment-by-visit interaction and baseline-by-visit interaction. | Modified intent-to-treat (mITT) population: All randomized participants who received at least one dose of study drug, had baseline and at least one post-baseline weight measurement, excluding participants from the excluded study site. | Posted | Least Squares Mean | Standard Error | kilograms (kg) | Baseline, 24 weeks |
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| Secondary | Percentage of Participants With Clinically Significant Weight Change | Clinically significant change in body weight is defined as either an increase or decrease in weight of ≥7% from baseline. | Modified intent-to-treat (mITT) population: All randomized participants who received at least one dose of study drug, had a baseline and at least one post-baseline weight measurement, excluding participants from the excluded study site. | Posted | Number | percentage of participants | Baseline up to 24 weeks |
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| Secondary | Change From Baseline up to 24 Weeks in Barnes Akathisia Scale (BAS) | The BAS is a 4-item instrument that evaluates akathisia associated with use of antipsychotic medications. Item 4 Global Clinical Assessment of Akathisia is rated on a 6- point scale, with scores range from 0 (no symptoms) to 5 (increased severity of symptoms); Only Item 4 was analyzed and presented. The Mixed Model Repeated Measures (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values were adjusted for baseline, treatment, gender, pooled investigative site, visit, predefined subpopulation, treatment-by-visit interaction and baseline-by-visit interaction. | Modified intent-to-treat (mITT) population: All randomized participants who received at least one dose of study drug, had a baseline and at least one post-baseline BAS global score measurement, excluding participants from the excluded study site. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline, 24 weeks |
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| Secondary | Change From Baseline up to 24 Weeks in Simpson-Angus Scale (SAS) | The SAS is used to measure Parkinsonian-type symptoms in participants exposed to antipsychotics. SAS consists of 10 items, each rated on a 5-point scale: 0 (complete absence of the condition) to 4 (presence of the condition in extreme form). The SAS Total Score is obtained by adding the ten items, and ranges from 0 to 40. Higher scores indicate greater severity of illness. The Mixed Model Repeated Measures (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values were adjusted for baseline, treatment, gender, pooled investigative site, visit, predefined subpopulation, treatment by-visit-interaction and baseline-by-visit interaction. | Modified intent-to-treat (mITT) population: All randomized participants who received at least one dose of study drug, had a baseline and at least one post-baseline SAS total score measurement, excluding participants from the excluded study site. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline, 24 weeks |
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| Secondary | Change From Baseline up to 24 Weeks in Abnormal Involuntary Movement Scale (AIMS) | AIMS is a 12-item scale designed to record the occurrence of dyskinetic movements. Items 1 to 10 are rated on a 5- point scale: 0 (no dyskinetic movements) to 4 (severe dyskinetic movements). Items 11 and 12 are yes/no questions regarding the dental condition of a participant. The AIMS 1-7 Total Score is the sum of Items 1 through 7 of the AIMS, and ranges from 0 to 28. Higher scores indicate greater severity of illness. Only AIMS 1-7 Total Score was analyzed and presented. The Mixed Model Repeated Measures (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values were adjusted for baseline, treatment, gender, pooled investigative site, visit, predefined subpopulation, treatment-by-visit interaction and baseline-by-visit interaction. | Modified intent-to-treat (mITT) population: All randomized participants who received at least one dose of study drug, had a baseline and at least one post-baseline AIMS 1-7 Total Score measurement, excluding participants from the excluded study site. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline, 24 weeks |
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| Secondary | Change From Baseline up to 24 Weeks in Positive and Negative Syndrome Scale (PANSS) Total and Subscale Scores | The PANSS consists of 30 items and 3 subscales and is designed to measure severity of psychopathology in schizophrenia. The PANSS Positive Subscale and the PANSS Negative Subscale each contain 7 items, and the remaining 16 items make up the PANSS General Psychopathology Subscale. Each item is rated from 1 (symptom not present) to 7 (symptom extremely severe). The PANSS Total Score is the sum of the 30 items, with scores range from 30 to 210. The PANSS Positive Subscale and PANSS Negative Subscale scores each range from 7 to 49. The PANSS General Psychopathology subscale score ranges from 16 to 112. Higher scores indicate greater severity of illness. The Mixed Model Repeated Measures (MMRM) analysis was used to calculate Least Squares (LS) mean and 95% confidence interval. LS mean values were adjusted for baseline, treatment, gender, pooled investigative site, visit, predefined subpopulation, treatment-by-visit interaction and baseline-by-visit interaction. | Modified intent-to-treat (mITT) population: All randomized participants who received at least one dose of study drug, had a baseline and at least one post-baseline PANSS measurement, excluding participants from the excluded study site. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline, 24 weeks |
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| Secondary | Change From Baseline up to 24 Weeks in EuroQol-5 Dimensions Questionnaire (EQ-5D) Visual Analog Scale (VAS) Health State Score | The EQ-5D is a generic, multidimensional, health-related, quality-of-life instrument that contains 2 parts: a health status profile and a visual analog scale (VAS) to rate global health-related quality of life. VAS health state scores range from 0 (worst imaginable health state) to 100 (best imaginable health state). The Mixed Model Repeated Measures (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values were adjusted for baseline, treatment, gender, pooled investigative site, visit, predefined subpopulation, treatment-by-visit interaction and baseline-by-visit interaction. | Modified intent-to-treat (mITT) population: All randomized participants who received at least one dose of study drug, had a baseline and at least one post-baseline VAS health state measurement, excluding participants from the excluded study site. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline, 24 weeks |
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| Secondary | Schizophrenia Resource Utilization Module (S-RUM) - Number of Emergency Room (ER) or Equivalent Facility Visits and Outpatient Medical Visits | The S-RUM is a 31-item questionnaire to assess the participant's occupation (work and home), living arrangements, encounters with law enforcement, victimization, ER visits, and outpatient medical visits for a specified period of time. Item 1 asks about the number of ER or equivalent facility visits a participant had for psychiatric (psych) illness. Item 2 asks about the number of ER or equivalent facility visits a participant had for non-psychiatric (non-psych) illness or injury. Item 5 asks about the number of outpatient visits to other physicians (not psychiatrists or dentists). Analysis of variance (ANOVA) was used to calculate Least Squares (LS) mean and standard error. LS mean values were adjusted for pooled investigator, gender and treatment. | Modified intent-to-treat (mITT) population: All randomized participants who received at least one dose of study drug and had S-RUM assessment, excluding participants from the excluded study site. Last observation carried forward (LOCF) principle was used. | Posted | Least Squares Mean | Standard Error | visits | Baseline to 24 weeks |
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| Secondary | Schizophrenia Resource Use Module (S-RUM) - Number of Sessions With a Psychiatrist | The S-RUM is a 31-item questionnaire to assess the participant's occupation (work and home), living arrangements, encounters with law enforcement, victimization, emergency room (ER) visits, and outpatient medical visits for a specified period of time. Item 4 asks about the number of sessions with a psychiatrist a participant had. Analysis of variance (ANOVA) was used to calculate Least Squares (LS) mean and standard error. LS mean values were adjusted for pooled investigator, gender and treatment. | Modified intent-to-treat (mITT) population: All randomized participants who received at least one dose of study drug and had S-RUM assessment, excluding participants from the excluded study site. Last observation carried forward (LOCF) principle was used. | Posted | Least Squares Mean | Standard Error | sessions | Baseline to 24 weeks |
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| Secondary | Change From Baseline up to 24 Weeks in Subjective Well-Being Under Neuroleptic Treatment Scale- Short Form (SWN-SF) Total Score | The SWN-SF measures subjective well-being of the participant for the previous 7 days. The 20-item scale covers 5 health domains (subscales; 4 items each): emotional regulation, self-control, mental functioning, social integration, and physical functioning. Individual scores range from 1 (not at all) to 6 (very much). Each of the 5 subscale scores range from 4 to 24. SWN-SF Total Scores range from 20 to 120. Higher scores indicate greater well-being. The Mixed Model Repeated Measures (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values were adjusted for baseline, treatment, gender, pooled investigative site, visit, predefined subpopulation, treatment-by-visit interaction and baseline-by-visit interaction. | Modified intent-to-treat (mITT) population: All randomized participants who received at least one dose of study drug, had a baseline and at least one post-baseline SWN-SF Total Score measurement, excluding participants from the excluded study site. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline, 24 weeks |
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| Secondary | Change From Baseline up to 24 Weeks in Personal and Social Performance (PSP) Score | The PSP scale is a 100-point (minimum 1, maximum 100), single item, clinician-rated scale to assess a participant's overall functioning, including personal and social relationships, socially useful activities, self-care, and disturbing and aggressive behaviors. Higher scores indicate a higher level of functioning. The Mixed Model Repeated Measures (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values were adjusted for baseline, treatment, gender, pooled investigative site, visit, predefined subpopulation, treatment-by-visit interaction and baseline-by-visit interaction. | Modified intent-to-treat (mITT) population: All randomized participants who received at least one dose of study drug, had a baseline and at least one post-baseline PSP measurement, excluding participants from the excluded study site. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline, 24 weeks |
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| Secondary | Change From Baseline up to 24 Weeks in Clinical Global Impression-Severity Scale (CGI-S) | The CGI-S instrument is used to record the severity of mental illness at the time of assessment. The score ranges from 1 (normal, not at all ill) to 7 (among the most extremely ill). Higher scores indicate greater severity of illness. The Mixed Model Repeated Measures (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values were adjusted for baseline, treatment, gender, pooled investigative site, visit, predefined subpopulation, treatment-by-visit interaction and baseline-by-visit interaction. | Modified intent-to-treat (mITT) population: All randomized participants who received at least one dose of study drug, had a baseline and at least one post-baseline CGI-S measurement, excluding participants from the excluded study site. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline, 24 weeks |
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| Secondary | Change From Baseline up to 24 Weeks in 16-Item Negative Symptom Assessment (NSA-16) | The NSA-16 scale is used to help clinicians rate behaviors (not psychopathology) commonly associated with negative symptoms of schizophrenia. The scale rates participants on 16 "anchors". Each item ("anchor") is rated from 1 (better) to 6 (worse). The NSA-16 Total Score is the sum of the 16 specific items and ranges from 16 to 96. Higher scores indicate greater severity of illness. The Mixed Model Repeated Measures (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values were adjusted for baseline, treatment, gender, pooled investigative site, visit, predefined subpopulation, treatment-by-visit interaction and baseline-by-visit interaction. | Modified intent-to-treat (mITT) population: All randomized participants who received at least one dose of study drug, had a baseline and at least one post-baseline NSA-16 Total Score measurement, excluding participants from the excluded study site. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline, 24 weeks |
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| Secondary | Number of Participants With 30% or Greater Decrease in Positive and Negative Syndrome Scale (PANSS) Total Score | The PANSS assesses the positive symptoms, negative symptoms, and general psychopathology specifically associated with schizophrenia. The scale consists of 30 items. Each item is rated on a scale from 1 (absence of symptoms) to 7 (symptoms extremely severe). The sum of the 30 items is defined as the PANSS Total Score and ranges from 30 to 210. Higher scores indicate greater severity of illness. Data presented are the number of participants with 30% or greater decrease from baseline in PANSS Total score. | Modified intent-to-treat (mITT) population: All randomized participants who received at least one dose of study drug, had a baseline and at least one post-baseline PANSS measurement, excluding participants from the excluded study site. Last observation carried forward (LOCF) principle was used. | Posted | Number | participants | Baseline up to 24 weeks |
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| Secondary | Number of Participants With Suicidal Behaviors and Ideations Measured by Columbia Suicide Severity Rating Scale (C-SSRS) | Columbia Suicide Rating Scale (C-SSRS) captures occurrence, severity, and frequency of suicide-related thoughts and behaviors. Suicidal ideation: a "yes" answer to any one of 5 suicidal ideation questions: wish to be dead, and 4 different categories of active suicidal ideation. Suicidal behavior: a "yes" answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Data presented are the number of participants with treatment-emergent suicidal ideation or behavior during the treatment period (with a change from lead-in baseline in C-SSRS). | Modified intent-to-treat (mITT) population: All randomized participants who received at least one dose of study drug, had a baseline and at least one post-baseline C-SSRS measurement, excluding participants from the excluded study site. | Posted | Number | participants | Baseline to 24 weeks |
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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 randomization and discontinuation date. The time to discontinuation was analyzed using Kaplan-Meier estimated survival curves. Participants who completed the study were considered censored. | Modified intent-to-treat (mITT) population: All randomized participants who received at least one dose of study drug, excluding participants from the excluded study site. Participants who completed the study were considered censored: 229 for LY2140023 group and 84 for Aripiprazole group. | Posted | Median | Full Range | days | Randomization up to 24 weeks |
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Not provided
Adverse events were reported for all randomized participants who received at least 1 dose of study drug, excluding participants from a Good Clinical Practice (GCP) noncompliant study site.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | LY2140023-DB | 40 milligrams (mg) LY2140023 administered orally, twice daily for 24 weeks during the Double-Blind (DB) Phase. Dose was adjustable to 20 mg twice daily or 80 mg twice daily. | 42 | 511 | 358 | 511 | ||
| EG001 | Aripiprazole-DB | 15 mg aripiprazole administered orally, once daily for 24 weeks during the Double-Blind (DB) Phase. Dose was adjustable to 10 mg once daily or 30 mg once daily. | 5 | 161 | 107 | 161 | ||
| EG002 | LY2140023-OL | 40mg LY2140023 administered orally, twice daily for 28 weeks during the Open -Label (OL) Phase, following the treatment with either 40 mg LY2140023 or 15 mg aripiprazole during the Double-Blind Phase. Dose was adjustable to 20 mg twice daily or 80 mg twice daily. | 12 | 270 | 112 | 270 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Wolff-parkinson-white syndrome | Cardiac disorders | MedDRA 15.1 | Systematic Assessment |
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| Ileus | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
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| Cholelithiasis | Hepatobiliary disorders | MedDRA 15.1 | Systematic Assessment |
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| Appendicitis | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
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| Diverticulitis | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
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| Alcohol poisoning | Injury, poisoning and procedural complications | MedDRA 15.1 | Systematic Assessment |
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| Laceration | Injury, poisoning and procedural complications | MedDRA 15.1 | Systematic Assessment |
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| Ligament rupture | Injury, poisoning and procedural complications | MedDRA 15.1 | Systematic Assessment |
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| Lower limb fracture | Injury, poisoning and procedural complications | MedDRA 15.1 | Systematic Assessment |
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| Maternal exposure during pregnancy | Injury, poisoning and procedural complications | MedDRA 15.1 | Systematic Assessment |
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| Tibia fracture | Injury, poisoning and procedural complications | MedDRA 15.1 | Systematic Assessment |
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| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA 15.1 | Systematic Assessment |
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| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 15.1 | Systematic Assessment |
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| Convulsion | Nervous system disorders | MedDRA 15.1 | Systematic Assessment | Event was determined not to be a seizure by Seizure Adjudication Committee. |
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| Dizziness | Nervous system disorders | MedDRA 15.1 | Systematic Assessment |
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| Dystonia | 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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| Anxiety | Psychiatric disorders | MedDRA 15.1 | Systematic Assessment |
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| Anxiety disorder | Psychiatric disorders | MedDRA 15.1 | Systematic Assessment |
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| Completed suicide | Psychiatric disorders | MedDRA 15.1 | Systematic Assessment | Event resulted in death. |
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| Confusional state | Psychiatric disorders | MedDRA 15.1 | Systematic Assessment |
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| Delusion | Psychiatric disorders | MedDRA 15.1 | Systematic Assessment |
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| Depression | Psychiatric disorders | MedDRA 15.1 | Systematic Assessment |
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| Hallucination, auditory | Psychiatric disorders | MedDRA 15.1 | Systematic Assessment |
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| Homicidal ideation | 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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| Sleep disorder | Psychiatric disorders | MedDRA 15.1 | Systematic Assessment |
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| Stress | Psychiatric disorders | MedDRA 15.1 | Systematic Assessment |
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| Suicidal ideation | Psychiatric disorders | MedDRA 15.1 | Systematic Assessment |
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| Suicide attempt | Psychiatric disorders | MedDRA 15.1 | Systematic Assessment |
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| Pulmonary thrombosis | Respiratory, thoracic and mediastinal disorders | MedDRA 15.1 | Systematic Assessment |
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| Hip arthroplasty | Surgical and medical procedures | MedDRA 15.1 | Systematic Assessment |
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| Hypertensive crisis | Vascular disorders | MedDRA 15.1 | Systematic Assessment |
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| Shock haemorrhagic | Vascular disorders | MedDRA 15.1 | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Left atrial dilatation | Cardiac disorders | MedDRA 15.1 | Systematic Assessment |
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| Abdominal discomfort | Gastrointestinal 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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| Dry mouth | 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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| Fatigue | General disorders | MedDRA 15.1 | Systematic Assessment |
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| Irritability | General disorders | MedDRA 15.1 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA 15.1 | Systematic Assessment |
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| Therapeutic response unexpected | General disorders | MedDRA 15.1 | Systematic Assessment |
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| Influenza | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | 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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| Excoriation | Injury, poisoning and procedural complications | MedDRA 15.1 | Systematic Assessment |
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| Laceration | Injury, poisoning and procedural complications | MedDRA 15.1 | Systematic Assessment |
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| Maternal exposure during pregnancy | Injury, poisoning and procedural complications | MedDRA 15.1 | Systematic Assessment |
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| Aspartate aminotransferase increased | Investigations | MedDRA 15.1 | Systematic Assessment |
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| Blood creatine phosphokinase increased | Investigations | MedDRA 15.1 | Systematic Assessment |
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| Weight decreased | Investigations | MedDRA 15.1 | Systematic Assessment |
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| Weight 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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| Increased appetite | Metabolism and nutrition 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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| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 15.1 | Systematic Assessment |
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| Muscle tightness | Musculoskeletal and connective tissue disorders | MedDRA 15.1 | Systematic Assessment |
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| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 15.1 | Systematic Assessment |
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| Neck 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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| Disturbance in attention | 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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| Extrapyramidal disorder | 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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| Myoclonus | Nervous system disorders | MedDRA 15.1 | Systematic Assessment |
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| Sedation | 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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| Agitation | Psychiatric disorders | MedDRA 15.1 | Systematic Assessment |
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| Anxiety | Psychiatric disorders | MedDRA 15.1 | Systematic Assessment |
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| Bruxism | Psychiatric disorders | MedDRA 15.1 | Systematic Assessment |
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| Hallucination, auditory | Psychiatric disorders | MedDRA 15.1 | Systematic Assessment |
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| Insomnia | Psychiatric disorders | MedDRA 15.1 | Systematic Assessment |
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| Restlessness | Psychiatric disorders | MedDRA 15.1 | Systematic Assessment |
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| Schizophrenia | Psychiatric disorders | MedDRA 15.1 | Systematic Assessment |
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| Erectile dysfunction | Reproductive system and breast disorders | MedDRA 15.1 | Systematic Assessment |
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| Asthma | Respiratory, thoracic and mediastinal disorders | MedDRA 15.1 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 15.1 | Systematic Assessment |
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| Nasal congestion | Respiratory, thoracic and mediastinal 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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| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA 15.1 | Systematic Assessment |
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| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 15.1 | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA 15.1 | Systematic Assessment |
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| Menopause | Social circumstances | MedDRA 15.1 | Systematic Assessment |
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| Female sterilisation | Surgical and medical procedures | MedDRA 15.1 | Systematic Assessment |
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| Tooth extraction | Surgical and medical procedures | MedDRA 15.1 | Systematic Assessment |
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| Hypertension | Vascular disorders | MedDRA 15.1 | Systematic Assessment |
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The study was terminated early. 97% of participants had completed or discontinued from the DB Phase prior to termination. Outcome measure populations excluded data from a site that had significant GCP noncompliance issues (3 participants).
Not provided
| 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 |
Not provided
Not provided
| ID | Term |
|---|---|
| C534551 | LY 2140023 |
| D000068180 | Aripiprazole |
| ID | Term |
|---|---|
| D010879 | Piperazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D015363 | Quinolones |
| D011804 | Quinolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
Not provided
Not provided
| Lost to Follow-up |
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| Adverse Event |
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| Lack of Efficacy |
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| Withdrawal by Subject |
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| Scheduling conflict |
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| Subject is moving or has moved |
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| Entry Criteria Not Met |
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| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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| United States |
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| Puerto Rico |
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| Spain |
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| Belgium |
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| Poland |
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| Romania |
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| Austria |
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| Germany |
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| Sweden |
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| OG001 |
| Aripiprazole-DB |
15 mg aripiprazole administered orally, once daily for 24 weeks during the Double-Blind (DB) Phase. Dose was adjustable to 10 mg once daily or 30 mg once daily. |
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15 mg aripiprazole administered orally, once daily for 24 weeks during the Double-Blind (DB) Phase. Dose was adjustable to 10 mg once daily or 30 mg once daily.
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| Units | Counts |
|---|---|
| Participants |
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15 mg aripiprazole administered orally, once daily for 24 weeks during the Double-Blind (DB) Phase. Dose was adjustable to 10 mg once daily or 30 mg once daily.
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| Units | Counts |
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| Participants |
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| Units | Counts |
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| Participants |
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