A Phase 2 interventional study of LY2140023 and Placebo in Schizophrenia, sponsored by Denovo Biopharma LLC. Completed at 9 sites in 4 countries. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2022-09-07.
Sponsored by Denovo Biopharma LLC · Phase 2, Interventional, and Treatment
The purpose of this study is to determine whether LY2140023, when added to standard-of-care antipsychotic treatment, will improve negative symptoms.
The primary objective of this study was to test the hypothesis that treatment with LY2140023 compared to placebo, when added to a fixed dose of a standard of care (SOC) antipsychotic, would demonstrate significantly greater reduction of negative symptoms, as assessed by the 16-item Negative Symptom Assessment scale (NSA-16), in patients with schizophrenia. Patients included in this study were concurrently receiving 1 of 4 second generation antipsychotics (SGAs): aripiprazole, olanzapine, risperidone, or quetiapine.
3,539 studies on the registry are indexed under Schizophrenia; 473 are open to participants now.
This study's enrollment of 167 is above the median of 70 across 2,924 interventional studies indexed under Schizophrenia.
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40 mg/day, given orally twice daily (BID) as a 20-mg tablet. LY2140023 dosage was adjustable from 10 mg to 40 mg BID.
Drug: LY2140023 · Drug: Standard of Care
Placebo tablets to match LY2140023 tablets
Drug: Placebo · Drug: Standard of Care
40 milligrams (mg), oral tablets, twice daily: 20 mg in the morning, 20 mg in the evening, for 16 or 17 weeks. The dose may be adjusted to a minimum of 20 mg or a maximum of 80 mg.
Also known as: pomaglumetad methionil
Placebo oral tablets, twice daily: in the morning and in the evening, for 16 or 17 weeks.
United States (U.S.) label prescribed dose of one of the following Standard of Care Antipsychotics (aripiprazole, olanzapine, risperidone, quetiapine)
Change From Baseline in the 16-Item Negative Symptoms 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 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 Measure (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values are controlled for visit, pooled investigative site, treatment, standard of care (SOC) type, baseline positive symptom stratum, treatment\*visit, baseline NSA-16 total score, and baseline NSA-16 total score\*visit.
Time frame: Baseline, randomization treatment Week 16
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score
The PANSS Scale consists of 30 items and is designed to measure the severity of psychopathology in schizophrenia. 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 and has a score ranging from 30 to 210. Higher scores indicate greater severity of illness. The Mixed Model Repeated Measure (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values are controlled for visit, pooled investigative site, treatment, standard of care (SOC) type, baseline positive symptom stratum, treatment\*visit, baseline PANSS total score, and baseline PANSS total score\*visit.
Time frame: Baseline, randomization treatment Week 16
Change From Baseline in Clinical Global Impression Severity (CGI-S) Scale
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 Measure (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values are controlled for visit, pooled investigative site, treatment, standard of care (SOC) type, baseline positive symptom stratum, treatment\*visit, baseline CGI-S score, and baseline CGI-S score\*visit.
Time frame: Baseline, randomization treatment Week 16
Change From Baseline in Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB) Overall Composite T-Score
MCCB is an instrument that contains 10 tests to measure cognitive performance in 7 cognitive domains: speed processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition. The MCCB overall composite T-score combines the individual scores of the 10 tests and scores them on a normative scale to derive a T-score, where the mean is 50 and a standard deviation is 10 for the MCCB overall composite T-score. Higher scores indicate better cognition. The Mixed Model Repeated Measure (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values are controlled for visit, pooled investigative site, treatment, standard of care (SOC) type, baseline positive symptom stratum, treatment\*visit, baseline MCCB overall composite T-score, and baseline MCCB overall composite T-score\*visit.
Time frame: Baseline, randomization treatment Week 16
Change From Baseline in University of California at San Diego Performance-Based Skills Assessment-Brief Version (UPSA-B) Total Score
The UPSA-B is a performance-based assessment of improvement in functional capacity. Participants are asked to role-play tasks in 2 areas of functioning: communication and finances. Raw scores for the 2 subscales are converted into an UPSA-B Total Score (range = 0-100) with higher scores indicating a greater level of functional capacity. Scores of 75 or higher are associated with independent living. The Mixed Model Repeated Measure (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values are controlled for visit, pooled investigative site, treatment, standard of care (SOC) type, baseline positive symptom stratum, treatment\*visit, baseline UPSA-B total score, and baseline UPSA-B total score\*visit.
Time frame: Baseline, randomization treatment Week 16
Change From Baseline in Barnes-Akathisia Scale (BAS) Global Score
The BAS is a 4-item instrument that evaluates akathisia associated with use of antipsychotic medications. Item 4 is the Global Clinical Assessment and is rated 0 to 5 (0 = absent, 5 = severe). The Mixed Model Repeated Measure (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values are controlled for visit, pooled investigative site, treatment, standard of care (SOC) type, baseline positive symptom stratum, treatment\*visit, baseline BAS global score, and baseline BAS global score\*visit.
Time frame: Baseline, randomization treatment Week 16
Change From Baseline in Simpson Angus Scale (SAS) Total Score
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, with 0 meaning complete absence of the condition and 4 meaning the presence of the condition in extreme form. The 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 Measure (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values are controlled for visit, pooled investigative site, treatment, standard of care (SOC) type, baseline positive symptom stratum, treatment\*visit, baseline SAS total score, and baseline SAS total score\*visit.
Time frame: Baseline, randomization treatment Week 16
Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score
The 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, with 0 being no dyskinetic movements and 4 being severe dyskinetic movements. Items 11 and 12 are yes/no questions regarding the dental condition of a subject. The AIMS 1-7 total score is the total of items 1 through 7 of the AIMS, and ranges from 0 to 28. Higher scores indicate greater severity of illness. The Mixed Model Repeated Measure (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values are controlled for visit, pooled investigative site, treatment, standard of care (SOC) type, baseline positive symptom stratum, treatment\*visit, baseline AIMS 1-7 total score, and baseline AIMS 1-7 total score\*visit.
Time frame: Baseline, randomization treatment Week 16
Number of Participants With Incidence of Epileptiform Activity Outside of Normal Range in Electroencephalograms (EEGs)
Incidence of epileptiform activity outside of normal range in EEGs is based on the changes from normal (E0) or within normal range (E1) at baseline to questionably epileptiform (E2) or clearly epileptiform (E3) or seizure (E4) post-baseline. E0 = Normal; E1 (within normal range) = fewer than 3 focal abnormalities or non-epileptiform abnormalities; E2 (questionably epileptiform) = 3 to 10 focal discharges and/or 1 to 10 multifocal or generalized discharges; E3 (clearly epileptiform) = Sharp/slow complex, runs of epileptiform abnormalities, greater than 10 total epileptiform discharges; and E4 = seizure.
Time frame: Baseline to randomization treatment Week 16
Number of Participants With Incidence of Potentially Clinically Significant Changes in Corrected (for Rate) Cardiac QT Interval Using Fridericia's Formula (QTcF) Electrocardiograms (ECGs)
QT interval is a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle. QTcF is the QT interval corrected for heart rate using the Fridericia formula. A potentially clinically significant change in QTcF is defined as \>450 milliseconds (ms) for male and \>470 ms for female.
Time frame: Baseline to randomization treatment Week 16
Percentage of Participants With a Worsening of Neurological Symptoms From Baseline to Endpoint on the Neurological Examination
Neurological change from baseline was assessed using a 17-item neurological examination and defined as treatment-emergent tremor \[increased score on any Item 1- 5; each ranged from 0 (absent) to 3 (interferes with motor function)\], nystagmus \[increased score for Item 6 or 7; each ranged 0 (absent) to 3 (present on forward gaze)\], increased reflexes \[increased score and absolute score \>2 on any Item 8-11; each ranged 0 (absent) to 4 (clonic)\], decreased reflexes \[decreased score and absolute score \<2 on any Item 8-11; each ranged 0 (absent) to 4 (clonic)\], abnormal finger-nose test (Item 12; normal to abnormal), Romberg's sign (Item 13; absent to present), abnormal gait (Item 14; normal to abnormal), decreased muscle strength \[decreased score for Item 15 or 16; each ranged 0 (no muscle contraction) to 5 (full and normal power against resistance)\], myoclonic jerks \[increased score for Item 17; ranged from 0 (absent) to 3 (frequent and across several body regions)\].
Time frame: Baseline to randomization treatment Week 16
Change From Baseline in Standing Blood Pressure (BP)
The Mixed Model Repeated Measure (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values are controlled for visit, pooled investigative site, treatment, standard of care (SOC) type, baseline positive symptom stratum, treatment\*visit, baseline standing BP, and baseline standing BP\*visit.
Time frame: Baseline, randomization treatment Week 16
Change From Baseline in Standing Pulse Rate
The Mixed Model Repeated Measure (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values are controlled for visit, pooled investigative site, treatment, standard of care (SOC) type, baseline positive symptom stratum, treatment\*visit, baseline standing pulse rate, and baseline standing pulse rate\*visit.
Time frame: Baseline, randomization treatment Week 16
Change From Baseline in Weight
The Mixed Model Repeated Measure (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values are controlled for visit, pooled investigative site, treatment, standard of care (SOC) type, baseline positive symptom stratum, treatment\*visit, baseline weight, and baseline weight\*visit.
Time frame: Baseline, randomization treatment Week 16
Number of Participants With Incidence of Potentially Clinically Significant (PCS) Change in Laboratory Values Any Time Post-Baseline - General
PCS change in laboratory values were defined as a laboratory value which reached a predefined alert level at any time post-baseline. PCS change in liver function: alanine transaminase (ALT) or aspartate aminotransferase (AST) ≥2\* the upper limit of normal (ULN) or total bilirubin ≥1.5\*ULN any time post-baseline regardless of the baseline value. Hy's rule: ALT ≥3\*ULN, total bilirubin ≥1.5\*ULN and alkaline phosphatase \<2\*ULN at the same time any time post-baseline regardless of the baseline value. PCS change in eosinophil counts: \>1.5\*10³ cells/microliter any time post-baseline regardless of the baseline value. PCS change in blood creatine phosphokinase: ≥5\*ULN any time post-baseline regardless of the baseline value.
Time frame: Baseline to randomization treatment Week 16
Number of Participants With Incidence of Potentially Clinically Significant (PCS) Change in Laboratory Values Any Time Post-Baseline - Fasting Cholesterol
PCS change in laboratory values were defined as a laboratory value which reached a predefined alert level at any time post-baseline. PCS change in total cholesterol: Normal (N) to High (H) \<200 milligrams/deciliter (mg/dL) at baseline and ≥240 mg/dL post-baseline; Borderline (B) to H ≥200 mg/dL and \<240 mg/dL at baseline and ≥240 mg/dL post-baseline; N/B to H \<240 mg/dL at baseline and ≥240 mg/dL post-baseline; N to B/H \<200 mg/dL at baseline, ≥200 mg/dL post-baseline. PCS change in low-density lipoprotein (LDL) cholesterol: N to H \<100 mg/dL at baseline and ≥160 mg/dL post-baseline; B to H ≥100 mg/dL and \<160 mg/dL at baseline and ≥160 mg/dL post-baseline; N/B to H \<160 mg/dL at baseline and ≥160 mg/dL post-baseline; N to B/H \<100 mg/dL at baseline, ≥100 mg/dL post-baseline. PCS change in high-density lipoprotein (HDL) cholesterol: ≥40 mg/dL at baseline and \<40 mg/dL post-baseline.
Time frame: Baseline to randomization treatment Week 16
Number of Participants With Incidence of Potentially Clinically Significant (PCS) Change in Laboratory Values Any Time Post-Baseline - Fasting Triglycerides
PCS change in laboratory values were defined as a laboratory value which reached a predefined alert level at any time post-baseline. PCS change for Normal (N) to High (H) \<150 milligrams/deciliter (mg/dL) at baseline and ≥200 mg/dL post-baseline; N/Borderline (B) to H \<200 mg/dL at baseline and ≥200 mg/dL post-baseline; N to very H \<150 mg/dL at baseline and ≥500 mg/dL post-baseline; B to H \>150 and \<200 mg/dL at baseline and ≥200 mg/dL post-baseline; B to very H \>150 and \<200 mg/dL at baseline and ≥500 mg/dL post-baseline; N/B to very H \<200 mg/dL at baseline and ≥500 mg/dL post-baseline; N to B/H/very H \<150 mg/dL at baseline and ≥150 mg/dL post-baseline.
Time frame: Baseline to randomization treatment Week 16
Number of Participants With Incidence of Potentially Clinically Significant (PCS) Change in Laboratory Values Any Time Post-Baseline - Fasting Glucose
PCS change in laboratory values were defined as a laboratory value which reached a predefined alert level at any time post-baseline. PCS change for Normal to High: \<100 milligrams/deciliter (mg/dL) at baseline and ≥126 mg/dL post-baseline; Impaired to High ≥100 mg/dL and \<126 mg/dL at baseline and ≥126 mg/dL any time post-baseline; Normal/Impaired to High \<126 mg/dL at baseline and ≥126 mg/dL any time post-baseline.
Time frame: Baseline to randomization treatment Week 16
Percentage of Participants With Incidence of Potentially Clinically Significant Change of 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. Percentage of participants with incidence of potentially clinically significant change of the C-SSRS was calculated as the number of participants with an increase in suicidal behavior or ideation over baseline, divided by the total number of participants multiplied by 100.
Time frame: Baseline to randomization treatment Week 16
Change From Baseline to Endpoint in Personal and Social Performance (PSP) Scale
The PSP scale is a 100-point, 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. The higher scores indicate a higher level of functioning. The Mixed Model Repeated Measure (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values are controlled for visit, pooled investigative site, treatment, standard of care (SOC) type, baseline positive symptom stratum, treatment\*visit, baseline PSP score, and baseline PSP score\*visit.
Time frame: Baseline, randomization treatment Week 16
Time to Discontinuation From the Study Due to Any Reason
The time to discontinuation due to any reason was defined as the total number of days between the date of first dose and discontinuation date. The time to discontinuation was analyzed using Kaplan-Meier estimated survival curves. Participants who completed the study were considered censored. Less than 50% of participants discontinued from study at randomization treatment Week 16 endpoint, therefore median values were not calculated.
Time frame: First dose to randomization treatment Week 16
Schizophrenia Resource Use 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).
Time frame: Baseline to randomization treatment Week 16
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.
Time frame: Baseline to randomization treatment Week 16
Change From Baseline to Endpoint in the EuroQol Questionnaire-5 Dimension (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 Measure (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values are controlled for visit, pooled investigative site, treatment, standard of care (SOC) type, baseline positive symptom stratum, treatment\*visit, baseline VAS health state score, and baseline VAS health state score\*visit.
Time frame: Baseline, randomization treatment Week 16
Change From Baseline to Endpoint in the Subjective Well-Being Under Neuroleptic Treatment-Short Form (SWN-SF) Total Score
The SWN-SF measures subjective well-being 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 Measure (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values are controlled for visit, pooled investigative site, treatment, standard of care (SOC) type, baseline positive symptom stratum, treatment\*visit, baseline SWN-SF total score, and baseline SWN-SF total score\*visit.
Time frame: Baseline, randomization treatment Week 16
| Milestone | LY2140023 + SOC | Placebo + SOC |
|---|---|---|
| Started | 84 | 83 |
| Received at least 1 dose of study drug | 82 | 82 |
| Completed | 50 | 60 |
| Not completed | 34 | 23 |
| Withdrew: Adverse event | 10 | 6 |
| Withdrew: Entry criteria not met | 3 | 1 |
| Withdrew: Lost to follow-up | 3 | 5 |
| Withdrew: Protocol violation | 10 | 4 |
| Withdrew: Scheduling conflict | 2 | 1 |
| Withdrew: Sponsor decision | 2 | 0 |
| Withdrew: Withdrawal by subject | 3 | 6 |
| Withdrew: Perceived lack of efficacy | 1 | 0 |
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 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 Measure (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values are controlled for visit, pooled investigative site, treatment, standard of care (SOC) type, baseline positive symptom stratum, treatment\*visit, baseline NSA-16 total score, and baseline NSA-16 total score\*visit.
| units on a scale | LY2140023 + SOC | Placebo + SOC |
|---|---|---|
| Change From Baseline in the 16-Item Negative Symptoms Assessment (NSA-16) | -2.7 ± 1.2 | -3.6 ± 1.2 |
The PANSS Scale consists of 30 items and is designed to measure the severity of psychopathology in schizophrenia. 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 and has a score ranging from 30 to 210. Higher scores indicate greater severity of illness. The Mixed Model Repeated Measure (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values are controlled for visit, pooled investigative site, treatment, standard of care (SOC) type, baseline positive symptom stratum, treatment\*visit, baseline PANSS total score, and baseline PANSS total score\*visit.
| units on a scale | LY2140023 + SOC | Placebo + SOC |
|---|---|---|
| Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score | -4.4 ± 1.62 | -6.6 ± 1.55 |
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 Measure (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values are controlled for visit, pooled investigative site, treatment, standard of care (SOC) type, baseline positive symptom stratum, treatment\*visit, baseline CGI-S score, and baseline CGI-S score\*visit.
| units on a scale | LY2140023 + SOC | Placebo + SOC |
|---|---|---|
| Change From Baseline in Clinical Global Impression Severity (CGI-S) Scale | -0.4 ± 0.1 | -0.3 ± 0.1 |
MCCB is an instrument that contains 10 tests to measure cognitive performance in 7 cognitive domains: speed processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition. The MCCB overall composite T-score combines the individual scores of the 10 tests and scores them on a normative scale to derive a T-score, where the mean is 50 and a standard deviation is 10 for the MCCB overall composite T-score. Higher scores indicate better cognition. The Mixed Model Repeated Measure (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values are controlled for visit, pooled investigative site, treatment, standard of care (SOC) type, baseline positive symptom stratum, treatment\*visit, baseline MCCB overall composite T-score, and baseline MCCB overall composite T-score\*visit.
| T-scores | LY2140023 + SOC | Placebo + SOC |
|---|---|---|
| Change From Baseline in Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB) Overall Composite T-Score | 3.2 ± 1.0 | 1.8 ± 1.0 |
The UPSA-B is a performance-based assessment of improvement in functional capacity. Participants are asked to role-play tasks in 2 areas of functioning: communication and finances. Raw scores for the 2 subscales are converted into an UPSA-B Total Score (range = 0-100) with higher scores indicating a greater level of functional capacity. Scores of 75 or higher are associated with independent living. The Mixed Model Repeated Measure (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values are controlled for visit, pooled investigative site, treatment, standard of care (SOC) type, baseline positive symptom stratum, treatment\*visit, baseline UPSA-B total score, and baseline UPSA-B total score\*visit.
| units on a scale | LY2140023 + SOC | Placebo + SOC |
|---|---|---|
| Change From Baseline in University of California at San Diego Performance-Based Skills Assessment-Brief Version (UPSA-B) Total Score | 6.5 ± 1.9 | 4.9 ± 1.8 |
The BAS is a 4-item instrument that evaluates akathisia associated with use of antipsychotic medications. Item 4 is the Global Clinical Assessment and is rated 0 to 5 (0 = absent, 5 = severe). The Mixed Model Repeated Measure (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values are controlled for visit, pooled investigative site, treatment, standard of care (SOC) type, baseline positive symptom stratum, treatment\*visit, baseline BAS global score, and baseline BAS global score\*visit.
| units on a scale | LY2140023 + SOC | Placebo + SOC |
|---|---|---|
| Change From Baseline in Barnes-Akathisia Scale (BAS) Global Score | -0.1 ± 0.0 | 0.0 ± 0.0 |
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, with 0 meaning complete absence of the condition and 4 meaning the presence of the condition in extreme form. The 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 Measure (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values are controlled for visit, pooled investigative site, treatment, standard of care (SOC) type, baseline positive symptom stratum, treatment\*visit, baseline SAS total score, and baseline SAS total score\*visit.
| units on a scale | LY2140023 + SOC | Placebo + SOC |
|---|---|---|
| Change From Baseline in Simpson Angus Scale (SAS) Total Score | -0.2 ± 0.2 | -0.1 ± 0.1 |
The 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, with 0 being no dyskinetic movements and 4 being severe dyskinetic movements. Items 11 and 12 are yes/no questions regarding the dental condition of a subject. The AIMS 1-7 total score is the total of items 1 through 7 of the AIMS, and ranges from 0 to 28. Higher scores indicate greater severity of illness. The Mixed Model Repeated Measure (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values are controlled for visit, pooled investigative site, treatment, standard of care (SOC) type, baseline positive symptom stratum, treatment\*visit, baseline AIMS 1-7 total score, and baseline AIMS 1-7 total score\*visit.
| units on a scale | LY2140023 + SOC | Placebo + SOC |
|---|---|---|
| Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score | 0.0 ± 0.2 | 0.1 ± 0.2 |
Incidence of epileptiform activity outside of normal range in EEGs is based on the changes from normal (E0) or within normal range (E1) at baseline to questionably epileptiform (E2) or clearly epileptiform (E3) or seizure (E4) post-baseline. E0 = Normal; E1 (within normal range) = fewer than 3 focal abnormalities or non-epileptiform abnormalities; E2 (questionably epileptiform) = 3 to 10 focal discharges and/or 1 to 10 multifocal or generalized discharges; E3 (clearly epileptiform) = Sharp/slow complex, runs of epileptiform abnormalities, greater than 10 total epileptiform discharges; and E4 = seizure.
| participants | LY2140023 + SOC | Placebo + SOC |
|---|---|---|
| Number of Participants With Incidence of Epileptiform Activity Outside of Normal Range in Electroencephalograms (EEGs) | 1 | 0 |
QT interval is a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle. QTcF is the QT interval corrected for heart rate using the Fridericia formula. A potentially clinically significant change in QTcF is defined as \>450 milliseconds (ms) for male and \>470 ms for female.
| participants | LY2140023 + SOC | Placebo + SOC |
|---|---|---|
| Number of Participants With Incidence of Potentially Clinically Significant Changes in Corrected (for Rate) Cardiac QT Interval Using Fridericia's Formula (QTcF) Electrocardiograms (ECGs) | 3 | 1 |
Neurological change from baseline was assessed using a 17-item neurological examination and defined as treatment-emergent tremor \[increased score on any Item 1- 5; each ranged from 0 (absent) to 3 (interferes with motor function)\], nystagmus \[increased score for Item 6 or 7; each ranged 0 (absent) to 3 (present on forward gaze)\], increased reflexes \[increased score and absolute score \>2 on any Item 8-11; each ranged 0 (absent) to 4 (clonic)\], decreased reflexes \[decreased score and absolute score \<2 on any Item 8-11; each ranged 0 (absent) to 4 (clonic)\], abnormal finger-nose test (Item 12; normal to abnormal), Romberg's sign (Item 13; absent to present), abnormal gait (Item 14; normal to abnormal), decreased muscle strength \[decreased score for Item 15 or 16; each ranged 0 (no muscle contraction) to 5 (full and normal power against resistance)\], myoclonic jerks \[increased score for Item 17; ranged from 0 (absent) to 3 (frequent and across several body regions)\].
| percentage of participants | LY2140023 + SOC | Placebo + SOC |
|---|---|---|
| Tremor | 11.0 | 12.2 |
| Nystagmus | 2.4 | 2.4 |
| Increased Reflexes | 3.7 | 4.9 |
| Decreased Reflexes | 7.3 | 8.5 |
| Abnormal Finger-Nose Test | 1.2 | 3.7 |
| Romberg's Sign | 1.2 | 0.0 |
| Abnormal Gait | 2.4 | 2.4 |
| Decreased Muscle Strength | 3.7 | 4.9 |
| Myoclonus Jerks | 4.9 | 2.4 |
The Mixed Model Repeated Measure (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values are controlled for visit, pooled investigative site, treatment, standard of care (SOC) type, baseline positive symptom stratum, treatment\*visit, baseline standing BP, and baseline standing BP\*visit.
| millimeters of mercury (mmHg) | LY2140023 + SOC | Placebo + SOC |
|---|---|---|
| Standing Systolic BP | -2.0 ± 1.6 | -2.0 ± 1.6 |
| Standing Diastolic BP | 1.4 ± 1.1 | -2.4 ± 1.1 |
The Mixed Model Repeated Measure (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values are controlled for visit, pooled investigative site, treatment, standard of care (SOC) type, baseline positive symptom stratum, treatment\*visit, baseline standing pulse rate, and baseline standing pulse rate\*visit.
| beats per minute (bpm) | LY2140023 + SOC | Placebo + SOC |
|---|---|---|
| Change From Baseline in Standing Pulse Rate | -2.3 ± 1.7 | -1.8 ± 1.6 |
The Mixed Model Repeated Measure (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values are controlled for visit, pooled investigative site, treatment, standard of care (SOC) type, baseline positive symptom stratum, treatment\*visit, baseline weight, and baseline weight\*visit.
| kilograms (kg) | LY2140023 + SOC | Placebo + SOC |
|---|---|---|
| Change From Baseline in Weight | -1.25 ± 0.56 | -0.81 ± 0.55 |
PCS change in laboratory values were defined as a laboratory value which reached a predefined alert level at any time post-baseline. PCS change in liver function: alanine transaminase (ALT) or aspartate aminotransferase (AST) ≥2\* the upper limit of normal (ULN) or total bilirubin ≥1.5\*ULN any time post-baseline regardless of the baseline value. Hy's rule: ALT ≥3\*ULN, total bilirubin ≥1.5\*ULN and alkaline phosphatase \<2\*ULN at the same time any time post-baseline regardless of the baseline value. PCS change in eosinophil counts: \>1.5\*10³ cells/microliter any time post-baseline regardless of the baseline value. PCS change in blood creatine phosphokinase: ≥5\*ULN any time post-baseline regardless of the baseline value.
| participants | LY2140023 + SOC | Placebo + SOC |
|---|---|---|
| ALT | 4 | 5 |
| AST | 1 | 3 |
| Total bilirubin | 2 | 0 |
| Hy's rule | 0 | 0 |
| Eosinophil counts | 0 | 0 |
| Blood creatine phosphokinase | 7 | 7 |
PCS change in laboratory values were defined as a laboratory value which reached a predefined alert level at any time post-baseline. PCS change in total cholesterol: Normal (N) to High (H) \<200 milligrams/deciliter (mg/dL) at baseline and ≥240 mg/dL post-baseline; Borderline (B) to H ≥200 mg/dL and \<240 mg/dL at baseline and ≥240 mg/dL post-baseline; N/B to H \<240 mg/dL at baseline and ≥240 mg/dL post-baseline; N to B/H \<200 mg/dL at baseline, ≥200 mg/dL post-baseline. PCS change in low-density lipoprotein (LDL) cholesterol: N to H \<100 mg/dL at baseline and ≥160 mg/dL post-baseline; B to H ≥100 mg/dL and \<160 mg/dL at baseline and ≥160 mg/dL post-baseline; N/B to H \<160 mg/dL at baseline and ≥160 mg/dL post-baseline; N to B/H \<100 mg/dL at baseline, ≥100 mg/dL post-baseline. PCS change in high-density lipoprotein (HDL) cholesterol: ≥40 mg/dL at baseline and \<40 mg/dL post-baseline.
| participants | LY2140023 + SOC | Placebo + SOC |
|---|---|---|
| Total Cholesterol N to H | 1 | 0 |
| Total Cholesterol B to H | 8 | 7 |
| Total Cholesterol N/B to H | 9 | 7 |
| Total Cholesterol N to B/H | 9 | 9 |
| LDL Cholesterol N to H | 0 | 0 |
| LDL Cholesterol B to H | 13 | 13 |
| LDL Cholesterol N/B to H | 13 | 13 |
| LDL Cholesterol N to B/H | 9 | 2 |
| HDL Cholesterol N to Low | 24 | 24 |
PCS change in laboratory values were defined as a laboratory value which reached a predefined alert level at any time post-baseline. PCS change for Normal (N) to High (H) \<150 milligrams/deciliter (mg/dL) at baseline and ≥200 mg/dL post-baseline; N/Borderline (B) to H \<200 mg/dL at baseline and ≥200 mg/dL post-baseline; N to very H \<150 mg/dL at baseline and ≥500 mg/dL post-baseline; B to H \>150 and \<200 mg/dL at baseline and ≥200 mg/dL post-baseline; B to very H \>150 and \<200 mg/dL at baseline and ≥500 mg/dL post-baseline; N/B to very H \<200 mg/dL at baseline and ≥500 mg/dL post-baseline; N to B/H/very H \<150 mg/dL at baseline and ≥150 mg/dL post-baseline.
| participants | LY2140023 + SOC | Placebo + SOC |
|---|---|---|
| N to H | 10 | 7 |
| N/B to H | 20 | 13 |
| N to very H | 0 | 0 |
| B to H | 10 | 6 |
| B to very H | 0 | 0 |
| N/B to very H | 0 | 0 |
| N to B/H/very H | 18 | 17 |
PCS change in laboratory values were defined as a laboratory value which reached a predefined alert level at any time post-baseline. PCS change for Normal to High: \<100 milligrams/deciliter (mg/dL) at baseline and ≥126 mg/dL post-baseline; Impaired to High ≥100 mg/dL and \<126 mg/dL at baseline and ≥126 mg/dL any time post-baseline; Normal/Impaired to High \<126 mg/dL at baseline and ≥126 mg/dL any time post-baseline.
| participants | LY2140023 + SOC | Placebo + SOC |
|---|---|---|
| Normal to High | 2 | 8 |
| Impaired to High | 10 | 5 |
| Normal/Impaired to High | 12 | 13 |
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. Percentage of participants with incidence of potentially clinically significant change of the C-SSRS was calculated as the number of participants with an increase in suicidal behavior or ideation over baseline, divided by the total number of participants multiplied by 100.
| percentage of participants | LY2140023 + SOC | Placebo + SOC |
|---|---|---|
| Treatment-Emergent Suicidal Ideation | 2.4 | 4.9 |
| Treatment-Emergent Suicidal Behavior | 0.0 | 1.2 |
The PSP scale is a 100-point, 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. The higher scores indicate a higher level of functioning. The Mixed Model Repeated Measure (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values are controlled for visit, pooled investigative site, treatment, standard of care (SOC) type, baseline positive symptom stratum, treatment\*visit, baseline PSP score, and baseline PSP score\*visit.
| units on a scale | LY2140023 + SOC | Placebo + SOC |
|---|---|---|
| Change From Baseline to Endpoint in Personal and Social Performance (PSP) Scale | 8.9 ± 1.3 | 7.9 ± 1.3 |
The time to discontinuation due to any reason was defined as the total number of days between the date of first dose and discontinuation date. The time to discontinuation was analyzed using Kaplan-Meier estimated survival curves. Participants who completed the study were considered censored. Less than 50% of participants discontinued from study at randomization treatment Week 16 endpoint, therefore median values were not calculated.
| months | LY2140023 + SOC | Placebo + SOC |
|---|---|---|
| Time to Discontinuation From the Study Due to Any Reason | NA (NA to NA) | NA (NA to NA) |
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).
| visits | LY2140023 + SOC | Placebo + SOC |
|---|---|---|
| ER/Facility (Psych) visits | 0.6 ± 4.11 | 0.2 ± 1.79 |
| ER/Facility (Non-Psych) visits | 0.2 ± 0.43 | 0.1 ± 0.56 |
| Outpatient (Non-Psych or Dentist) visits | 0.7 ± 1.33 | 1.2 ± 2.99 |
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.
| sessions | LY2140023 + SOC | Placebo + SOC |
|---|---|---|
| Schizophrenia Resource Use Module (S-RUM) - Number of Sessions With a Psychiatrist | 3.4 ± 17.49 | 1.5 ± 2.76 |
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 Measure (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values are controlled for visit, pooled investigative site, treatment, standard of care (SOC) type, baseline positive symptom stratum, treatment\*visit, baseline VAS health state score, and baseline VAS health state score\*visit.
| units on a scale | LY2140023 + SOC | Placebo + SOC |
|---|---|---|
| Change From Baseline to Endpoint in the EuroQol Questionnaire-5 Dimension (EQ-5D) Visual Analog Scale (VAS) Health State Score | 3.7 ± 2.6 | 5.4 ± 2.4 |
The SWN-SF measures subjective well-being 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 Measure (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values are controlled for visit, pooled investigative site, treatment, standard of care (SOC) type, baseline positive symptom stratum, treatment\*visit, baseline SWN-SF total score, and baseline SWN-SF total score\*visit.
| units on a scale | LY2140023 + SOC | Placebo + SOC |
|---|---|---|
| Change From Baseline to Endpoint in the Subjective Well-Being Under Neuroleptic Treatment-Short Form (SWN-SF) Total Score | 3.9 ± 2.0 | 4.4 ± 1.9 |
Non-serious events are listed at a 3% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| LY2140023 + SOC | — | 8/82 (9.8%) | 54/82 (65.9%) |
| Placebo + SOC | — | 4/82 (4.9%) | 51/82 (62.2%) |
| Event | LY2140023 + SOC | Placebo + SOC |
|---|---|---|
| Psychotic disorderPsychiatric disorders | 3/82 | 1/82 |
| SchizophreniaPsychiatric disorders | 3/82 | 1/82 |
| CholangitisHepatobiliary disorders | 1/82 | 0/82 |
| CellulitisInfections and infestations | 1/82 | 0/82 |
| Ischaemic strokeNervous system disorders | 0/82 | 1/82 |
| Suicidal ideationPsychiatric disorders | 0/82 | 1/82 |
| AsthmaRespiratory, thoracic and mediastinal disorders | 0/82 | 1/82 |
| Event | LY2140023 + SOC | Placebo + SOC |
|---|---|---|
| NauseaGastrointestinal disorders | 11/82 | 4/82 |
| HeadacheNervous system disorders | 11/82 | 11/82 |
| VomitingGastrointestinal disorders | 10/82 | 2/82 |
| Dry mouthGastrointestinal disorders | 2/82 | 9/82 |
| Blood creatine phosphokinase increasedInvestigations | 6/82 | 7/82 |
| DiarrhoeaGastrointestinal disorders | 5/82 | 2/82 |
| ArthralgiaMusculoskeletal and connective tissue disorders | 2/82 | 5/82 |
| Vulvovaginal mycotic infectionInfections and infestations | 1/19 | 0/18 |
| FatigueGeneral disorders | 1/82 | 4/82 |
| NasopharyngitisInfections and infestations | 3/82 | 4/82 |
All randomized participants who received at least one dose of study drug.
| Age, Continuous(years) | LY2140023 + SOC | Placebo + SOC | Total |
|---|---|---|---|
| Mean | 43.7 ± 11.22 | 42.8 ± 10.23 | 43.3 ± 10.71 |
| Sex: Female, Male(Participants) | LY2140023 + SOC | Placebo + SOC | Total |
|---|---|---|---|
| Female | 19 | 18 | 37 |
| Male | 63 | 64 | 127 |
| Race/Ethnicity, Customized(participants) | LY2140023 + SOC | Placebo + SOC | Total |
|---|---|---|---|
| Asian | 0 | 1 | 1 |
| Black or African American | 41 | 43 | 84 |
| Multiple | 0 | 2 | 2 |
| White | 41 | 35 | 76 |
| Missing | 0 | 1 | 1 |
| Region of Enrollment(participants) | LY2140023 + SOC | Placebo + SOC | Total |
|---|---|---|---|
| United States | 58 | 61 | 119 |
| Spain | 9 | 7 | 16 |
| Israel | 11 | 9 | 20 |
| Italy | 2 | 2 | 4 |
| Puerto Rico | 2 | 3 | 5 |
The record gives a start of Jan 2010, a primary completion of Jun 2012 and a completion of Jun 2012. It does not say whether these dates are actual or estimated.
Results were first posted in Sep 2021, 9 years 3 months after primary completion. A results delay was requested in Sep 2012.
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This study is completed, as verified in Aug 2022. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: LY 2140023