Schizophrenia
Conditions
Keywords
schizophrenia, LY2140023, pomaglumetad methionil
Brief summary
The purpose of this study is to determine whether or not people with schizophrenia who take LY2140023 become physically dependent on it, and experience a series of symptoms such as craving to have the drug when they stop using it. This trial consists of two phases: An open-label phase consisting of up to 4 weeks and a double-blind phase consisting of up to 3 weeks.
Detailed description
This was a short-term, multicenter, placebo-controlled, randomized withdrawal study comparing LY2140023 with placebo in the treatment of outpatients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR \[APA 2000\]) schizophrenia. Patients were male or female outpatients, 18 to 65 years of age (inclusive) at study entry, with a diagnosis of schizophrenia as defined in the DSM-IV-TR The primary objective of this study was to assess whether LY2140023, when administered in an acute-treatment trial with flexible doses (40 mg or 80 mg) BID, was associated with physical dependence, as measured by the occurrence of withdrawal symptoms during a randomized withdrawal phase in patients diagnosed with schizophrenia. Assessment was to be based on a comparison of randomized LY2140023-treated patients with those on placebo, as measured by the maximum of the 3-day moving average of the patient's total score on the Discontinuation Symptom Checklist-Modified Rickels (DSCMR).
Interventions
DRUGLY2140023
Administered orally
DRUGPlacebo
Administered orally
Sponsors
Denovo Biopharma LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Clinical diagnosis of schizophrenia * Female participants of childbearing potential must test negative for pregnancy at study entry and agree to use a single, effective, medically acceptable method of birth control * Participants must require a modification of antipsychotic medication or the initiation of antipsychotic medication, as indicated by their present clinical psychiatric status and/or treatment tolerability as outpatients * Participants must be considered reliable and have a level of understanding sufficient to perform all tests and examinations required, and be willing to perform all study procedures * Participants must be able to understand the nature of the study and have given their own informed consent
Exclusion criteria
* Have a Clinical Global Impression-Severity Scale (CGI-S) score \>4 at study entry * Have any other psychiatric diagnoses in addition to schizophrenia * Participants who have a history of inadequate clinical response to antipsychotic treatment for schizophrenia * Participants who have received an adequate treatment trial, in the opinion of the investigator, with clozapine at doses \>200 mg daily within 12 months prior to study entry, or who have received any clozapine at all during the month before study entry * Participants who are actively suicidal * Female participants who are pregnant, nursing, or who intend to become pregnant within 30 days of completing the study * Have known, uncorrected, narrow-angle glaucoma * Participants who have had electroconvulsive therapy (ECT) within 3 months of study entry or who will have ECT at any time during the study * Participants with known medical history of human immunodeficiency virus positive (HIV+) status * Participants who test positive for Hepatitis C virus antibody or Hepatitis B surface antigen (HBsAg) with or without positive Hepatitis B core total antibody * Participants with current or a history of seizure disorder, uncontrolled diabetes, certain diseases of the liver, renal insufficiency, uncontrolled thyroid condition or other serious or unstable illnesses * Participants with a corrected QT interval (Bazett's; QTcB) \>450 milliseconds (msec) (male) or \>470 msec (female) at study entry (based on the central vendor's electrocardiogram \[ECG\] overread) * Have previously completed or withdrawn from this study, or any other study investigating LY2140023 or any predecessor molecules with glutamatergic activity * Are currently enrolled in, or discontinued within the last 60 days from, a clinical trial involving an investigational product for unapproved use of a drug or device, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum 3-Day Moving Average (MA) of the Discontinuation Symptom Checklist-Modified Rickels Total Score | Randomization up to Week 2 of randomization treatment | The checklist is a 30-item, participant-rated scale that asks whether participants experience symptoms such as nausea, vomiting, loss of appetite, anxiety, irritability, or craving for study drug during the previous day to assess potential symptoms of drug withdrawal. Each item is rated on a 0 (not at all) to 3 (severe). Total scores range from 0-90. Higher scores indicate greater severity of symptoms. The 3-day MA was calculated starting the third day until the last day of double-blind, randomized period. The 3-day MA was the average of scores from that day and previous 2 days. If scores from any of the days during the 3-day was missing, the average was based on the non-missing days. If there was no total scores for any day of the 3-day, the average was considered to be missing. An analysis of covariance (ANCOVA) was used to calculate Least Squares (LS) mean and standard error. LS mean values are controlled for baseline total score, treatment, pooled investigative site and gender. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Randomization to Week 2 in Barnes Akathisia Scale (BAS) Global Score | Randomization, randomization treatment Week 2 | The BAS is a 4-item instrument that evaluates akathisia associated with use of antipsychotic medications. Item 4 is the Global Clinical Assessment (Global Score) 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 baseline BAS global score, treatment, gender, pooled investigative site, visit, baseline BAS global score\*visit and treatment\*visit. |
| Change From Randomization to Week 2 in Simpson-Angus Scale (SAS) Total Score | Randomization, randomization treatment Week 2 | 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 baseline SAS total score, treatment, gender, pooled investigative site, visit, baseline SAS total score\*visit and treatment\*visit. |
| Change From Randomization to Week 2 in Abnormal Involuntary Movement Scale (AIMS) Total Score | Randomization, randomization treatment Week 2 | 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 baseline AIMS 1-7 total score, treatment, gender, pooled investigative site, visit, baseline AIMS 1-7 total score\*visit and treatment\*visit. |
| Change From Randomization up to Week 2 in the Clinical Institute Withdrawal Assessment of Alcohol Scale (CIWA-Ar) Total Score | Randomization, randomization treatment Weeks 0.5 and 1 and 1.5 and 2 | The CIWA-Ar is a 10-item scale that was used to monitor for symptoms of drug withdrawal. The scale includes the following domains/criteria: nausea, vomiting; anxiety; paroxysmal sweats; tactile disturbances; visual disturbances; tremors; agitation; orientation and clouding of sensorium; auditory disturbances; and headache. Items 1-9 have possible scores of 0 (no symptom)-7 (severe symptom), and item 10 has possible scores of 0 (no symptom)-4 (severe symptom). Total scores range from 0-67. Higher scores indicate greater severity of symptom. The Mixed Model Repeated Measure (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values are controlled for baseline CIWA-Ar total score, treatment, gender, pooled investigative site, visit, baseline CIWA-Ar total score\*visit and treatment\*visit. |
| Percentage of Participants With Suicidal Behaviors and Ideations Measured Using the Columbia Suicide Severity Rating Scale (C-SSRS) During Double-Blind Randomized Treatment Period | Randomization up to Week 2 of randomization treatment | 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. The percentage of participants with treatment-emergent suicidal ideation or behavior during double-blind randomized treatment period (with a change from baseline in C-SSRS) was calculated as the number of participants with an increase in suicidal behavior or ideation over baseline (randomization), divided by the total number of participants multiplied by 100. |
| Change From Randomization to Week 2 in Clinical Global Impression-Severity Scale (CGI-S) | Randomization, randomization treatment Week 2 | 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 baseline CGI-S score, treatment, gender, pooled investigative site, visit, baseline CGI-S score\*visit and treatment\*visit. |
| Change From Randomization to Week 2 in Brief Psychiatric Rating Scale (BPRS) Total Scores | Randomization, randomization treatment Week 2 | BPRS is an 18-item clinician-administered scale used to assess the degree of severity of a participant's general psychopathological symptoms. Item scores range from 1 (not present) to 7 (extremely severe). Total Scores range from 18 to 126. 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 baseline BPRS total score, treatment, gender, pooled investigative site, visit, baseline BPRS total score\*visit and treatment\*visit. |
| Percentage of Participants With Suicidal Behaviors and Ideations Measured Using the Columbia Suicide Severity Rating Scale (C-SSRS) During Open-Label Treatment Period | Baseline up to Week 4 of open-label treatment | 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. The percentage of participants with treatment-emergent suicidal ideation or behavior during open-label treatment period (with a change from baseline in C-SSRS) was calculated as the number of participants with an increase in suicidal behavior or ideation over baseline (before open-label treatment), divided by the total number of participants multiplied by 100. |
Countries
Greece, United States
Participant flow
Pre-assignment details
This study consisted of a 4-week open-label treatment period and a 2-week double-blind randomized withdrawal treatment period.
Participants by arm
| Arm | Count |
|---|---|
| All Participants 40 milligram (mg) or 80 mg LY2140023 administered orally, twice daily for 4 weeks during open-label treatment period.
Placebo, or 40 mg or 80 mg LY2140023 administered orally, twice daily for 2 weeks during double-blind, randomized withdrawal treatment period. | 123 |
| Total | 123 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Open-Label Treatment | Adverse Event | 5 | 0 | 0 |
| Open-Label Treatment | Lost to Follow-up | 4 | 0 | 0 |
| Open-Label Treatment | Perceived lack of efficacy | 3 | 0 | 0 |
| Open-Label Treatment | Protocol Violation | 4 | 0 | 0 |
| Open-Label Treatment | Sponsor Decision | 1 | 0 | 0 |
| Open-Label Treatment | Subject is moving or has moved | 1 | 0 | 0 |
| Open-Label Treatment | Withdrawal by Subject | 2 | 0 | 0 |
| Randomization Treatment | Adverse Event | 0 | 0 | 2 |
| Randomization Treatment | Sponsor Decision | 0 | 1 | 0 |
| Randomization Treatment | Subject is moving or has moved | 0 | 1 | 0 |
| Randomization Treatment | Withdrawal by Subject | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 42.86 years STANDARD_DEVIATION 11.45 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 118 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 82 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 35 Participants |
| Region of Enrollment Greece | 16 participants |
| Region of Enrollment United States | 107 participants |
| Sex: Female, Male Female | 30 Participants |
| Sex: Female, Male Male | 93 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 83 / 123 | 13 / 50 | 20 / 53 |
| serious Total, serious adverse events | 0 / 123 | 0 / 50 | 0 / 53 |
Outcome results
Primary
Maximum 3-Day Moving Average (MA) of the Discontinuation Symptom Checklist-Modified Rickels Total Score
The checklist is a 30-item, participant-rated scale that asks whether participants experience symptoms such as nausea, vomiting, loss of appetite, anxiety, irritability, or craving for study drug during the previous day to assess potential symptoms of drug withdrawal. Each item is rated on a 0 (not at all) to 3 (severe). Total scores range from 0-90. Higher scores indicate greater severity of symptoms. The 3-day MA was calculated starting the third day until the last day of double-blind, randomized period. The 3-day MA was the average of scores from that day and previous 2 days. If scores from any of the days during the 3-day was missing, the average was based on the non-missing days. If there was no total scores for any day of the 3-day, the average was considered to be missing. An analysis of covariance (ANCOVA) was used to calculate Least Squares (LS) mean and standard error. LS mean values are controlled for baseline total score, treatment, pooled investigative site and gender.
Time frame: Randomization up to Week 2 of randomization treatment
Population: All randomized participants who received at least one dose of study drug and had Discontinuation Symptom Checklist-Modified Rickels total score measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Randomization) | Maximum 3-Day Moving Average (MA) of the Discontinuation Symptom Checklist-Modified Rickels Total Score | 13.23 units on a scale | Standard Error 0.96 |
| LY2140023 (Randomization) | Maximum 3-Day Moving Average (MA) of the Discontinuation Symptom Checklist-Modified Rickels Total Score | 11.50 units on a scale | Standard Error 0.99 |
p-value: 0.17Type 3 sums of squares
Secondary
Change From Randomization to Week 2 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 baseline AIMS 1-7 total score, treatment, gender, pooled investigative site, visit, baseline AIMS 1-7 total score\*visit and treatment\*visit.
Time frame: Randomization, randomization treatment Week 2
Population: All randomized participants who received at least one dose of study drug and had AIMS total score measurement at randomization and at least one post-randomization AIMS total score.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Randomization) | Change From Randomization to Week 2 in Abnormal Involuntary Movement Scale (AIMS) Total Score | 0.0 units a scale | Standard Error 0.1 |
| LY2140023 (Randomization) | Change From Randomization to Week 2 in Abnormal Involuntary Movement Scale (AIMS) Total Score | -0.0 units a scale | Standard Error 0.1 |
p-value: 0.515Type 3 sums of squares
Secondary
Change From Randomization to Week 2 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 (Global Score) 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 baseline BAS global score, treatment, gender, pooled investigative site, visit, baseline BAS global score\*visit and treatment\*visit.
Time frame: Randomization, randomization treatment Week 2
Population: All randomized participants who received at least one dose of study drug and had BAS global score measurement at randomization and at least one post-randomization BAS global score.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Randomization) | Change From Randomization to Week 2 in Barnes Akathisia Scale (BAS) Global Score | -0.0 units on a scale | Standard Error 0 |
| LY2140023 (Randomization) | Change From Randomization to Week 2 in Barnes Akathisia Scale (BAS) Global Score | -0.0 units on a scale | Standard Error 0 |
p-value: 0.762Type 3 sums of squares
Secondary
Change From Randomization to Week 2 in Brief Psychiatric Rating Scale (BPRS) Total Scores
BPRS is an 18-item clinician-administered scale used to assess the degree of severity of a participant's general psychopathological symptoms. Item scores range from 1 (not present) to 7 (extremely severe). Total Scores range from 18 to 126. 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 baseline BPRS total score, treatment, gender, pooled investigative site, visit, baseline BPRS total score\*visit and treatment\*visit.
Time frame: Randomization, randomization treatment Week 2
Population: All randomized participants who received at least one dose of study drug and had BPRS total score measurement at randomization and at least one post-randomization BPRS total score.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Randomization) | Change From Randomization to Week 2 in Brief Psychiatric Rating Scale (BPRS) Total Scores | -2.20 units on a scale | Standard Error 0.55 |
| LY2140023 (Randomization) | Change From Randomization to Week 2 in Brief Psychiatric Rating Scale (BPRS) Total Scores | -1.28 units on a scale | Standard Error 0.54 |
p-value: 0.895Type 3 sums of squares
Secondary
Change From Randomization to Week 2 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 Measure (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values are controlled for baseline CGI-S score, treatment, gender, pooled investigative site, visit, baseline CGI-S score\*visit and treatment\*visit.
Time frame: Randomization, randomization treatment Week 2
Population: All randomized participants who received at least one dose of study drug and had CGI-S measurement at randomization and at least one post-randomization CGI-S measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Randomization) | Change From Randomization to Week 2 in Clinical Global Impression-Severity Scale (CGI-S) | -0.2 units on a scale | Standard Error 0.1 |
| LY2140023 (Randomization) | Change From Randomization to Week 2 in Clinical Global Impression-Severity Scale (CGI-S) | -0.0 units on a scale | Standard Error 0.1 |
p-value: 0.966Type 3 sums of squares
Secondary
Change From Randomization to Week 2 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 baseline SAS total score, treatment, gender, pooled investigative site, visit, baseline SAS total score\*visit and treatment\*visit.
Time frame: Randomization, randomization treatment Week 2
Population: All randomized participants who received at least one dose of study drug and had SAS total score measurement at randomization and at least one post-randomization SAS total score.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Randomization) | Change From Randomization to Week 2 in Simpson-Angus Scale (SAS) Total Score | -0.0 units on a scale | Standard Error 0 |
| LY2140023 (Randomization) | Change From Randomization to Week 2 in Simpson-Angus Scale (SAS) Total Score | 0.0 units on a scale | Standard Error 0 |
p-value: 0.506Type 3 sums of squares
Secondary
Change From Randomization up to Week 2 in the Clinical Institute Withdrawal Assessment of Alcohol Scale (CIWA-Ar) Total Score
The CIWA-Ar is a 10-item scale that was used to monitor for symptoms of drug withdrawal. The scale includes the following domains/criteria: nausea, vomiting; anxiety; paroxysmal sweats; tactile disturbances; visual disturbances; tremors; agitation; orientation and clouding of sensorium; auditory disturbances; and headache. Items 1-9 have possible scores of 0 (no symptom)-7 (severe symptom), and item 10 has possible scores of 0 (no symptom)-4 (severe symptom). Total scores range from 0-67. Higher scores indicate greater severity of symptom. The Mixed Model Repeated Measure (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values are controlled for baseline CIWA-Ar total score, treatment, gender, pooled investigative site, visit, baseline CIWA-Ar total score\*visit and treatment\*visit.
Time frame: Randomization, randomization treatment Weeks 0.5 and 1 and 1.5 and 2
Population: All randomized participants who received at least one dose of study drug and had CIWA-Ar measurements at randomization and specified post-randomization visits.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Randomization) | Change From Randomization up to Week 2 in the Clinical Institute Withdrawal Assessment of Alcohol Scale (CIWA-Ar) Total Score | Week 0.5 | -0.7 units on a scale | Standard Error 0.3 |
| Placebo (Randomization) | Change From Randomization up to Week 2 in the Clinical Institute Withdrawal Assessment of Alcohol Scale (CIWA-Ar) Total Score | Week 1 | -0.9 units on a scale | Standard Error 0.3 |
| Placebo (Randomization) | Change From Randomization up to Week 2 in the Clinical Institute Withdrawal Assessment of Alcohol Scale (CIWA-Ar) Total Score | Week 1.5 | -0.8 units on a scale | Standard Error 0.3 |
| Placebo (Randomization) | Change From Randomization up to Week 2 in the Clinical Institute Withdrawal Assessment of Alcohol Scale (CIWA-Ar) Total Score | Week 2 | -0.4 units on a scale | Standard Error 0.3 |
| LY2140023 (Randomization) | Change From Randomization up to Week 2 in the Clinical Institute Withdrawal Assessment of Alcohol Scale (CIWA-Ar) Total Score | Week 2 | -0.5 units on a scale | Standard Error 0.3 |
| LY2140023 (Randomization) | Change From Randomization up to Week 2 in the Clinical Institute Withdrawal Assessment of Alcohol Scale (CIWA-Ar) Total Score | Week 0.5 | 0.0 units on a scale | Standard Error 0.3 |
| LY2140023 (Randomization) | Change From Randomization up to Week 2 in the Clinical Institute Withdrawal Assessment of Alcohol Scale (CIWA-Ar) Total Score | Week 1.5 | -0.6 units on a scale | Standard Error 0.3 |
| LY2140023 (Randomization) | Change From Randomization up to Week 2 in the Clinical Institute Withdrawal Assessment of Alcohol Scale (CIWA-Ar) Total Score | Week 1 | -0.5 units on a scale | Standard Error 0.3 |
p-value: 0.109Type 3 sums of squares
p-value: 0.372Type 3 sums of squares
p-value: 0.555Type 3 sums of squares
p-value: 0.806Type 3 sums of squares
Secondary
Percentage of Participants With Suicidal Behaviors and Ideations Measured Using the Columbia Suicide Severity Rating Scale (C-SSRS) During Double-Blind Randomized Treatment Period
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. The percentage of participants with treatment-emergent suicidal ideation or behavior during double-blind randomized treatment period (with a change from baseline in C-SSRS) was calculated as the number of participants with an increase in suicidal behavior or ideation over baseline (randomization), divided by the total number of participants multiplied by 100.
Time frame: Randomization up to Week 2 of randomization treatment
Population: All participants who received at least one dose of study drug and had C-SSRS measurement at randomization and at least one post-randomization C-SSRS measurement.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo (Randomization) | Percentage of Participants With Suicidal Behaviors and Ideations Measured Using the Columbia Suicide Severity Rating Scale (C-SSRS) During Double-Blind Randomized Treatment Period | Treatment-Emergent Suicidal Ideation | 0.0 percentage of participants |
| Placebo (Randomization) | Percentage of Participants With Suicidal Behaviors and Ideations Measured Using the Columbia Suicide Severity Rating Scale (C-SSRS) During Double-Blind Randomized Treatment Period | Treatment-Emergent Suicidal Behavior | 0.0 percentage of participants |
| LY2140023 (Randomization) | Percentage of Participants With Suicidal Behaviors and Ideations Measured Using the Columbia Suicide Severity Rating Scale (C-SSRS) During Double-Blind Randomized Treatment Period | Treatment-Emergent Suicidal Ideation | 0.0 percentage of participants |
| LY2140023 (Randomization) | Percentage of Participants With Suicidal Behaviors and Ideations Measured Using the Columbia Suicide Severity Rating Scale (C-SSRS) During Double-Blind Randomized Treatment Period | Treatment-Emergent Suicidal Behavior | 0.0 percentage of participants |
Secondary
Percentage of Participants With Suicidal Behaviors and Ideations Measured Using the Columbia Suicide Severity Rating Scale (C-SSRS) During Open-Label Treatment Period
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. The percentage of participants with treatment-emergent suicidal ideation or behavior during open-label treatment period (with a change from baseline in C-SSRS) was calculated as the number of participants with an increase in suicidal behavior or ideation over baseline (before open-label treatment), divided by the total number of participants multiplied by 100.
Time frame: Baseline up to Week 4 of open-label treatment
Population: All enrolled participants who received at least one dose of study drug and had a baseline (before open-label treatment) and at least one post-baseline (during open-label treatment) C-SSRS measurement.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo (Randomization) | Percentage of Participants With Suicidal Behaviors and Ideations Measured Using the Columbia Suicide Severity Rating Scale (C-SSRS) During Open-Label Treatment Period | Treatment-Emergent Suicidal Ideation | 1.6 percentage of participants |
| Placebo (Randomization) | Percentage of Participants With Suicidal Behaviors and Ideations Measured Using the Columbia Suicide Severity Rating Scale (C-SSRS) During Open-Label Treatment Period | Treatment-Emergent Suicidal Behavior | 0.0 percentage of participants |