A Physical Dependence Study in Schizophrenia
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: LY2140023/LY2140023 Open label phase: 40 milligram (mg) LY2140023 administered orally; given twice daily for up to 4 weeks. At the discretion of the investigator, dose may be adjusted one time to 80 mg. 80 mg dose may be adjusted back to 40 mg one time. Current dose level at randomization will remain constant through the double blind phase. Double blind phase: 40 mg or 80 mg LY2140023 administered orally; given twice daily for up to 3 weeks. |
Drug: LY2140023
Administered orally
Other Names:
|
| Placebo Comparator: LY2140023/Placebo Open label phase: 40 mg LY2140023 administered orally; given twice daily for up to 4 weeks. At the discretion of the investigator, dose may be adjusted one time to 80 mg. 80 mg dose may be adjusted back to 40 mg one time. Double blind phase: placebo administered orally; given twice daily for up to 3 weeks. |
Drug: LY2140023
Administered orally
Other Names:
Drug: Placebo
Administered orally
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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.
- 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.
- 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.
- 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.
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | 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 | United States | 94612 |
| 2 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | San Diego | California | United States | 92123 |
| 3 | 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. | Torrance | California | United States | 90502 |
| 4 | 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 | United States | 33161 |
| 5 | 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. | Lake Charles | Louisiana | United States | 70629 |
| 6 | 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. | Flowood | Mississippi | United States | 39232 |
| 7 | 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. | Philadelphia | Pennsylvania | United States | 19139 |
| 8 | 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. | Bellevue | Washington | United States | 98007 |
| 9 | 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. | Haidari | Greece | 12462 | |
| 10 | 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. | Tripoli | Greece | 22100 |
Sponsors and Collaborators
- Denovo Biopharma LLC
Investigators
- Study Director: 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 Documents (Full-Text)
None provided.More Information
Publications
None provided.- 14326
- H8Y-MC-HBDF
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | This study consisted of a 4-week open-label treatment period and a 2-week double-blind randomized withdrawal treatment period. |
| Arm/Group Title | LY2140023 (Open-Label ) | Placebo (Randomization) | LY2140023 (Randomization) |
|---|---|---|---|
| Arm/Group Description | 40 milligram (mg) or 80 mg LY2140023 administered orally, twice daily for 4 weeks during open-label treatment period. | Placebo administered orally, twice daily for 2 weeks during double-blind, randomized withdrawal treatment period. | 40 mg or 80 mg LY2140023 administered orally, twice daily for 2 weeks during double-blind, randomized withdrawal treatment period. |
| Period Title: Open-Label Treatment | |||
| STARTED | 123 | 0 | 0 |
| Received at Least 1 Dose of Study Drug | 123 | 0 | 0 |
| COMPLETED | 103 | 0 | 0 |
| NOT COMPLETED | 20 | 0 | 0 |
| Period Title: Open-Label Treatment | |||
| STARTED | 0 | 50 | 53 |
| Received at Least 1 Dose of Study Drug | 0 | 50 | 53 |
| COMPLETED | 0 | 47 | 51 |
| NOT COMPLETED | 0 | 3 | 2 |
Baseline Characteristics
| Arm/Group Title | All Participants |
|---|---|
| Arm/Group Description | 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. |
| Overall Participants | 123 |
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
42.86
(11.45)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
30
24.4%
|
| Male |
93
75.6%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |
| Hispanic or Latino |
5
4.1%
|
| Not Hispanic or Latino |
118
95.9%
|
| Unknown or Not Reported |
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |
| American Indian or Alaska Native |
3
2.4%
|
| Asian |
1
0.8%
|
| Native Hawaiian or Other Pacific Islander |
1
0.8%
|
| Black or African American |
82
66.7%
|
| White |
35
28.5%
|
| More than one race |
1
0.8%
|
| Unknown or Not Reported |
0
0%
|
| Region of Enrollment (participants) [Number] | |
| United States |
107
87%
|
| Greece |
16
13%
|
Outcome Measures
| Title | Maximum 3-Day Moving Average (MA) of the Discontinuation Symptom Checklist-Modified Rickels Total Score |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least one dose of study drug and had Discontinuation Symptom Checklist-Modified Rickels total score measurement. |
| Arm/Group Title | Placebo (Randomization) | LY2140023 (Randomization) |
|---|---|---|
| Arm/Group Description | Placebo administered orally, twice daily for 2 weeks during double-blind, randomized withdrawal treatment period. | 40 mg or 80 mg LY2140023 administered orally, twice daily for 2 weeks during double-blind, randomized withdrawal treatment period. |
| Measure Participants | 50 | 52 |
| Least Squares Mean (Standard Error) [units on a scale] |
13.23
(0.96)
|
11.50
(0.99)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo (Randomization), LY2140023 (Randomization) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.170 |
| Comments | Two-sided p-value. | |
| Method | Type 3 sums of squares | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Differences |
| Estimated Value | -1.73 | |
| Confidence Interval |
() 95% to |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.25 |
|
| Estimation Comments | ||
| Title | Change From Randomization up to Week 2 in the Clinical Institute Withdrawal Assessment of Alcohol Scale (CIWA-Ar) Total Score |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Placebo (Randomization) | LY2140023 (Randomization) |
|---|---|---|
| Arm/Group Description | Placebo administered orally, twice daily for 2 weeks during double-blind, randomized withdrawal treatment period. | 40 mg or 80 mg LY2140023 administered orally, twice daily for 2 weeks during double-blind, randomized withdrawal treatment period. |
| Measure Participants | 50 | 53 |
| Week 0.5 (n=50, 53) |
-0.7
(0.3)
|
0.0
(0.3)
|
| Week 1 (n=49, 52) |
-0.9
(0.3)
|
-0.5
(0.3)
|
| Week 1.5 (n=47, 51) |
-0.8
(0.3)
|
-0.6
(0.3)
|
| Week 2 (n=47, 51) |
-0.4
(0.3)
|
-0.5
(0.3)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo (Randomization), LY2140023 (Randomization) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.109 |
| Comments | Two-sided p-value. P-value is for Week 0.5. | |
| Method | Type 3 sums of squares | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Differences |
| Estimated Value | 0.8 | |
| Confidence Interval |
() 95% to |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.5 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo (Randomization), LY2140023 (Randomization) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.372 |
| Comments | Two-sided p-value. P-value is for Week 1. | |
| Method | Type 3 sums of squares | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Differences |
| Estimated Value | 0.4 | |
| Confidence Interval |
() 95% to |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.4 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Placebo (Randomization), LY2140023 (Randomization) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.555 |
| Comments | Two-sided p-value. P-value is for Week 1.5. | |
| Method | Type 3 sums of squares | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Differences |
| Estimated Value | 0.2 | |
| Confidence Interval |
() 95% to |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.4 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Placebo (Randomization), LY2140023 (Randomization) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.806 |
| Comments | Two-sided p-value. P-value is for Week 2. | |
| Method | Type 3 sums of squares | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Differences |
| Estimated Value | -0.1 | |
| Confidence Interval |
() 95% to |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.4 |
|
| Estimation Comments | ||
| Title | Change From Randomization to Week 2 in Barnes Akathisia Scale (BAS) Global Score |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Placebo (Randomization) | LY2140023 (Randomization) |
|---|---|---|
| Arm/Group Description | Placebo administered orally, twice daily for 2 weeks during double-blind, randomized withdrawal treatment period. | 40 mg or 80 mg LY2140023 administered orally, twice daily for 2 weeks during double-blind, randomized withdrawal treatment period. |
| Measure Participants | 50 | 53 |
| Least Squares Mean (Standard Error) [units on a scale] |
-0.0
(0.0)
|
-0.0
(0.0)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo (Randomization), LY2140023 (Randomization) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.762 |
| Comments | Two-sided p-value. | |
| Method | Type 3 sums of squares | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Differences |
| Estimated Value | -0.0 | |
| Confidence Interval |
() 95% to |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0 |
|
| Estimation Comments | ||
| Title | Change From Randomization to Week 2 in Simpson-Angus Scale (SAS) Total Score |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Placebo (Randomization) | LY2140023 (Randomization) |
|---|---|---|
| Arm/Group Description | Placebo administered orally, twice daily for 2 weeks during double-blind, randomized withdrawal treatment period. | 40 mg or 80 mg LY2140023 administered orally, twice daily for 2 weeks during double-blind, randomized withdrawal treatment period. |
| Measure Participants | 50 | 53 |
| Least Squares Mean (Standard Error) [units on a scale] |
-0.0
(0.0)
|
0.0
(0.0)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo (Randomization), LY2140023 (Randomization) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.506 |
| Comments | Two-sided p-value. | |
| Method | Type 3 sums of squares | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Differences |
| Estimated Value | 0.0 | |
| Confidence Interval |
() 95% to |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.1 |
|
| Estimation Comments | ||
| Title | Change From Randomization to Week 2 in Abnormal Involuntary Movement Scale (AIMS) Total Score |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Placebo (Randomization) | LY2140023 (Randomization) |
|---|---|---|
| Arm/Group Description | Placebo administered orally, twice daily for 2 weeks during double-blind, randomized withdrawal treatment period. | 40 mg or 80 mg LY2140023 administered orally, twice daily for 2 weeks during double-blind, randomized withdrawal treatment period. |
| Measure Participants | 50 | 53 |
| Least Squares Mean (Standard Error) [units a scale] |
0.0
(0.1)
|
-0.0
(0.1)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo (Randomization), LY2140023 (Randomization) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.515 |
| Comments | Two-sided p-value. | |
| Method | Type 3 sums of squares | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Differences |
| Estimated Value | -0.1 | |
| Confidence Interval |
() 95% to |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.1 |
|
| Estimation Comments | ||
| Title | Percentage of Participants With Suicidal Behaviors and Ideations Measured Using the Columbia Suicide Severity Rating Scale (C-SSRS) During Open-Label Treatment Period |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | All Participants |
|---|---|
| Arm/Group Description | 40 milligram (mg) or 80 mg LY2140023 administered orally, twice daily for 4 weeks during open-label treatment period. |
| Measure Participants | 122 |
| Treatment-Emergent Suicidal Ideation |
1.6
1.3%
|
| Treatment-Emergent Suicidal Behavior |
0.0
0%
|
| Title | Percentage of Participants With Suicidal Behaviors and Ideations Measured Using the Columbia Suicide Severity Rating Scale (C-SSRS) During Double-Blind Randomized Treatment Period |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Placebo (Randomization) | LY2140023 (Randomization) |
|---|---|---|
| Arm/Group Description | Placebo administered orally, twice daily for 2 weeks during double-blind randomized withdrawal treatment period. | 40 mg or 80 mg LY2140023 administered orally, twice daily for 2 weeks during double-blind randomized withdrawal treatment period. |
| Measure Participants | 50 | 53 |
| Treatment-Emergent Suicidal Ideation |
0.0
0%
|
0.0
NaN
|
| Treatment-Emergent Suicidal Behavior |
0.0
0%
|
0.0
NaN
|
| Title | Change From Randomization to Week 2 in Clinical Global Impression-Severity Scale (CGI-S) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Placebo (Randomization) | LY2140023 (Randomization) |
|---|---|---|
| Arm/Group Description | Placebo administered orally, twice daily for 2 weeks during double-blind, randomized withdrawal treatment period. | 40 mg or 80 mg LY2140023 administered orally, twice daily for 2 weeks during double-blind, randomized withdrawal treatment period. |
| Measure Participants | 50 | 53 |
| Least Squares Mean (Standard Error) [units on a scale] |
-0.2
(0.1)
|
-0.0
(0.1)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo (Randomization), LY2140023 (Randomization) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.966 |
| Comments | One-sided p-value. | |
| Method | Type 3 sums of squares | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Differences |
| Estimated Value | 0.2 | |
| Confidence Interval |
() 95% to |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.1 |
|
| Estimation Comments | ||
| Title | Change From Randomization to Week 2 in Brief Psychiatric Rating Scale (BPRS) Total Scores |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Placebo (Randomization) | LY2140023 (Randomization) |
|---|---|---|
| Arm/Group Description | Placebo administered orally, twice daily for 2 weeks during double-blind, randomized withdrawal treatment period. | 40 mg or 80 mg LY2140023 administered orally, twice daily for 2 weeks during double-blind, randomized withdrawal treatment period. |
| Measure Participants | 49 | 52 |
| Least Squares Mean (Standard Error) [units on a scale] |
-2.20
(0.55)
|
-1.28
(0.54)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo (Randomization), LY2140023 (Randomization) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.895 |
| Comments | One-sided p-value. | |
| Method | Type 3 sums of squares | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Differences |
| Estimated Value | 0.92 | |
| Confidence Interval |
() 95% to |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.73 |
|
| Estimation Comments | ||
Adverse Events
| Time Frame | ||||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||
| Arm/Group Title | LY2140023 (Open-Label ) | Placebo (Randomization) | LY2140023 (Randomization) | |||
| Arm/Group Description | 40 milligram (mg) or 80 mg LY2140023 administered orally, twice daily for 4 weeks during open-label treatment period. | Placebo administered orally, twice daily for 2 weeks during double-blind randomized withdrawal treatment period. | 40 mg or 80 mg LY2140023 administered orally, twice daily for 2 weeks during double-blind randomized withdrawal treatment period. | |||
All Cause Mortality |
||||||
| LY2140023 (Open-Label ) | Placebo (Randomization) | LY2140023 (Randomization) | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| LY2140023 (Open-Label ) | Placebo (Randomization) | LY2140023 (Randomization) | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/123 (0%) | 0/50 (0%) | 0/53 (0%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| LY2140023 (Open-Label ) | Placebo (Randomization) | LY2140023 (Randomization) | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 83/123 (67.5%) | 13/50 (26%) | 20/53 (37.7%) | |||
| Ear and labyrinth disorders | ||||||
| Hearing impaired | 3/123 (2.4%) | 3 | 2/50 (4%) | 2 | 0/53 (0%) | 0 |
| Eye disorders | ||||||
| Visual impairment | 2/123 (1.6%) | 2 | 2/50 (4%) | 2 | 1/53 (1.9%) | 1 |
| Gastrointestinal disorders | ||||||
| Constipation | 6/123 (4.9%) | 6 | 1/50 (2%) | 1 | 1/53 (1.9%) | 1 |
| Diarrhoea | 5/123 (4.1%) | 7 | 1/50 (2%) | 1 | 0/53 (0%) | 0 |
| Nausea | 35/123 (28.5%) | 39 | 1/50 (2%) | 1 | 3/53 (5.7%) | 3 |
| Vomiting | 10/123 (8.1%) | 17 | 0/50 (0%) | 0 | 2/53 (3.8%) | 2 |
| Investigations | ||||||
| Blood creatine phosphokinase increased | 9/123 (7.3%) | 9 | 0/50 (0%) | 0 | 3/53 (5.7%) | 3 |
| Nervous system disorders | ||||||
| Dizziness | 6/123 (4.9%) | 6 | 0/50 (0%) | 0 | 0/53 (0%) | 0 |
| Headache | 19/123 (15.4%) | 20 | 4/50 (8%) | 4 | 1/53 (1.9%) | 2 |
| Somnolence | 7/123 (5.7%) | 7 | 0/50 (0%) | 0 | 0/53 (0%) | 0 |
| Tremor | 10/123 (8.1%) | 12 | 1/50 (2%) | 1 | 2/53 (3.8%) | 2 |
| Psychiatric disorders | ||||||
| Agitation | 8/123 (6.5%) | 9 | 1/50 (2%) | 1 | 4/53 (7.5%) | 4 |
| Anxiety | 10/123 (8.1%) | 11 | 4/50 (8%) | 4 | 4/53 (7.5%) | 4 |
| Insomnia | 6/123 (4.9%) | 6 | 0/50 (0%) | 0 | 0/53 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||
| Hyperhidrosis | 7/123 (5.7%) | 7 | 0/50 (0%) | 0 | 2/53 (3.8%) | 2 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | Chief Medical Officer |
|---|---|
| Organization | Eli Lilly and Company |
| Phone | 800-545-5979 |
- 14326
- H8Y-MC-HBDF