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A Study in Schizophrenic Patients

Primary Purpose

Schizophrenia

Status

Terminated

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

LY2140023

Placebo

About this trial

This is an interventional treatment trial for Schizophrenia

Eligibility Criteria

20 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Diagnosis of schizophrenia as defined in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR; APA 2000) (Disorganized, 295.10; Catatonic, 295.20; Paranoid 295.30; or Undifferentiated, 295.90) and confirmed by the Structured Clinical Interview for DSM-IV-TR (SCID)
Non pregnant female participants who agree to use acceptable birth control
At entry to the study must be considered moderately ill in the opinion of the investigator
1 year history of Schizophrenia prior to entering the study
At study entry participants with a history of antipsychotic treatment must have a lifetime history of at least one hospitalization for the treatment of schizophrenia, not including the hospitalization required for study based on the investigator's clinical judgment. Participants who have never taken antipsychotic treatment may enter the study even without a history of hospitalization
At study entry participants with a history of antipsychotic treatment must have a history of at least one episode of illness exacerbation requiring an intensification of treatment intervention or care in the last 2 years, not including the present episode of illness. Participants who have never taken antipsychotic treatment may enter the study without a past history of illness exacerbation and intensification of treatment in the last 2 years
At study entry participants must have experienced an exacerbation of illness within the 4 weeks prior to entering the study, leading to an intensification of psychiatric care in the opinion of the investigator. If exacerbation occurs in participants who are presently hospitalized, the participants must not have been hospitalized longer than 60 days at entry of the study

Exclusion Criteria:

Participated in any clinical trial with any pharmacological treatment intervention for which they received a study-related medication in the 6 months prior to visit 1
Previously completed or withdrawn from this study, or any other study investigating LY2140023 or any predecessor molecules with glutamatergic activity
Have any known history of receiving treatment with clozapine at any dose, as determined at baseline
Have received treatment with a depot formulation of an antipsychotic medication within the 6 months prior entering the study
Participants who are currently suicidal
Females who are pregnant, nursing, or who intend to become pregnant within 30 days of completing the study
Participants with uncorrected narrow-angle glaucoma, uncontrolled diabetes, certain diseases of the liver, renal insufficiency, untreated thyroid condition or other serious or unstable illnesses
Have a history of one or more seizures, except for those who experienced a single simple febrile seizure between ages 6 months and 5 years
Participants are excluded if their biological father, mother, brother, sister, or child has a history of idiopathic epilepsy
Within 1 year of study enrollment, participants have a history of central nervous system infection, uncontrolled migraine, transient ischemic attack (TIA), or head trauma with loss of consciousness or a post-concussive
Participants are excluded if they have a lifetime history of any of the following:
- head trauma, stroke, or central nervous system (CNS) infection with persistent neurological deficit (focal or diffuse);
- brain surgery;
- an electroencephalogram with paroxysmal (epileptiform) activity, or
- brain structural lesion, including developmental abnormalities, as determined by examination or previous neuroimaging studies that are consistent with a diagnosable neurological disease or syndrome
Electroconvulsive therapy (ECT) within 3 months of entering the study or who will have ECT at any time during the study
Leukopenia
Medical history of Human Immunodeficiency Virus positive (HIV+) status
Higher than normal blood prolactin levels
Certain electrocardiogram results

Sites / Locations

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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Placebo Comparator

Arm Label

10 milligrams (mg) LY2140023

80 mg LY2140023

160 mg LY2140023

Placebo

Arm Description

Outcomes

Primary Outcome Measures

Clinical Utility Index (CUI)

CUI measures the efficacy (response), tolerability (time on treatment) and safety [incidence of adverse events (AEs)] by quantifying these 3 attributes and provides a single metric for overall treatment outcome. Each component is given a score ranging from 0 to 5. The CUI Total Score is the sum of the 3 items and ranges from 0 to 15. The greater the CUI Total Score, the more effective the treatment. If a participant experiences a drug-related seizure/death, the safety component is given a score of 0 resulting in an overall CUI Total Score of 0. Analysis of variance (ANOVA) was used to calculate Least Squares (LS) mean and standard error. LS mean values were controlled for treatment, gender and pooled investigators.

Secondary Outcome Measures

Change From Baseline to Week 6 Endpoint in the Positive and Negative Syndrome Scale (PANSS) Total Score, Positive Score, Negative Score, and Psychopathology Subscale

The PANSS consists of 30 items and 3 subscales designed to measure severity of psychopathology in schizophrenia. The PANSS Positive Subscale and the PANSS Negative Subscale each contain 7 items, and the remaining 16 items make up the PANSS General Psychopathology Subscale. Each item is rated from 1 (symptom not present) to 7 (symptom extremely severe). The PANSS Total Score is the sum of the 30 items (range from 30 to 210). The PANSS Positive Subscale and PANSS Negative Subscale scores each range from 7 to 49. The PANSS General Psychopathology Subscale score ranges from 16 to 112. Higher scores indicate greater severity of illness. The Mixed Model Repeated Measures (MMRM) analysis was used to calculate Least Squares (LS) mean and 95% confidence interval. LS mean values were controlled for baseline, treatment, gender, pooled investigator, visit, treatment*visit and baseline*visit.

Change From Baseline to Week 6 Endpoint in the Clinical Global Impression-Severity Scale (CGI-S)

The CGI-S instrument is used to record the severity of mental illness at the time of assessment. The score ranges from 1 (normal, not at all ill) to 7 (among the most extremely ill). Higher scores indicate greater severity of illness. The Mixed Model Repeated Measures (MMRM) analysis was used to calculate Least Squares (LS) mean and 95% confidence interval. LS mean values were controlled for baseline, treatment, gender, pooled investigator, visit, treatment*visit and baseline*visit.

Change From Baseline to Week 6 Endpoint 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 NSA-16 Total Score is the sum of the 16 specific items and ranges from 16 to 96. Higher scores indicate greater severity of illness. The Mixed Model Repeated Measures (MMRM) analysis was used to calculate Least Squares (LS) mean and 95% confidence interval. LS mean values were controlled for baseline, treatment, gender, pooled investigator, visit, treatment*visit and baseline*visit.

The Number of Participants With Treatment-Emergent Suicidal Ideation and Behavior Based on the 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, non-fatal suicide attempt, and completed suicide. The number of participants with statistically significant changes of the C-SSRS was the number of participants with a treatment-emergent suicidal ideation and behavior (an increase in suicidal behavior or ideation over lead-in baseline.)

Percentage of Participants Who Discontinued (Rate of Discontinuation)

Rate of discontinuation was calculated as the number of participants who discontinued from study due to any reason divided by the total number of participants who received study drug, then multiplied by 100.

Full Information

NCT ID

NCT01125358

First Posted

May 17, 2010

Last Updated

August 17, 2021

Sponsor

Denovo Biopharma LLC

1. Study Identification

Unique Protocol Identification Number

NCT01125358

Brief Title

A Study in Schizophrenic Patients

Official Title

A Multicenter, Double-Blind, Placebo-Controlled Study of 3 Doses of LY2140023 in Patients With DSM-IV-TR Schizophrenia

Study Type

Interventional

2. Study Status

Record Verification Date

November 2012

Overall Recruitment Status

Terminated

Why Stopped

The decision to stop the trial was based on efficacy results in the overall schizophrenia participant population.

Study Start Date

May 2010 (undefined)

Primary Completion Date

September 2012 (Actual)

Study Completion Date

September 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Denovo Biopharma LLC

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This study is designed to compare 3 doses of LY2140023 for the treatment of schizophrenia as assessed at endpoint (up to 7 weeks) using the Clinical Utility Index (CUI), a measure of efficacy, safety, and tolerability.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Schizophrenia

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

82 (Actual)

8. Arms, Groups, and Interventions

Arm Title

10 milligrams (mg) LY2140023

Arm Type

Experimental

Arm Title

80 mg LY2140023

Arm Type

Experimental

Arm Title

160 mg LY2140023

Arm Type

Experimental

Arm Title

Placebo

Arm Type

Placebo Comparator

Intervention Type

Drug

Intervention Name(s)

LY2140023

Intervention Description

Administered orally, twice daily for up to 7 weeks of treatment

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Administered orally, twice daily for up to 7 weeks of treatment

Primary Outcome Measure Information:

Title

Clinical Utility Index (CUI)

Description

Time Frame

Baseline through Week 6

Secondary Outcome Measure Information:

Title

Change From Baseline to Week 6 Endpoint in the Positive and Negative Syndrome Scale (PANSS) Total Score, Positive Score, Negative Score, and Psychopathology Subscale

Description

Time Frame

Baseline, Week 6

Title

Change From Baseline to Week 6 Endpoint in the Clinical Global Impression-Severity Scale (CGI-S)

Description

Time Frame

Baseline, Week 6

Title

Change From Baseline to Week 6 Endpoint in the 16-item Negative Symptoms Assessment (NSA-16)

Description

Time Frame

Baseline, Week 6

Title

The Number of Participants With Treatment-Emergent Suicidal Ideation and Behavior Based on the Columbia Suicide Severity Rating Scale (C-SSRS)

Description

Time Frame

Baseline up to Week 6

Title

Percentage of Participants Who Discontinued (Rate of Discontinuation)

Description

Time Frame

Baseline through Week 6

10. Eligibility

Sex

All

Minimum Age & Unit of Time

20 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Diagnosis of schizophrenia as defined in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR; APA 2000) (Disorganized, 295.10; Catatonic, 295.20; Paranoid 295.30; or Undifferentiated, 295.90) and confirmed by the Structured Clinical Interview for DSM-IV-TR (SCID) Non pregnant female participants who agree to use acceptable birth control At entry to the study must be considered moderately ill in the opinion of the investigator 1 year history of Schizophrenia prior to entering the study At study entry participants with a history of antipsychotic treatment must have a lifetime history of at least one hospitalization for the treatment of schizophrenia, not including the hospitalization required for study based on the investigator's clinical judgment. Participants who have never taken antipsychotic treatment may enter the study even without a history of hospitalization At study entry participants with a history of antipsychotic treatment must have a history of at least one episode of illness exacerbation requiring an intensification of treatment intervention or care in the last 2 years, not including the present episode of illness. Participants who have never taken antipsychotic treatment may enter the study without a past history of illness exacerbation and intensification of treatment in the last 2 years At study entry participants must have experienced an exacerbation of illness within the 4 weeks prior to entering the study, leading to an intensification of psychiatric care in the opinion of the investigator. If exacerbation occurs in participants who are presently hospitalized, the participants must not have been hospitalized longer than 60 days at entry of the study Exclusion Criteria: Participated in any clinical trial with any pharmacological treatment intervention for which they received a study-related medication in the 6 months prior to visit 1 Previously completed or withdrawn from this study, or any other study investigating LY2140023 or any predecessor molecules with glutamatergic activity Have any known history of receiving treatment with clozapine at any dose, as determined at baseline Have received treatment with a depot formulation of an antipsychotic medication within the 6 months prior entering the study Participants who are currently suicidal Females who are pregnant, nursing, or who intend to become pregnant within 30 days of completing the study Participants with uncorrected narrow-angle glaucoma, uncontrolled diabetes, certain diseases of the liver, renal insufficiency, untreated thyroid condition or other serious or unstable illnesses Have a history of one or more seizures, except for those who experienced a single simple febrile seizure between ages 6 months and 5 years Participants are excluded if their biological father, mother, brother, sister, or child has a history of idiopathic epilepsy Within 1 year of study enrollment, participants have a history of central nervous system infection, uncontrolled migraine, transient ischemic attack (TIA), or head trauma with loss of consciousness or a post-concussive Participants are excluded if they have a lifetime history of any of the following: head trauma, stroke, or central nervous system (CNS) infection with persistent neurological deficit (focal or diffuse); brain surgery; an electroencephalogram with paroxysmal (epileptiform) activity, or brain structural lesion, including developmental abnormalities, as determined by examination or previous neuroimaging studies that are consistent with a diagnosable neurological disease or syndrome Electroconvulsive therapy (ECT) within 3 months of entering the study or who will have ECT at any time during the study Leukopenia Medical history of Human Immunodeficiency Virus positive (HIV+) status Higher than normal blood prolactin levels Certain electrocardiogram results

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Call 1-877-CTLILLY(1-877-285-4559) or 1-317-615-4459 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

Organizational Affiliation

Eli Lilly and Company

Official's Role

Study Director

Facility Information:

Facility Name

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.

City

Aichi

ZIP/Postal Code

470-1168

Country

Japan

Facility Name

City

Kanagawa

ZIP/Postal Code

216-0003

Country

Japan

Facility Name

City

Kumamoto

ZIP/Postal Code

861-0002

Country

Japan

Facility Name

City

Kyoto

ZIP/Postal Code

625-8502

Country

Japan

Facility Name

City

Nagano

ZIP/Postal Code

384-8540

Country

Japan

Facility Name

City

Nagasaki

ZIP/Postal Code

856-0847

Country

Japan

Facility Name

City

Nara

ZIP/Postal Code

634-8522

Country

Japan

Facility Name

City

Osaka

ZIP/Postal Code

569-1041

Country

Japan

Facility Name

City

Saga

ZIP/Postal Code

842-0192

Country

Japan

Facility Name

City

Tokyo

ZIP/Postal Code

114-0024

Country

Japan

Facility Name

City

Toyama

ZIP/Postal Code

939-8073

Country

Japan

Facility Name

City

Yamaguchi

ZIP/Postal Code

759-6321

Country

Japan

Facility Name

City

Goyang-Si

ZIP/Postal Code

410-719

Country

Korea, Republic of

Facility Name

City

Incheon

ZIP/Postal Code

400-711

Country

Korea, Republic of

Facility Name

City

Naju

ZIP/Postal Code

520-833

Country

Korea, Republic of

Facility Name

City

Seoul

ZIP/Postal Code

150-713

Country

Korea, Republic of

Facility Name

City

Suwon-City

ZIP/Postal Code

442-723

Country

Korea, Republic of

Facility Name

City

Yongin

ZIP/Postal Code

446-769

Country

Korea, Republic of

Facility Name

City

Changhua

ZIP/Postal Code

50550

Country

Taiwan

Facility Name

City

Hsinchu

ZIP/Postal Code

802

Country

Taiwan

Facility Name

City

Taipei

ZIP/Postal Code

110

Country

Taiwan

Facility Name

City

Taipei

ZIP/Postal Code

114

Country

Taiwan

12. IPD Sharing Statement

Citations:

PubMed Identifier

25890643

Citation

Kinon BJ, Millen BA, Zhang L, McKinzie DL. Exploratory analysis for a targeted patient population responsive to the metabotropic glutamate 2/3 receptor agonist pomaglumetad methionil in schizophrenia. Biol Psychiatry. 2015 Dec 1;78(11):754-62. doi: 10.1016/j.biopsych.2015.03.016. Epub 2015 Mar 19.

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A Study in Schizophrenic Patients

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