A Study in Schizophrenia Patients

• ClinicalTrials.gov Identifier: NCT01086748
• Recruitment Status: Completed
• First Posted: March 15, 2010
• Last Update Posted: September 25, 2012
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

Tracking Information

• First Submitted Date: March 12, 2010
• First Posted Date: March 15, 2010
• Last Update Posted Date: September 25, 2012
• Study Start Date: March 2010
• Actual Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 12, 2010)

• A change from baseline in the Positive and Negative Syndrome Scale (PANSS) total score in overall schizophrenia population [ Time Frame: baseline, up to 7 weeks of treatment ]
• A change from baseline in the Positive and Negative Syndrome Scale (PANSS) total score in a genetic subgroup of schizophrenia patients [ Time Frame: baseline, up to 7 weeks of treatment ]

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 12, 2010)

• A change from baseline in the Personal and Social Performance (PSP) score in the overall schizophrenia population [ Time Frame: baseline, up to 7 weeks of treatment ]
• A change from baseline in the Personal and Social Performance (PSP) score in a genetic subgroup of schizophrenia patients [ Time Frame: baseline, up to 7 weeks of treatment ]
• A change from baseline in the PANSS positive scale [ Time Frame: baseline, up to 7 weeks of treatment ]
• A change from baseline in the PANSS negative scale [ Time Frame: baseline, up to 7 weeks of treatment ]
• A change from baseline in PANSS General Psychopathology subscale [ Time Frame: baseline, up to 7 weeks of treatment ]
• A change from baseline in the Clinical Global Impression-Severity Scale (CGI-S) [ Time Frame: baseline, up to 7 weeks of treatment ]
• A change from baseline in the 16-item Negative Symptoms Assessment (NSA-16) [ Time Frame: baseline, up to 7 weeks of treatment ]
• A change from baseline in the Montgomery-Ǻsberg Depression Rating Scale (MADRS) [ Time Frame: baseline, up to 7 weeks of treatment ]
• PANSS total score [ Time Frame: up to 7 weeks of treatment ]
• A change from baseline in the Positive and Negative Syndrome Scale (PANSS) total score in a female patients [ Time Frame: baseline, up to 7 weeks of treatment ]
• Rate of discontinuation [ Time Frame: baseline, up to 7 weeks of treatment ]
• Time to discontinuation [ Time Frame: baseline, up to 7 weeks of treatment ]
• A change from baseline on the EuroQol - 5 Dimensions (EQ-5D) Questionnaire [ Time Frame: baseline, up to 7 weeks of treatment ]
• A change from baseline on resource utilization, as measured by the Schizophrenia Resource Use Model (S-RUM) [ Time Frame: Baseline up to 7 weeks of treatment ]
• A change from baseline on functional capacity, as measured by the Subjective Well-Being Under Neuroleptic Treatment Scale - Short Form (SWN-S) [ Time Frame: baseline, up to 7 weeks of treatment ]
• A change from baseline in Barnes Akathisia Scale (BAS) [ Time Frame: baseline, up to 7 weeks of treatment ]
• A change from baseline in Simpson-Angus Scale (SAS) [ Time Frame: baseline, up to 7 weeks of treatment ]
• A change from baseline in Abnormal Involuntary Movement Scale (AIMS) [ Time Frame: baseline, up to 7 weeks of treatment ]
• A mean change from baseline in Prolactin levels [ Time Frame: baseline, up to 7 weeks of treatment ]
• A change from baseline in weight [ Time Frame: baseline, up to 7 weeks of treatment ]
• Number of Treatment Emergent Adverse Events (TEAEs) [ Time Frame: Up to 7 weeks of treatment ]
• Change from baseline in electrocardiogram parameters [ Time Frame: baseline, up to 7 weeks of treatment ]
• A change from baseline in neurological examination [ Time Frame: baseline, up to 7 weeks of treatment ]
• Statistically different changes in vital signs from baseline [ Time Frame: baseline, up to 7 weeks of treatment ]
• Statistically different changes in lab values from baseline [ Time Frame: baseline, up to 7 weeks of treatment ]
• Population pharmacokinetics (PK) of LY2140023 [ Time Frame: baseline, up to 7 weeks of treatment ]
• A change from baseline in Columbia- Suicide Severity Rating Scale (C-SSRS) [ Time Frame: baseline, up to 7 weeks of treatment ]

Original Secondary Outcome Measures (submitted: March 12, 2010)

• A change from baseline in the Personal and Social Performance (PSP) score in the overall schizophrenia population [ Time Frame: baseline, up to 7 weeks of treatment ]
• A change from baseline in the Personal and Social Performance (PSP) score in a genetic subgroup of schizophrenia patients [ Time Frame: baseline, up to 7 weeks of treatment ]
• A change from baseline in the PANSS positive scale [ Time Frame: baseline, up to 7 weeks of treatment ]
• A change from baseline in the PANSS negative scale [ Time Frame: baseline, up to 7 weeks of treatment ]
• A change from baseline in PANSS General Psychopathology subscale [ Time Frame: baseline, up to 7 weeks of treatment ]
• A change from baseline in the Clinical Global Impression-Severity Scale (CGI-S) [ Time Frame: baseline, up to 7 weeks of treatment ]
• A change from baseline in the 16-item Negative Symptoms Assessment (NSA-16) [ Time Frame: baseline, up to 7 weeks of treatment ]
• A change from baseline on the MATRICS Consensus Cognitive Battery (MCCB) [ Time Frame: baseline, up to 7 weeks of treatment ]
• A change from baseline in the Montgomery-Ǻsberg Depression Rating Scale (MADRS) [ Time Frame: baseline, up to 7 weeks of treatment ]
• PANSS total score [ Time Frame: up to 7 weeks of treatment ]
• A change from baseline in the Positive and Negative Syndrome Scale (PANSS) total score in a female patients [ Time Frame: baseline, up to 7 weeks of treatment ]
• Rate of discontinuation [ Time Frame: baseline, up to 7 weeks of treatment ]
• Time to discontinuation [ Time Frame: baseline, up to 7 weeks of treatment ]
• A change from baseline on the EuroQol - 5 Dimensions (EQ-5D) Questionnaire [ Time Frame: baseline, up to 7 weeks of treatment ]
• resource utilization, as measured by the Schizophrenia Resource Use Model (S-RUM) [ Time Frame: up to 7 weeks of treatment ]
• A change from baseline on functional capacity, as measured by UCSD Performance-based Skills Assessment - Brief Version (UPSA-B) [ Time Frame: baseline, up to 7 weeks of treatment ]
• A change from baseline on functional capacity, as measured by the Subjective Well-Being Under Neuroleptic Treatment Scale - Short Form (SWN-S). [ Time Frame: baseline, up to 7 weeks of treatment ]
• A change from baseline in Barnes Akathisia Scale (BAS) [ Time Frame: baseline, up to 7 weeks of treatment ]
• A change from baseline in Simpson-Angus Scale (SAS) [ Time Frame: baseline, up to 7 weeks of treatment ]
• A change from baseline in Abnormal Involuntary Movement Scale (AIMS) [ Time Frame: baseline, up to 7 weeks of treatment ]
• A mean change from baseline in Prolactin levels [ Time Frame: baseline, up to 7 weeks of treatment ]
• A change from baseline in weight [ Time Frame: baseline, up to 7 weeks of treatment ]
• Number of Treatment Emergent Adverse Events (TEAEs) [ Time Frame: Up to 7 weeks of treatment ]
• Change from baseline in electrocardiogram parameters [ Time Frame: baseline, up to 7 weeks of treatment ]
• A change from baseline in neurological examination [ Time Frame: baseline, up to 7 weeks of treatment ]
• Statistically different changes in vital signs from baseline [ Time Frame: baseline, up to 7 weeks of treatment ]
• Statistically different changes in lab values from baseline [ Time Frame: baseline, up to 7 weeks of treatment ]
• Population pharmacokinetics (PK) of LY2140023 [ Time Frame: baseline, up to 7 weeks of treatment ]
• A change from baseline in Columbia- Suicide Severity Rating Scale (C-SSRS) [ Time Frame: baseline, up to 7 weeks of treatment ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study in Schizophrenia Patients
• Official Title: A Phase 2, Multicenter, Double-Blind, Placebo-Controlled Comparator Study of 2 Doses of LY2140023 Versus Placebo in Patients With DSM-IV-TR Schizophrenia
• Brief Summary: An inpatient/outpatient study to see if LY2140023 is better than placebo in acutely ill patients with schizophrenia.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Schizophrenia

Intervention

• Drug: Risperidone
  Administered orally.
• Drug: Placebo
  Administered orally.
• Drug: LY2140023
  Administered orally.

Study Arms

• Experimental: 160 mg LY2140023
  80 mg LY2140023 administered orally, twice daily (BID) for up to 7 weeks.
  Intervention: Drug: LY2140023
• Active Comparator: 4 mg Risperidone
  2 mg risperidone administered orally, BID for up to 7 weeks.
  Intervention: Drug: Risperidone
• Placebo Comparator: Placebo
  Placebo administered orally, BID for up to 7 weeks.
  Intervention: Drug: Placebo
• Experimental: 80 mg LY2140023
  40 mg LY2140023 administered orally, BID for up to 7 weeks.
  Intervention: Drug: LY2140023

Publications *

• 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.
• Downing AM, Kinon BJ, Millen BA, Zhang L, Liu L, Morozova MA, Brenner R, Rayle TJ, Nisenbaum L, Zhao F, Gomez JC. A Double-Blind, Placebo-Controlled Comparator Study of LY2140023 monohydrate in patients with schizophrenia. BMC Psychiatry. 2014 Dec 10;14:351. doi: 10.1186/s12888-014-0351-3.

Recruitment Information

• Recruitment Status: Completed
• Estimated Enrollment (submitted: March 12, 2010): 880
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: May 2012
• Actual Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)

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 patients who agree to use acceptable birth control
• At entry to the study must be considered moderately ill in the opinion of the investigator
• Willing to participate in a minimum of 3 weeks of inpatient hospitalization and this must be appropriate for the patient in the clinical judgment of the investigator.
• 1 year history of Schizophrenia prior to entering the study
• At study entry patients 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. Patients who have never taken antipsychotic treatment may enter the study even without a history of hospitalization.
• At study entry patients 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. Patients 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 patients must have experienced an exacerbation of illness within the 2 weeks prior to entering the study, leading to an intensification of psychiatric care in the opinion of the investigator. If exacerbation occurs in patients who are presently hospitalized, the patient 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.
• Treatment with clozapine at doses greater than 200 mg daily within 12 months prior to entering the study, or who have received any clozapine at all during the month before entering the study
• Patients currently receiving treatment (within 1 dosing interval, minimum of 4 weeks, prior entering the study) with a depot formulation of an antipsychotic medication.
• Patients who are currently suicidal.
• Females who are pregnant, nursing, or who intend to become pregnant within 30 days of completing the study.
• Patients with uncorrected narrow-angle glaucoma, uncontrolled diabetes, certain diseases of the liver, renal insufficiency, uncontrolled 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
• Patients are excluded if their, biological father, mother, brother, sister, or child has a history of idiopathic epilepsy.
• Within 1 year of study enrollment, patients 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

• Patients are excluded if they have a lifetime history of any of the following:

  • head trauma, stroke, or 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Croatia, Russian Federation, United States
• Removed Location Countries: Germany, Puerto Rico

Administrative Information

• NCT Number: NCT01086748
• Other Study ID Numbers: 11958; H8Y-MC-HBBM ( Other Identifier: Eli Lilly and Company )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Eli Lilly and Company
• Study Sponsor: Eli Lilly and Company
• Collaborators: Not Provided

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

• PRS Account: Eli Lilly and Company
• Verification Date: May 2012