Clinical trial NCT01307800: A Study of LY2140023 in Patients With Schizophrenia
Official title: A Phase 3, Multicenter, Double-Blind, Placebo-Controlled Study of 3 Doses of LY2140023 Monohydrate in the Acute Treatment of Patients With DSM-IV-TR Schizophrenia
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Schizophrenia
Lead sponsor: Denovo Biopharma LLC
Sponsor class: INDUSTRY
First posted: 2011-03-03
Enrollment: 567
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether at least 1 dose level of LY2140023 given to acutely ill patients with schizophrenia will demonstrate significantly greater efficacy as compared to placebo.

Detailed description: The primary objective of this study was to test the hypothesis that at least 1 dose level of LY2140023, given orally to patients with schizophrenia at doses of 80 mg twice daily (BID), 40 mg BID, or 10 mg BID, would demonstrate significantly greater efficacy than placebo at Visit 9, as measured by the change from baseline in the Positive and Negative Syndrome Scale (PANSS) total score.

This was a multicenter, randomized, double-blind, parallel, fixed-dose, Phase 3 study in patients with schizophrenia. The study consisted of 3 periods: a screening and antipsychotic taper phase, a 7-day placebo lead-in phase that was blinded to investigators and patients, and a 6-week active treatment phase.

Eligible patients were those for whom a modification of antipsychotic medication was acutely indicated, in the opinion of the investigator. To be included in the study, patients must have experienced an exacerbation of their illness within the 2 weeks prior to study entry, leading to an intensification of the level of psychiatric care.

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); and confirmed by the Structured Clinical Interview for DSM-IV-TR (SCID)
* Non pregnant female patients who agree to use acceptable birth control
* Participants must be considered moderately ill in the opinion of the investigator
* Patients in whom a modification of antipsychotic medication or initiation of antipsychotic medication is acutely indicated in the opinion of the investigator
* Willing to participate in a minimum of 2 weeks of inpatient hospitalization
* One 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.
* Patients must be considered reliable and have a level of understanding sufficient to perform all tests and examinations required by the protocol, and be willing to perform all study procedures

Exclusion Criteria:

* Patients who have a history of inadequate clinical response to antipsychotic treatment for schizophrenia
* Diagnosis of substance dependence or substance abuse within 6 month of study entry
* Diagnosis of substance-induced psychosis within 7 days of study entry
* Currently enrolled in, or discontinued within 6 months from a clinical trial involving an investigational product or unapproved use of a drug or device
* Participated in any clinical trial with any pharmacological treatment intervention for which they received a study-related medication in the 6 months prior to study entry
* 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 study entry
* 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
* Electroconvulsive therapy (ECT) within 3 months of entering the study or who will have ECT at any time during the study
* History of low white blood cell count
* Medical history of Human Immunodeficiency Virus positive (HIV+) status.
* Higher than normal blood prolactin levels
* Abnormal electrocardiogram results

Primary outcomes:
measure: Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score
timeFrame: Baseline, Week 6
Secondary outcomes:
measure: Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score in a Predefined Subpopulation of Schizophrenia Participants
timeFrame: Baseline, Week 6
measure: Change From Baseline in the Personal and Social Performance (PSP) Score
timeFrame: Baseline, Week 6
measure: Change From Baseline in the Personal and Social Performance (PSP) Score in a Predefined Subpopulation
timeFrame: Baseline, Week 6
measure: Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score in Females
timeFrame: Baseline, Week 6
measure: Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Subscores
timeFrame: Baseline, Week 6
measure: Percentage of Participants Who Are Responders
timeFrame: Baseline, Week 6
measure: Time to Response
timeFrame: Baseline up to Week 6
measure: Change From Baseline in the Clinical Global Impression-Severity (CGI-S) Scale
timeFrame: Baseline, Week 6
measure: Change From Baseline in the 16-Item Negative Symptoms Assessment (NSA-16) Total Score
timeFrame: Baseline, Week 6
measure: Change From Baseline on the European Quality of Life-5 Dimension (EQ-5D) Questionnaire
timeFrame: Baseline, Week 6
measure: Change From Baseline on Schizophrenia Resource Utilization Module (S-RUM): Emergency Room (ER) Visits and Outpatient Visits
timeFrame: Baseline and Week (Wk) 6
measure: Change From Baseline on Schizophrenia Resource Utilization Module (S-RUM): Sessions With a Psychiatrist
timeFrame: Baseline and Week 6
measure: Change From Baseline on Subjective Well-Being Under Neuroleptic Treatment Scale - Short Form (SWN-S) Total Score
timeFrame: Baseline, Week 6
measure: Change From Baseline in Barnes Akathisia Scale (BAS) Global Score
timeFrame: Baseline, Week 6
measure: Change From Baseline in Simpson-Angus Scale (SAS) Total Score
timeFrame: Baseline, Week 6
measure: Change From Baseline in Abnormal Involuntary Movement Scales (AIMS) 1-7 Total Score
timeFrame: Baseline, Week 6
measure: Percentage of Participants With a Change From Baseline in Suicidal Behaviors and Ideations Measured by the Columbia-Suicide Severity Rating Scale (C-SSRS)
timeFrame: Baseline up to Week 6
measure: Number of Participants Who Discontinued
timeFrame: Randomization up to Week 6
measure: Time to Discontinuation
timeFrame: Randomization up to Week 6
measure: Change From Baseline in Prolactin
timeFrame: Baseline, Week 6
measure: Change From Baseline in Weight
timeFrame: Baseline, Week 6
Other outcomes:
measure: Serious Adverse Events (SAEs) Which Occurred During 30 Days After Last Dose of Study Drug
timeFrame: Last dose (either early discontinuation or Week 6) through 30-day follow-up period
Locations:
city: Wichita
country: United States
facility: 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.
state: Kansas
city: Guadalajara
country: Mexico
facility: 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: Monterrey
country: Mexico
facility: 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: San Juan
country: Puerto Rico
facility: 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: Lipetsk
country: Russian Federation
facility: 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: Moscow
country: Russian Federation
facility: 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: Saint Petersburg
country: Russian Federation
facility: 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: Saratov
country: Russian Federation
facility: 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: Voronezh
country: Russian Federation
facility: 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: Donetsk
country: Ukraine
facility: 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: Kiev
country: Ukraine
facility: 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: Lviv
country: Ukraine
facility: 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: Vinnytsya
country: Ukraine
facility: 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.
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References:
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.