A Study of LY2140023 in Patients With Schizophrenia

NCT01307800 | Terminated Phase 3 Results DMC

• 2 other identifiers: 12430H8Y-MC-HBBN
• Study Type: interventional
• Target: 567
• Locations: 5 countries
• Sites: 13

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.

Conditions

Schizophrenia

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score

  The PANSS scale assessed participants (pts) for positive symptoms, negative symptoms, and general psychopathology specifically associated with schizophrenia. The scale consisted of 30 items. Each item was rated from 1 (absence of symptoms) to 7 (symptoms extremely severe). The sum of the 30 items was defined as the PANSS total score and ranged from 30 to 210. The least squares (LS) mean was estimated using a mixed-effects model with repeated measures (MMRM) that included the fixed, categorical effects of treatment, pooled investigative site, visit, treatment-by-visit interaction, gender, and predefined subpopulation ('yes/no'), as well as the continuous, fixed covariates of baseline score and baseline score-by-visit interaction.

  Baseline, Week 6

Secondary Outcomes (21)

• Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score in a Predefined Subpopulation of Schizophrenia Participants

  Baseline, Week 6

• Change From Baseline in the Personal and Social Performance (PSP) Score

  Baseline, Week 6

• Change From Baseline in the Personal and Social Performance (PSP) Score in a Predefined Subpopulation

  Baseline, Week 6

• Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score in Females

  Baseline, Week 6

• Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Subscores

  Baseline, Week 6

Other Outcomes (1)

• Serious Adverse Events (SAEs) Which Occurred During 30 Days After Last Dose of Study Drug

  Last dose (either early discontinuation or Week 6) through 30-day follow-up period

Study Arms (4)

80 milligrams (mg) LY2140023, BID

EXPERIMENTAL

An 80-mg LY2140023 tablet administered orally, twice daily (BID) for 6 weeks. Prior to randomization, participants will complete a 1-week placebo lead-in period, during which time placebo tablets identical to LY2140023 are administered orally, BID.

Drug: LY2140023

40 mg LY2140023, BID

EXPERIMENTAL

A 40-mg LY2140023 tablet administered orally, BID for 6 weeks. Prior to randomization, participants will complete a 1-week placebo lead-in period, during which time, placebo tablets identical to LY2140023 are administered orally, BID.

Drug: LY2140023

10 mg LY2140023, BID

EXPERIMENTAL

A 10-mg LY2140023 tablet administered orally, BID for 6 weeks. Prior to randomization, participants will complete a 1-week placebo lead-in period, during which time, placebo tablets identical to LY2140023 are administered orally, BID.

Drug: LY2140023

Placebo

PLACEBO COMPARATOR

A placebo tablet administered orally, BID for 7 weeks.

Drug: Placebo

Interventions

LY2140023 DRUG

Administered orally

Also known as: pomaglumetad methionil

10 mg LY2140023, BID; 40 mg LY2140023, BID; 80 milligrams (mg) LY2140023, BID

Placebo DRUG

Administered orally

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Denovo Biopharma LLC: lead

Study Sites (13)

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.

Wichita, Kansas, 67207, United States

Location

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.

Guadalajara, 44340, Mexico

Location

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.

Monterrey, 64060, Mexico

Location

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 Juan, 00926, Puerto Rico

Location

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.

Lipetsk, 399007, Russia

Location

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.

Moscow, 109559, Russia

Location

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.

Saint Petersburg, 190005, Russia

Location

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.

Saratov, 410060, Russia

Location

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.

Voronezh, 394071, Russia

Location

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.

Donetsk, 83037, Ukraine

Location

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.

Kiev, 2660, Ukraine

Location

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.

Lviv, 79021, Ukraine

Location

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.

Vinnytsia, 21005, Ukraine

Location

Related Publications (1)

• 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.

  PMID: 25890643 DERIVED

MeSH Terms

Conditions

Schizophrenia

Interventions

LY 2140023; pomaglumetad methionil

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Limitations and Caveats

An interim analysis for futility was planned and conducted, using a pre-defined threshold. Since probability of trial meeting primary efficacy objectives, given available interim data, was below pre-defined level, trial was stopped early.

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

800-545-5979

Study Officials

• 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 DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 1, 2011
• First Posted: March 3, 2011
• Study Start: March 1, 2011
• Primary Completion: September 1, 2012
• Study Completion: September 1, 2012
• Last Updated: October 18, 2022
• Results First Posted: October 18, 2022

Record last verified: 2022-09

Locations

ME (2); PR (1); UA (4); RU (5); US (1)