A Physical Dependence Study in Schizophrenia

NCT ID: NCT01452919

Last Updated: 2022-09-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 123 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-11-30
• Study Completion Date: 2012-09-30

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.

Detailed Description

This was a short-term, multicenter, placebo-controlled, randomized withdrawal study comparing LY2140023 with placebo in the treatment of outpatients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR [APA 2000]) schizophrenia. Patients were male or female outpatients, 18 to 65 years of age (inclusive) at study entry, with a diagnosis of schizophrenia as defined in the DSM-IV-TR

The primary objective of this study was to assess whether LY2140023, when administered in an acute-treatment trial with flexible doses (40 mg or 80 mg) BID, was associated with physical dependence, as measured by the occurrence of withdrawal symptoms during a randomized withdrawal phase in patients diagnosed with schizophrenia. Assessment was to be based on a comparison of randomized LY2140023-treated patients with those on placebo, as measured by the maximum of the 3-day moving average of the patient's total score on the Discontinuation Symptom Checklist-Modified Rickels (DSCMR).

Conditions

Schizophrenia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

LY2140023

Intervention Type: DRUG

Administered orally

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.

Group Type: PLACEBO_COMPARATOR

LY2140023

Intervention Type: DRUG

Administered orally

Placebo

Intervention Type: DRUG

Administered orally

Interventions

LY2140023

Administered orally

Intervention Type: DRUG

Placebo

Administered orally

Intervention Type: DRUG

Other Intervention Names

pomaglumetad methionil

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Denovo Biopharma LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

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

Eli Lilly and Company

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.

Oakland, California, United States

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

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

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

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

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

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

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

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.

Chaïdári, Athens, Greece

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

Countries

United States; Greece

References

Stauffer VL, Baygani SK, Kinon BJ, Krikke-Workel JO. A short-term, multicenter, placebo-controlled, randomized withdrawal study of a metabotropic glutamate 2/3 receptor agonist using an electronic patient-reported outcome device in patients with schizophrenia. J Clin Psychopharmacol. 2014 Oct;34(5):552-8. doi: 10.1097/JCP.0000000000000187.

Reference Type: DERIVED

PMID: 25006819 (View on PubMed)

Other Identifiers

H8Y-MC-HBDF

Identifier Type: OTHER

Identifier Source: secondary_id

14326

Identifier Type: -

Identifier Source: org_study_id