A Physical Dependence Study in Schizophrenia

NCT01452919 | Completed Phase 3 Results

• 2 other identifiers: 14326H8Y-MC-HBDF
• Study Type: interventional
• Target: 123
• Locations: 2 countries
• Sites: 10

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.

Conditions

Schizophrenia

Keywords

schizophrenia, LY2140023, pomaglumetad methionil

Outcome Measures

Primary Outcomes (1)

• Maximum 3-Day Moving Average (MA) of the Discontinuation Symptom Checklist-Modified Rickels Total Score

  The checklist is a 30-item, participant-rated scale that asks whether participants experience symptoms such as nausea, vomiting, loss of appetite, anxiety, irritability, or craving for study drug during the previous day to assess potential symptoms of drug withdrawal. Each item is rated on a 0 (not at all) to 3 (severe). Total scores range from 0-90. Higher scores indicate greater severity of symptoms. The 3-day MA was calculated starting the third day until the last day of double-blind, randomized period. The 3-day MA was the average of scores from that day and previous 2 days. If scores from any of the days during the 3-day was missing, the average was based on the non-missing days. If there was no total scores for any day of the 3-day, the average was considered to be missing. An analysis of covariance (ANCOVA) was used to calculate Least Squares (LS) mean and standard error. LS mean values are controlled for baseline total score, treatment, pooled investigative site and gender.

  Randomization up to Week 2 of randomization treatment

Secondary Outcomes (8)

• Change From Randomization up to Week 2 in the Clinical Institute Withdrawal Assessment of Alcohol Scale (CIWA-Ar) Total Score

  Randomization, randomization treatment Weeks 0.5 and 1 and 1.5 and 2

• Change From Randomization to Week 2 in Barnes Akathisia Scale (BAS) Global Score

  Randomization, randomization treatment Week 2

• Change From Randomization to Week 2 in Simpson-Angus Scale (SAS) Total Score

  Randomization, randomization treatment Week 2

• Change From Randomization to Week 2 in Abnormal Involuntary Movement Scale (AIMS) Total Score

  Randomization, randomization treatment Week 2

• Percentage of Participants With Suicidal Behaviors and Ideations Measured Using the Columbia Suicide Severity Rating Scale (C-SSRS) During Open-Label Treatment Period

  Baseline up to Week 4 of open-label treatment

Study Arms (2)

LY2140023/LY2140023

EXPERIMENTAL

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.

Drug: LY2140023

LY2140023/Placebo

PLACEBO COMPARATOR

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.

Drug: LY2140023; Drug: Placebo

Interventions

LY2140023 DRUG

Administered orally

Also known as: pomaglumetad methionil

LY2140023/LY2140023; LY2140023/Placebo

Placebo DRUG

Administered orally

LY2140023/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:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Denovo Biopharma LLC: lead

Study Sites (10)

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, 94612, 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.

San Diego, California, 92123, 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.

Torrance, California, 90502, 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.

North Miami, Florida, 33161, 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.

Lake Charles, Louisiana, 70629, 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.

Flowood, Mississippi, 39232, 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.

Philadelphia, Pennsylvania, 19139, 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.

Bellevue, Washington, 98007, 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.

Chaïdári, Athens, 12462, Greece

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.

Tripoli, 22100, Greece

Location

Related Publications (1)

• 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.

  PMID: 25006819 DERIVED

MeSH Terms

Conditions

Schizophrenia

Interventions

LY 2140023; pomaglumetad methionil

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

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: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 12, 2011
• First Posted: October 17, 2011
• Study Start: November 1, 2011
• Primary Completion: September 1, 2012
• Study Completion: September 1, 2012
• Last Updated: September 14, 2022
• Results First Posted: September 16, 2021

Record last verified: 2022-08

Locations

GR (2); US (8)