Clinical trial NCT01452919: A Physical Dependence Study in Schizophrenia
Official title: A Phase 3, Short-Term, Multicenter, Placebo-Controlled, Randomized Withdrawal Study of LY2140023 Monohydrate in Patients With DSM-IV-TR Schizophrenia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Schizophrenia
Keywords: schizophrenia, LY2140023, pomaglumetad methionil
Lead sponsor: Denovo Biopharma LLC
Sponsor class: INDUSTRY
First posted: 2011-10-17
Enrollment: 123
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 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).

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

Primary outcomes:
measure: Maximum 3-Day Moving Average (MA) of the Discontinuation Symptom Checklist-Modified Rickels Total Score
timeFrame: Randomization up to Week 2 of randomization treatment
Secondary outcomes:
measure: Change From Randomization up to Week 2 in the Clinical Institute Withdrawal Assessment of Alcohol Scale (CIWA-Ar) Total Score
timeFrame: Randomization, randomization treatment Weeks 0.5 and 1 and 1.5 and 2
measure: Change From Randomization to Week 2 in Barnes Akathisia Scale (BAS) Global Score
timeFrame: Randomization, randomization treatment Week 2
measure: Change From Randomization to Week 2 in Simpson-Angus Scale (SAS) Total Score
timeFrame: Randomization, randomization treatment Week 2
measure: Change From Randomization to Week 2 in Abnormal Involuntary Movement Scale (AIMS) Total Score
timeFrame: Randomization, randomization treatment Week 2
measure: Percentage of Participants With Suicidal Behaviors and Ideations Measured Using the Columbia Suicide Severity Rating Scale (C-SSRS) During Open-Label Treatment Period
timeFrame: Baseline up to Week 4 of open-label treatment
measure: Percentage of Participants With Suicidal Behaviors and Ideations Measured Using the Columbia Suicide Severity Rating Scale (C-SSRS) During Double-Blind Randomized Treatment Period
timeFrame: Randomization up to Week 2 of randomization treatment
measure: Change From Randomization to Week 2 in Clinical Global Impression-Severity Scale (CGI-S)
timeFrame: Randomization, randomization treatment Week 2
measure: Change From Randomization to Week 2 in Brief Psychiatric Rating Scale (BPRS) Total Scores
timeFrame: Randomization, randomization treatment Week 2
Other outcomes:
Locations:
city: Oakland
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: California
city: San Diego
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: California
city: Torrance
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: California
city: North Miami
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: Florida
city: Lake Charles
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: Louisiana
city: Flowood
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: Mississippi
city: Philadelphia
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: Pennsylvania
city: Bellevue
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: Washington
city: Chaïdári
country: Greece
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: Athens
city: Tripoli
country: Greece
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: 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.