A Phase 3, Short-Term, Multicenter, Placebo-Controlled, Randomized Withdrawal Study of LY2140023 Monohydrate in Patients With DSM-IV-TR Schizophrenia
Overview
- Phase
- Phase 3
- Intervention
- LY2140023
- Conditions
- Schizophrenia
- Sponsor
- Denovo Biopharma LLC
- Enrollment
- 123
- Locations
- 1
- Primary Endpoint
- Maximum 3-Day Moving Average (MA) of the Discontinuation Symptom Checklist-Modified Rickels Total Score
- Status
- Completed
- Last Updated
- 3 years ago
Overview
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).
Investigators
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
Arms & Interventions
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.
Intervention: LY2140023
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.
Intervention: LY2140023
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.
Intervention: Placebo
Outcomes
Primary Outcomes
Maximum 3-Day Moving Average (MA) of the Discontinuation Symptom Checklist-Modified Rickels Total Score
Time Frame: Randomization up to Week 2 of randomization treatment
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.
Secondary Outcomes
- 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)
- Percentage of Participants With Suicidal Behaviors and Ideations Measured Using the Columbia Suicide Severity Rating Scale (C-SSRS) During Double-Blind Randomized Treatment Period(Randomization up to Week 2 of randomization treatment)
- Change From Randomization to Week 2 in Clinical Global Impression-Severity Scale (CGI-S)(Randomization, randomization treatment Week 2)
- Change From Randomization to Week 2 in Brief Psychiatric Rating Scale (BPRS) Total Scores(Randomization, randomization treatment Week 2)