Clinical trial NCT00845026: A Safety Study Comparing LY2140023 to Atypical Antipsychotic Standard Treatment in Schizophrenic Patients
Official title: A Long-Term, Phase 2, Multicenter, Randomized, Open-Label Comparative Safety Study of LY2140023 Versus Atypical Antipsychotic Standard of Care in Patients With DSM-IV-TR Schizophrenia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Schizophrenia
Lead sponsor: Denovo Biopharma LLC
Sponsor class: INDUSTRY
First posted: 2009-02-16
Enrollment: 261
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 primary objective of this study was to assess time to discontinuation due to lack of tolerability among patients with schizophrenia receiving LY2140023, given orally twice daily for 24 weeks, versus those on atypical antipsychotic standard-of-care (SOC) treatment. Lack of tolerability was defined as discontinuation due to adverse events (AEs).

Patients who completed the active treatment phase were eligible to continue to an optional 28 weeks of treatment extension phase. This extension phase assessed key safety and efficacy measures.

Detailed description: A Phase 2, multicenter, randomized, parallel, open-label study comparing the long-term safety and tolerability of LY2140023 with atypical antipsychotic agents considered to be the current SOC for patients with schizophrenia. The study included a 24-week active treatment phase and an optional 28-week active treatment extension phase.

The time to discontinuation due to AEs during Study Period III (24-week active treatment phase) was compared between LY2140023 and standard of care using the log-rank test from the Kaplan-Meier survival analysis. Patients who completed Study Period III or who discontinued for a reason other than AEs were considered as censored observations.

Secondary objectives were assessed during both Study Period III \[Active Treatment Phase\] and Study Period IV \[Active Treatment Extension Phase\]) except for treatment-emergent adverse events (TEAEs), extrapyramidal symptoms (EPS), electroencephalograms (EEGs), electrocardiograms (ECGs) (analysis for Study Period III only) (indicated in "Time Frame" in "Results" section)

Eligibility criteria: Inclusion Criteria:

* Clinical diagnosis of schizophrenia
* Patients, in the investigator's opinion, must require a switch to another antipsychotic medication as clinically indicated or initiation of an antipsychotic agent
* Patients must be willing and able to be hospitalized, or to remain hospitalized (if already hospitalized), for up to 17 days
* The investigator expects, at the time of enrollment, that the patient will be able to be discharged from the hospital after the first 2 weeks of active treatment
* Disease symptoms must meet a certain range as assessed by the clinician
* Patients must have evidence of functional impairment (i.e. social or vocational deficiency)
* Patients must be considered reliable, have a level of understanding sufficient to perform all tests and examinations required by the protocol, and be willing to perform all study procedures
* Patients must be able to understand the nature of the study and have given their informed consent

Exclusion Criteria:

* Patients who are actively suicidal
* Patients who are pregnant or nursing
* Patients who have had electroconvulsive therapy (ECT) within 3 months of screening or who will have ECT at any time during the study
* Patients with uncorrected narrow-angle glaucoma, seizures, uncontrolled diabetes, certain diseases of the liver, uncontrolled thyroid condition or other serious or unstable illnesses
* Patients with Parkinson's disease, psychosis related to dementia or related disorders
* Patients with known Human Immunodeficiency Virus positive (HIV+) status

Primary outcomes:
measure: Time to Discontinuation Due to Adverse Event (AE)
timeFrame: Baseline through 24 weeks
Secondary outcomes:
measure: Number of Participants With Shift From Baseline to Maximum Post-Baseline Grading in Electroencephalograms (EEGs)
timeFrame: Baseline through 52 weeks
measure: Number of Participants With Potentially Clinically Significant Changes in QT Intervals Electrocardiograms (ECGs)
timeFrame: Baseline through 24 weeks
measure: Number of Participants With Treatment-Emergent Change in Neurological Examination
timeFrame: Baseline through 52 weeks
measure: Change From Baseline in Blood Pressure (BP) at 52 Weeks Endpoint
timeFrame: Baseline, 52 weeks
measure: Change From Baseline in Weight at 52 Weeks Endpoint
timeFrame: Baseline, 52 weeks
measure: Change From Baseline in Pulse Rate at 52 Weeks Endpoint
timeFrame: Baseline, 52 weeks
measure: Number of Participants With Potentially Clinical Significant Change in Fasting Glucose Level
timeFrame: Baseline through 52 weeks
measure: Number of Participants With Potentially Clinical Significant Change in Lipids Level
timeFrame: Baseline through 52 weeks
measure: Number of Participants With Suicidal Behaviors and Ideations Baseline Through 52 Weeks
timeFrame: Baseline through 52 weeks
measure: Change From Baseline in Positive and Negative Syndrome Scale (PANSS) at 52 Weeks Endpoint
timeFrame: Baseline, 52 weeks
measure: Change From Baseline in Clinical Global Impression Severity Scale (CGI-S) at 52 Weeks Endpoint
timeFrame: Baseline, 52 weeks
measure: Change From Baseline in 16-Item Negative Symptoms Assessment (NSA-16) Total Score at 52 Weeks Endpoint
timeFrame: Baseline, 52 weeks
measure: Change From Baseline in Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB): Overall Composite T-Score at 52 Weeks Endpoint
timeFrame: Baseline, 52 weeks
measure: Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at 52 Weeks Endpoint
timeFrame: Baseline, 52 weeks
measure: Change From Baseline in University of California-San Diego (UCSD) Performance-Based Skills Assessment-B (UPSA-B) Total Score at 52 Weeks Endpoint
timeFrame: Baseline, 52 weeks
measure: Percentage of Participants With Response (Rate of Response) at 6 and 24 Weeks Endpoints
timeFrame: 6 and 24 weeks
measure: Percentage of Participants With Remission (Rate of Remission) at Week 24 Endpoint
timeFrame: 24 weeks
measure: Percentage of Participants With Relapse (Rate of Relapse)
timeFrame: Baseline through 52 weeks
measure: Change From Baseline in Subjective Well-Being Under Neuroleptic Treatment-Short Form (SWN-S) Total Score at 52 Weeks Endpoint
timeFrame: Baseline, 52 weeks
measure: Change From Baseline in Personal and Social Performance (PSP) at 52 Weeks Endpoint
timeFrame: Baseline, 52 weeks
measure: Change From Baseline in EuroQoL Questionnaire-5 Dimension (EQ-5D) at 52 Weeks Endpoint
timeFrame: Baseline, 52 weeks
measure: Change From Baseline in Number of Psychiatric Visits at 24 Weeks Endpoint
timeFrame: Baseline, 24 weeks
measure: Change From Baseline in Barnes Akathisia Scale (BAS) Global Score at 52 Weeks Endpoint
timeFrame: Baseline, 52 weeks
measure: Change From Baseline in Simpson-Angus Scale (SAS) Total Score at 52 Weeks Endpoint
timeFrame: Baseline, 52 weeks
measure: Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score at 52 Weeks Endpoint
timeFrame: Baseline, 52 weeks
Other outcomes:
Locations:
city: Escondido
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: Garden Grove
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: Washington
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: District of Columbia
city: Chicago
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: Illinois
city: Hoffman Estates
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: Illinois
city: Indianapolis
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: Indiana
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: Willingboro
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: New Jersey
city: Amityville
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: New York
city: Oklahoma City
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: Oklahoma
city: DeSoto
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: Texas
city: Jena
country: Germany
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.
city: Mannheim
country: Germany
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.
city: Wiesbaden
country: Germany
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.
city: Guadalajara
country: Mexico
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.
city: Mexico City
country: Mexico
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.
city: Monterrey
country: Mexico
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.
city: Khotkovo
country: Russian Federation
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.
city: Lipetsk
country: Russian Federation
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.
city: Moscow
country: Russian Federation
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.
city: Nizhniy Novgorod
country: Russian Federation
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.
city: Saint Petersburg
country: Russian Federation
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.
city: Samara
country: Russian Federation
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: