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A Study to Investigate the Efficacy, Safety and Tolerability of Four Different Doses of BI 409306 Compared to Placebo Given for 12 Weeks in Patients With Schizophrenia on Stable Antipsychotic Treatment.

Phase 2
Completed
Conditions
Schizophrenia
Interventions
Drug: BI 498306 50 mg QD
Drug: BI 409306 10 mg QD
Drug: BI 409306 100 mg QD
Drug: BI 498306 25 mg QD
Drug: Placebo
Registration Number
NCT02281773
Lead Sponsor
Boehringer Ingelheim
Brief Summary

The objective of the study is to investigate the efficacy, safety and tolerability of four different doses of BI 409306 once daily compared to placebo given for 12 weeks in patients with schizophrenia on stable antipsychotic treatment.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
518
Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
dose 3BI 498306 50 mg QD-
dose 1BI 409306 10 mg QD-
dose 4BI 409306 100 mg QD-
dose 2BI 498306 25 mg QD-
placeboPlacebo-
Primary Outcome Measures
NameTimeMethod
Suicidality as Assessed by Columbia Suicidal Severity Rating Scale (C-SSRS)Up to 12 weeks

C-SSRS: Number (%) of subjects with an event of Suicidal Ideation (Wish to be dead, Non-specific active suicidal thoughts, Active suicidal ideation with any methods (not plan) without intent to act, Active suicidal ideation with some intent to act without specific plan, Active suicidal ideation with specific plan and intent) or Suicidal Behavior (Preparatory acts or behavior, Aborted attempt, Interrupted attempt, Non-fatal suicide attempt, Completed suicide) or Self-injurious behavior without suicidal intent is presented. C-SSRS used only to evaluate whether the patient developed suicidal ideation or behavior and no composite score will be used. Questions in the 1st section of suicidal ideation and suicidal behavior assessments in C-SSRS are "yes" and "no" type questions. If patient had suicidal ideation or behavior, 2nd section will be performed to evaluate the details with the scale from 0 to 5 or 0 to 2 and the larger number means the more severe condition.

Occurrence of Serious Adverse Events (SAEs) (Including the Abnormalities of Physical Examination, Vital Signs, Electrocardiogram (ECG) Test and Laboratory Tests)Up to 20 weeks

Occurrence of serious adverse events (SAEs) (including the abnormalities of physical examination, vital signs, electrocardiogram (ECG) test and laboratory tests).

Dramatic Worsening of Disease State as Assessed by Positive and Negative Syndrome Scale (PANSS)Baseline, Week 6 and Week 12

Dramatic worsening of disease state as assessed by Positive and Negative Syndrome Scale (PANSS). It contains 30-items including seven positive symptom items, seven negative symptom items and 16 general psychopathology symptom items. Each item was scored on the same seven point severity scale. Fourteen of the PANSS items required input from an informant. Total score ranges from 30 to 210 (minimum is better). The descriptive statistics of change from baseline (CFB) in PANSS score at week 6 (W6) and week 12 (W12) are presented.

Occurrence of Protocol-specified Adverse Events of Special Interest (AESI)Up to 20 weeks

Occurrence of Protocol-specified adverse events of special interest (AESI).

Change From Baseline in the Composite Score of Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) After 12 Weeks of TreatmentBaseline and Week 12

MCCB comprises 10 tests, which assess 7 cognitive domains, including speed of processing, attention vigilance, working memory, verbal learning, visual learning, reasoning problem solving, and social cognition. The composite score was calculated by summing over the standardised score of each domain for analysis and it varies from -20 to 99 with higher score indicating better outcome. The trial was set up as "learn and confirm" model including 2 stages. Stage 1 analysis was conducted to identify the meaningful cognition endpoint(s) (CANTAB domain(s)) and the selected endpoint(s) were to be pre-specified as the primary endpoint(s) for Stage 2 analysis. Since none of the CANTAB outcome measures was selected in the Stage 1 analysis at planned time based on the pre-specified criteria, the MCCB composite score was chosen as the primary endpoint in the Stage 2 analysis, as pre-defined.

Secondary Outcome Measures
NameTimeMethod
Change From Baseline in Clinical Global Impressions-Severity (CGI-S) Scale Score After 12 Weeks of TreatmentBaseline and Week 12

Change from baseline in Clinical Global Impressions-Severity (CGI-S) scale score after 12 weeks of treatment. The CGI-S is a one-item evaluation completed by the clinician on the patient's severity of psychopathology. The CGI-S was rated ordinally from one to 7. Higher scores indicate more severe symptoms.

Change in Psychopathology Symptoms as Assessed by Positive and Negative Syndrome Scale (PANSS)Baseline, Week 6 and Week 12

Change in psychopathology symptoms as assessed by Positive and Negative Syndrome Scale (PANSS). It contains 30-items including seven positive symptom items, seven negative symptom items and 16 general psychopathology symptom items. Each item was scored on the same seven point severity scale. Fourteen of the PANSS items required input from an informant. Total score ranges from 30 to 210 (minimum is better). The descriptive statistics of change from baseline (CFB) in PANSS score at week 6 (W6) and week 12 (W12) are presented.

Patient Global Impressions-Improvement (PGI-I) Scale Score Measured After 12 Weeks of TreatmentUp to 12 weeks

Patient Global Impressions-Improvement (PGI-I) scale score measured after 12 weeks of treatment. The PGI of improvement is a simple evaluation completed by the patient to assess the patient's overall evaluation of his/her status. The PGI of improvement was rated ordinally from one to 7. Higher scores indicate more severe symptoms.

Change From Baseline in PANSS Negative Symptom Factor Score After 12 Weeks of Treatment (for Subset of Patients Diagnosed With Negative Symptom)Baseline and Week 12

Change from baseline in PANSS negative symptom factor score after 12 weeks of treatment (for subset of patients diagnosed with negative symptom). This outcome measure was not analysed due to low number of patients in the PANSS negative symptom subgroup. The PANSS negative symptom scale has 7 items. Each was rated from one to 7 points. The total factor score was the summation of the 7 points for each item, leading the total score ranging from 7 to 49.

Change From Baseline in Everyday Functional Capacity as Measured by Schizophrenia Cognition Rating Scale (SCoRS) Global Ratings After 12 Weeks of TreatmentBaseline and Week 12

Change from baseline in everyday functional capacity as measured by Schizophrenia Cognition Rating Scale (SCoRS) global ratings after 12 weeks of treatment. SCoRS is a 20-item interview-based assessment of cognitive deficits and the degree to which they affect day-to-day functions. Each item was rated on a 4-point scale. Higher ratings reflected a greater degree of impairment. The SCoRS global total scores is the sum of the 20 items and it varies from 20 to 80 with 20 being the best outcome and 80 being the worst. If any individual item was missing, it was imputed with the average of that patient's non missing responses. If \>5 items were missing, the total score was missing.

Trial Locations

Locations (42)

Artemis Institute for Clinical Research, LLC

🇺🇸

San Diego, California, United States

Uptown Research Institute

🇺🇸

Chicago, Illinois, United States

Comprehensive Clinical Development, Inc.

🇺🇸

Cerritos, California, United States

Collaborative Neuroscience Network

🇺🇸

Torrance, California, United States

Pacific Institute of Medical Research

🇺🇸

Los Angeles, California, United States

NRC Research Institute

🇺🇸

Orange, California, United States

Florida Clinical Research Center

🇺🇸

Maitland, Florida, United States

Innovative Clinical Research

🇺🇸

Lauderhill, Florida, United States

Behavioral Clinical Research, Inc.

🇺🇸

North Miami, Florida, United States

Northwestern University

🇺🇸

Chicago, Illinois, United States

Atlanta Center

🇺🇸

Atlanta, Georgia, United States

Mid-America Clinical Research, LLC

🇺🇸

Saint Louis, Missouri, United States

Neurobehavioral Research, Inc.

🇺🇸

Cedarhurst, New York, United States

Lake Charles Clinical Trials LLC

🇺🇸

Lake Charles, Louisiana, United States

St. Louis Clinical Trials

🇺🇸

Saint Louis, Missouri, United States

Finger Lakes Research

🇺🇸

Rochester, New York, United States

Community Clinical Research, Inc.

🇺🇸

Austin, Texas, United States

Richmond Behavioral Associates

🇺🇸

Staten Island, New York, United States

InSite Clinical Research

🇺🇸

DeSoto, Texas, United States

Depression, Mood Disorders and Schizophrenia Treatment Centr

🇨🇦

Burlington, Ontario, Canada

LVR-Klinikum Düsseldorf

🇩🇪

Düsseldorf, Germany

Uniklinikum Heidelberg

🇩🇪

Heidelberg, Germany

Universitätsklinikum Köln (AöR)

🇩🇪

Köln, Germany

Hokkaido University Hospital

🇯🇵

Hokkaido, Sapporo, Japan

Nara Medical University Hospital

🇯🇵

Nara, Kashihara, Japan

Kansai Med. Univ. Med. Ctr., Osaka, Neuropsychiatry

🇯🇵

Osaka, Moriguchi-city, Japan

Iwaki Clinic, Tokushima, Psychosomatic Medicine

🇯🇵

Tokushima, Anan, Japan

Showa University East Hospital

🇯🇵

Tokyo, Shinagawa, Japan

Chang-Hua Christian Hospital

🇨🇳

Changhua, Taiwan

Taipei City Hospital

🇨🇳

Taipei, Taiwan

Hizen Psychiatric Center, Saga, PSY

🇯🇵

Saga, Kanzaki-gun, Japan

Comprehensive Clinical Development

🇺🇸

Washington, D.C., District of Columbia, United States

Fujita Health University Hospital

🇯🇵

Aichi, Toyoake, Japan

Kai-Syuan Psychiatric Hospital

🇨🇳

Kaohsiung, Taiwan

University of Rochester Medical Center

🇺🇸

Rochester, New York, United States

K and S Professional Research Services, LLC

🇺🇸

Little Rock, Arkansas, United States

Dr. Alexander McIntyre Inc.

🇨🇦

Penticton, British Columbia, Canada

Kobe University Hospital

🇯🇵

Hyogo, Kobe, Japan

National Center Neurology and Psychiatry

🇯🇵

Tokyo, Kodaira, Japan

Showa University Karasuyama Hospital

🇯🇵

Tokyo, Setagaya, Japan

NCKUH

🇨🇳

Tainan, Taiwan

SRSD, Inc. dba Synergy San Diego

🇺🇸

National City, California, United States

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