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.

NCT02281773 | Completed Phase 2 Results

• 2 other identifiers: 1289.62013-005015-28
• Study Type: interventional
• Target: 518
• Locations: 5 countries
• Sites: 43

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.

Conditions

Schizophrenia

Outcome Measures

Primary Outcomes (5)

• 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 Treatment

  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.

  Baseline and Week 12

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

  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 Protocol-specified Adverse Events of Special Interest (AESI)

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

  Up to 20 weeks

• Dramatic Worsening of Disease State as Assessed by Positive and Negative Syndrome Scale (PANSS)

  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.

  Baseline, Week 6 and Week 12

• Suicidality as Assessed by Columbia Suicidal Severity Rating Scale (C-SSRS)

  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.

  Up to 12 weeks

Secondary Outcomes (5)

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

  Baseline and Week 12

• Change From Baseline in Clinical Global Impressions-Severity (CGI-S) Scale Score After 12 Weeks of Treatment

  Baseline and Week 12

• Patient Global Impressions-Improvement (PGI-I) Scale Score Measured After 12 Weeks of Treatment

  Up to 12 weeks

• 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 in Psychopathology Symptoms as Assessed by Positive and Negative Syndrome Scale (PANSS)

  Baseline, Week 6 and Week 12

Study Arms (5)

dose 1

EXPERIMENTAL

Drug: BI 409306 10 mg QD

dose 2

EXPERIMENTAL

Drug: BI 498306 25 mg QD

dose 3

EXPERIMENTAL

Drug: BI 498306 50 mg QD

dose 4

EXPERIMENTAL

Drug: BI 409306 100 mg QD

placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

BI 409306 100 mg QD DRUG

dose 4

BI 498306 50 mg QD DRUG

dose 3

Placebo DRUG

placebo

BI 498306 25 mg QD DRUG

dose 2

BI 409306 10 mg QD DRUG

dose 1

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Patients with established diagnoses of schizophrenia (per Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5)) with the following clinical features:
• a) Clinically stable and are in the residual (non-acute) phase of their illness for at least 8 weeks b) Current antipsychotic and concomitant psychotropic medications must meet the criteria below: b)-1 Maintained on current atypical (second generation) antipsychotic medications (in any approved dosage form) other than Clozapine and on current dose for at least 8 weeks prior to randomisation, and/or b)-2 Maintained on current typical (first generation) antipsychotic medications and on current dose for at least 6 months, optionally combined with anticholinergics if treated with a stable dose for at least 6 months prior to randomisation, and/or b)-3 Maintained on current concomitant psychotropic medications other than anticholinergics, antiepileptics and lithium, and on current dose for at least 8 weeks prior to randomisation. Antiepileptics and lithium are allowed if initiated at least 6 months prior to randomisation.
• b)-4 Anticholinergics, antiepileptics and lithium have been washed out for at least 6 months prior to randomisation if the treatments that patients were using before entering the clinical trial are discontinued.
• c) Have no more than a "moderate" severity rating on hallucinations and delusions (Positive and Negative Syndrome Scale (PANSS)-positive syndrome Hallucinatory Behavior item score \< =4 and Delusions item score \< = 4) d) Have no more than a "moderate" severity rating on positive formal thought disorder (PANSS-positive syndrome Conceptual Disorganization item score \< = 4) e) Have a minimal level of extrapyramidal symptoms (Simpson-Angus Scale total score \< 6) and depressive symptoms (PANSS-general psychopathology syndrome Depression item score \< = 4)
• Male or female patients age 18 to 55 years
• Patients must exhibit reliability, physiologic capability, and an educational level sufficient to comply with all protocol procedures,in the investigator's opinion.
• Signed and dated written informed consent by date of Visit 1 in accordance with GCP and the local legislation. If the patient needs a legal representative, then this legal representative must give written informed consent as well.
• Patients must have an identified informant who will be consistent throughout the study. The informant must interact with the subject at least 2 times a week.
• Note: Informant ratings are needed for SCoRS global ratings at Randomisation Visit (Visit 2) and (early) End of Treatment Visit. In person informant ratings on the study visits are preferred whenever possible. However, if the informant is not available for in person ratings, telephone interview is acceptable. The informant must be available for a telephone interview at Visit 2 and (e)EOT Visit.

You may not qualify if:

• Patient treated with more than two antipsychotic medications (including more than two dosage forms)
• Patient's cognitive impairment severity compromises the validity of the cognitive outcome measures, in the clinical judgment of the investigator
• Any suicidal behavior in the past 2 years (i.e. actual attempt, interrupted attempt, aborted attempt, or preparatory acts or behavior)
• Any suicidal ideation of type 4 or 5 in the Columbia Suicidal Severity Rating Scale (C-SSRS) in the past 3 months (i.e. active suicidal thought with intent but without specific plan, or active suicidal thought with plan and intent)
• In the judgment of the investigator, any clinically significant finding of the medical examination (including BP, PR and ECG) or laboratory value deviating from normal or any evidence of a clinically significant concomitant disease or any other clinical condition that would jeopardize a patient's safety while participating in the clinical trial
• History or diagnosis of symptomatic and unstable/uncontrolled gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological, hematological or hormonal disorders
• For female patients:
• Pre-menopausal women (last menstruation \< =1 year prior to informed consent) who:
• are nursing or pregnant or
• are of child-bearing potential and are not practicing an acceptable method of birth control, or do not plan to continue using this method throughout the trial until 28 days after the last treatment administration, and do not agree to submit to periodic pregnancy testing during participation in the trial. Acceptable methods of birth control include tubal ligation, vasectomized partner, transdermal patch, intra uterine devices/systems (IUDs/IUSs), combined estrogen-progestin oral contraceptives as well as implantable or injectable hormonal contraceptives. Complete sexual abstinence (if acceptable by local health authorities) is allowed when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptom-thermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. Double barrier methods are permissible (if acceptable by local health authorities, note that this is not an acceptable method in EU countries).
• For male patients:
• Men who are able to father a child, unwilling to be abstinent or use adequate contraception for the duration of study participation and for at least 28 days after treatment has ended.
• Known history of HIV infection
• Diseases of the central nervous system (including but not limited to any kind of seizures, stroke or any psychiatric disorders other than schizophrenia)
• Any subject who on the Mini-international neuropsychiatric Interview (M.I.N.I.) has a categorical diagnosis of another current major psychiatric disorder.

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (43)

K and S Professional Research Services, LLC

Little Rock, Arkansas, 72201, United States

Location

Comprehensive Clinical Development, Inc.

Cerritos, California, 90703, United States

Location

Collaborative Neuroscience Network

Garden Grove, California, 92845, United States

Location

Pacific Institute of Medical Research

Los Angeles, California, 90024, United States

Location

SRSD, Inc. dba Synergy San Diego

National City, California, 91950, United States

Location

NRC Research Institute

Orange, California, 92868, United States

Location

Artemis Institute for Clinical Research, LLC

San Diego, California, 92103, United States

Location

Collaborative Neuroscience Network

Torrance, California, 90502, United States

Location

Comprehensive Clinical Development

Washington D.C., District of Columbia, 20016, United States

Location

Innovative Clinical Research

Lauderhill, Florida, 33319, United States

Location

Florida Clinical Research Center

Maitland, Florida, 32751, United States

Location

Behavioral Clinical Research, Inc.

North Miami, Florida, 33161, United States

Location

Atlanta Center

Atlanta, Georgia, 30331, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Uptown Research Institute

Chicago, Illinois, 60640, United States

Location

Lake Charles Clinical Trials LLC

Lake Charles, Louisiana, 70629, United States

Location

Mid-America Clinical Research, LLC

St Louis, Missouri, 63109, United States

Location

St. Louis Clinical Trials

St Louis, Missouri, 63141, United States

Location

Neurobehavioral Research, Inc.

Cedarhurst, New York, 11516, United States

Location

Finger Lakes Research

Rochester, New York, 14618, United States

Location

University of Rochester Medical Center

Rochester, New York, 14623, United States

Location

Richmond Behavioral Associates

Staten Island, New York, 10312, United States

Location

Community Clinical Research, Inc.

Austin, Texas, 78754, United States

Location

InSite Clinical Research

DeSoto, Texas, 75115, United States

Location

Dr. Alexander McIntyre Inc.

Penticton, British Columbia, V2A 4M4, Canada

Location

Depression, Mood Disorders and Schizophrenia Treatment Centr

Burlington, Ontario, L7R4E2, Canada

Location

Universitätsklinikum Köln (AöR)

Cologne, 50937, Germany

Location

LVR-Klinikum Düsseldorf

Düsseldorf, 40629, Germany

Location

Uniklinikum Heidelberg

Heidelberg, 69115, Germany

Location

Fujita Health University Hospital

Aichi, Toyoake, 470-1192, Japan

Location

Hokkaido University Hospital

Hokkaido, Sapporo, 060-8648, Japan

Location

Kobe University Hospital

Hyogo, Kobe, 650-0017, Japan

Location

Nara Medical University Hospital

Nara, Kashihara, 634-8522, Japan

Location

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

Osaka, Moriguchi-city, 570-8507, Japan

Location

Hizen Psychiatric Center, Saga, PSY

Saga, Kanzaki-gun, 842-0192, Japan

Location

Iwaki Clinic, Tokushima, Psychosomatic Medicine

Tokushima, Anan, 774-0014, Japan

Location

National Center Neurology and Psychiatry

Tokyo, Kodaira, 187-8851, Japan

Location

Showa University Karasuyama Hospital

Tokyo, Setagaya, 157-8577, Japan

Location

Showa University East Hospital

Tokyo, Shinagawa, 142-0054, Japan

Location

Chang-Hua Christian Hospital

Changhua, 500, Taiwan

Location

Kai-Syuan Psychiatric Hospital

Kaohsiung City, 802, Taiwan

Location

NCKUH

Tainan, 704, Taiwan

Location

Taipei City Hospital

Taipei, 110, Taiwan

Location

Related Publications (2)

• Dorner-Ciossek C, Kroker KS, Rosenbrock H. Role of PDE9 in Cognition. Adv Neurobiol. 2017;17:231-254. doi: 10.1007/978-3-319-58811-7_9.

  PMID: 28956335 DERIVED

• Georgiades A, Davis VG, Atkins AS, Khan A, Walker TW, Loebel A, Haig G, Hilt DC, Dunayevich E, Umbricht D, Sand M, Keefe RSE. Psychometric characteristics of the MATRICS Consensus Cognitive Battery in a large pooled cohort of stable schizophrenia patients. Schizophr Res. 2017 Dec;190:172-179. doi: 10.1016/j.schres.2017.03.040. Epub 2017 Apr 20.

  PMID: 28433500 DERIVED

MeSH Terms

Conditions

Schizophrenia

Interventions

BI 409306

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Limitations and Caveats

"Change from baseline in PANSS negative symptom factor score after 12 weeks of treatment" was not analysed because as per internal BI rules, descriptive statistics are not calculated if data is available for less than 2/3rds of participants

Results Point of Contact

• Title: Boehringer Ingelheim, Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 31, 2014
• First Posted: November 4, 2014
• Study Start: November 10, 2014
• Primary Completion: May 26, 2016
• Study Completion: June 13, 2016
• Last Updated: October 19, 2017
• Results First Posted: October 19, 2017

Record last verified: 2017-09

Locations

CA (2); JP (10); TW (4); US (24); DE (3)