Clinical trial NCT03859973: This Study Tests Whether BI 425809 Together With Brain Training Using a Computer Improves Mental Functioning in Patients With Schizophrenia
Official title: A Phase II Randomized, Double-blinded, Placebo-controlled Parallel Group Trial to Examine the Efficacy and Safety of BI 425809 Once Daily With Adjunctive Computerized Cognitive Training Over 12 Week Treatment Period in Patients With Schizophrenia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Schizophrenia
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2019-03-01
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a study in adults with schizophrenia. The study tests whether a medicine called BI 425809 together with brain training improves mental abilities.

Participants take study medication once a day for 12 weeks. At the start of the study, the participants are put into 2 groups. It is decided by chance who gets into which group. One group gets BI 425809 tablets every day. The other group gets placebo tablets every day. Placebo tablets look like the BI 425809 tablets, but contain no medicine. During the study, all participants do brain training using a computer.

The doctors regularly test mental abilities of the participants. The results of the mental ability tests are compared between the groups. The doctors also check the general health of the patients.


Eligibility criteria: Inclusion Criteria:

* Signed and dated written informed consent in accordance with ICH Harmonized Tripartite Guideline for Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial.
* Male or female patients who are 18-50 years (inclusive) of age at time of consent.
* Established schizophrenia (as per DSM-5) with the following clinical features:

  * Outpatient, with no hospitalization for worsening of schizophrenia within 3 months prior to randomization
  * Psychiatrically stable without symptom exacerbation within 3 months prior to randomization
  * PANSS score ≤ 5 on positive items P1, P3-P7 and ≤ 4 on positive item P2 at Visit 1, and confirmed at Visit 2
* Patients must be on stable antipsychotic treatment; also, current antipsychotic medications and concomitant anticholinergics, antiepileptics, lithium and allowed antidepressants must meet the criteria below:

  * Patients must take 1 and may take up to 2 antipsychotics (typical and/or atypical), except for clozapine
  * Patients must be stable on current antipsychotics, anticholinergics, antiepileptics, lithium and allowed antidepressants for at least 3 months prior to randomization and be on current dose for at least 30 days prior to randomization o Patients on Long-Acting Injectable (LAI) antipsychotics should be on the same medication and dose for at least 3 months prior to randomization
* Women of childbearing potential (WOCBP)2 must be ready and able to use highly effective methods of birth control per Non-Clinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals (ICH M3 (R2)) that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria is provided in Section 4.2.2.3. Such methods should be used throughout the trial, and for a period of at least 35 days after last trial drug intake, and the patient must agree to periodic pregnancy testing during participation in the trial.
* Patients must demonstrate their ability to properly use the CCT device and program, as well as be compliant with CCT run-in (defined as completing at least 2 hours per week for two weeks, totalling 4 hours CCT, during the screening period)3.
* Patients must be able to comply with all protocol procedures, in the investigator's opinion.
* Patients must have a study partner who will preferably be consistent throughout the study. It is recommended that the study partner should interact (in-person or telephone) with the subject at least 2 times a week.

Exclusion Criteria:

* Patients who have a categorical diagnosis of another current major psychiatric disorder on the Mini-International Neuropsychiatric Interview (M.I.N.I.).
* Diseases of the central nervous system (CNS) that may impact the assessment of the cognitive tests as per investigator's opinion. A movement disorder due to antipsychotic treatment not currently controlled with anti- EPS treatment or another movement disorder (e.g. Parkinson´s disease).
* Patients with a history of participating in any formal cognitive remediation program for 10 or more training sessions.
* Patients who were treated with any of the following medications within the last 6 months prior to randomization:

  * Bitopertin, BI 409306, encenicline or other investigational drug testing effects on cognition in schizophrenia
  * Clozapine (atypical antipsychotic medication)
  * Sarcosine, cycloserine, serine and glycine
  * Stimulants (e.g. methylphenidate, dextroamphetamine, modafinil)
  * Tricyclic antidepressants
* Patients receiving any other investigational drug (other than a potential cognitive enhancing drug) within 30 days or 6 half-lives (whichever is longer) prior to randomization. For investigational LAI antipsychotics, the last injection must be at least 3 months or two administration cycles (i.e. 6 months if administration is every 3 months) prior to randomization, whichever is longer.
* Patients who have participated in a clinical trial with repeated assessments (i.e. a single assessment is not exclusionary) with the MATRICS Consensus Cognitive Battery (MCCB) within the last 6 months prior to randomization.
* Patients who required a change in ongoing benzodiazepine or sleep medication dose or regimen within the last 30 days prior to randomization.
* Patients with known active infection with SARS-CoV-2 within the last 30 days prior to randomization.
* Other exclusion criteria apply

Primary outcomes:
measure: Change From Baseline in Neurocognitive Function as Measured by the Neurocognitive Composite Score of the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) After 12 Weeks of Treatment
timeFrame: At screening (28 days prior to first drug drug administration), at baseline and at Weeks 6 and 12 after first drug administration.
Secondary outcomes:
measure: Change From Baseline in Cognitive Function as Measured by the Overall MCCB Composite T Score (Including Social Cognition) After 12 Weeks of Treatment
timeFrame: At screening (28 days prior to first drug drug administration), at baseline and at Weeks 6 and 12 after first drug administration.
measure: Change From Baseline in the Effect of Cognitive Deficit on Day-to-day Functioning as Measured by SCoRS Total Score After 12 Weeks of Treatment
timeFrame: At baseline and at 12 weeks after first drug administration.
measure: Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score After 12 Weeks of Treatment
timeFrame: At baseline and at Weeks 6 and 12 after first drug administration.
measure: Percentage of Patients With Any Adverse Event (AE) and With Serious Adverse Events (SAEs)
timeFrame: From first dose of study drug administration until four weeks after the last dose of study drug administration, up to 16 weeks.
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Atria Clinical Research
state: Arkansas
city: Rogers
country: United States
facility: Woodland Research Northwest
state: Arkansas
city: Encino
country: United States
facility: Encino Hospital Medical Center
state: California
city: Garden Grove
country: United States
facility: Collaborative Neuroscience Network, LLC (CNS)
state: California
city: Lemon Grove
country: United States
facility: Synergy San Diego
state: California
city: Montclair
country: United States
facility: Catalina Research Institute, LLC
state: California
city: Oakland
country: United States
facility: Pacific Research Partners, LLC
state: California
city: Orange
country: United States
facility: NRC Research Institute
state: California
city: Pico Rivera
country: United States
facility: CNRI - Los Angeles
state: California
city: San Diego
country: United States
facility: CNRI-San Diego, LLC
state: California
city: Torrance
country: United States
facility: Collaborative Neuroscience Network, LLC (CNS)
state: California
city: Maitland
country: United States
facility: Meridien Research
state: Florida
city: Miami
country: United States
facility: Premier Clinical Research Institute
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Tallahassee
country: United States
facility: Apalachee Center
state: Florida
city: West Palm Beach
country: United States
facility: Jerome Golden Center for Behavioral Health
state: Florida
city: Atlanta
country: United States
facility: Synexus
state: Georgia
city: Chicago
country: United States
facility: Uptown Research Institute
state: Illinois
city: Lake Charles
country: United States
facility: Lake Charles Clinical Trials LLC
state: Louisiana
city: Grand Rapids
country: United States
facility: Cherry Health
state: Michigan
city: Kansas City
country: United States
facility: Center for Behavioral Medicine
state: Missouri
city: New York
country: United States
facility: Synexus Clinical Research US, Inc.
state: New York
city: Raleigh
country: United States
facility: UNC Center for Excellence in Community Mental Health, North Carolina Psychiatric Research Center
state: North Carolina
city: Dayton
country: United States
facility: Midwest Clinical Research
state: Ohio
city: Dallas
country: United States
facility: FutureSearch Trials of Dallas, LP
state: Texas
city: Richardson
country: United States
facility: Pillar Clinical Research, LLC
state: Texas
city: Richmond
country: United States
facility: Office of Dr. Aqeel Hashmi, MD, PA
state: Texas
city: Bellevue
country: United States
facility: Northwest Clinical Research Center
state: Washington
city: Elizabeth Vale
country: Australia
facility: Lyell McEwin Hospital
state: South Australia
city: Clayton
country: Australia
facility: Monash Medical Centre
state: Victoria
city: Fitzroy
country: Australia
facility: St Vincent's Hospital Melbourne
state: Victoria
city: Melbourne
country: Australia
facility: Monash Alfred Psychiatry Research Centre
state: Victoria
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
city: Vancouver
country: Canada
facility: BC Mental Health and Addictions Research Institute (University of British Columbia)
state: British Columbia
city: Toronto
country: Canada
facility: Centre for Addiction and Mental Health (CAMH)
state: Ontario
city: Montreal
country: Canada
facility: IUSMM Institut Universitaire en Sante Mentale de Montreal
state: Quebec
city: Caen
country: France
facility: CTR Esquirol
city: Dijon
country: France
facility: HOP Dijon-Bourgogne
city: Douai
country: France
facility: CAB Médical Psyché
city: Montpellier
country: France
facility: HOP la Colombière
city: Nantes
country: France
facility: HOP Saint-Jacques
city: Nice
country: France
facility: HOP Pasteur
city: Paris
country: France
facility: GHU Paris Psychiatrie et Neurosciences
city: Saint Priest en Jarez
country: France
facility: HOP Nord
city: Takpuna Auckland
country: New Zealand
facility: North Shore Hospital, Takapuna
city: Cheltenham
country: United Kingdom
facility: The Fritchie Centre
city: Edinburgh
country: United Kingdom
facility: Royal Edinburgh Hospital
city: Glasgow
country: United Kingdom
facility: Queen Elizabeth University Hospital
city: London
country: United Kingdom
facility: Maudsley Hospital
city: Oxford
country: United Kingdom
facility: Warneford Hospital
Study officials:
References:
citation: Harvey PD, Bowie CR, McDonald S, Podhorna J. Evaluation of the Efficacy of BI 425809 Pharmacotherapy in Patients with Schizophrenia Receiving Computerized Cognitive Training: Methodology for a Double-blind, Randomized, Parallel-group Trial. Clin Drug Investig. 2020 Apr;40(4):377-385. doi: 10.1007/s40261-020-00893-8.