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
Overview
- Phase
- Phase 2
- Intervention
- BI 425809
- Conditions
- Schizophrenia
- Sponsor
- Boehringer Ingelheim
- Enrollment
- 200
- Locations
- 49
- Primary Endpoint
- 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
- Status
- Completed
- Last Updated
- 2 years ago
Overview
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.
Investigators
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.
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.
Arms & Interventions
BI 425809 10 mg + Computerized Cognitive Training
Intervention: BI 425809
Placebo + Computerized Cognitive Training
Intervention: Placebo
Outcomes
Primary Outcomes
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
Time Frame: At screening (28 days prior to first drug drug administration), at baseline and at Weeks 6 and 12 after first drug administration.
MCCB neurocognitive composite T-score assesses 6 cognitive domains, including speed of processing, attention vigilance, working memory, verbal learning, visual learning, reasoning and problem solving. MCCB neurocognitive T-scores in the general population have a mean of 50 and standard deviation of 10. A higher T-score indicates better cognition. Change from baseline in MCCB neurocognitive composite T-score at Week 12 was modelled based on a restricted maximum likelihood (REML) based approach using a mixed model with repeated measurements (MMRM) which included the following fixed effects: categorical factor of planned treatment, visit (screening, baseline, week 6 and Week 12), planned treatment by visit interaction, continuous covariate of baseline value, baseline by visit interaction, categorical factor of age group, and continuous covariate of change from screening to baseline value. The Least Squares Mean (95 % Confidence Interval) at Week 12 is reported.
Secondary Outcomes
- Change From Baseline in Cognitive Function as Measured by the Overall MCCB Composite T Score (Including Social Cognition) After 12 Weeks of Treatment(At screening (28 days prior to first drug drug administration), at baseline and at Weeks 6 and 12 after first drug administration.)
- Percentage of Patients With Any Adverse Event (AE) and With Serious Adverse Events (SAEs)(From first dose of study drug administration until four weeks after the last dose of study drug administration, up to 16 weeks.)
- 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(At baseline and at 12 weeks after first drug administration.)
- Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score After 12 Weeks of Treatment(At baseline and at Weeks 6 and 12 after first drug administration.)