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NCT02281773

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.

Completed Phase 2 Results posted Last updated 19 October 2017
What this trial tests

Phase 2 trial testing BI 409306 100 mg QD in Schizophrenia in 518 participants. Completed in 13 June 2016.

Timeline
10 November 2014
Primary endpoint
26 May 2016
13 June 2016

Quick facts

Lead sponsorBoehringer Ingelheim
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposetreatment
Enrollment518
Start date10 November 2014
Primary completion26 May 2016
Estimated completion13 June 2016
Sites43 locations across Japan, Taiwan, Germany, Canada, United States

Drugs / interventions tested

Conditions studied

Sponsor

Boehringer Ingelheim — full company profile →

Who can join

Adults 18 to 55, any sex, with Schizophrenia. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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 Primary · Baseline 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-s

GroupValue95% CI
BI 409306 - 10 Milligram1.2± 0.71
BI 409306 - 25 Milligram2.7± 0.74
BI 409306 - 50 Milligram2.8± 0.75
BI 409306 - 100 Milligram1.8± 0.73
Placebo2.5± 0.57
Occurrence of Serious Adverse Events (SAEs) (Including the Abnormalities of Physical Examination, Vital Signs, Electrocardiogram (ECG) Test and Laboratory Tests) Primary · Up to 20 weeks

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

GroupValue95% CI
BI 409306 - 10 Milligram0.0
BI 409306 - 25 Milligram0.0
BI 409306 - 50 Milligram0.0
BI 409306 - 100 Milligram0.0
Placebo5.8
Occurrence of Protocol-specified Adverse Events of Special Interest (AESI) Primary · Up to 20 weeks

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

GroupValue95% CI
BI 409306 - 10 Milligram0.0
BI 409306 - 25 Milligram0.0
BI 409306 - 50 Milligram0.0
BI 409306 - 100 Milligram0.0
Placebo0.0
Dramatic Worsening of Disease State as Assessed by Positive and Negative Syndrome Scale (PANSS) Primary · 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.

W6-Number of participants analyzed:79,74,67,71,154
GroupValue95% CI
BI 409306 - 10 Milligram-0.68± 6.022
BI 409306 - 25 Milligram-0.28± 4.507
BI 409306 - 50 Milligram-1.09± 5.415
BI 409306 - 100 Milligram-1.20± 5.426
Placebo-1.81± 5.895
W12-Number of participant analyzed:83,78,76,81,157
GroupValue95% CI
BI 409306 - 10 Milligram-2.59± 5.342
BI 409306 - 25 Milligram-0.97± 5.420
BI 409306 - 50 Milligram-1.58± 6.990
BI 409306 - 100 Milligram-0.94± 6.315
Placebo-1.66± 6.942
Suicidality as Assessed by Columbia Suicidal Severity Rating Scale (C-SSRS) Primary · 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 idea

GroupValue95% CI
BI 409306 - 10 Milligram0.0± 3.677
BI 409306 - 25 Milligram1.2± 3.262
BI 409306 - 50 Milligram2.5± 3.759
BI 409306 - 100 Milligram1.2± 3.497
Placebo3.6± 3.954
Change From Baseline in Everyday Functional Capacity as Measured by Schizophrenia Cognition Rating Scale (SCoRS) Global Ratings After 12 Weeks of Treatment Secondary · Baseline 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 pati

GroupValue95% CI
BI 409306 - 10 Milligram-2.2± 0.53
BI 409306 - 25 Milligram-3.1± 0.56
BI 409306 - 50 Milligram-2.0± 0.56
BI 409306 - 100 Milligram-2.3± 0.54
Placebo-2.5± 0.39
Change From Baseline in Clinical Global Impressions-Severity (CGI-S) Scale Score After 12 Weeks of Treatment Secondary · Baseline 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.

GroupValue95% CI
BI 409306 - 10 Milligram-0.1± 0.05
BI 409306 - 25 Milligram-0.1± 0.05
BI 409306 - 50 Milligram-0.1± 0.05
BI 409306 - 100 Milligram-0.1± 0.05
Placebo-0.1± 0.03
Patient Global Impressions-Improvement (PGI-I) Scale Score Measured After 12 Weeks of Treatment Secondary · Up 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.

GroupValue95% CI
BI 409306 - 10 Milligram2.988± 1.117
BI 409306 - 25 Milligram2.883± 1.124
BI 409306 - 50 Milligram3.192± 1.101
BI 409306 - 100 Milligram3.049± 1.342
Placebo3.038± 1.109
Change in Psychopathology Symptoms as Assessed by Positive and Negative Syndrome Scale (PANSS) Secondary · 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.

W6-Number of participants analyzed:79,74,67,71,154
GroupValue95% CI
BI 409306 - 10 Milligram-0.39± 3.677
BI 409306 - 25 Milligram-0.22± 3.262
BI 409306 - 50 Milligram-0.31± 3.759
BI 409306 - 100 Milligram-0.79± 3.497
Placebo-0.99± 3.954
W12-Number of participant analyzed:83,78,76,81,157
GroupValue95% CI
BI 409306 - 10 Milligram-1.36± 3.039
BI 409306 - 25 Milligram-0.79± 3.277
BI 409306 - 50 Milligram-0.68± 4.253
BI 409306 - 100 Milligram-0.38± 3.587
Placebo-0.76± 4.007

Adverse events — posted to ClinicalTrials.gov

Time frame: From first drug administration until 4 weeks after the last drug administration, up to 16 weeks. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

BI 409306 - 10 Milligram
Serious: 0/87 (0%)
Deaths:
BI 409306 - 25 Milligram
Serious: 0/85 (0%)
Deaths:
BI 409306 - 50 Milligram
Serious: 0/85 (0%)
Deaths:
BI 409306 - 100 Milligram
Serious: 0/86 (0%)
Deaths:
Placebo
Serious: 10/173 (6%)
Deaths:

Serious adverse events (7 terms)

ReactionSystemBI 409306 - 10 MilligramBI 409306 - 25 MilligramBI 409306 - 50 MilligramBI 409306 - 100 MilligramPlacebo
SchizophreniaPsychiatric disorders
Suicidal ideationPsychiatric disorders
Acute myocardial infarctionCardiac disorders
Ischaemic cardiomyopathyCardiac disorders
EmpyemaInfections and infestations
Psychotic disorderPsychiatric disorders
Hypertensive crisisVascular disorders
Other adverse events (3 terms — click to expand)

ReactionSystemBI 409306 - 10 MilligramBI 409306 - 25 MilligramBI 409306 - 50 MilligramBI 409306 - 100 MilligramPlacebo
HeadacheNervous system disorders
PhotophobiaEye disorders
Visual brightnessEye disorders

Most-reported serious reactions: Schizophrenia, Suicidal ideation, Acute myocardial infarction, Ischaemic cardiomyopathy, Empyema, Psychotic disorder, Hypertensive crisis.

Data from ClinicalTrials.gov NCT02281773 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. cGMP: a unique 2nd messenger molecule - recent developments in cGMP research and development.
    Friebe A, Sandner P, Schmidtko A. · · 2020 · cited 102× · PMID 31853617 · DOI 10.1007/s00210-019-01779-z
  2. New and emerging treatments for schizophrenia: a narrative review of their pharmacology, efficacy and side effect profile relative to established antipsychotics.
    Lobo MC, Whitehurst TS, Kaar SJ, Howes OD. · · 2022 · cited 74× · PMID 34838528 · DOI 10.1016/j.neubiorev.2021.11.032
  3. Evaluation of the Efficacy, Safety, and Tolerability of BI 409306, a Novel Phosphodiesterase 9 Inhibitor, in Cognitive Impairment in Schizophrenia: A Randomized, Double-Blind, Placebo-Controlled, Phase II Trial.
    Brown D, Nakagome K, Cordes J, Brenner R, et al · · 2019 · cited 34× · PMID 29718385 · DOI 10.1093/schbul/sby049
  4. Overview of Novel Antipsychotic Drugs: State of the Art, New Mechanisms, and Clinical Aspects of Promising Compounds.
    Biso L, Carli M, Scarselli M, Longoni B. · · 2025 · cited 8× · PMID 39857669 · DOI 10.3390/biomedicines13010085
  5. Abstracts for the Sixth Biennial SIRS Conference
    · 2018
  6. T65. EVALUATING PATTERNS OF SEMANTIC AND EXECUTIVE DYSFUNCTION IN SCHIZOPHRENIA: A CLUSTER ANALYSIS APPROACH
    Tan E, Meyer D, Neill E, Gurvich C, et al · · 2018
  7. T64. Submission Withdrawn
    · 2018
  8. T63. TOWARDS A COMPREHENSIVE SEMANTIC MEMORY NETWORK IN SCHIZOPHRENIA: PRELIMINARY RESULTS USING MAGNETOENCEPHALOGRAPHY (MEG) IN SCHIZOTYPY
    Batty R, Woods W, Rossell S. · · 2018

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