Clinical trial NCT02824055 (phase 1, status: completed)
Conditions: schizophrenia
ICD codes: F20.0, F20.1, F20.2, F20.3, F20.5, F20.89, F20.9
Drugs: placebo, ro5545965
SMILES: CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
Eligibility criteria:

        Inclusion Criteria:

          -  A diagnostic and statistical manual of mental disorders-5 (DSM-5) diagnosis of
             schizophrenia as established by structured clinical interview for DSM-5-clinical trial
             (SCID-5-CT) at screening

          -  Participants with no hospitalization for worsening of schizophrenia within 3 months
             prior to screening

          -  Male and female participants with no childbearing capacity; females must be either
             surgically sterile or postmenopausal for at least 1 year

          -  Body mass index (BMI) greater than (>) 18.5 kilograms per square meter (kg/m^2) and
             less than (<) 35 kg/m^2

          -  Fluent in English, even if English is not the primary language

          -  Participants with clinical global impression-severity (CGI-S) score greater than or
             equal to (>/=) 3 (mildly ill)

          -  Participants with a score of less than or equal to (</=) 4 (moderate) on positive and
             negative syndrome scale (PANSS) items P7 (hostility), G8 (uncooperativeness) and G6
             (depression)

          -  Participants with PANSS negative symptom factor score >/=18

          -  Participants with calgary depression rating scale for schizophrenia (CDSS) score </=8

          -  Participants on stable treatment, that is 6 weeks without change, with no more than
             two antipsychotics prior to screening

        Exclusion Criteria:

          -  Moderate to severe substance use disorder within 6 months as defined by DSM-5

          -  Positive urine drug screen for amphetamines, methamphetamines, opiates, buprenorphine,
             methadone, cannabinoids, cocaine and barbiturates

          -  Participants at significant risk of suicide or harming him or herself or others
             according to the Investigator's judgment

          -  History of neuroleptic malignant syndrome

          -  A prior or current general medical condition that might be impairing cognition or
             other psychiatric functioning

          -  A movement disorder due to antipsychotic treatment not currently controlled with
             anti-extrapyramidal symptoms (anti-EPS) treatment or another movement disorder which
             might affect the ratings on the EPS scales

          -  Participants with a score >2 (mild) in any of the four CGI-S items of the
             extrapyramidal symptom rating scale (ESRS-A)

          -  History of human immunodeficiency virus (HIV) infection, Hepatitis B, or Hepatitis C
             infection

          -  QTcF interval >450 milliseconds (msec) (470 msec for females) or other significant
             abnormality on screening electrocardiogram (ECG) based on centralized reading

          -  Clinically significant abnormalities in laboratory safety test results

          -  Significant or unstable physical condition

          -  Receipt of an investigational drug within 90 days or 5 times the half-life of the
             investigational drug, whatever is longer, prior to screening

          -  Previously received RO5545965

          -  Electroconvulsive treatment (ECT) within 6 months prior to screening

          -  Current or 6 months prior to screening treatment with olanzapine or clozapine

          -  Change in benzodiazepine or sleep medication regimen within 2 weeks prior to screening

          -  Change in anti-EPS medication within two weeks prior to screening

          -  Use of prohibited medications taken within 14 days or within 5 times the elimination
             half-life of the medication before the first study drug administration

          -  Use of any strong or moderate inhibitor of cytochrome P 450 3A (CYP3A) or CYP2C8 and
             any inducer of CYP3A within 14 days or within 5 times the elimination half-life of the
             medication (whichever is longer) before the first study drug administration

          -  Use of any other nutrients known to modulate CYP3A activity within 1 week before the
             first study drug administration