A Study to Evaluate The Effects of RO5545965 in Participants With Negative Symptoms of Schizophrenia Treated With Antipsychotics

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