A Study to Assess the Effects of RO6889450 in Participants With Schizophrenia or Schizoaffective Disorder and Negative Symptoms

Inclusion Criteria:

- Patients with a Diagnostic and Statistical Manual of Mental Disorders (DSM-5)
diagnosis of schizophrenia or schizoaffective disorder as confirmed by the Mini
International Neuropsychiatric Interview (MINI)

- Medically stable during the six months prior to study entry

- Outpatient with no hospitalization for worsening of schizophrenia or schizoaffective
disorder within six months prior to study entry

- PANSS negative symptom factor score of 18 or higher

- The following rating on items of the PANSS: (a) less than 5 on P1 (delusions), P3
(hallucinations), and P6 (suspiciousness/persecution); (b) less than 4 on P4
(excitement/hyperactivity), P7 (hostility), G8 (uncooperativeness), and G14 (poor
impulse control)

- Has an informant who is considered reliable by the Investigator

- Part B only: Stable treatment with a dopamine/serotonin (D2/5HT2A) antagonist or a D2
partial agonist for a minimum of 6 months and receiving no more than two
antipsychotics

Exclusion Criteria:

- Part A only: Confirmed suicidal behavior based on Investigator judgment or violent
behavior resulting in injury or property damage in the prior five years

- Part A only: Lifetime history of homicidal behavior

- Moderate to severe substance use disorder within six months of study entry (excluding
nicotine or caffeine) as defined by DSM-5

- Other current DSM-5 diagnosis (e.g., bipolar disorder, major depressive disorder)

- PANSS item G6 (depression) greater than or equal to 4

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

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

- Tardive dyskinesia that is moderate to severe or requires treatment

- History of neuroleptic malignant syndrome

- On more than one antidepressant, or if on one antidepressant, a change in dose within
28 days prior to screening

- History of clozapine treatment

- Receipt of an investigational drug within 28 days or five times the half-life of the
investigational drug (whichever is longer) before the first study drug administration