A Trial of the Efficacy and the Safety of RO6889450 (Ralm... | NCT04512066

Label	Type	Description	Intervention Names
150 mg Once Daily (QD) RO6889450	Experimental	Participants will receive 150 mg of RO6889450 QD for 4 weeks or 12 weeks or 48 weeks.	Drug: RO6889450
45 mg QD RO6889450	Experimental	Participants will receive 45 mg of RO6889450 QD for 4 weeks or 12 weeks or 48 weeks.	Drug: RO6889450
Placebo	Placebo Comparator	Participants will receive oral placebo QD for 4 weeks. Participants from this arm that continue to the extension period will be randomized to either 45 mg or 150 mg QD of RO6889450 for up to an additional 8 weeks or additional 44 weeks (optional 36-Week Safety Extension Phase).	Drug: Placebo
4 mg QD Risperidone	Active Comparator	Participants will receive 4 mg of risperidone QD for 4 weeks or 12 weeks or 48 weeks.	Drug: Risperidone

Name	Type	Description	Arm Group Labels	Other Names
RO6889450	Drug	Participants will receive oral RO6889450 QD.	150 mg Once Daily (QD) RO6889450 45 mg QD RO6889450

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Mean Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score at Week 4	The PANSS is a 30-item rating scale that evaluates positive, negative, and other symptoms in patients with schizophrenia. The Positive subscale is a 7-item scale that assesses features in schizophrenia that are not present in a normal mental state. The Negative subscale is a 7-item scale that assesses features absent in schizophrenia but present in those with a normal mental state. Items are rated on a 7-point scale, where 1 = absent and 7 = extreme, for a maximum score of 49 for each scale. The General subscale is a 16-item scale that assesses the overall severity of schizophrenia and the risk of aggression. Items are rated on the same scale, with a minimum score of 16 and a maximum score of 112. Total scores are calculated by adding subscale scores together, for a minimum score of 30 and a maximum score of 210. Higher scores indicate higher severity.	Week 4 (Day 28)

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline in PANSS Factor Scores at Week 4	PANSS factors are modified groupings of the 30 PANSS items from the original three subscales (positive, negative, and general psychopathology). Each item is rated on a scale of 1 (absent) to 7 (most extreme). The positive symptom factor contains 8 items (score range 8-56); the negative symptom and disorganized thought/cognition factors contain 7 items (score range 7-49); the uncontrolled hostility/excitement, expressive deficit, and anxiety/depression factors contain 4 items (score range 4-28); and the avolition domain contains 3 items (score range 3-21). The negative and positive totals each have a range of 7-49 and the general total has a range of 16-112. Higher scores indicate higher symptom severity.

Eligibility Module

Eligibility Criteria

Inclusion criteria

Participant must be 18 to 45 years of age inclusive
Participants with a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnosis of schizophrenia or schizoaffective disorder as confirmed by the Mini International Neuropsychiatric Interview (MINI)
Disease duration </=10 years
Have a current acute exacerbation of schizophrenia of no more than 8 weeks before screening visit and no current signs of apparent lack of treatment response
At the time of screening, the participant needs to be either hospitalized or requiring inpatient psychiatric care according to clinical judgment. If the participant has been hospitalized for the current exacerbation, the hospitalization has to be of a maximum of 1 week prior to screening.
In previous exacerbations and hospitalizations, the subject has shown a pattern of response to appropriate antipsychotic treatment
Medically stable over a period of 3 months (non-psychiatric conditions) prior to screening visit and not expected to require hospitalization or change of treatment for non-psychiatric conditions for the duration of the study
Screening and baseline CGI-S >/=4 (moderate or worse)
Screening and baseline PANSS total score >= 80
Based on screening and baseline PANSS, scores of >/= 4 (moderate or worse) on 2 or more of the following items: delusions, conceptual disorganization, unusual thought content, hallucinatory behavior, or suspiciousness/persecution
Body mass index between 18 and 35 kg/m2 inclusive
Male and female participants; female participants agree to remain abstinent or use acceptable contraceptive methods during the treatment period and for at least 28 days after the last dose of study drug

Additional inclusion criteria for optional 36-Week Safety Extension Phase

Successful completion of the 12-week treatment period
No signs or symptoms of worsening of the psychiatric or medical status that would preclude the patient from the participation in the 36-Week Safety Extension Phase or affect their ability to comply with the study requirements.

Exclusion criteria

Has been inpatient for > 1 week or had any other hospitalization for acute exacerbation of schizophrenia or schizoaffective disorder within the prior 8 weeks or signs of lack of response to antipsychotic treatment
Disease duration > 10 years
Is currently an inpatient on an involuntary basis
Subject answers "yes" to "Suicidal Ideation" Item 4 (active suicidal ideation with some intent to act, without specific plan) or item 5 (active suicidal ideation with specific plan and intent) or any suicidal behavior on the Columbia-Suicide Severity Rating Scale (C-SSRS) assessment within one month from screening or between screening and baseline
Lifetime history of homicidal behavior
Moderate to severe substance use disorder within six months (excluding nicotine) as defined by DSM-5
Other current DSM-5 diagnosis (e.g., bipolar disorder, major depressive disorder)
A prior or current general medical condition that might be impairing cognition or other psychiatric functioning (e.g., migraine headaches requiring prophylaxis treatment, head trauma, dementia, seizure disorder, stroke; or neurodegenerative, inflammatory, infectious, neoplastic, toxic, metabolic, or endocrine conditions)
Clinically significant abnormalities in laboratory safety test results (including hepatic and renal panels, complete blood count, chemistry panel and urinalysis), including a) Aspartate aminotransferase (AST), OR alanine aminotransferase (ALT) 2 x upper limit of normal (ULN), OR total bilirubin > 1.5 ULN with the exception of known Gilbert syndrome. b) Serum creatinine > 1.5 ULN
Positive result at screening for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV, untreated), or human immunodeficiency virus (HIV)-1 and -2. HCV participants who have been successfully treated and who test negative for HCV RNA are eligible for entry into the study
Tardive dyskinesia that is moderate to severe or requires treatment
History of neuroleptic malignant syndrome
Average triplicate QTcF interval greater than 450 msec for males and 470 msec for females or other clinically significant abnormality on screening ECG based on centralized reading
Participant for whom risperidone is contraindicated or who have a documented history of lack of response or intolerance to risperidone or paliperidone or participants with known hypersensitivity to risperidone, paliperidone, or to any excipients in Risperdal
Participant treated with a long acting injectable antipsychotic or other antipsychotics that cannot be washed-out within the allotted screening period
History of electro-convulsive therapy (ECT) for any reason
Participant treated with clozapine at any dose within 12 months of screening visit or participants treated with clozapine at 200 mg/day or above at any time; low dose (< 200mg/day) use for insomnia or dyskinesia longer than 12 months prior to screening visit is permitted
Participants currently receiving a psychotropic or other medication used as a psychotropic, which cannot be discontinued during the screening period
Positive urine drug screen for amphetamines, methamphetamines, opiates, buprenorphine, methadone, cocaine and barbiturates. In case of positive urine drug screen for cannabinoids, the participant may be allowed to enter the study if approved by Medical Monitor
Participant has previously received RO6889450
Participant received an investigational drug within 28 days or five times the half-life of the investigational drug prior to the first study drug administration
Diagnosis of COVID-19 infection (confirmed or presumptive) 4 weeks prior to screening or during screening. Participants can be re-screened after 4 weeks of full recovery in addition to investigator and/or institutional approval to enroll

Name	Affiliation	Role
Clinical Trials	Hoffmann-La Roche	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Woodland International Research Group Inc.		Little Rock	Arkansas	72211	United States
CITrials, Inc.

PubMed Identifier	Type	Citation	Retractions
36369028	Derived	Halff EF, Rutigliano G, Garcia-Hidalgo A, Howes OD. Trace amine-associated receptor 1 (TAAR1) agonism as a new treatment strategy for schizophrenia and related disorders. Trends Neurosci. 2023 Jan;46(1):60-74. doi: 10.1016/j.tins.2022.10.010. Epub 2022 Nov 8.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Placebo	Participants received oral placebo QD for 4 weeks. Participants from this arm that continued on to the extension period were randomized to either 45 mg or 150 mg QD of RO6889450 for up to an additional 8 weeks, or up to an additional 44 weeks if they continued to the optional 36-week safety extension. Note: This arm was only in the double-blind treatment period.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Oct 6, 2021	Jun 16, 2023

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Mean Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score at Week 4

The PANSS is a 30-item rating scale that evaluates positive, negative, and other symptoms in patients with schizophrenia. The Positive subscale is a 7-item scale that assesses features in schizophrenia that are not present in a normal mental state. The Negative subscale is a 7-item scale that assesses features absent in schizophrenia but present in those with a normal mental state. Items are rated on a 7-point scale, where 1 = absent and 7 = extreme, for a maximum score of 49 for each scale. The General subscale is a 16-item scale that assesses the overall severity of schizophrenia and the risk of aggression. Items are rated on the same scale, with a minimum score of 16 and a maximum score of 112. Total scores are calculated by adding subscale scores together, for a minimum score of 30 and a maximum score of 210. Higher scores indicate higher severity.

The efficacy analysis population (EAP) included all randomized participants who received at least one dose of study medication and who had primary efficacy assessments at baseline and on at least one occasion post-baseline.

Posted

Mean

Standard Deviation

Units on a scale

Week 4 (Day 28)

ID	Title	Description
OG000	Placebo	Participants received oral placebo QD for 4 weeks. Participants from this arm that continued on to the extension period were randomized to either 45 mg or 150 mg QD of RO6889450 for up to an additional 8 weeks, or up to an additional 44 weeks if they continued to the optional 36-week safety extension. Note: This arm was only in the double-blind treatment period.
OG001	RO6889450 45 mg	Participants received 45 mg of RO6889450 QD for 4, 12, or 48 weeks.
OG002	RO6889450 150 mg	Participants received 150 mg of RO6889450 QD for 4, 12, or 48 weeks.
OG003	Risperidone 4 mg	Participants received 4 mg of risperidone QD for 4, 12, or 48 weeks.

Units	Counts
Participants	OG00072 OG00165 OG00268 OG003

Title	Denominators	Categories
Baseline	ParticipantsOG00072 ParticipantsOG00165 ParticipantsOG00268 ParticipantsOG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Mixed Models Analysis		0.849		treatment effect	0.60			2-Sided	90	-4.58	5.78					Other
OG000 OG002		Mixed Models Analysis		0.362

Secondary

Change From Baseline in PANSS Factor Scores at Week 4

PANSS factors are modified groupings of the 30 PANSS items from the original three subscales (positive, negative, and general psychopathology). Each item is rated on a scale of 1 (absent) to 7 (most extreme). The positive symptom factor contains 8 items (score range 8-56); the negative symptom and disorganized thought/cognition factors contain 7 items (score range 7-49); the uncontrolled hostility/excitement, expressive deficit, and anxiety/depression factors contain 4 items (score range 4-28); and the avolition domain contains 3 items (score range 3-21). The negative and positive totals each have a range of 7-49 and the general total has a range of 16-112. Higher scores indicate higher symptom severity.

The EAP included all randomized participants who received at least one dose of study medication and who had primary efficacy assessments at baseline and on at least one occasion post-baseline.

Posted

Mean

Standard Deviation

Units on a scale

Week 4 (Day 28)

ID	Title	Description
OG000	Placebo	Participants received oral placebo QD for 4 weeks. Participants from this arm that continued on to the extension period were randomized to either 45 mg or 150 mg QD of RO6889450 for up to an additional 8 weeks, or up to an additional 44 weeks if they continued to the optional 36-week safety extension. Note: This arm was only in the double-blind treatment period.
OG001	RO6889450 45 mg

Secondary

Proportion of Participants With at Least 20% or 50% Improvement From Baseline in the PANSS Total Score

The EAP included all randomized participants who received at least one dose of study medication and who had primary efficacy assessments at baseline and on at least one occasion post-baseline.

Posted

Number

Proportion expressed as percentage

Baseline to Week 12

ID	Title	Description
OG000	Placebo	Participants received oral placebo QD for 4 weeks. Participants from this arm that continued on to the extension period were randomized to either 45 mg or 150 mg QD of RO6889450 for up to an additional 8 weeks, or up to an additional 44 weeks if they continued to the optional 36-week safety extension. Note: This arm was only in the double-blind treatment period.

Secondary

Change From Baseline in Clinical Global Impression Severity (CGI-S) Scores

The CGI-S measures global severity of illness at a given point in time using a 7-point scale, where 1 = no symptoms and 7 = very severe symptoms.

The EAP included all randomized participants who received at least one dose of study medication and who had primary efficacy assessments at baseline and on at least one occasion post-baseline.

Posted

Mean

Standard Deviation

Units on a scale

Week 4 (Day 28)

ID	Title	Description
OG000	Placebo	Participants received oral placebo QD for 4 weeks. Participants from this arm that continued on to the extension period were randomized to either 45 mg or 150 mg QD of RO6889450 for up to an additional 8 weeks, or up to an additional 44 weeks if they continued to the optional 36-week safety extension. Note: This arm was only in the double-blind treatment period.
OG001	RO6889450 45 mg	Participants received 45 mg of RO6889450 QD for 4, 12, or 48 weeks.
OG002	RO6889450 150 mg	Participants received 150 mg of RO6889450 QD for 4, 12, or 48 weeks.
OG003

Secondary

Clinical Global Impression - Improvement (CGI-I) Scores

The CGI-I measures change from the baseline state at subsequent visits using a 7-point scale, where 1 = very much improved and 7 = very much worse.

The EAP included all randomized participants who received at least one dose of study medication and who had primary efficacy assessments at baseline and on at least one occasion post-baseline.

Posted

Mean

Standard Deviation

Units on a scale

Week 4 (Day 28)

ID	Title	Description
OG000	Placebo	Participants received oral placebo QD for 4 weeks. Participants from this arm that continued on to the extension period were randomized to either 45 mg or 150 mg QD of RO6889450 for up to an additional 8 weeks, or up to an additional 44 weeks if they continued to the optional 36-week safety extension. Note: This arm was only in the double-blind treatment period.
OG001	RO6889450 45 mg	Participants received 45 mg of RO6889450 QD for 4, 12, or 48 weeks.
OG002	RO6889450 150 mg	Participants received 150 mg of RO6889450 QD for 4, 12, or 48 weeks.
OG003

Secondary

PANSS Total Score at Week 12

The EAP included all randomized participants who received at least one dose of study medication and who had primary efficacy assessments at baseline and on at least one occasion post-baseline.

Posted

Mean

Standard Deviation

Units on a scale

Week 12

ID	Title	Description
OG000	Placebo - RO6889450 45 mg	Participants from the placebo arm in the double-blind treatment period that continued on to the extension period were randomized to either 45 mg or 150 mg once daily (QD) of RO6889450 for up to an additional 8 weeks, or up to an additional 44 weeks if they continued to the optional 36-week safety extension. Note: This arm started in the extension period.
OG001

Secondary

Proportion of Participants With at Least 20% or 50% Improvement in the PANSS Total Score up to Week 12

The EAP included all randomized participants who received at least one dose of study medication and who had primary efficacy assessments at baseline and on at least one occasion post-baseline.

Posted

Number

Proportion expressed as a percentage

Weeks 4, 8, and 12

ID	Title	Description
OG000	Placebo - RO6889450 45 mg	Participants from the placebo arm in the double-blind treatment period that continued on to the extension period were randomized to either 45 mg or 150 mg once daily (QD) of RO6889450 for up to an additional 8 weeks, or up to an additional 44 weeks if they continued to the optional 36-week safety extension. Note: This arm started in the extension period.

Secondary

CGI-S up to Week 12

The CGI-S measures global severity of illness at a given point in time using a 7-point scale, where 1 = no symptoms and 7 = very severe symptoms.

Posted

Mean

Standard Deviation

Units on a scale

Up to Week 12

ID	Title	Description
OG000	Placebo - RO6889450 45 mg	Participants from the placebo arm in the double-blind treatment period that continued on to the extension period were randomized to either 45 mg or 150 mg once daily (QD) of RO6889450 for up to an additional 8 weeks, or up to an additional 44 weeks if they continued to the optional 36-week safety extension. Note: This arm started in the extension period.
OG001	Placebo - RO6889450 150 mg	Participants from the placebo arm in the double-blind treatment period that continued on to the extension period were randomized to either 45 mg or 150 mg QD of RO6889450 for up to an additional 8 weeks, or up to an additional 44 weeks if they continued to the optional 36-week safety extension. Note: This arm started in the extension period.
OG002	RO6889450 45 mg

Secondary

CGI-I up to Week 12

The CGI-I measures change from the baseline state at subsequent visits using a 7-point scale, where 1 = very much improved and 7 = very much worse.

Posted

Mean

Standard Deviation

Units on a scale

Up to Week 12

ID	Title	Description
OG000	Placebo - RO6889450 45 mg	Participants from the placebo arm in the double-blind treatment period that continued on to the extension period were randomized to either 45 mg or 150 mg once daily (QD) of RO6889450 for up to an additional 8 weeks, or up to an additional 44 weeks if they continued to the optional 36-week safety extension. Note: This arm started in the extension period.
OG001	Placebo - RO6889450 150 mg	Participants from the placebo arm in the double-blind treatment period that continued on to the extension period were randomized to either 45 mg or 150 mg QD of RO6889450 for up to an additional 8 weeks, or up to an additional 44 weeks if they continued to the optional 36-week safety extension. Note: This arm started in the extension period.
OG002	RO6889450 45 mg

Secondary

Participants Ready for Discharge From First Randomized Treatment Intake to Readiness for Discharge as Assessed by the Readiness for Discharge Questionnaire (RDQ) at 4-Week Treatment

The RDQ is a tool used to assess inpatients with schizophrenia on their readiness for discharge from inpatient treatment. It consists of five items that assess suicidality/homicidality, control of aggression/impulsivity, activities of daily living, medication-taking, and delusions/hallucinations interfering with functioning and global status. An additional item examines the overall clinical state of the patient and the final question assesses readiness for discharge. The values reported are the proportion (expressed as a percentage) of participants in each analysis group considered ready for discharge according to the RDQ.

Posted

Number

95% Confidence Interval

Percentage of participants

after 4-week treatment

ID	Title	Description
OG000	Placebo	Participants received oral placebo QD for 4 weeks. Participants from this arm that continued on to the extension period were randomized to either 45 mg or 150 mg QD of RO6889450 for up to an additional 8 weeks, or up to an additional 44 weeks if they continued to the optional 36-week safety extension. Note: This arm was only in the double-blind treatment period.
OG001	RO6889450 45 mg

Secondary

Plasma Concentration of RO6889450

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Day 7 - Day 336

ID	Title	Description
OG000	Placebo - RO6889450 45 mg	Participants from the placebo arm in the double-blind treatment period that continued on to the extension period were randomized to either 45 mg or 150 mg once daily (QD) of RO6889450 for up to an additional 8 weeks, or up to an additional 44 weeks if they continued to the optional 36-week safety extension. Note: This arm started in the extension period.
OG001	Placebo - RO6889450 150 mg	Participants from the placebo arm in the double-blind treatment period that continued on to the extension period were randomized to either 45 mg or 150 mg QD of RO6889450 for up to an additional 8 weeks, or up to an additional 44 weeks if they continued to the optional 36-week safety extension. Note: This arm started in the extension period.
OG002	RO6889450 45 mg	Participants received 45 mg of RO6889450 QD for 4, 12, or 48 weeks.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Participants received oral placebo QD for 4 weeks. Participants from this arm that continued on to the extension period were randomized to either 45 mg or 150 mg QD of RO6889450 for up to an additional 8 weeks, or up to an additional 44 weeks if they continued to the optional 36-week safety extension. Note: This arm was only in the double-blind treatment period.	0	72	1	72	23	72
EG001	RO6889450 45 mg (Double-blind Treatment Period)	Participants received 45 mg of RO6889450 QD for 4, 12, or 48 weeks.	0	65	2	65	14	65
EG002	RO6889450 150 mg (Double-blind Treatment Period)	Participants received 150 mg of RO6889450 QD for 4, 12, or 48 weeks.	0	68	1	68	23	68
EG003	Risperidone 4 mg (Double-blind Treatment Period)	Participants received 4 mg of risperidone QD for 4, 12, or 48 weeks.	0	71	0	71	36	71
EG004	Placebo - RO6889450 45 mg	Participants from the placebo arm in the double-blind treatment period that continued on to the extension period were randomized to either 45 mg or 150 mg once daily (QD) of RO6889450 for up to an additional 8 weeks, or up to an additional 44 weeks if they continued to the optional 36-week safety extension. Note: This arm started in the extension period.	0	25	3	25	5	25
EG005	Placebo - RO6889450 150 mg	Participants from the placebo arm in the double-blind treatment period that continued on to the extension period were randomized to either 45 mg or 150 mg QD of RO6889450 for up to an additional 8 weeks, or up to an additional 44 weeks if they continued to the optional 36-week safety extension. Note: This arm started in the extension period.	1	25	3	25	6	25
EG006	RO6889450 45 mg (Extension Period)	Participants received 45 mg of RO6889450 QD for 4, 12, or 48 weeks.	0	41	1	41	7	41
EG007	RO6889450 150 mg (Extension Period)	Participants received 150 mg of RO6889450 QD for 4, 12, or 48 weeks.	0	45	6	45	12	45
EG008	Risperidone 4 mg (Extension Period)	Participants received 4 mg of risperidone QD for 4, 12, or 48 weeks.	0	53	1	53	5	53

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anxiety	Psychiatric disorders	MedDRA v25.0	Non-systematic Assessment	EG0006 affected72 at risk EG0013 affected65 at risk EG0022 affected68 at risk EG0035 affected71 at risk EG0040 affected25 at risk EG0050 affected25 at risk EG0060 affected41 at risk EG0071 affected45 at risk EG0080 affected53 at risk
Insomnia	Psychiatric disorders	MedDRA v25.0	Non-systematic Assessment	EG0001 affected72 at risk EG0013 affected65 at risk EG0025 affected68 at risk EG003
Agitation	Psychiatric disorders	MedDRA v25.0	Non-systematic Assessment	EG0002 affected72 at risk EG0010 affected65 at risk EG0028 affected68 at risk EG003
Headache	Nervous system disorders	MedDRA v25.0	Non-systematic Assessment	EG0004 affected72 at risk EG0014 affected65 at risk EG0025 affected68 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA v25.0	Non-systematic Assessment	EG0004 affected72 at risk EG0010 affected65 at risk EG0022 affected68 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA v25.0	Non-systematic Assessment	EG0002 affected72 at risk EG0010 affected65 at risk EG0021 affected68 at risk EG003
Weight increased	Investigations	MedDRA v25.0	Non-systematic Assessment	EG0001 affected72 at risk EG0012 affected65 at risk EG0020 affected68 at risk EG003
Schizophrenia	Psychiatric disorders	MedDRA v25.0	Non-systematic Assessment	EG0003 affected72 at risk EG0012 affected65 at risk EG0020 affected68 at risk EG003

ID	Term
D011744	Pyrimidinones
D011743	Pyrimidines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds

ID	Title	Description
BG000	Placebo	Participants received oral placebo QD for 4 weeks. Participants from this arm that continued on to the extension period were randomized to either 45 mg or 150 mg QD of RO6889450 for up to an additional 8 weeks, or up to an additional 44 weeks if they continued to the optional 36-week safety extension. Note: This arm was only in the double-blind treatment period.
BG001	RO6889450 45 mg	Participants received 45 mg of RO6889450 QD for 4, 12, or 48 weeks.
BG002	RO6889450 150 mg	Participants received 150 mg of RO6889450 QD for 4, 12, or 48 weeks.
BG003	Risperidone 4 mg	Participants received 4 mg of risperidone QD for 4, 12, or 48 weeks.
BG004	Total	Total of all reporting groups

ID	Term
D019967	Schizophrenia Spectrum and Other Psychotic Disorders
D001523	Mental Disorders