A Study to Assess the Effects of RO6889450 (Ralmitaront)... | NCT03669640

NCT03669640

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Part A: Monotherapy	Experimental	Participants will receive RO6889450 or a dose-matched placebo. NOTE: Part A has completed enrollment.	Drug: RO6889450 Drug: Placebo
Part B: Add-On Therapy	Experimental	Participants will receive a low or high dose of RO6889450 or a dose-matched placebo in addition to their usual anti-psychotic treatment(s).	Drug: RO6889450 Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
RO6889450	Drug	Participants will receive a once-daily, oral dose of RO6889450 for 12 weeks.	Part A: Monotherapy Part B: Add-On Therapy

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Brief Negative Symptoms Scale (BNSS) Avolition/Apathy Subscore and Total Score at Baseline and Week 12	The BNSS is a 13-item instrument designed for clinical trials that measures the severity of the negative symptoms of schizophrenia in five domains. There are 13 items organized into 6 subscales (anhedonia, distress, asociality, avolition, blunted affect, and alogia), each rated on a 7-point scale (0-6) where 0 = absent symptoms and 6 = severe symptoms. The total score is calculated by summing the individual items (13) of each subscale and has a range of 0-78. The avolition/apathy subscale contains 2 items with a total score range of 0-12.	Baseline to Week 12

Secondary Outcomes

Measure	Description	Time Frame
Clinical Global Impression Severity (CGI-S) Overall Scores	The CGI-S is an absolute measure assessing how mentally ill the participant is at the time of the assessment on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). On the scale, the value 0 corresponds to 'not assessed', which will be excluded from the analyses. The values 1 to 7 will be transformed into the 0 to 6 range prior to statistical analysis for the question on the measure ("Considering your total clinical experience with this particular population, how mentally ill is the patient at this time?"), making the total score range 0-6.

Eligibility Module

Eligibility Criteria

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)
Part B only: Stable treatment with a dopamine/serotonin (D2/5HT2A) antagonist or pure D2 antagonist(s), or a D2 partial agonist for a minimum of 6 months and receiving no more than two antipsychotics
Medically stable during the 3 months prior to study entry
Participant is an outpatient with no psychiatric hospitalizations within the prior 6 months
PANSS negative symptom factor score of 18 or higher
The following rating on items of the PANSS: (a) less than 5 on G8 (uncooperativeness), P1 (delusions), P3 (hallucinations), P4 (excitement/hyperactivity), and P6 (suspiciousness/persecution); (b) less than 4 on P7 (hostility), and G14 (poor impulse control)
Has an informant who is considered reliable by the Investigator
Body mass index (BMI) between 18-40 kg/m2 inclusive
Female participants are eligible to participate if not pregnant, not breastfeeding and 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

Exclusion Criteria:

Moderate to severe substance use disorder within six months of study entry (excluding nicotine or caffeine) as defined by DSM-5
Extrapyramidal symptom rating scale (ESRS-A CGI) subscore greater than or equal to 3
Other current DSM-5 diagnosis (e.g., bipolar disorder, major depressive disorder)
PANSS item G6 (depression) greater than or equal to 5
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
Positive result at screening for hepatitis B surface antigen (HBsAg), hepatitis C (HCV), or HIV-1 and HIV-2. HCV antibody positive participants are eligible if HCV RNA is negative
Tardive dyskinesia that is moderate to severe or requires treatment
History of neuroleptic malignant syndrome
Average triplicate Fridericia's Correction Formula (QTcF) interval greater than 450 milliseconds (msec) for males and 470 msec for females or other clinically significant abnormality on screening electrocardiogram (ECG) based on centralized reading
Clinically significant abnormalities in laboratory safety test results
Significant or unstable physical condition that in the investigator's judgment might require a change in medication or hospitalization during the course of the study
On more than one antidepressant, or if on one antidepressant, a change in dose within 28 days prior to screening
History of clozapine treatment
History of treatment with electroconvulsive therapy (ECT)
Concomitant use of prohibited medications
Positive urine drug screen for amphetamines, methamphetamines, opiates, buprenomorphine, methadone, cannabinoids, cocaine, and barbiturates
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
Donation of blood over 400 mL within 3 months prior to screening
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

Contacts/Locations Module

Name	Affiliation	Role
Clinical Trials	Hoffmann-La Roche	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
CITrials, Inc.		Bellflower	California	90706	United States
Collaborative Neuroscience Network, Inc.

References Module

Citations

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.

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Part A: Monotherapy (Placebo)	Participants received placebo each day (QD) for 12 weeks after a 1-week washout from their usual antipsychotic therapy.
FG001	Part A: Monotherapy (150 mg)

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Sep 27, 2021	Mar 8, 2024

Derived Section

Miscellaneous Info Module

Submission Tracking

Condition Browse Module

Intervention Browse Module

No data available

No data is available for this block.

Masking Info

Participants received 150 mg of ralmitaront QD for 12 weeks after a 1-week washout from their usual antipsychotic therapy.

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	Part A: Monotherapy (Placebo)	Participants received placebo each day (QD) for 12 weeks after a 1-week washout from their usual antipsychotic therapy.
BG001	Part A: Monotherapy (150 mg)	Participants received 150 mg of ralmitaront QD for 12 weeks after a 1-week washout from their usual antipsychotic therapy.
BG002	Part B: Add-on Therapy (Placebo)	Participants received placebo QD for 12 weeks in addition to their usual antipsychotic therapy.
BG003	Part B: Add-on Therapy (45 mg)	Participants received 45 mg of ralmitaront QD 12 weeks in addition to their usual antipsychotic therapy (prior to protocol v5; arm was removed thereafter).
BG004	Part B: Add-on Therapy (150 mg)	Participants received 150 mg of ralmitaront QD 12 weeks in addition to their usual antipsychotic therapy.
BG005	Part B: Add-on Therapy (300 mg)	Participants received 300 mg of ralmitaront QD 12 weeks in addition to their usual antipsychotic therapy (after protocol v5).
BG006	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

Years

Title

Denominators

Categories

Title	Measurements
	BG00042.7± 9.9 BG00143.3± 6.6 BG00241.3± 9.7 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0003 BG0013 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0001 BG0010 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG002

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

Brief Negative Symptoms Scale (BNSS) Avolition/Apathy Subscore and Total Score at Baseline and Week 12

The BNSS is a 13-item instrument designed for clinical trials that measures the severity of the negative symptoms of schizophrenia in five domains. There are 13 items organized into 6 subscales (anhedonia, distress, asociality, avolition, blunted affect, and alogia), each rated on a 7-point scale (0-6) where 0 = absent symptoms and 6 = severe symptoms. The total score is calculated by summing the individual items (13) of each subscale and has a range of 0-78. The avolition/apathy subscale contains 2 items with a total score range of 0-12.

The modified intent-to-treat (mITT) population included all randomized participants who received at least one dose of study drug.

Posted

Mean

Standard Deviation

Units on a scale

Baseline to Week 12

ID	Title	Description
OG000	Part A: Monotherapy (Placebo)	Participants received placebo each day (QD) for 12 weeks after a 1-week washout from their usual antipsychotic therapy.
OG001	Part A: Monotherapy (150 mg)	Participants received 150 mg of ralmitaront QD for 12 weeks after a 1-week washout from their usual antipsychotic therapy.
OG002	Part B: Add-on Therapy (Placebo)	Participants received placebo QD for 12 weeks in addition to their usual antipsychotic therapy.
OG003	Part B: Add-on Therapy (45 mg)	Participants received 45 mg of ralmitaront QD 12 weeks in addition to their usual antipsychotic therapy (prior to protocol v5; arm was removed thereafter).
OG004	Part B: Add-on Therapy (150 mg)	Participants received 150 mg of ralmitaront QD 12 weeks in addition to their usual antipsychotic therapy.
OG005	Part B: Add-on Therapy (300 mg)	Participants received 300 mg of ralmitaront QD 12 weeks in addition to their usual antipsychotic therapy (after protocol v5).

Units	Counts
Participants	OG00015 OG00112 OG00237 OG003

Title	Denominators	Categories
Baseline Avolition/Apathy Subscore	ParticipantsOG00014 ParticipantsOG00112 ParticipantsOG00236 ParticipantsOG003

Secondary

Clinical Global Impression Severity (CGI-S) Overall Scores

The CGI-S is an absolute measure assessing how mentally ill the participant is at the time of the assessment on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). On the scale, the value 0 corresponds to 'not assessed', which will be excluded from the analyses. The values 1 to 7 will be transformed into the 0 to 6 range prior to statistical analysis for the question on the measure ("Considering your total clinical experience with this particular population, how mentally ill is the patient at this time?"), making the total score range 0-6.

The modified intent-to-treat (mITT) population included all randomized participants who received at least one dose of study drug. Data for this endpoint was not collected for Part B on Day 70.

Posted

Mean

Standard Deviation

Units on a scale

Baseline to week 12

ID	Title	Description
OG000	Part A: Monotherapy (Placebo)	Participants received placebo each day (QD) for 12 weeks after a 1-week washout from their usual antipsychotic therapy.
OG001	Part A: Monotherapy (150 mg)	Participants received 150 mg of ralmitaront QD for 12 weeks after a 1-week washout from their usual antipsychotic therapy.
OG002	Part B: Add-on Therapy (Placebo)

Secondary

CGI-S Negative Symptoms (NS) Scores

The CGI-S-NS is similar to the CGI-S and is assessed on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). On the scale, the value 0 corresponds to 'not assessed', which will be excluded from the analyses. The values 1 to 7 will be transformed into the 0 to 6 range prior to statistical analysis for the question on the measure, making the total score range 0-6.

The modified intent-to-treat (mITT) population included all randomized participants who received at least one dose of study drug. Data for this endpoint was not collected for Part B on Day 70.

Posted

Mean

Standard Deviation

Units on a scale

Baseline to week 12

ID	Title	Description
OG000	Part A: Monotherapy (Placebo)	Participants received placebo each day (QD) for 12 weeks after a 1-week washout from their usual antipsychotic therapy.
OG001	Part A: Monotherapy (150 mg)	Participants received 150 mg of ralmitaront QD for 12 weeks after a 1-week washout from their usual antipsychotic therapy.
OG002	Part B: Add-on Therapy (Placebo)	Participants received placebo QD for 12 weeks in addition to their usual antipsychotic therapy.

Secondary

Clinical Global Impression - Improvement (CGI-I) Overall Scores

The CGI-I assesses how much the participant's condition has changed at the time of the assessment in comparison to their condition at baseline. It uses a 7-point scale ranging from 1 (very much improved) to 7 (very much worse), where the value 0 corresponds to 'not assessed' and will be excluded from any analyses.

The modified intent-to-treat (mITT) population included all randomized participants who received at least one dose of study drug. Data for this endpoint was not collected for Part B Days 21, 35, and 70.

Posted

Mean

Standard Deviation

Units on a scale

Up to Week 12 (Day 84)

ID	Title	Description
OG000	Part A: Monotherapy (Placebo)	Participants received placebo each day (QD) for 12 weeks after a 1-week washout from their usual antipsychotic therapy.
OG001	Part A: Monotherapy (150 mg)	Participants received 150 mg of ralmitaront QD for 12 weeks after a 1-week washout from their usual antipsychotic therapy.
OG002	Part B: Add-on Therapy (Placebo)	Participants received placebo QD for 12 weeks in addition to their usual antipsychotic therapy.

Secondary

CGI-I Negative Symptoms Scores

The CGI-I NS is similar to the CGI-I and assesses how much the participant's condition has changed at the time of the assessment in comparison to their condition at baseline. It uses a 7-point scale, where:

= Very much improved
= Much improved
= Minimally improved
= No change
= Minimally worse
= Much worse
= Very much worse

The modified intent-to-treat (mITT) population included all randomized participants who received at least one dose of study drug.

Posted

Mean

Standard Deviation

Units on a scale

Up to Week 12 (Day 84)

ID	Title	Description
OG000	Part A: Monotherapy (Placebo)	Participants received placebo each day (QD) for 12 weeks after a 1-week washout from their usual antipsychotic therapy.
OG001	Part A: Monotherapy (150 mg)	Participants received 150 mg of ralmitaront QD for 12 weeks after a 1-week washout from their usual antipsychotic therapy.
OG002	Part B: Add-on Therapy (Placebo)	Participants received placebo QD for 12 weeks in addition to their usual antipsychotic therapy.
OG003

Secondary

Positive and Negative Syndrome Scale (PANSS) Total Scores

The PANSS Marder factors examine schizophrenia symptoms in five domains: positive symptoms, negative symptoms, disorganized thought, uncontrolled hostility/excitement, and depression/anxiety. The Marder factor positive symptom score (range = 8-56) measures responses to 8 items (P1,P3,P5,P6,N7,G1,G9,G12) while the negative symptom factor score (range = 7-49) consists of 7 items (N1,N2,N3,N4,N6,G7,G16). Each item is scored on a scale of 1-7, where 1 = an absence of symptoms and 7 = extreme symptoms. The positive and negative syndrome scale total score is the sum of the scores from each domain (range = 15-105); higher scores indicate greater severity of symptoms.

The modified intent-to-treat (mITT) population included all randomized participants who received at least one dose of study drug.

Posted

Mean

Standard Deviation

Units on a scale

Baseline to week 12

ID	Title	Description
OG000	Part A: Monotherapy (Placebo)	Participants received placebo each day (QD) for 12 weeks after a 1-week washout from their usual antipsychotic therapy.
OG001	Part A: Monotherapy (150 mg)	Participants received 150 mg of ralmitaront QD for 12 weeks after a 1-week washout from their usual antipsychotic therapy.
OG002	Part B: Add-on Therapy (Placebo)

Secondary

PANSS Symptom Factor Scores

The modified intent-to-treat (mITT) population included all randomized participants who received at least one dose of study drug.

Posted

Mean

Standard Deviation

Units on a scale

Baseline to week 12

ID	Title	Description
OG000	Part A: Monotherapy (Placebo)	Participants received placebo each day (QD) for 12 weeks after a 1-week washout from their usual antipsychotic therapy.
OG001	Part A: Monotherapy (150 mg)	Participants received 150 mg of ralmitaront QD for 12 weeks after a 1-week washout from their usual antipsychotic therapy.
OG002	Part B: Add-on Therapy (Placebo)	Participants received placebo QD for 12 weeks in addition to their usual antipsychotic therapy.

Secondary

Brief Negative Symptom Scale (BNSS) Total Scores

The modified intent-to-treat (mITT) population included all randomized participants who received at least one dose of study drug.

Posted

Mean

Standard Deviation

Units on a scale

Baseline to week 12

ID	Title	Description
OG000	Part A: Monotherapy (Placebo)	Participants received placebo each day (QD) for 12 weeks after a 1-week washout from their usual antipsychotic therapy.
OG001	Part A: Monotherapy (150 mg)	Participants received 150 mg of ralmitaront QD for 12 weeks after a 1-week washout from their usual antipsychotic therapy.
OG002	Part B: Add-on Therapy (Placebo)	Participants received placebo QD for 12 weeks in addition to their usual antipsychotic therapy.

Secondary

Defeatist Performance Attitude Scale (DPAS) Scores

The DPAS is a 15-item, patient-rated assessment that evaluates expectations of failures or self-defeating beliefs related to prior failed experiences as well as illness on a 7-point Likert scale (total range = 15-105) ranging from totally agree (1) to totally disagree (7).

The modified intent-to-treat (mITT) population included all randomized participants who received at least one dose of study drug.

Posted

Mean

Standard Deviation

Units on a scale

Baseline to week 12

ID	Title	Description
OG000	Part A: Monotherapy (Placebo)	Participants received placebo each day (QD) for 12 weeks after a 1-week washout from their usual antipsychotic therapy.
OG001	Part A: Monotherapy (150 mg)	Participants received 150 mg of ralmitaront QD for 12 weeks after a 1-week washout from their usual antipsychotic therapy.
OG002	Part B: Add-on Therapy (Placebo)	Participants received placebo QD for 12 weeks in addition to their usual antipsychotic therapy.
OG003	Part B: Add-on Therapy (45 mg)

Secondary

Number of Participants With Suicidal Ideation or Behavior, and Self-injurious Behavior Without Suicidal Intent on the Columbia Suicide Severity Rating Scale (C-SSRS)

The C-SSRS is a suicide risk assessment tool used to help identify the risk of suicide.

The safety population included all randomized participants who received at least one dose of study drug.

Posted

Number

Number of participants

Baseline through Day 84

ID	Title	Description
OG000	Part A: Monotherapy (Placebo)	Participants received placebo each day (QD) for 12 weeks after a 1-week washout from their usual antipsychotic therapy.
OG001	Part A: Monotherapy (150 mg)	Participants received 150 mg of ralmitaront QD for 12 weeks after a 1-week washout from their usual antipsychotic therapy.
OG002	Part B: Add-on Therapy (Placebo)	Participants received placebo QD for 12 weeks in addition to their usual antipsychotic therapy.
OG003	Part B: Add-on Therapy (45 mg)

Secondary

Extrapyramidal Symptom Rating Scale, Abbreviated (ESRS-A)

The ESRS-A is used to evaluate the presence and severity of extrapyramidal symptoms. Items are rated on a scale of 0 (no symptoms) to 5 (extreme symptoms).

The safety population included all randomized participants who received at least one dose of study drug.

Posted

Mean

Standard Deviation

Units on a scale

Baseline through Day 84

ID	Title	Description
OG000	Part A: Monotherapy (Placebo)	Participants received placebo each day (QD) for 12 weeks after a 1-week washout from their usual antipsychotic therapy.
OG001	Part A: Monotherapy (150 mg)	Participants received 150 mg of ralmitaront QD for 12 weeks after a 1-week washout from their usual antipsychotic therapy.
OG002	Part B: Add-on Therapy (Placebo)	Participants received placebo QD for 12 weeks in addition to their usual antipsychotic therapy.
OG003	Part B: Add-on Therapy (45 mg)	Participants received 45 mg of ralmitaront QD 12 weeks in addition to their usual antipsychotic therapy (prior to protocol v5; arm was removed thereafter).

Secondary

Maximum Serum Concentration (Cmax) of RO6889450

The pharmacokinetic population consisted of all participants who received at least one dose of study drug and who had data from at least one post-dose sample. It was pre-specified to not summarize and report Part A PK data, which was used only for model building.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Day 42

ID	Title	Description
OG000	Part B: Add-on Therapy (45 mg)	Participants received 45 mg of ralmitaront QD 12 weeks in addition to their usual antipsychotic therapy (prior to protocol v5; arm was removed thereafter).
OG001	Part B: Add-on Therapy (150 mg)	Participants received 150 mg of ralmitaront QD 12 weeks in addition to their usual antipsychotic therapy.
OG002	Part B: Add-on Therapy (300 mg)	Participants received 300 mg of ralmitaront QD 12 weeks in addition to their usual antipsychotic therapy (after protocol v5).

Units	Counts

Secondary

Area Under the Curve at Steady State (AUCss) of RO6889450

Posted

Geometric Mean

Geometric Coefficient of Variation

h*ng/mL

Day 42

ID	Title	Description
OG000	Part B: Add-on Therapy (45 mg)	Participants received 45 mg of ralmitaront QD 12 weeks in addition to their usual antipsychotic therapy (prior to protocol v5; arm was removed thereafter).
OG001	Part B: Add-on Therapy (150 mg)	Participants received 150 mg of ralmitaront QD 12 weeks in addition to their usual antipsychotic therapy.
OG002	Part B: Add-on Therapy (300 mg)	Participants received 300 mg of ralmitaront QD 12 weeks in addition to their usual antipsychotic therapy (after protocol v5).

Units	Counts

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	Part A: Monotherapy (Placebo)	Participants received placebo each day (QD) for 12 weeks after a 1-week washout from their usual antipsychotic therapy.	0	15	0	15	7	15
EG001	Part A: Monotherapy (150 mg)	Participants received 150 mg of ralmitaront QD for 12 weeks after a 1-week washout from their usual antipsychotic therapy.	0	12	1	12	4	12
EG002	Part B: Add-on Therapy (Placebo)	Participants received placebo QD for 12 weeks in addition to their usual antipsychotic therapy.	1	37	1	37	9	37
EG003	Part B: Add-on Therapy (45 mg)	Participants received 45 mg of ralmitaront QD 12 weeks in addition to their usual antipsychotic therapy (prior to protocol v5; arm was removed thereafter).	0	5	0	5	2	5
EG004	Part B: Add-on Therapy (150 mg)	Participants received 150 mg of ralmitaront QD 12 weeks in addition to their usual antipsychotic therapy.	0	30	2	30	8	30
EG005	Part B: Add-on Therapy (300 mg)	Participants received 300 mg of ralmitaront QD 12 weeks in addition to their usual antipsychotic therapy (after protocol v5).	0	32	0	32	4	32

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Accidental death	General disorders	MedDRA v22.1	Systematic Assessment	EG0000 events0 affected15 at risk EG0010 events0 affected12 at risk EG0021 events1 affected37 at risk EG0030 events0 affected5 at risk EG0040 events0 affected30 at risk EG0050 events0 affected32 at risk
Rhinovirus infection	Infections and infestations	MedDRA v22.1	Systematic Assessment	EG0000 events0 affected15 at risk EG0010 events0 affected12 at risk EG0020 events0 affected37 at risk EG003
Tumour haemorrhage	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v22.1	Systematic Assessment	EG0000 events0 affected15 at risk EG0010 events0 affected12 at risk EG0020 events0 affected37 at risk EG003
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA v22.1	Systematic Assessment	EG0000 events0 affected15 at risk EG0010 events0 affected12 at risk EG0020 events0 affected37 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA v22.1	Systematic Assessment	EG0000 events0 affected15 at risk EG0011 events1 affected12 at risk EG0020 events0 affected37 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Lip pain	Gastrointestinal disorders	MedDRA v22.1	Systematic Assessment	EG0000 events0 affected15 at risk EG0010 events0 affected12 at risk EG0020 events0 affected37 at risk EG0031 events1 affected5 at risk EG0040 events0 affected30 at risk EG0050 events0 affected32 at risk
Fatigue	General disorders	MedDRA v22.1	Systematic Assessment	EG0000 events0 affected15 at risk EG0010 events0 affected12 at risk EG0021 events1 affected37 at risk EG003
Non-cardiac chest pain	General disorders	MedDRA v22.1	Systematic Assessment	EG0000 events0 affected15 at risk EG0010 events0 affected12 at risk EG0020 events0 affected37 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA v22.1	Systematic Assessment	EG0000 events0 affected15 at risk EG0010 events0 affected12 at risk EG0022 events2 affected37 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA v22.1	Systematic Assessment	EG0002 events2 affected15 at risk EG0010 events0 affected12 at risk EG0020 events0 affected37 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA v22.1	Systematic Assessment	EG0000 events0 affected15 at risk EG0010 events0 affected12 at risk EG0020 events0 affected37 at risk EG003
Dizziness	Nervous system disorders	MedDRA v22.1	Systematic Assessment	EG0000 events0 affected15 at risk EG0010 events0 affected12 at risk EG0021 events1 affected37 at risk EG003
Dizziness postural	Nervous system disorders	MedDRA v22.1	Systematic Assessment	EG0000 events0 affected15 at risk EG0010 events0 affected12 at risk EG0020 events0 affected37 at risk EG003
Headache	Nervous system disorders	MedDRA v22.1	Systematic Assessment	EG0000 events0 affected15 at risk EG0010 events0 affected12 at risk EG0023 events3 affected37 at risk EG003
Somnolence	Nervous system disorders	MedDRA v22.1	Systematic Assessment	EG0000 events0 affected15 at risk EG0010 events0 affected12 at risk EG0022 events2 affected37 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA v22.1	Systematic Assessment	EG0000 events0 affected15 at risk EG0010 events0 affected12 at risk EG0020 events0 affected37 at risk EG003
Insomnia	Psychiatric disorders	MedDRA v22.1	Systematic Assessment	EG0001 events1 affected15 at risk EG0013 events2 affected12 at risk EG0020 events0 affected37 at risk EG003
Libido decreased	Psychiatric disorders	MedDRA v22.1	Systematic Assessment	EG0001 events1 affected15 at risk EG0010 events0 affected12 at risk EG0020 events0 affected37 at risk EG003
Schizophrenia	Psychiatric disorders	MedDRA v22.1	Systematic Assessment	EG0001 events1 affected15 at risk EG0010 events0 affected12 at risk EG0020 events0 affected37 at risk EG003
Influenza	Infections and infestations	MedDRA v22.1	Systematic Assessment	EG0001 events1 affected15 at risk EG0010 events0 affected12 at risk EG0020 events0 affected37 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA v22.1	Systematic Assessment	EG0000 events0 affected15 at risk EG0011 events1 affected12 at risk EG0020 events0 affected37 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA v22.1	Systematic Assessment	EG0000 events0 affected15 at risk EG0012 events2 affected12 at risk EG0020 events0 affected37 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA v22.1	Systematic Assessment	EG0000 events0 affected15 at risk EG0011 events1 affected12 at risk EG0020 events0 affected37 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA v22.1	Systematic Assessment	EG0000 events0 affected15 at risk EG0011 events1 affected12 at risk EG0020 events0 affected37 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA v22.1	Systematic Assessment	EG0001 events1 affected15 at risk EG0010 events0 affected12 at risk EG0020 events0 affected37 at risk EG003
Blood glucose increased	Investigations	MedDRA v22.1	Systematic Assessment	EG0000 events0 affected15 at risk EG0011 events1 affected12 at risk EG0020 events0 affected37 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA v22.1	Systematic Assessment	EG0001 events1 affected15 at risk EG0010 events0 affected12 at risk EG0021 events1 affected37 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA v22.1	Systematic Assessment	EG0000 events0 affected15 at risk EG0011 events1 affected12 at risk EG0020 events0 affected37 at risk EG003
Anaemia	Blood and lymphatic system disorders	MedDRA v22.1	Systematic Assessment	EG0000 events0 affected15 at risk EG0011 events1 affected12 at risk EG0020 events0 affected37 at risk EG003

First MCP Posted Date

ID	Term
D012559	Schizophrenia
D011618	Psychotic Disorders

Participants received 45 mg of ralmitaront QD 12 weeks in addition to their usual antipsychotic therapy (prior to protocol v5; arm was removed thereafter).

EG0041 events1 affected30 at risk