NCT03669640

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

Terminated Phase 2 Results posted Last updated 12 August 2024

What this trial tests

Phase 2 trial testing RO6889450 in Schizophrenia, Schizoaffective Disorder in 131 participants. Terminated before completion.

Timeline

4 December 2018

Primary endpoint
12 March 2023

12 March 2023

Quick facts

Lead sponsor	Hoffmann-La Roche
Phase	Phase 2
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	131
Start date	4 December 2018
Primary completion	12 March 2023
Estimated completion	12 March 2023
Sites	45 locations across Ukraine, Japan, United States, Spain

Drugs / interventions tested

• RO6889450 — full drug profile →
• Placebo

Conditions studied

• Schizophrenia, Schizoaffective Disorder — all drugs for Schizophrenia, Schizoaffective Disorder →

Sponsor

Hoffmann-La Roche — full company profile →

Who can join

Adults 18 to 55, any sex, with Schizophrenia, Schizoaffective Disorder. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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

Group	Value	95% CI
Part A: Monotherapy (Placebo)	5.71	± 2.81
Part A: Monotherapy (150 mg)	5.50	± 2.71
Part B: Add-on Therapy (Placebo)	6.0	± 2.3
Part B: Add-on Therapy (45 mg)	6.2	± 1.3
Part B: Add-on Therapy (150 mg)	5.8	± 1.9
Part B: Add-on Therapy (300 mg)	5.9	± 2.4

Week 12 (Day 84) Avolition/Apathy Subscore

Group	Value	95% CI
Part A: Monotherapy (Placebo)	5.50	± 2.55
Part A: Monotherapy (150 mg)	4.67	± 3.27
Part B: Add-on Therapy (Placebo)	5.0	± 1.9
Part B: Add-on Therapy (45 mg)	5.3	± 1.0
Part B: Add-on Therapy (150 mg)	4.1	± 2.1
Part B: Add-on Therapy (300 mg)	4.7	± 2.1

Clinical Global Impression Severity (CGI-S) Overall Scores Secondary · Baseline to week 12

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.

Baseline

Group	Value	95% CI
Part A: Monotherapy (Placebo)	3.600	± 0.507
Part A: Monotherapy (150 mg)	3.667	± 0.492
Part B: Add-on Therapy (Placebo)	4.1	± 0.7
Part B: Add-on Therapy (45 mg)	3.8	± 0.4
Part B: Add-on Therapy (150 mg)	3.9	± 0.7
Part B: Add-on Therapy (300 mg)	4.0	± 0.7

Day 14

Group	Value	95% CI
Part A: Monotherapy (Placebo)	3.467	± 0.516
Part A: Monotherapy (150 mg)	3.700	± 0.483
Part B: Add-on Therapy (Placebo)	4.0	± 0.6
Part B: Add-on Therapy (45 mg)	3.8	± 0.5
Part B: Add-on Therapy (150 mg)	3.8	± 0.6
Part B: Add-on Therapy (300 mg)	4.0	± 0.8

Day 28

Group	Value	95% CI
Part A: Monotherapy (Placebo)	3.500	± 0.527
Part A: Monotherapy (150 mg)	3.333	± 0.500
Part B: Add-on Therapy (Placebo)	3.9	± 0.8
Part B: Add-on Therapy (45 mg)	3.8	± 0.5
Part B: Add-on Therapy (150 mg)	3.8	± 0.6
Part B: Add-on Therapy (300 mg)	3.7	± 0.7

Day 42

Group	Value	95% CI
Part A: Monotherapy (Placebo)	3.636	± 0.809
Part A: Monotherapy (150 mg)	3.375	± 0.744
Part B: Add-on Therapy (Placebo)	3.8	± 0.8
Part B: Add-on Therapy (45 mg)	3.8	± 0.5
Part B: Add-on Therapy (150 mg)	3.6	± 0.6
Part B: Add-on Therapy (300 mg)	3.6	± 0.7

Day 56

Group	Value	95% CI
Part A: Monotherapy (Placebo)	3.636	± 0.505
Part A: Monotherapy (150 mg)	3.143	± 0.378
Part B: Add-on Therapy (Placebo)	3.8	± 0.8
Part B: Add-on Therapy (45 mg)	3.8	± 0.5
Part B: Add-on Therapy (150 mg)	3.5	± 0.7
Part B: Add-on Therapy (300 mg)	3.5	± 0.8

Day 70

Group	Value	95% CI
Part A: Monotherapy (Placebo)	3.500	± 0.707
Part A: Monotherapy (150 mg)	3.143	± 0.690

Day 84

Group	Value	95% CI
Part A: Monotherapy (Placebo)	3.700	± 0.483
Part A: Monotherapy (150 mg)	3.000	± 0.632
Part B: Add-on Therapy (Placebo)	3.7	± 0.8
Part B: Add-on Therapy (45 mg)	3.8	± 0.5
Part B: Add-on Therapy (150 mg)	3.4	± 0.6
Part B: Add-on Therapy (300 mg)	3.5	± 0.7

CGI-S Negative Symptoms (NS) Scores Secondary · Baseline to week 12

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.

Baseline

Group	Value	95% CI
Part A: Monotherapy (Placebo)	3.867	± 0.743
Part A: Monotherapy (150 mg)	3.917	± 0.669
Part B: Add-on Therapy (Placebo)	4.4	± 0.6
Part B: Add-on Therapy (45 mg)	4.2	± 0.4
Part B: Add-on Therapy (150 mg)	4.3	± 0.7
Part B: Add-on Therapy (300 mg)	4.3	± 0.7

Day 14

Group	Value	95% CI
Part A: Monotherapy (Placebo)	3.600	± 0.632
Part A: Monotherapy (150 mg)	3.800	± 0.632
Part B: Add-on Therapy (Placebo)	4.3	± 0.7
Part B: Add-on Therapy (45 mg)	4.3	± 0.5
Part B: Add-on Therapy (150 mg)	3.9	± 0.7
Part B: Add-on Therapy (300 mg)	4.1	± 0.7

Day 28

Group	Value	95% CI
Part A: Monotherapy (Placebo)	3.800	± 0.632
Part A: Monotherapy (150 mg)	3.778	± 0.667
Part B: Add-on Therapy (Placebo)	4.1	± 0.8
Part B: Add-on Therapy (45 mg)	4.3	± 0.5
Part B: Add-on Therapy (150 mg)	3.8	± 0.7
Part B: Add-on Therapy (300 mg)	3.9	± 0.7

Day 42

Group	Value	95% CI
Part A: Monotherapy (Placebo)	3.727	± 0.467
Part A: Monotherapy (150 mg)	3.625	± 0.518
Part B: Add-on Therapy (Placebo)	3.9	± 0.9
Part B: Add-on Therapy (45 mg)	4.0	± 0.0
Part B: Add-on Therapy (150 mg)	3.8	± 0.7
Part B: Add-on Therapy (300 mg)	3.7	± 0.7

Day 56

Group	Value	95% CI
Part A: Monotherapy (Placebo)	3.636	± 0.674
Part A: Monotherapy (150 mg)	3.714	± 0.756
Part B: Add-on Therapy (Placebo)	3.9	± 0.8
Part B: Add-on Therapy (45 mg)	4.0	± 0.0
Part B: Add-on Therapy (150 mg)	3.6	± 0.7
Part B: Add-on Therapy (300 mg)	3.5	± 0.7

Day 70

Group	Value	95% CI
Part A: Monotherapy (Placebo)	3.500	± 0.527
Part A: Monotherapy (150 mg)	3.286	± 0.756

Day 84

Group	Value	95% CI
Part A: Monotherapy (Placebo)	3.400	± 0.516
Part A: Monotherapy (150 mg)	3.167	± 0.753
Part B: Add-on Therapy (Placebo)	3.9	± 0.8
Part B: Add-on Therapy (45 mg)	3.8	± 0.5
Part B: Add-on Therapy (150 mg)	3.4	± 0.6
Part B: Add-on Therapy (300 mg)	3.5	± 0.9

Clinical Global Impression - Improvement (CGI-I) Overall Scores Secondary · Up to Week 12 (Day 84)

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.

Day 14

Group	Value	95% CI
Part A: Monotherapy (Placebo)	3.71	± 0.91
Part A: Monotherapy (150 mg)	3.56	± 0.53
Part B: Add-on Therapy (Placebo)	3.7	± 0.4
Part B: Add-on Therapy (45 mg)	4.0	± 0.0
Part B: Add-on Therapy (150 mg)	3.6	± 0.5
Part B: Add-on Therapy (300 mg)	3.6	± 0.6

Day 21

Group	Value	95% CI
Part A: Monotherapy (Placebo)	4.00	± NA
Part A: Monotherapy (150 mg)	2.00	± NA

Day 28

Group	Value	95% CI
Part A: Monotherapy (Placebo)	3.56	± 0.73
Part A: Monotherapy (150 mg)	3.50	± 0.76
Part B: Add-on Therapy (Placebo)	3.5	± 0.7
Part B: Add-on Therapy (45 mg)	4.0	± 0.0
Part B: Add-on Therapy (150 mg)	3.5	± 0.8
Part B: Add-on Therapy (300 mg)	3.4	± 0.8

Day 35

Group	Value	95% CI
Part A: Monotherapy (Placebo)	3.50	± 0.71

Day 42

Group	Value	95% CI
Part A: Monotherapy (Placebo)	3.73	± 0.65
Part A: Monotherapy (150 mg)	3.29	± 0.76
Part B: Add-on Therapy (Placebo)	3.4	± 0.7
Part B: Add-on Therapy (45 mg)	3.8	± 0.5
Part B: Add-on Therapy (150 mg)	3.3	± 0.8
Part B: Add-on Therapy (300 mg)	3.3	± 0.9

Day 56

Group	Value	95% CI
Part A: Monotherapy (Placebo)	3.70	± 0.48
Part A: Monotherapy (150 mg)	3.14	± 0.69
Part B: Add-on Therapy (Placebo)	3.4	± 0.7
Part B: Add-on Therapy (45 mg)	3.8	± 0.5
Part B: Add-on Therapy (150 mg)	3.4	± 0.9
Part B: Add-on Therapy (300 mg)	3.1	± 1.0

Day 70

Group	Value	95% CI
Part A: Monotherapy (Placebo)	3.50	± 0.71
Part A: Monotherapy (150 mg)	2.86	± 0.90

Day 84

Group	Value	95% CI
Part A: Monotherapy (Placebo)	3.80	± 0.42
Part A: Monotherapy (150 mg)	3.00	± 0.63
Part B: Add-on Therapy (Placebo)	3.2	± 0.7
Part B: Add-on Therapy (45 mg)	3.8	± 0.5
Part B: Add-on Therapy (150 mg)	3.0	± 0.9
Part B: Add-on Therapy (300 mg)	3.0	± 1.0

CGI-I Negative Symptoms Scores Secondary · Up to Week 12 (Day 84)

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: 1. = Very much improved 2. = Much improved 3. = Minimally improved 4. = No change 5. = Minimally worse 6. = Much worse 7. = Very much worse

Day 14

Group	Value	95% CI
Part A: Monotherapy (Placebo)	3.71	± 0.61
Part A: Monotherapy (150 mg)	3.44	± 0.73
Part B: Add-on Therapy (Placebo)	3.7	± 0.5
Part B: Add-on Therapy (45 mg)	4.0	± 0.0
Part B: Add-on Therapy (150 mg)	3.5	± 0.6
Part B: Add-on Therapy (300 mg)	3.5	± 0.6

Day 21

Group	Value	95% CI
Part A: Monotherapy (Placebo)	5.00	± NA
Part A: Monotherapy (150 mg)	4.00	± NA

Day 28

Group	Value	95% CI
Part A: Monotherapy (Placebo)	3.44	± 0.73
Part A: Monotherapy (150 mg)	3.38	± 0.74
Part B: Add-on Therapy (Placebo)	3.5	± 0.7
Part B: Add-on Therapy (45 mg)	4.0	± 0.0
Part B: Add-on Therapy (150 mg)	3.3	± 0.7
Part B: Add-on Therapy (300 mg)	3.2	± 0.8

Day 35

Group	Value	95% CI
Part A: Monotherapy (Placebo)	4.50	± 0.71

Day 42

Group	Value	95% CI
Part A: Monotherapy (Placebo)	3.45	± 0.69
Part A: Monotherapy (150 mg)	3.43	± 0.79
Part B: Add-on Therapy (Placebo)	3.3	± 0.6
Part B: Add-on Therapy (45 mg)	3.5	± 0.6
Part B: Add-on Therapy (150 mg)	3.3	± 0.8
Part B: Add-on Therapy (300 mg)	3.2	± 0.8

Day 56

Group	Value	95% CI
Part A: Monotherapy (Placebo)	3.50	± 0.71
Part A: Monotherapy (150 mg)	3.43	± 0.53
Part B: Add-on Therapy (Placebo)	3.2	± 0.7
Part B: Add-on Therapy (45 mg)	3.5	± 0.6
Part B: Add-on Therapy (150 mg)	3.2	± 0.8
Part B: Add-on Therapy (300 mg)	2.9	± 0.8

Day 70

Group	Value	95% CI
Part A: Monotherapy (Placebo)	3.40	± 0.70
Part A: Monotherapy (150 mg)	3.00	± 0.82

Day 84

Group	Value	95% CI
Part A: Monotherapy (Placebo)	3.10	± 0.74
Part A: Monotherapy (150 mg)	2.83	± 0.41
Part B: Add-on Therapy (Placebo)	3.1	± 0.7
Part B: Add-on Therapy (45 mg)	3.0	± 0.8
Part B: Add-on Therapy (150 mg)	2.9	± 0.9
Part B: Add-on Therapy (300 mg)	2.8	± 0.9

Positive and Negative Syndrome Scale (PANSS) Total Scores Secondary · Baseline to week 12

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 (r

Baseline

Group	Value	95% CI
Part A: Monotherapy (Placebo)	67.43	± 9.35
Part A: Monotherapy (150 mg)	67.92	± 10.86
Part B: Add-on Therapy (Placebo)	71.4	± 10.3
Part B: Add-on Therapy (45 mg)	62.8	± 6.7
Part B: Add-on Therapy (150 mg)	69.6	± 11.1
Part B: Add-on Therapy (300 mg)	67.8	± 11.1

Day 14

Group	Value	95% CI
Part A: Monotherapy (Placebo)	68.38	± 10.37
Part A: Monotherapy (150 mg)	69.00	± 11.40
Part B: Add-on Therapy (Placebo)	67.3	± 8.5
Part B: Add-on Therapy (45 mg)	69.5	± 13.5
Part B: Add-on Therapy (150 mg)	67.4	± 10.5
Part B: Add-on Therapy (300 mg)	67.9	± 13.6

Day 28

Group	Value	95% CI
Part A: Monotherapy (Placebo)	66.10	± 10.38
Part A: Monotherapy (150 mg)	65.44	± 7.30
Part B: Add-on Therapy (Placebo)	67.0	± 10.9
Part B: Add-on Therapy (45 mg)	81.3	± 4.7
Part B: Add-on Therapy (150 mg)	66.8	± 11.4
Part B: Add-on Therapy (300 mg)	66.5	± 11.1

Day 42

Group	Value	95% CI
Part A: Monotherapy (Placebo)	70.09	± 10.88
Part A: Monotherapy (150 mg)	65.88	± 12.01
Part B: Add-on Therapy (Placebo)	68.3	± 12.7
Part B: Add-on Therapy (45 mg)	73.3	± 9.8
Part B: Add-on Therapy (150 mg)	61.8	± 10.9
Part B: Add-on Therapy (300 mg)	64.1	± 12.5

Day 56

Group	Value	95% CI
Part A: Monotherapy (Placebo)	66.60	± 8.13
Part A: Monotherapy (150 mg)	61.14	± 6.91
Part B: Add-on Therapy (Placebo)	64.3	± 11.7
Part B: Add-on Therapy (45 mg)	70.0	± 7.1
Part B: Add-on Therapy (150 mg)	63.2	± 14.4
Part B: Add-on Therapy (300 mg)	61.4	± 11.7

Day 70

Group	Value	95% CI
Part A: Monotherapy (Placebo)	68.50	± 7.65
Part A: Monotherapy (150 mg)	59.57	± 7.14

Day 84 (Week 12)

Group	Value	95% CI
Part A: Monotherapy (Placebo)	64.70	± 13.92
Part A: Monotherapy (150 mg)	59.17	± 6.27
Part B: Add-on Therapy (Placebo)	64.4	± 12.2
Part B: Add-on Therapy (45 mg)	74.8	± 7.2
Part B: Add-on Therapy (150 mg)	59.0	± 11.1
Part B: Add-on Therapy (300 mg)	60.9	± 11.3

PANSS Symptom Factor Scores Secondary · Baseline to week 12

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.

Baseline - Negative symptoms

Group	Value	95% CI
Part A: Monotherapy (Placebo)	21.29	± 4.45
Part A: Monotherapy (150 mg)	21.00	± 5.20
Part B: Add-on Therapy (Placebo)	23.0	± 4.7
Part B: Add-on Therapy (45 mg)	20.6	± 3.3
Part B: Add-on Therapy (150 mg)	23.3	± 4.7
Part B: Add-on Therapy (300 mg)	23.5	± 4.1

Day 14 - Negative symptoms

Group	Value	95% CI
Part A: Monotherapy (Placebo)	22.46	± 5.13
Part A: Monotherapy (150 mg)	20.40	± 3.95
Part B: Add-on Therapy (Placebo)	22.9	± 3.4
Part B: Add-on Therapy (45 mg)	20.8	± 2.9
Part B: Add-on Therapy (150 mg)	21.8	± 4.5
Part B: Add-on Therapy (300 mg)	22.2	± 5.3

Day 28 - Negative symptoms

Group	Value	95% CI
Part A: Monotherapy (Placebo)	18.40	± 6.67
Part A: Monotherapy (150 mg)	20.44	± 3.68
Part B: Add-on Therapy (Placebo)	20.9	± 4.8
Part B: Add-on Therapy (45 mg)	20.3	± 3.1
Part B: Add-on Therapy (150 mg)	21.5	± 4.0
Part B: Add-on Therapy (300 mg)	22.1	± 4.9

Day 42 - Negative symptoms

Group	Value	95% CI
Part A: Monotherapy (Placebo)	21.09	± 5.45
Part A: Monotherapy (150 mg)	19.00	± 5.50
Part B: Add-on Therapy (Placebo)	21.3	± 4.5
Part B: Add-on Therapy (45 mg)	22.3	± 3.2
Part B: Add-on Therapy (150 mg)	21.5	± 5.1
Part B: Add-on Therapy (300 mg)	20.7	± 5.1

Day 56 - Negative symptoms

Group	Value	95% CI
Part A: Monotherapy (Placebo)	21.10	± 5.93
Part A: Monotherapy (150 mg)	18.71	± 4.72
Part B: Add-on Therapy (Placebo)	20.4	± 4.7
Part B: Add-on Therapy (45 mg)	21.8	± 4.2
Part B: Add-on Therapy (150 mg)	19.8	± 4.9
Part B: Add-on Therapy (300 mg)	20.3	± 5.7

Day 70 - Negative symptoms

Group	Value	95% CI
Part A: Monotherapy (Placebo)	21.20	± 5.07
Part A: Monotherapy (150 mg)	17.71	± 2.75

Day 84 (Week 12) - Negative symptoms

Group	Value	95% CI
Part A: Monotherapy (Placebo)	18.90	± 5.38
Part A: Monotherapy (150 mg)	15.33	± 3.08
Part B: Add-on Therapy (Placebo)	20.5	± 5.9
Part B: Add-on Therapy (45 mg)	22.5	± 4.8
Part B: Add-on Therapy (150 mg)	18.6	± 4.4
Part B: Add-on Therapy (300 mg)	19.4	± 4.8

Baseline - Positive symptoms

Group	Value	95% CI
Part A: Monotherapy (Placebo)	17.93	± 3.99
Part A: Monotherapy (150 mg)	19.75	± 3.93
Part B: Add-on Therapy (Placebo)	18.9	± 4.6
Part B: Add-on Therapy (45 mg)	18.0	± 3.7
Part B: Add-on Therapy (150 mg)	17.6	± 4.2
Part B: Add-on Therapy (300 mg)	17.2	± 5.4

Brief Negative Symptom Scale (BNSS) Total Scores Secondary · Baseline to 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.

Baseline

Group	Value	95% CI
Part A: Monotherapy (Placebo)	34.79	± 14.98
Part A: Monotherapy (150 mg)	35.17	± 13.68
Part B: Add-on Therapy (Placebo)	36.6	± 14.9
Part B: Add-on Therapy (45 mg)	36.4	± 6.7
Part B: Add-on Therapy (150 mg)	38.1	± 13.7
Part B: Add-on Therapy (300 mg)	38.4	± 13.8

Day 14

Group	Value	95% CI
Part A: Monotherapy (Placebo)	35.08	± 12.48
Part A: Monotherapy (150 mg)	32.90	± 13.47
Part B: Add-on Therapy (Placebo)	36.1	± 11.4
Part B: Add-on Therapy (45 mg)	29.3	± 11.1
Part B: Add-on Therapy (150 mg)	34.1	± 12.8
Part B: Add-on Therapy (300 mg)	35.2	± 12.8

Day 28

Group	Value	95% CI
Part A: Monotherapy (Placebo)	29.90	± 14.49
Part A: Monotherapy (150 mg)	33.25	± 8.94
Part B: Add-on Therapy (Placebo)	32.6	± 12.9
Part B: Add-on Therapy (45 mg)	32.7	± 7.4
Part B: Add-on Therapy (150 mg)	33.1	± 13.4
Part B: Add-on Therapy (300 mg)	36.5	± 10.3

Day 42

Group	Value	95% CI
Part A: Monotherapy (Placebo)	34.09	± 11.95
Part A: Monotherapy (150 mg)	36.38	± 14.79
Part B: Add-on Therapy (Placebo)	35.1	± 11.3
Part B: Add-on Therapy (45 mg)	35.0	± 11.8
Part B: Add-on Therapy (150 mg)	35.5	± 12.6
Part B: Add-on Therapy (300 mg)	32.7	± 13.4

Day 56

Group	Value	95% CI
Part A: Monotherapy (Placebo)	37.40	± 18.60
Part A: Monotherapy (150 mg)	34.00	± 12.12
Part B: Add-on Therapy (Placebo)	30.3	± 12.1
Part B: Add-on Therapy (45 mg)	37.5	± 16.3
Part B: Add-on Therapy (150 mg)	30.8	± 11.8
Part B: Add-on Therapy (300 mg)	32.3	± 13.6

Day 70

Group	Value	95% CI
Part A: Monotherapy (Placebo)	33.10	± 7.23
Part A: Monotherapy (150 mg)	34.00	± 15.15

Day 84 (Week 12)

Group	Value	95% CI
Part A: Monotherapy (Placebo)	30.40	± 12.86
Part A: Monotherapy (150 mg)	28.17	± 20.44
Part B: Add-on Therapy (Placebo)	32.7	± 13.4
Part B: Add-on Therapy (45 mg)	33.3	± 10.6
Part B: Add-on Therapy (150 mg)	29.6	± 9.2
Part B: Add-on Therapy (300 mg)	29.2	± 12.4

Defeatist Performance Attitude Scale (DPAS) Scores Secondary · Baseline to week 12

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).

Baseline

Group	Value	95% CI
Part A: Monotherapy (Placebo)	34.73	± 13.92
Part A: Monotherapy (150 mg)	30.25	± 12.43
Part B: Add-on Therapy (Placebo)	40.2	± 14.6
Part B: Add-on Therapy (45 mg)	40.0	± 6.4
Part B: Add-on Therapy (150 mg)	38.2	± 15.9
Part B: Add-on Therapy (300 mg)	35.9	± 16.2

Day 42

Group	Value	95% CI
Part A: Monotherapy (Placebo)	40.54	± 16.37
Part A: Monotherapy (150 mg)	27.50	± 18.65
Part B: Add-on Therapy (Placebo)	37.5	± 14.2
Part B: Add-on Therapy (45 mg)	39.3	± 9.3
Part B: Add-on Therapy (150 mg)	38.8	± 16.2
Part B: Add-on Therapy (300 mg)	36.0	± 16.2

Day 84 (Week 12)

Group	Value	95% CI
Part A: Monotherapy (Placebo)	38.80	± 13.42
Part A: Monotherapy (150 mg)	16.00	± 4.98
Part B: Add-on Therapy (Placebo)	36.0	± 15.2
Part B: Add-on Therapy (45 mg)	54.3	± 16.4
Part B: Add-on Therapy (150 mg)	39.0	± 19.9
Part B: Add-on Therapy (300 mg)	32.2	± 13.6

Number of Participants With Suicidal Ideation or Behavior, and Self-injurious Behavior Without Suicidal Intent on the Columbia Suicide Severity Rating Scale (C-SSRS) Secondary · Baseline through Day 84

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

Suicidal ideation or behavior

Group	Value	95% CI
Part A: Monotherapy (Placebo)	0
Part A: Monotherapy (150 mg)	0
Part B: Add-on Therapy (Placebo)	1
Part B: Add-on Therapy (45 mg)	0
Part B: Add-on Therapy (150 mg)	2
Part B: Add-on Therapy (300 mg)	1

Self-injurious behavior without suicidal intent

Group	Value	95% CI
Part A: Monotherapy (Placebo)	1
Part A: Monotherapy (150 mg)	0
Part B: Add-on Therapy (Placebo)	0
Part B: Add-on Therapy (45 mg)	0
Part B: Add-on Therapy (150 mg)	0
Part B: Add-on Therapy (300 mg)	0

Extrapyramidal Symptom Rating Scale, Abbreviated (ESRS-A) Secondary · Baseline through Day 84

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).

Akathisia Baseline

Group	Value	95% CI
Part A: Monotherapy (Placebo)	0.07	± 0.26
Part A: Monotherapy (150 mg)	0.08	± 0.29
Part B: Add-on Therapy (Placebo)	0.27	± 0.87
Part B: Add-on Therapy (45 mg)	0.00	± 0.00
Part B: Add-on Therapy (150 mg)	0.27	± 0.83
Part B: Add-on Therapy (300 mg)	0.38	± 0.98

Akathisia Day 84

Group	Value	95% CI
Part A: Monotherapy (Placebo)	0.00	± 0.00
Part A: Monotherapy (150 mg)	0.00	± 0.00
Part B: Add-on Therapy (Placebo)	0.29	± 0.94
Part B: Add-on Therapy (45 mg)	0.00	± 0.00
Part B: Add-on Therapy (150 mg)	0.10	± 0.45
Part B: Add-on Therapy (300 mg)	0.10	± 0.44

Dyskinesia Baseline

Group	Value	95% CI
Part A: Monotherapy (Placebo)	0.00	± 0.00
Part A: Monotherapy (150 mg)	0.33	± 0.89
Part B: Add-on Therapy (Placebo)	0.46	± 1.95
Part B: Add-on Therapy (45 mg)	0.75	± 0.96
Part B: Add-on Therapy (150 mg)	0.17	± 0.38
Part B: Add-on Therapy (300 mg)	0.63	± 1.68

Dyskinesia Day 84

Group	Value	95% CI
Part A: Monotherapy (Placebo)	0.10	± 0.32
Part A: Monotherapy (150 mg)	0.00	± 0.00
Part B: Add-on Therapy (Placebo)	0.16	± 0.90
Part B: Add-on Therapy (45 mg)	0.00	± 0.00
Part B: Add-on Therapy (150 mg)	0.15	± 0.49
Part B: Add-on Therapy (300 mg)	0.29	± 0.72

Dystonia Baseline

Group	Value	95% CI
Part A: Monotherapy (Placebo)	0.07	± 0.26
Part A: Monotherapy (150 mg)	0.00	± 0.00
Part B: Add-on Therapy (Placebo)	0.24	± 0.86
Part B: Add-on Therapy (45 mg)	0.00	± 0.00
Part B: Add-on Therapy (150 mg)	0.03	± 0.18
Part B: Add-on Therapy (300 mg)	0.16	± 0.51

Dystonia Day 84

Group	Value	95% CI
Part A: Monotherapy (Placebo)	0.00	± 0.00
Part A: Monotherapy (150 mg)	0.00	± 0.00
Part B: Add-on Therapy (Placebo)	0.26	± 1.03
Part B: Add-on Therapy (45 mg)	0.00	± 0.00
Part B: Add-on Therapy (150 mg)	0.05	± 0.22
Part B: Add-on Therapy (300 mg)	0.00	± 0.00

Parkinsonism Baseline

Group	Value	95% CI
Part A: Monotherapy (Placebo)	0.13	± 0.52
Part A: Monotherapy (150 mg)	0.42	± 1.00
Part B: Add-on Therapy (Placebo)	1.03	± 2.36
Part B: Add-on Therapy (45 mg)	2.20	± 1.92
Part B: Add-on Therapy (150 mg)	2.00	± 3.24
Part B: Add-on Therapy (300 mg)	2.22	± 4.15

Parkinsonism Day 84

Group	Value	95% CI
Part A: Monotherapy (Placebo)	0.20	± 0.63
Part A: Monotherapy (150 mg)	0.33	± 0.82
Part B: Add-on Therapy (Placebo)	1.03	± 2.87
Part B: Add-on Therapy (45 mg)	0.33	± 0.58
Part B: Add-on Therapy (150 mg)	1.15	± 2.68
Part B: Add-on Therapy (300 mg)	1.00	± 2.30

Maximum Serum Concentration (Cmax) of RO6889450 Secondary · Day 42

Group	Value	95% CI
Part B: Add-on Therapy (45 mg)	157	± 58.7
Part B: Add-on Therapy (150 mg)	794	± 40.3
Part B: Add-on Therapy (300 mg)	1550	± 43.9

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to Day 84 (Week 12). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Part A: Monotherapy (Placebo)

Serious: 0/15 (0%)

Deaths: 0/15

Part A: Monotherapy (150 mg)

Serious: 1/12 (8%)

Deaths: 0/12

Part B: Add-on Therapy (Placebo)

Serious: 1/37 (3%)

Deaths: 1/37

Part B: Add-on Therapy (45 mg)

Serious: 0/5 (0%)

Deaths: 0/5

Part B: Add-on Therapy (150 mg)

Serious: 2/30 (7%)

Deaths: 0/30

Part B: Add-on Therapy (300 mg)

Serious: 0/32 (0%)

Deaths: 0/32

Serious adverse events (5 terms)

Reaction	System	Part A: Monotherapy (Place…	Part A: Monotherapy (150 mg)	Part B: Add-on Therapy (Pl…	Part B: Add-on Therapy (45…	Part B: Add-on Therapy (15…	Part B: Add-on Therapy (30…
Accidental death	General disorders	—	—	—	—	—	—
Rhinovirus infection	Infections and infestations	—	—	—	—	—	—
Tumour haemorrhage	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—	—
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—	—	—

Other adverse events (24 terms — click to expand)

Reaction	System	Part A: Monotherapy (Place…	Part A: Monotherapy (150 mg)	Part B: Add-on Therapy (Pl…	Part B: Add-on Therapy (45…	Part B: Add-on Therapy (15…	Part B: Add-on Therapy (30…
Nasopharyngitis	Infections and infestations	—	—	—	—	—	—
Headache	Nervous system disorders	—	—	—	—	—	—
Fatigue	General disorders	—	—	—	—	—	—
Upper respiratory tract infection	Infections and infestations	—	—	—	—	—	—
Dizziness	Nervous system disorders	—	—	—	—	—	—
Somnolence	Nervous system disorders	—	—	—	—	—	—
Rash	Skin and subcutaneous tissue disorders	—	—	—	—	—	—
Insomnia	Psychiatric disorders	—	—	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—	—	—
Lip pain	Gastrointestinal disorders	—	—	—	—	—	—
Non-cardiac chest pain	General disorders	—	—	—	—	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—
Dizziness postural	Nervous system disorders	—	—	—	—	—	—
Libido decreased	Psychiatric disorders	—	—	—	—	—	—
Schizophrenia	Psychiatric disorders	—	—	—	—	—	—
Influenza	Infections and infestations	—	—	—	—	—	—
Urinary tract infection	Infections and infestations	—	—	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—	—	—
Alanine aminotransferase increased	Investigations	—	—	—	—	—	—
Blood glucose increased	Investigations	—	—	—	—	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—	—	—	—	—
Hyperglycaemia	Metabolism and nutrition disorders	—	—	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—	—	—

Most-reported serious reactions: Accidental death, Rhinovirus infection, Tumour haemorrhage, Chronic obstructive pulmonary disease, Constipation.

Data from ClinicalTrials.gov NCT03669640 adverse events section.

Sponsor's own description

This study investigates the effects of RO6889450 on the negative symptoms associated with schizophrenia and schizoaffective disorder.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. The future of psychopharmacology: a critical appraisal of ongoing phase 2/3 trials, and of some current trends aiming to de-risk trial programmes of novel agents.
   Correll CU, Solmi M, Cortese S, Fava M, et al · · 2023 · cited 90× · PMID 36640403 · DOI 10.1002/wps.21056
2. Therapeutic Potential of TAAR1 Agonists in Schizophrenia: Evidence from Preclinical Models and Clinical Studies.
   Dedic N, Dworak H, Zeni C, Rutigliano G, et al · · 2021 · cited 78× · PMID 34947997 · DOI 10.3390/ijms222413185
3. New and emerging treatments for schizophrenia: a narrative review of their pharmacology, efficacy and side effect profile relative to established antipsychotics.
   Lobo MC, Whitehurst TS, Kaar SJ, Howes OD. · · 2022 · cited 74× · PMID 34838528 · DOI 10.1016/j.neubiorev.2021.11.032
4. TAAR1 dependent and independent actions of the potential antipsychotic and dual TAAR1/5-HT_1A receptor agonist SEP-383856.
   Saarinen M, Mantas I, Flais I, Ågren R, et al · · 2022 · cited 30× · PMID 36100653 · DOI 10.1038/s41386-022-01421-2
5. New Developments in the Treatment of Schizophrenia: An Expert Roundtable.
   Kantrowitz JT, Correll CU, Jain R, Cutler AJ. · · 2023 · cited 23× · PMID 36932673 · DOI 10.1093/ijnp/pyad011
6. Unlocking the Therapeutic Potential of Ulotaront as a Trace Amine-Associated Receptor 1 Agonist for Neuropsychiatric Disorders.
   Kuvarzin SR, Sukhanov I, Onokhin K, Zakharov K, et al · · 2023 · cited 17× · PMID 37509616 · DOI 10.3390/biomedicines11071977
7. In Vitro Comparison of Ulotaront (SEP-363856) and Ralmitaront (RO6889450): Two TAAR1 Agonist Candidate Antipsychotics.
   Ågren R, Betari N, Saarinen M, Zeberg H, et al · · 2023 · cited 16× · PMID 37549917 · DOI 10.1093/ijnp/pyad049
8. Increased Metabolic Potential, Efficacy, and Safety of Emerging Treatments in Schizophrenia.
   Meyer JM, Correll CU. · · 2023 · cited 11× · PMID 37470979 · DOI 10.1007/s40263-023-01022-7